Memorandum from Research Councils UK
1. Research Councils UK (RCUK) is a strategic
partnership that champions the research supported by the eight
UK Research Councils. Through RCUK the Research Councils are creating
a common framework for research, training and knowledge transfer.
2. This memorandum is submitted by Research
Councils UK on behalf of four of the Research Councils (the Biotechnology
and Biological Sciences Research Council, Economic and Social
Research Council, Medical Research Council and Natural Environment
Research Council) and represents our independent views. It does
not include or necessarily reflect the views of the Office of
Science and Technology (OST). RCUK welcomes the opportunity to
respond to the Committee's Inquiry.
3. This memorandum provides evidence from
RCUK in response to the questions outlined in the inquiry document,
in addition to supplementary information from:
|Biotechnology and Biological Sciences Research Council (BBSRC)
|Economic and Social Research Council (ESRC)
|Medical Research Council (MRC)||Annex 3
|Natural Environment Research Council (NERC)
Because of their different interests, Councils have focused
on different questions below, and the responses are attributed
accordingly. We emphasise that the annexes contain important additional
information about specific research aims and collaborations.
How is the risk of pandemic influenza emerging in south east
Asia, and reaching the UK, being assessed; and how can this assessment
4. The WHO works closely with individual countries and
the international community to monitor and verify the emergence
of new flu strains and suspected human cases of zoonotic strains.
It coordinates the WHO Global Influenza Surveillance Network,
established in 1952, which now links four international WHO Collaborating
Centres (of which the WIC at NIMR is one, see paragraph 1 of Annex
3) with some 112 National Influenza Centres. The Network makes
recommendations to the WHO on influenza vaccine formulation and
acts as a global alert mechanism for new and dangerous influenza
strains. The rapid control of Severe Acute Respiratory Syndrome
virus (SARS) in 2003-04 owes much to the effectiveness of the
5. Strong surveillance and reporting systems in affected
countries are crucial. The WHO reports that some affected countries
do not yet have the requisite laboratory and epidemiological capacity.
International collaborative support for affected countries in
strengthening their capacity for national and local surveillance,
active case-finding and rapid response is a critical investment
for the world.
6. Collaboration with south east Asian partners to maximise
the rapid collection and analysis of high-quality clinical data
and samples in the pre- and early pandemic periods is crucial.
International efforts must support rather than compete with national
research aspirations and development of capacity in surveillance
and research. The international community must take every opportunity
to promote strong science and health protection strategies, and
every effort must be made to mitigate conflicts that arise between
international and local interests.
7. Reliable and rapid diagnostic tests that are robust
under field conditions could be especially valuable in south east
Asia. The OST's Foresight Project on the Detection & Identification
of Infectious Disease may provide valuable insights into smart,
adaptable technologies: the Project is due to report later in
2005. The potential value of testing at home (self-tests")
and in healthcare settings needs to be considered also in the
context of a UK epidemic.
8. UK mathematical modelling of outbreaks is at the international
forefront. Professor Neil Ferguson (Imperial College) and others
have published a strategy for the containment of a pandemic strain
in south east Asia,
pinpointing the importance of rapid (within days) recognition
of small clusters of cases and intervention with antiviral drugs
and other measures such as geographic and social separation. It
is less clear how effective these strategies would be in the face
of a gradual evolution of strains with more efficient human-to-human
transmission, and/or diffuse emergence on a widely dispersed geographic
front in remote districts with poor communications.
9. There are significant questions about the appropriate
intervention strategies at different stages of an outbreak and
pandemic. For instance, would antiviral drugs be more effectively
used as a prophylactic, or for early treatment (allowing a degree
of exposure to the virus and potentially engagement of the immune
system) - and under what circumstances? UK laboratories could
contribute to answering such questions through collaborative research
with clinical teams in south east Asia.
10. Assessment is largely based on co-ordination of the
information obtained from serological studies combined with molecular
analysis, virus isolation, epidemiological observation in birds
and in humans and assessment of the impact of control measures
based on animal slaughter, and the use of antivirals. The quality
of assessments could be improved by extending the range of virological
studies in south east Asia and in Europe, including the UK. See
Annex 4 for detailed suggestions.
11. In particular, it is important that UK wildlife species,
especially birds, be monitored for relevant antibodies before,
during and after the arrival of any pandemic influenza virus -
work in train at the Centre for Ecology and Hydrology. The possibility
that strains other than H5N1 might pose a threat (see paragraph
15) makes such monitoring all the more important. For it to be
carried out effectively, virologists must have access to the relevant
viruses. This need should be borne in mind when controls are imposed
for biosecurity purposes, so that circulating viruses are not
unnecessarily over-classified, making it hard for many researchers
to carry out survey work. A library of avian, equine, porcine
and human influenza viruses, freely available to all virologists
in the UK (not just to a limited number of laboratories), would
greatly facilitate the gathering of survey data.
