Select Committee on Science and Technology Written Evidence


Memorandum from Research Councils UK

INTRODUCTION

  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) Annex 1
Economic and Social Research Council (ESRC) Annex 2
Medical Research Council (MRC)Annex 3
Natural Environment Research Council (NERC) Annex 4

  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.

THE RISK

How is the risk of pandemic influenza emerging in south east Asia, and reaching the UK, being assessed; and how can this assessment be improved?

MRC

  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[2], 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 WHO Network.

  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,[3] 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.

NERC

  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.

BBSRC

  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?

MRC

  13.  Avian Influenza: Assessing the Pandemic Threat,[4] 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 veterinary research.

  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 SARS.

NERC

  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?

MRC

  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.

ESRC

  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.

CONTINGENCY PLANNING IN THE UK

  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 or non-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)?

ESRC

  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 be considered.

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?

ESRC

  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 communities.

How well prepared and co-ordinated are health, emergency and other essential services for responding to a pandemic?

ESRC

  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 should react?

ESRC

  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[5] 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 behaviour.

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?

ESRC

  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?

BBSRC

  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.

MRC

  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 influenza?

BBSRC

  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.

ESRC

  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.

MRC

  36.  Research is required across the board both in relation to questions needing answers in the short term, and longer-term issues:

    -   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 community settings.

  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 flu vaccine.

  38.  MRC's interim priorities for emerging infections with epidemic and pandemic potential are set out in Annex 3.

September 2005



2   http://www.who.int/csr/disease/influenza/surveillance/en/ Back

3   Ferguson et al.(2005), Nature 437, pp 209-214. Back

4   http://www.who.int/csr/disease/influenza/en/H5N1-9reduit.pdf Back

5   Pidgeon, N (1 August 1999) Risk Decision and Policy, Volume 4, Number 2, pp 145-159. Back


 
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