Memorandum submitted by the Ministry of
Agriculture, Fisheries and Food (R 8)
(A) RESEARCH
INTO TSES
Size of MAFF's research programme
1. MAFF's expenditure on TSE research has increased
from a zero base in 1986-87 to an estimated spend of £17.3
million in 2001-02. Annual expenditure figures during this period
are shown in Table 1.
Table 1
MAFF EXPENDITURE ON TSE RESEARCH BETWEEN
1986-87 AND 2001-02 (£000)
1986-87
| 1987-88 | 1988-89
| 1989-90 | 1990-91
| 1991-92 | 1992-93
| 1993-94 |
0 | 200 |
900 | 1,000 |
2,300 | 4,200
| 5,700 | 6,200
|
|
| | |
| |
| |
1994-95 | 1995-96
| 1996-97 | 1997-98
| 1998-99 | 1999-2000
| 2000-01 | 2001-02
| TOTAL |
5,800 | 5,600 | 6,800
| 10,100 | 12,651
| 15,026 | 13,450
| 17,348 | 107,275 |
| |
| | |
| |
| |
2. This expenditure represents 54 per cent of the total government
expenditure on TSE research during the same period. The remaining
46 per cent was provided by BBSRC, MRC and DH and, since its establishment,
FSA. Responsibility for 11 TSE projects and £2.5 million
of MAFF's research funding was transferred to FSA in April 2000.
Co-ordination of the Research Effort
3. Co-ordination with other funders' programmes is achieved
through two committees, the High Level Committee on Research into
TSEs and the TSE R & D Joint Funders' Co-ordination Group.
The terms of reference and current membership of these committees
are shown in Annex 1.
4. The High Level Committee was established in 1997 with
the role of overseeing the TSE research programme and ensuring
that progress is as rapid and as effective as possible. The role
of this committee is being reviewed as part of the follow-up to
the Phillips Inquiry.
5. Also in 1997, the remit of the Joint Funders' Group was
extended to achieve co-ordination between research into animal
and human TSEs. The Joint Funders maintain a database of all the
TSE research in the UK. This can be found on the MRC's website
and is accessible by the general public. They also arrange workshops
so that the funding organisations can monitor the progress of
the research and discuss the implications of emerging results.
Regular reviews of this kind allow new areas of work and gaps
in the programme to be identified.
6. These co-ordination mechanisms represent a considerable
advance on the position that pertained in the period covered by
the Phillips Inquiry. One of the conclusions in the Inquiry Report
was that "where a problem in animal and human health arises
that leads to demands for research on the scale and diversity
required by BSE it is desirable that Government Departments and
Agencies co-ordinate their efforts" (Volume 1, paragraph
1289).
7. In the case of TSE research these two committees have
provided effective co-ordination. However, the conclusion has
implications for government research in general and how this might
be addressed is being considered currently by the Office of Science
and Technology.
Capital Investment
8. Research on TSEs requires specialised laboratory facilities
designed to provide a high level of disease containment. In the
case of animal TSEs large animal housing is also required. Historically
the availability of such facilities was as much of a limiting
factor as the availability of research funding.
9. Since 1997 MAFF has invested £54.6 million in
capital expenditure at the Veterinary Laboratory Agency on new
facilities for TSE research. This has resulted in the establishment
of the biggest large animal facility ever in the history of veterinary
research. The procurement of these facilities has taken time,
not only because of the time needed to build facilities on this
scale, but also because of the requirements of the Animal Scientific
Procedures Order of 1986 and the evolving and more demanding requirements
from Health and Safety guidance and legislation. This was supplemented
in 2000 by an additional capital sum of £13.9 million to
expand the facilities available for work on TSEs in sheep. This
sum was provided from the Treasury's capital modernisation fund
and is providing new facilities for both VLA and the Institute
for Animal Health.
Focus of MAFF's TSE Research Programme
10. The focus of MAFF's research programme has gradually
changed as new scientific findings have emerged and as the BSE
epidemic has responded to the control measures put in place to
prevent its dissemination by meat and bone meal. Greater emphasis
has now been placed on TSEs in sheep and the knowledge that is
needed to avoid the reoccurrence of a BSE-like problem. This change
in emphasis is illustrated in table 2 which shows how the percentage
spend on sheep has increased over time.
Table 2
RELATIVE SPEND ON SHEEP TSE RESEARCH
Year | 1992-93 |
1993-94 | 1994-95 |
1995-96 | 1996-97 |
Sheep TSE Research (£) | 1,038,649
| 1,892,465 | 1,544,798 | 1,754,925
| 2,422,024 |
Total TSE Research (£) | 5,700,000
| 6,200,000 | 5,800,000 | 5,600,000
| 6,800,000 |
% sheep/total | 18.22 | 30.52
| 26.63 | 31.34 | 35.62
|
| |
| | | |
Year | 1997-98 |
1998-99 | 1999-2000
| 2000-01* | |
Sheep TSE Research (£) | 3,764,982
| 5,087,377 | 7,205,227 | 8,304,721
| |
Total TSE Research (£) | 10,100,000
| 12,651,000 | 15,026,523 |
13,450,000 | |
% sheep/total | 37.28 | 40.21
| 47.95 | 61.75 |
|
| | |
| | |
* 2000-01 not final figures. Baseline fell due to transfer of
projects totalling £2.5 million to the FSA.