12. BBSRC is funding research to examine the epidemiology
of the influenza virus related to the genetic structure of the
virus population, both within an individual and in a host population,
and the underlying genetic factors that allow strains of the virus
to change host organism, which are thought to be related to suppression
of virus replication in the host cells. This work is essential
to support efforts to successfully predict the spread of avian
influenza through populations.
How great are the risks, and what confidence can be placed
in these figures?
13. Avian Influenza: Assessing the Pandemic Threat,
published by WHO in January 2005 concluded that The confirmation
of human cases gave the outbreaks in poultry a new dimension.
They were now a health threat to populations in affected countries
and, possibly, throughout the world. All prerequisites for the
start of a pandemic had been met save one, namely the onset of
efficient human-to-human transmission. Should the virus improve
its transmissibility, everyone in the world would be vulnerable
to infection by a pathogen - passed along by a cough or a sneeze
- entirely foreign to the human immune system." It could
be argued that the N1 (neuraminidase) component of H5N1 is not
entirely foreign, since it has been circulating in other strains
for several years, and that residual antibodies could reduce disease
severity, but the degree of protection that previous exposure
to N1 would offer is uncertain.
14. The fact that viruses of avian origin contributed
to all three 20th Century pandemics suggests that the likelihood
of another zoonotic strain becoming efficiently transmissible
between people is high. Population vulnerability to H5N1 and other
strains that are not susceptible to existing neutralising antibodies
is likely to be high. The WHO considers it likely that an antigenically
novel, efficiently transmitted zoonotic strain would very rapidly
spread, causing high morbidity and mortality, and seriously threatening
the capacity of health systems to respond.
15. However, much remains uncertain about the biology,
clinical characteristics and epidemiology on which risk estimates
are based. Consequently, while experts believe that a pandemic
will occur, parameters such as timing, spread and scale are unpredictable.
Further, despite the current focus on avian H5N1, there is no
guarantee that the next pandemic challenge will be from either
avian H5N1 or indeed an H5 strain.
16. The WHO is coordinating action to strengthen surveillance
systems regionally in south east Asia and its advice to countries
is readily accessible. In relation to the zoonotic threat to human
health, the WHO works with the World Organisation for Animal Health
(OIE) and the Food and Agriculture Organisation (FAO). The OIE
and FAO have in recent years been assisting countries in south
east Asia to control the severe avian influenza epidemic in poultry.
The culling in 1997 of the entire national poultry flock of 1.5
million birds in the Hong Kong Special Administrative Region is
considered by the WHO to have averted a human pandemic. Effective
surveillance of bird populations, outbreak and panzootic prevention
and response are all essential to the protection of human health.
This work needs to be underpinned by strong research that fully
exploits the opportunities for collaboration between human and
17. The containment, despite its rapid intercontinental
spread, of SARS offers some comfort as well as lessons. However,
influenza is more highly contagious than SARS and is considered
less likely to be contained by public health measures than was
18. Current evidence indicates that the avian viruses
in Asia have retained their preference for avian hosts. This implies
that unless the situation changes the risk of human pandemic influenza
emerging in south east Asia is not as great as might initially
have been anticipated. However, it is difficult to estimate reliably
the risk because there is insufficient knowledge concerning the
likelihood of the appropriate genetic exchange or mutation required
to produce a human pandemic virus. The risk is not negligible
because of the high number of exposures of humans to avian influenza
viruses in south east Asia, and if a high-virulence human strain
emerges in south east Asia, the risk of it reaching the UK is
likely to be high.
How is the UK working with international bodies to: monitor
the development of the virus; and reduce the risk of pandemic
influenza emerging and spreading?
19. As described in paragraphs 4 above and paragraph
1 of Annex 3, the WHO World Influenza Centre at the NIMR plays
a significant collaborative role internationally in meeting the
challenges for human health of potentially pandemic viruses.
20. Spontaneous changes in micro-organisms that potentially
lead to pandemics are unpredictable so it is vital to take a broad
view in order to identify the most important risks associated
with infectious diseases, such as avian flu. The pathways by which
the disease can spread are often influenced by socio-economic
drivers, which might include governance systems, conflict, or
poverty. These are complex, multifactorial systems. The risks
also depend on the socio-economic factors that influence the chances
of a change occurring in infectious agents in the first place.
Much of what the UK can do to prevent the spread of disease would
be contingent on how it handled these socio-economic interactions
and drivers both within the UK and beyond its borders. From Foot
and Mouth Disease (FMD) experience, researchers have shown the
importance of informal and opportunistic behaviour in the presence
of a sudden threat. Undue emphasis should not be given to considering
only formal communication, nor should public spiritedness be assumed.