Note 1: Sheep projects include research into
BSE in sheep.
Note 2: Some projects cover both sheep and other
TSE work or are relevant to both (eg diagnostics). These figures
should be taken only as a guide to the relative spends.
11. Research in an area such as this does take time however,
and many of the studies commissioned some years ago are still
ongoing and are only now coming to fruition. This is inevitable
because of the protracted incubation period, which, in the case
of BSE under natural conditions, is on average five years.
12. MAFF's current TSE programme can be divided broadly into
four areas: transmission, epidemiology, pathogenesis and diagnostics.
There is not perfect demarcation between these areas as some projects
could be said to fit into more than one category. Nevertheless,
it does provide a useful breakdown for the purposes of describing
the programme.
TRANSMISSION
13. Although there is general agreement that ruminant
derived meat and bone meal was the means by which BSE was spread
in the cattle population it remains important to establish whether
there are alternative routes of transmission. Gaining a better
understanding of how this and other TSEs are transmitted will
assist with control and eradication policies and in preventing
another TSE causing a problem of the magnitude of BSE.
14. The Phillips Inquiry report notes the value of further
work on transmission. It states (Volume 2, paragraph 3.161) that
"Future studies of risk factors for vCJD, and further investigation
of TSE transmission in general, are likely to be important in
furthering our understanding of what determined whether or not
an individual animal contracted BSE following exposure to the
agent".
15. In the MAFF programme transmission studies have focused
on providing information in the following areas.
Whether BSE can be transmitted to other food species
16. Studies with pigs and domestic fowl have been undertaken
in which these species have been challenged with BSE by the oral
route and by direct injection into the brain. These studies are
largely complete and responsibility for them transferred to FSA
in April 2000. In their recent review of BSE controls, the FSA
recommended that more work should be done in this area. SEAC has
made a similar recommendation. MAFF will be discussing how this
might be taken forward with FSA.
Lateral and maternal transmission
17. In cattle the work on lateral and maternal transmission
is largely historic. The possibility of lateral transmission was
examined by analysis of the within herd incidence data collected
during the course of the BSE epidemic. This provides no evidence
for lateral transmission.
18. Maternal transmission was looked at in a cohort study
which compared the development of BSE in groups of 300 calves
from affected and non-affected dams. This was completed in 1997.
Analysis of the results indicated that the risk of maternal transmission
could be around 10 per cent for calves born to dams that were
clinically affected, or were within the last six months of clinical
onset.
19. The role of the placenta and foetal membranes has
also been investigated. However, attempts to transmit BSE from
these tissues taken from parturient BSE cases to calves by the
oronasal route have failed. Infectivity has not been detected
in embryos, udder or milk either. The mechanism for maternal transmission
therefore remains unclear.
20. The current programme is concentrating on transmission
of TSEs in sheep. The picture here is more complex due to differences
in the susceptibility to scrapie of different PrP genotypes in
sheep. Two studies are in progress and three new proposals aimed
at investigating natural routes of transmission are under consideration
for funding.
21. The first of the experiments in progress is looking
at the vertical transmission of BSE in sheep of three different
PrP genotypes. The second is investigating maternal transmission
using embryos of a genotype known to be susceptible to a particular
strain of scrapie. These are transferred to ewes, some of which
are resistant to scrapie. Lambs are either born naturally or are
delivered by caesarean and hand reared.
Embryos and semen
22. Studies have been undertaken in both cattle and sheep.
In cattle a project to determine whether BSE can be transmitted
by embryo transfer is coming to a close. There has been no evidence
that embryos collected from BSE-affected cows whether sired by
healthy or BSE-infected bulls, transmit disease.
23. Semen used for AI in cattle has not been found to
be a risk factor in the occurrence of BSE.
24. The work with sheep is ongoing. Fifty embryos from
donor ewes with naturally acquired scrapie infection have been
transferred into scrapie-free Suffolk ewes imported from New Zealand.
The resultant lambs were born in 2000 and remain scrapie free
to date.
Effective exposure
25. Studies investigating what constitutes effective
oral exposure in cattle have shown that as little as one gram
of BSE-affected material will transmit disease. A second study
is now underway with oral dose levels between one gram and one
milligram of BSE-affected brain.
Tissue sources of infection
26. Studies to determine which tissues carry infectivity
have been extremely important in identifying high risk materials
that should be kept out of the food chain. Most bioassays for
tissue infectivity have been conducted in panels of mice. As noted
by Phillips, comparative studies have shown that bioassay in cattle
is approximately 500-fold more sensitive than in mice. At present
work is underway to see whether cattle pick up lower levels of
infection than mice. A wide range of tissues collected from a
former study which has assessed their infectivity in mice have
been inoculated into cattle. So far there have been no transmissions
to cattle from tissues which did not also transmit to mice.
27. A relatively new study started in 2000 is looking
at the extent to which there is underestimation of the infectivity
of sheep BSE tissues when tested in mice.
28. The species barrier is one of the reasons why the
mouse bioassay is less sensitive than bioassay in cattle. However,
it is very expensive to use calves for bioassay and the current
programme includes projects in which transgenic mice have been
developed. In transgenic mice the mouse prion gene is replaced
by PrP gene alleles from another species. Our programme includes
work on sheep and bovine transgenics, but human transgenic mice
are also being used in the study of CJD.
29. Studies on abnormal prion protein (PrPsc) distribution
and tissue infectivity in sheep are also underway. These include
studies on sheep of different PrP genotypes infected with natural
scrapie and studies of PrPsc distribution and infectivity in sheep
experimentally infected with BSE.
30. This work is of importance in providing information
on whether tissues from sheep of genotypes that are thought to
be resistant to scrapie and BSE carry infectivity. The National
Scrapie Plan, which aims to reduce and eventually eradicate scrapie
by selective breeding for resistance, would be compromised if
such animals could carry infectivity and act as a source of infection
for other sheep without themselves succumbing to clinical disease.
Genetic predisposition
31. In cattle polymorphisms in the bovine prion gene
have not yet been linked to disease risk in BSE. One study, designed
primarily to identify diagnostic markers for TSE infection in
blood may, however, shed some light on whether other genetic factors
are involved.
32. As has been mentioned earlier, there is genetic variability
in the susceptibility of sheep to scrapie and BSE. Variations
in the amino acids at particular points on the prion gene are
responsible. Although this is known, more information on the genetic
influence on resistance and the course of disease development
in sheep of different genotypes is required. This will be helpful
in implementing the National Scrapie Plan and will be essential
for any contingency plan that may need to be put in place if BSE
were to be found in sheep. Ongoing work is providing this information
in a study in which groups of three breeds of scrapie free, New
Zealand sheep and one breed from a British scrapie-free flock
of different genotypes have been challenged with a characterised
strain of scrapie or with cattle BSE.
Environmental exposure
33. A project which has begun only very recently is investigating
if and to what extent infectivity can persist in the soil in experimental
systems. A study of natural transmission of scrapie, which will
also study whether infection can result from exposure to scrapie
contaminated pasture is due to begin shortly.
34. There are two studies investigating the possible
significance of forage mites in the transmission of BSE and scrapie.
One aims to establish if there is a connection between TSEs in
sheep and cattle and their exposure to mites. The study has found
no evidence for consistent differences in mite numbers between
high and low incidence TSE farms. The other study is evaluating
the potential for replication of PrPSC and PrPBSE purified from
sheep and cattle brains respectively. The mites are also being
tested for infectivity by mice bioassay. This study was prompted
by scientific evidence that mites may play a role in transmission
of scrapie in Iceland.
EPIDEMIOLOGY
35. Epidemiology studies involve the collection of data
about a disease, its incidence and spread and the factors that
may be involved in the spread of infection. Quantifying the effect
of these factors is important in determining whether a disease
is sustainable by the routes of infection identified and whether
other routes are likely to be involved. Knowledge of the risk
factors for a disease can be used to target surveillance more
accurately.
BSE epidemiological studies
36. From the start of the BSE epidemic case data have
been collected which have been subjected to extensive analysis
by epidemiologists at VLA and at Oxford. These studies were crucial
in identifying meat and bone meal as the most likely vector of
infection and in allowing predictions of the size of the epidemic
and its duration to be made. Data analysis has also allowed the
effectiveness of the control measures to be monitored.
37. This work is continuing and further analysis is being
undertaken in a collaborative project between epidemiologists
at VLA and Professor Morris at Massey University, in New Zealand.
These studies are thought to be the first in which the time course
of an entire animal disease epidemic has been described at national
level.
Origin of the epidemic
38. Analysis of the epidemiological data to establish
whether BSE was likely to have started from a single source or
multiple sources has led to various theories on the origin of
BSE. This was considered extensively by the Phillips Inquiry,
which concluded that the origin of BSE was not scrapie, but probably
originated from a novel source early in the 1970s as a result
of a gene mutation in cattle, or possibly in sheep.
39. This conclusion is not accepted by some scientists
working in the field. The origin of the disease is of considerable
public interest and has implications for future surveillance and
control policies. The Minister of Agriculture, Fisheries and Food
and the Secretary of State for Health have therefore commissioned
a review of the current scientific understanding of the origin
of BSE. The review is being led by Professor Gabriel Horn from
the University of Cambridge.
40. Information from two current studies in which cattle
have been challenged with scrapie will also contribute to our
understanding of the origin of BSE. One involves sources of scrapie
isolate obtained both before and during the BSE epidemic. The
other is looking at the effects of scrapie inoculum of known titre
before and after rendering.
41. Epidemiological research of BSE is still concerned
with investigating the origin of BSE through the extensive analyses
which are possible and through the use of simulation modelling.
EPIDEMIOLOGICAL STUDIES
WITH SHEEP
42. Epidemiological studies with sheep aim to identify
risk factors that are important in the introduction and maintenance
of scrapie infection and disease in sheep flocks. The studies
are being undertaken using commercial flocks which have been recruited
for the purpose. Data from these studies will be used to construct
a mathematical model that describes the dynamics of scrapie between
flocks and how this is affected by genotype. This will allow the
most likely routes of transmission to be identified. The model
will also provide an estimate of the current prevalence of scrapie
and the impact of different control policies.