21. Contingency planning is led by the UK Health Departments.
Research Councils have a role in underpinning those plans with
scientific advice (eg through the DH Scientific Advisory Group
on Pandemic Influenza) and generating new knowledge and in developing
and evaluating new technologies. It is crucial to build a strong
evidential base to public health interventions - whether medical
What is the current assessment of the likely impact of pandemic
influenza on the UK (both in terms of health and on wider society,
including the economy)?
22. The following important issues have been widely documented
and the Research Councils are aware that the Department of Health
has them under review. In the event of a pandemic, national authorities
would need to rapidly obtain numerous pharmaceutical products
including vaccines, to store and equitably distribute them and
to manage demand for health services (primary and secondary) and
social care. There would be a need to maintain social and economic
functions bearing in mind that if predominantly working-age adults
were affected by the pandemic, this would have a more severe impact
on the continuation of services and businesses. Closure of schools
would also impact on the number of adults at work and have a knock-on
effect on services and businesses.
23. The UK Influenza Pandemic Contingency Plan acknowledges
that it is possible that movement and gatherings of people would
be affected. This could include both local and international movement
and could either be enforced through contingency planning policy,
or result from people choosing not to travel or from the need
to scale down transport systems due to the effects of the pandemic
on their workforce and the availability of fuel. The first of
these three scenarios needs careful consideration in order to
balance the rights of citizens to freedom of movement with the
need to contain a pandemic.
24. A pandemic might also affect international trade
routes, and the possible effect of this on the economy needs to
Are the measures described in the revised UK Influenza Pandemic
Contingency Plan adequate to minimise the effects of a pandemic?
What more could be done?
25. The measures described in the UK Influenza Pandemic
Contingency Plan may be adequate to minimise the effects of a
pandemic as far as they can be foreseen. However, in relation
to contingency arrangements concerning hygiene, the following
observations are pertinent. The reception of what are intended
as health-promotion initiatives will vary according to public
trust in those giving the message. Local health professionals
are more trusted than politicians, for example. Vulnerable communities
are likely to show patterns of trust different from those of majority
How well prepared and co-ordinated are health, emergency and
other essential services for responding to a pandemic?
26. The effect of a pandemic on the whole community and
the need for sustained support should be considered. Medically
there is a need to think more widely than simply the supply of
drugs. The provision of nursing support and social care must also
be considered, including provision for those who live in more
remote areas or who are incapacitated. Support by volunteers and
NGOs could be considered in this context. The role of the military
services in supporting the emergency services and medical staff
could also be considered. It would be interesting to know if the
potential for businesses and industry to support essential services
has been explored.
What is being done to ensure that the general public are aware
of the risks and likely effects of a pandemic, and of how they
27. Development of best practice in terms of public reaction
and individual behaviour to a pandemic situation does not necessarily
mean that individuals will react in the way planned. The public,
or various publics, are diverse and this diversity is important
when considering the preparedness of the public and the communication
of warning information. Social science has a number of findings
relevant to appropriate risk communication. As we have seen with
BSE, salmonella in eggs and GMOs, poor communication can elevate
a problem to crisis levels. There is therefore a need to ensure
that public perception of the risks associated with avian flu
is proportionate. Public reaction to information about risks and
immediate danger depends on many social, cultural, environmental
and psychological factors. For example, the degree to which individuals
have pre-existing knowledge about the hazard and the appropriate
response, education, socio-economic status, experience, resources
to facilitate response, physiological constraints, geographical
proximity to the danger, source of information and membership
and characteristics of social networks will all affect the ways
that the public or publics react to information about a pandemic
and the associated risk.
28. It is important to understand how individuals perceive
levels of risk and how this differs between individuals. Social
science research has shown
that hazardous events interact with psychological, social, institutional
and cultural processes to attenuate or amplify perceptions of
risk and through this shape behaviour and physical consequences.
Further social science research shows that people do not draw
personal implications from risk information; they tend to perceive
negative events as less likely and positive events as more likely
to themselves than to others. This can hinder the adoption of
preventative interventions and undermine health-promotion efforts.
These complex interactions mean that a direct causal link cannot
necessarily be drawn between education of risks and level of risky
Is the UK's stockpile of antiviral treatments adequate, and
how will it be distributed? What steps are being taken to ensure
that the UK has access to sufficient antiviral treatment and vaccine
in the event of a flu pandemic?
29. Given the possibility of shortage of vaccine and
antiviral medicine, or at least the likelihood that treating all
those in need will take some time, care must be taken to prioritise,
and be seen to prioritise, treatment in a fair, robust and transparent
fashion. Those particularly at risk should be identified in advance
and distribution to all areas, including rural areas and areas
with little or no communication should be considered.