Strain typing
43. Differences in strain between TSE agents causing
disease are important epidemiologically in relation to the origin
of disease. Different strains may affect host species differently
and some may be more virulent than others, producing disease more
readily or more rapidly. Strain differences may also be important
diagnostically. Certainly in the case of BSE and scrapie a rapid
test that could differentiate between BSE and strains of scrapie
that have similar characteristics would be extremely valuable.
44. Part of MAFF's programme has been aimed at characterising
different strains of TSEs. To date, the characteristics of the
BSE agent have been very robust and only a single strain has been
identified. Throughout the BSE epidemic the VLA has undertaken
neuropathological monitoring of field cases to look for changes
in the biology of the causative agent and has failed to reveal
any. Most of the strain typing studies have been done with British
isolates however and it is possible that BSE in other countries
may show different characteristics. A new project which is due
to begin shortly will determine whether Swiss BSE is different
from the British one, although isolates examined early in the
Swiss epidemic behaved identically to those tested in Britain.
45. The position for scrapie is in marked contrast to
that for BSE. Here multiple strains of scrapie have been identified.
Strain typing, both to characterise the strains of scrapie encountered
in natural infection and to look for BSE in sheep in the national
UK flock is a feature of many of the sheep projects supported,
including the epidemiology projects referred to earlier.
Sheep surveillance
46. In its report published in April 1999 the SEAC sub-group
on research and surveillance for TSEs in sheep recommended that
more consideration should be given to ways of improving the ascertainment
of TSEs in sheep and that the possibility of undertaking some
targeted surveillance of farms that might be at higher risk from
BSE should be investigated. A SEAC sub-group on surveillance subsequently
considered the approaches that might be used to take forward this
recommendation.
47. In their report to the main committee the sub-group
identified the two most important objectives of the surveillance
as:
to look for BSE in the national sheep flock;
to provide a baseline assessment for the incidence
of scrapie so that change in incidence could be monitored.
48. They recommend that the approaches that should be
used to meet these aims were:
to define and agree the criteria that would be
used to determine what was and was not BSE;
to strain type all notified cases of scrapie,
provided the brains were in suitable condition;
to undertake a pilot study to identify the costs
and the practical constraints of undertaking a longitudinal study
of around 1,000 farms to establish a baseline for the incidence
of scrapie;
to repeat the anonymous postal survey of farmers
undertaken previously to establish how reproducible the results
were; and
to investigate which tissues carry infectivity
and are therefore the best to sample and the tests that might
be used to monitor changes in the prevalence of scrapie in sheep
going into slaughterhouses.
49. The main committee endorsed these recommendations
and a programme of work has now begun to take them forward.
50. To date BSE has not been found to have occurred naturally
in sheep. However, the Government is adopting a precautionary
approach and has for some time been operating a risk reduction
strategy in line with advice from SEAC and the Food Standards
Agency. This includes the research and surveillance programme
described here, the removal of specified risk material from the
food chain and the National Scrapie Plan to eliminate scrapie
from the national sheep flock.
51. The Government also has in hand preparation of a
contingency plan setting out actions that might be taken in different
scenarios if in the future BSE is found to be present in sheep.
Inactivation of the TSE agent
52. Most rendering processes fail to result in significant
inactivation of TSE infectivity, a finding noted in the Phillips
Inquiry report. BSE is particularly resistant to inactivation.
MAFF is funding a number of projects to see whether inactivation
can be achieved using new technology.
53. One of these is examining a novel system of biorefinement
involving high pressure steam which processes tissue at 1900C.
The second is testing a system which combines the processes of
autoclaving and exposure to alkali. If either of these systems
can be shown to inactivate TSEs fully it has potential for use
in processing large animal carcass waste and the UK meat and bone
meal currently in store.
54. The third project involves the use of highly thermostable
proteolytic enzymes. This would be particularly useful for veterinary
and medical applications to inactivate TSEs on equipment which
many otherwise have to be destroyed.
55. In addition to the work on novel processes there
is a study exploring how the older process of tallow separation
and solvent extraction affect PrPSC. Experimental evidence indicates
a reduction in TSE infectivity in meat and bone meal prepared
by processes which involve traditional tallow production as a
by-product. It is not known whether this is because the process
inactivates the infectivity in the meat and bone meal or partitions
it into the tallow and related extracts. This study should fill
in a number of gaps in our understanding of the levels of risk
occurring in the early 1980s.
PATHOGENESIS
56. This is the study of the disease process and the
pattern of development within the cells and organs of the body.
MAFF-funded work in this area has been extremely important in
the past in determining which tissues in the body of BSE infected
cattle carry infectivity. This has formed the basis of the legislation
which prohibits the inclusion of materials which carry a high
risk of infectivity in the human food chain. The current programme
includes the following additional areas.
BSE in sheep
57. Two complementary projects involving sheep of different
breeds and genotypes are exploring the pattern of tissue infectivity
that develops when sheep are challenged orally with BSE infected
cattle brain.
58. The question of whether BSE changes in appearance
when passed from one sheep to another is also being examined.
If it does, and if it becomes more like scrapie in appearance,
it will be harder to detect in sheep.
Scrapie in sheep
59. Several studies are exploring the pathogenesis of
natural scrapie, each focusing on different aspects. The effect
of genotype on PrP distribution and vacuolation is being examined
with emphasis on the identification of potential carrier states
and sub-clinically infected sheep in flocks heavily infected with
scrapie.
60. Because PrPSC accumulates in lymphoid tissue it has
been suggested that the detection of PrPSC in tonsils could provide
a useful means of monitoring the incidence of scrapie in flocks.
However, more needs to be known about the time after infection
at which PrPSC starts to accumulate in the tonsils and whether
this is consistent for different breeds and genotypes. Early evidence
suggests that it is not. A study aimed at exploring this issue
is underway.
Studies at the cellular level
61. An understanding of the early cellular events in
disease development would be beneficial in a number of respects.
It may help to shed light on why only a proportion of exposed
cattle develop BSE and may provide information valuable in prevention
and control of disease.
62. Several studies at the cellular level are underway.
One is exploring the cell types that sustain PrP accumulation
in the intestinal mucosa, the lymphoreticular system and the peripheral
nervous system in BSE in mice and cattle. A second is looking
at whether lysosomes are involved in the first identifiable changes
that occur in neuronal cell bodies during scrapie infection.
63. Cell lines have also been developed which allow the
effects of disease to be investigated in-vitro rather than using
assays in live animals. If these can show responses that are both
specific to the disease and reproducible in a shorter time frame
than assays in live animals they will be extremely valuable. In
addition to their contribution to our understanding of the pathogenesis
of the disease they provide scope for the development of ante-mortem
tests, monitoring inactivation, testing food for adulteration
and testing drugs for disease control. A study is underway which
is looking at the effect of the BSE agent on bovine cell lines.
The species barrier
64. The relative importance of three different factors
known to contribute to the effect of the species barrier are being
explored. Differences in pathogenesis between first and subsequent
passages in a new host is one of these.
DIAGNOSIS
65. One of the high priority areas for research is the
development of a sensitive diagnostic test for TSE infection.
The ideal test would be one that could be performed on the live
animal. Such a test could be used to prevent infected animals
entering the food chain and would provide invaluable support to
the programme to eradicate scrapie. The test would need to be
easy to use for large scale testing and cheap enough to be viable.
66. Diagnostics have been the subject of research since
the beginning of the epidemic, but a test that can be used routinely
in the live animal is still not available. A large international
effort has been put into the development of a diagnostic test
for TSEs under funding from EU Member States and some commercial
development. The main problem is finding a marker that can be
detected in the early stages of disease before clinical signs
are evident. The tests also need to be very sensitive and some
which show promise in the laboratory have neither the simplicity
nor the reproducibility required for a high throughput national
testing programme.
67. There has been greater success in developing post-mortem
tests for BSE. Currently three have been approved by the EU for
use in Member States' national testing programmes. However, these
have been validated only on central nervous system tissue from
cattle in the late stages of disease development. There is no
validated test for use on sheep to detect BSE or scrapie in peripheral
tissues. There is still an urgent need for further work in this
area.
68. At present the Joint Funders are trying to speed
up the progress on diagnostic test development by eliciting the
interest of biotechnology companies. A meeting has been arranged
for February which will bring together academics and small biotechnology
companies with a view to stimulating collaborative projects. The
Funders will be running a joint call for new research proposals
at the same time, funding for which will be available in 2001.
MAFF's current programme includes work in the following areas.
Production of tissues for test development
69. The development and validation of tests requires
tissues from animals at known stages of disease development. Tissues
and body fluids from many of MAFF's projects are banked for future
use. However, in addition there are some projects with the specific
aim of producing tissues for this purpose. Both cattle and sheep
tissues are being produced.
70. The Veterinary Laboratory Agency maintains the tissue
archive and wherever possible provides tissues to meet the needs
of other research workers both in the UK and overseas.
Evaluation of tests developed elsewhere
71. A long term project at the VLA provides funding for
the further development and evaluation of tests originally developed
elsewhere. This part of the programme includes the evaluation
of a blood test claimed to be able to detect scrapie infection
in sheep as early as three months after initial infection. The
test uses immuno-capillary electrophoresis and has become known
as the ICE test. Early results looked promising, however technical
problems with the equipment have hindered progress.
Search for new markers
72. The marker of infectivity used in most of the tests
that have been developed is the abnormal form of the prion protein.
Most tests for BSE are based on the interaction of specific antibodies
with PrPSC. Secondary substances produced as the result of infection
have also been identified in serum or urine. Research to test
their usefulness as a diagnostic marker is part of MAFF's programme.
73. Changes have been detected in the constituents of
urine of CJD patients, sheep with scrapie and cattle with BSE.
Molecules which may be disease specific have been found and work
is in progress to determine when the changes are first detectable
during the incubation period and whether they are sufficiently
specific to form the basis of a test. However, there are few signs
that this will lead to a viable test for BSE in cattle.