30. Although stockpiling of vaccine and antiviral medicine
can go some way to facilitating a quick response to the sudden
threat of an influenza pandemic, the exact requirements for treatment
will depend on the strain of influenza. This, together with the
fact that not every affected country will have been able to stockpile
sufficient medication, is likely to lead to inequality in supply
for countries lacking facilities to manufacture vaccines or lacking
resources to purchase supplies at a time when their cost is likely
to increase. These international inequalities in the basic defence
against the effects of a pandemic need to be addressed by the
pharmaceutical industry and international governments in advance
of a pandemic.
What will be the role of vaccine development, manufacture and
distribution in responding to a pandemic?
31. Although BBSRC does not fund research directly concerned
with the practical aspects of manufacture and distribution of
vaccines, it supports the underpinning research required to develop
new, more effective vaccines to tackle influenza.
32. In particular, BBSRC funds work that aims to understand
the fundamental biology of the influenza virus, both in isolation
and in its interaction with the host cell. BBSRC supports research
that examines host-pathogen interactions at a range of scales
from the molecular level, the cellular level and up to the level
of tissues/organs and the whole organism. Recent advances in Genomics
and Genetics in a number of species of poultry and waterfowl allow
us to develop a greater understanding of host-pathogen interactions
in these systems and to begin to understand variable host susceptibility
to infection. Using this knowledge researchers hope to understand
the action of the virus and the immune response of the host and
thereby identify new targets for vaccines and antiviral drugs
to more effectively combat the disease. Work to this effect is
discussed in the response from the Institute of Animal Health
and the Roslin Institute. In particular, the production of novel
vaccines based upon our knowledge of the genes and proteins involved
in the immune response of poultry will be vital.
33. See also Annex 3 for current MRC Programmes in Influenza
(eg item 6) and Interim Scientific Priorities (eg bullet 4).
What is the long-term strategy for reducing the threat of pandemic
34. The strategy must include research to enhance our
knowledge of disease processes through the study of fundamental
biology of the virus and host. This is important because a long-term
strategy to reduce the threat of a pandemic should include three
parts: firstly the source of infection (in this case the disease
in the animal hosts) needs to be removed or reduced, and the development
of intelligently designed, novel vaccines is essential here. BBSRC
funds research into identifying specific proteins involved with
pathogenicity and replication of the virus, both of which could
be targets for vaccines. This is discussed above and in detail
in the response from BBSRC Institutes. Secondly, the transmission
of virus from the host organism to humans must be controlled.
Again, BBSRC research can contribute to the production of effective
vaccines that will prevent transmission from hosts. Thirdly, the
transmission of the virus between people must be controlled. Although
this final aspect is outside BBSRC's remit it is important to
consider all three aspects when developing a strategy.
35. The long-term strategy should take into account the
points raised (by ESRC) above. It should recognise the international
context and consider the root causes of such an epidemic as well
as contingency measures should a pandemic occur. There are clearly
roles for social science professionals such as medical anthropologists
in, for example, understanding the role that human behaviour plays
in disease spread or in communicating with and mediating between
biomedical professionals and local communities. In ensuring that
policy-makers receive the best support and advice on issues such
as pandemic influenza we must strive to recognise and value contributions
from the full range of social science disciplines in order to
achieve a well-rounded view of the full array of socio-economic
factors involved. Furthermore, appropriate social science professionals
need to be embedded within interdisciplinary teams from the outset
so that, through cross-fertilisation of ideas with natural scientists,
questions are framed and response strategies developed based on
as full an understanding of the situation as possible.
36. Research is required across the board both in relation
to questions needing answers in the short term, and longer-term
- Biological mechanisms - as a basis for new and better
drugs and vaccines. The current ability of drugs and vaccines
to stem a pandemic is extremely precarious. Better drugs and vaccines
are also required for seasonal influenza;
- Clinical and translational research - to understand
the respective host and virus-mediated contributions to clinical
disease and outcome;
- Epidemiology - to support risk assessment and effective
intervention. Mathematical and epidemiological modelling to underpin
prevention and control strategies;
- Better delivery of vaccines - eg more rapid scale-up
of strain-specific vaccines in response to the emergence of dangerous
novel strains; antigen sparing strategies; novel adjuvants;
- Development and evaluation of public health intervention
strategies and technologies - for application in healthcare and
37. Industry has a crucial role to play in vaccine research
and development, but it is likely to do so only with the right
incentive structures. There may be room for further European and
national action to strengthen the market in Europe for seasonal
38. MRC's interim priorities for emerging infections
with epidemic and pandemic potential are set out in Annex 3.
Ferguson et al.(2005), Nature 437, pp 209-214. Back
Pidgeon, N (1 August 1999) Risk Decision and Policy, Volume 4,
Number 2, pp 145-159. Back