74. Certain proteins which are present in normal animals
are released in large quantities into the cerebro spinal fluid
as a result of damage to central nervous tissue in BSE. Work is
ongoing to establish whether they could be used as a basis for
a diagnostic test. Markers in blood are also being sought using
various analytical techniques. It has to be recognised however
that techniques that may be viable in humans may be too cumbersome
or dangerous for use on animals where samples have to be collected
on a farm rather than in a hospital environment.
Protein structure
75. Further knowledge about the physical and chemical
properties of the prion protein may help with the development
of diagnostic tests. Protein chemistry is an area of science that
would usually fall to the research councils to fund. However,
MAFF is funding one project with Professor Prusiner's laboratory
in California, where an assay dependent on the conformation of
the prion protein is being developed and tested.
(B) RESEARCH INTO
INTENSIVE FARMING
METHODS
76. The Committee has expressed an interest in looking
at the possible consequences for human and animal health of intensive
farming methods and specifically on the scale and focus of MAFF's
research into these issues.
MAFF'S RESEARCH
STRATEGY
77. The Ministry has consulted widely on the main elements
of its Research Strategy for the period 2001-05. A consultation
document setting out current work and future plans was issued
in August 2000.
78. At present, the Ministry is considering the results
of this consultation exerciseto which there are some 84
responses from a wide range of sectors. The newly-established
MAFF Science Committeecomprising senior officials and outside
interests representing the industry, consumers, academia, and
the research basewill shortly be considering revised drafts,
in the light of the consultation exercise. The final Research
Strategy will be published in the spring.
INTENSIVE FARMING
79. As the Committee will appreciate, the majority of
food animalsworldwideare kept in intensive rearing
systems of one kind or another. In terms of animal health, there
are a range of advantages and disadvantages in these systems.
Key drawbacks are:
in general, infections and diseases spread more
quickly and more readily when animals are in closer contact. This
can have obvious welfare, productivity and economic disbenefits;
and
animals can be kept in circumstances where they
have access to their own excreta, and the excreta of others in
their group. This can impact on their own health and welfare.
Most foodborne zoonoses arise from faecal contamination.
80. Against this, many intensive systems bring advantages
too:
there is an opportunity for cleaning and disinfecting
of the system between batches of animals, notably in systems for
rearing poultry and pigs. This can be a valuable means of breaking
potential cycles of infection;
many systems may allow better access to animals
(compared to truly extensive systems) so that a range of problems
can be detected and treated earlier, leading to improved disease
control, and better welfare plus productivity gains;
environments can often be better controlledsuch
as by heating and ventilation regimesleading to reduced
environmental stresses on animals (which themselves can lead to
disease or welfare problems); and
intensive systems allow regular and controlled
feeding regimes, with consequent potential improvements in diet
and nutrition, as well as economic and productivity gains. Control
of feeding regimes provides less opportunity for nutritional stress,
again linked to the amelioration of disease and welfare problems.
81. There is evidently a range of balances to be struck
in the use of intensive systems for rearing animals. The Committee
will be broadly familiar with these and they are not further discussed
here.
82. MAFF has two main objectives (out of 10) which are
relevant here:
Objective 1: to protect public health in relation
to farm produce and to animal diseases transmissible to humans;
and
Objective 8: to ensure that farmed animals and
fish are protected by high welfare standards and do not suffer
unnecessary pain or distress.
83. The Ministry has published eight public service agreement
targets, and the ones in relation to these two objectives are
as follows:
reduce the annual incidence of Bovine Spongiform
Encephalopathy (BSE) to fewer than 650 cases by 2001 and by 2004
be on track for fewer than 30 cases by 2006, a 99 per cent reduction
compared with 1997 when there were 4,312 cases; and
reduce the time taken to clear up cases of
poor welfare in farmed animals by five per cent by March 2004.
It also has more detailed delivery targets, in relation to
eliminating BSE and investigating reports of poor farm animal
welfare.
RELEVANT MAFF RESEARCH
84. The Committee will know that the Ministry supports
a substantial research programme, planned at about £106 million
per annum for the period to 2003-04. This research is of a strategic
and applied strategic nature and its purpose is to underpin policy
determination as well as regulatory and statutory duties. We also
have a substantial (circa £80 million) spend on surveillance
and monitoring. In relation to intensive systems, our research
and monitoring is designed to understand and deal with those aspects
where the use of intensive systems leads to undesirable or unacceptable
results. Examples here from the animal health viewpoint are:
increased risk of the spread of diseases and infections;
and
decreased welfareresulting perhaps from
overcrowding; levels of stress; poor physical conditions on farms,
in handling animals at markets or during transit, and at slaughter.
From the human health viewpoint, our main concerns are to
fund research which addresses particular problems of those diseases
which man may acquire from livestock, poultry and other animalsso
called zoonotic diseases.
ZOONOSES AND
APPROPRIATE CONTROL
METHODS FOR
ANIMAL DISEASES
85. Diseases which may pass from farm animals to humans
are a significant and increasing cause of public concern. Zoonoses
can threaten human health and can cause serious economic damage
to specific food sectors, as seen in recent "food scares".
It is important that we have reliable and high quality scientific
information on the risks and effects of zoonoses in order to allow
food markets to operate as efficiently as possible. Research also
underpins effective and efficient control and monitoring of zoonoses.
The planned spend for this programme in 2000-01 is £10.1
million.
86. Key policy objectives are:
the development of sustainable approaches to the
control or eradication of recognised zoonotic diseases;
the investigation of variations in disease caused
by recognised zoonoses and associated risks to public health;
the investigation of new and emerging diseases
that are detected through national surveillance or international
intelligence so as to assess any risks posed to humans;
the protection of public health through the use
of methods of control that reduce (for example) the risks from
residues of medicinal products and bacteria expressing antibiotic
resistance occurring in food; and
to ensure that the welfare of animals is protected
through the appropriate control of endemic animal diseases.
87. Of foodborne infections, several species of bacteria
occurring in animals are known to be capable of causing disease
in man. Salmonella and E-coli are well known examples: E-coli
0157H7 causes severe illness in man but often there may be little
or no disease in livestock. Control strategies depend upon reducing
infection in animals and developing efficient methods for detecting
infected animals or contaminated animal products.
88. Tuberculosis in cattle (bovine TB) was historically
a major source of infection to man. This was brought under control
through regular cattle testing, the removal of reactors and the
pasteurisation of milk. The risk of man acquiring TB from cattle
is now very low compared to the position in the early 1900s when
many cases of human TB could be traced to the consumption of infected
and unpasteurised milk. However, the incidence of TB in cattle
has been growing in recent years. The Committee will be familiar
with the recommendations of the Krebs Report and the wide ranging
research programme which has been established to investigate the
factors involved. This is looking at how the disease is being
maintained and transmitted, plus better methods of detection and
control. Research is in progress to investigate the involvement
of badgers in the maintenance of TB in cattle and other scientific
approaches include improved diagnostic methods and vaccines against
the disease in both cattle and badgers.
89. MAFF carries out research on other zoonoses recognised
as being of importance in the UK. For example, cryptosporidium,
a protozoan parasite, is now recognised as a cause of significant
human disease. The organism also occurs in farm animals; and outbreaks
of disease in man have been linked to contaminated water sources.
Field and laboratory studies are being supported to improve our
understanding of the disease and to develop better methods of
control.
90. There are a number of animal diseases already established
in the UK (ie endemic) which pose not only a considerable financial
burden on agriculture, but affect animal welfare, and in some
cases pose an indirect hazard to human health. Endemic disease
research has concentrated on those infectious agents known to
be of major economic or animal welfare importance. More recently,
the focus has been on the development of control methods which
minimise the use of pharmaceutical compounds. Antimicrobial resistance
is an increasing concern in both human and veterinary medicine
and the expression of resistance is associated with the frequent
use of antibiotics. Several antibiotics have been commonly included
as growth promoters in animal feeds. It is now recognised that
this can lead to the expression of antibiotic resistance by bacteria
of livestock, posing risks to human health through the food chain.
Reducing the use of antibiotics in the farming industry will lessen
this risk, as well as prolonging the effective life of these antimicrobials
in human and animal therapy.
91. The Ministry has important programmes of research
and surveillance designed to tackle particular diseases affecting
farm animals: these include research on mastitis, concentrating
on mechanisms of resistance as well as immunological and other
methods of control to reduce the use of antibiotics; new approaches
on vaccines for important poultry diseases (such as Marek's disease,
infectious bronchitis and coccidiosis); and alternative methods
for the control of sheep scab where the industry is currently
heavily reliant on the use of chemicals.
92. MAFF, the Department of Health and the devolved administrations
support a wide programme of surveillance of zoonotic diseases
in the UK. MAFF is represented on a number of cross-departmental
bodies, notably the Microbiological Safety of Food Funders Group
(MSFFG) which aims to co-ordinate research and inform the funding
departments and others on the research which they carry out or
commission. The views and recommendations of the Food Standards
Agency play a major role in identifying areas requiring research.
93. International experts as well as the Independent
Scientific Group of Experts contribute to an extensive programme
of research into bovine TB, in pursuit of the recommendations
of the Krebs Report.
94. On antimicrobial resistance, an Interdepartmental
Steering Group has been formed recently; within MAFF, the Microbial
Antibiotic Resistance Committee co-ordinates policy and research;
and an EU Scientific Steering Committee on Antimicrobial Resistance
advises on research and monitoring initiatives across Europe.
ANIMAL WELFARE
95. On animal welfare programmes, the current budget
allocation for research is almost £3.7 million. The Government
regulates farming practice so that the trade-off between food
production and animal welfare is struck at the right balance which
society deems acceptable. Research underpins efforts to achieve
this equilibrium in the most efficient manner, with best practice
adopted to take into account both productivity considerations
and the importance of the wellbeing of animals. Policy objectives
for the programme of research are thus:
to improve the welfare of food producing animals
in existing production and husbandry systems;
to ensure that transport and slaughter systems
are consistent with the highest available welfare standards;
to support regulatory policies to drive up standards
of animal welfare in the UK and across the EU;
to develop and promote alternatives to existing
systems; and
to determine and refine the methods used to measure
animal welfare.
96. Wherever possible, the Ministry seeks to promote
welfare improvements on a European basis. Our research underpins
our UK negotiating objectives in the EU, Council of Europe and
other fora. Research feeds into standard setting. The advice and
recommendations of the Farm Animal Welfare Council as well as
the need to comply with a range of EU directives governing farm
animal welfare are important.
97. Current research into the welfare of farm animals
is underpinned by work to improve our understanding and definition
of the parameters that can be used to measure animal welfare.
There are studies on pathological, behavioural, physical and cognitive
responses to the environment and stress, as well as the causes
and consequences of stress, including disease. Examples here are:
for pigs, the development of alternatives to farrowing
crates;
on poultry, finding ways of preventing feather
pecking and cannibalism in non-cage systems for laying hens which
do not involve beak trimming; for broilers, leg health and the
effect of feed control and lighting programmes. Research is also
addressing the effect of stocking density on welfare in commercial
systems;
in respect of ruminants, lameness in cattle and
sheep is under investigation, as are the welfare of intensively
managed dairy cows and the fundamental biology of sheep scab;
as regards welfare at slaughter, a programme aimed
at assessing the efficacy and welfare effects of existing slaughter
methods has been largely completed. New work has been commissioned
to evaluate the neurophysiological basis for electrical stunning
of poultry. The Ministry is also continuing to support the development
of new and alternative slaughtering systems; and
research in relation to the transport of farm
animals includes the effectiveness of ventilation; the development
of sensors which allow the monitoring of physiological stress;
and projects involving drinking, feeding and resting behaviour
in pigs. For calves and sheep, projects continue to develop secure
predictive models to improve transport environments, including
space allowances compatible with animal welfare.
2 February 2001
Annex 1
HIGH LEVEL
COMMITTEE TO
MONITOR THE
PROGRESS ON
RESEARCH RELATING
TO TSES
Terms of Reference:
To ensure that a research strategy, which fully addresses
UK Government's policy needs in relation to Human and Animal TSEs,
is in place and agreed by all funders;
To ensure that mechanisms are in place to implement the agreed
research strategy and that progress to implementation is taking
place as quickly as possible;
To ensure that all relevant sources of expertise are being
called upon and the information is being released to them as freely
and as quickly as possible;
To identify any barriers to progress and make recommendations
for overcoming them; and
To make regular reports to the Prime Minister.
Membership:
Sir Richard WilsonChair.
Richard Abel/Ashley IbbettPS to Sir Richard Wilson.
Professor Raymond BakerChief Executive, BBSRC.
Sir John PattisonDirector of Research and Development,
Department of Health.
Professor Sir George RaddaDirector, Medical Research
Council.
Mr Brian BenderPermanent Secretary, MAFF.
Professor Peter SmithActing Chairman, SEAC.
Dr John TaylorDirector General of Research Councils.
Professor Liam DonaldsonChief Medical Officer.
Professor David KingChief Scientific Advisor.
Professor Sir John KrebsChief Executive, FSA.
Ms Lindsay BellCabinet Office.
Mr David NorthNo 10 Policy Unit.
Joint Secretariat provided by Dr John Stephenson (DH) and
Dr Mandy Bailey (MAFF).
TSE RESEARCH AND
DEVELOPMENT FUNDERS'
CO -ORDINATION
GROUP
Terms of Reference
The aims of the Group are to ensure that the programmes of
Research and Development funded in this field address priority
issues of national interest and constitute a coherent strategy
when considered as a whole. To achieve this aim the Group will:
share information on the strategic direction of
current programmes of Research and Development and on priorities
and plans for future programmes, to produce a coherent Research
and Development strategy;
ensure as far as possible that there are no significant
gaps in programmes and that undesirable overlaps are avoided;
agree which body is most appropriate to take forward
significant priorities, and remit them to the appropriate body;
share information on selection processes and agree
standards for quality control and handling results;
provide a forum for discussion of joint work,
and joint funding of programmes, projects, facilities and expertise;
share information about funding and funding plans;
encourage collaboration between research teams
in this area, and the sharing of scientific knowledge; and
share information about funding and programmes
of research with relevant European bodies.
Membership:
Professor Sir John PattisonDH, Chairman.
Dr John StephensonDH.
Dr Elizabeth SmalesDH.
Dr Antonia LeighDH.
Mrs Jackie LittlechildDH.
Dr David ShannonMAFF.
Dr Mandy BaileyMAFF.
Mr Peter SoulMAFF.
Dr Hilary GatesMAFF.
Dr Ann NolanMAFF.
Dr Mark PitmanMRC.
Dr Katherine FinneyMRC.
Ms Kathryn NewellOST.
Ms Barbara RichardsFSA.
Dr Malcolm AndersonBBSRC.
Dr Patricia ChisholmThe Wellcome Trust.
Dr Martin DonaghyScottish Executive.
Dr Roland SalmonWelsh Assembly.
Ms Jillian DeansHSE.
Professor Bert RimaNorthern Ireland.
Joint Secretariat provided by Dr John Stephenson (DH) and
Dr Mandy Bailey (MAFF).
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