Select Committee on Science and Technology Written Evidence

Annex 3

Additional information from the Medical Research Council (MRC)


  1.  The MRC has made a long, sustained and significant contribution to influenza research. The human influenza virus was identified in 1933 at the MRC National Institute of Medical Research (NIMR). In 1948, the World Influenza Centre (WIC) was established at the NIMR at the behest of the then newly established World Health Organisation (WHO). The Centre, now directed by Dr Alan Hay, has continued to work with a network of collaborating laboratories to detect and characterise the emergence of new influenza viruses anywhere in the world. For instance, the Centre helped detect the avian H5N1 and H9N2 viruses that caused human infections in Hong Kong in 1997, 1999 and 2003. The Centre also has a key role advising the WHO on the composition of seasonal influenza vaccine. Sir John Skehel, Dr Hay and colleagues at the NIMR are also at the forefront of international research to discover how molecular changes in the virus affect its ability to infect people and cause disease.

  2.  The Council is committed to sustaining and developing its world-leading influenza research programmes and to galvanizing UK biomedical research to meet the challenges of pandemic influenza. Our current investment in influenza research is in the order of £1.6 million per annum. The programme portfolio is summarised briefly below.


  3.  MRC's Council considered in July 2005 the public health threat of pandemic influenza. It recognised the action being taken by the UK Health Departments and of health protection agencies nationally and internationally to prevent and plan for a pandemic, and the MRC's own contribution in this area. It approved activities for the MRC Infections & Immunity Board, chaired by Professor Andrew McMichael (Director of the MRC Human Immunology Unit), to review Council's strategy for emerging infections with epidemic and pandemic potential. Professor McMichael will lead a Council scientific mission to south east Asia in October 2005, focused on emerging infections. The mission will be followed by an expert & stakeholders' meeting in London in December. The Board's recommendations will be considered by Council in March 2006.

  4.  To cover the interim period, the MRC has issued a Highlight Notice (see ­Interim Scientific Priorities" below), inviting research proposals from the research community on emerging infections with epidemic or pandemic potential. The Council is keen to stimulate new research, and welcomes collaborative proposals, including proposals with overseas or industry partners. As an innovation, the Infections & Immunity Board is willing to consider in principle funding for ­readiness protocols." These will be to support research that can be put into effect only in the early stages of an epidemic - for example, clinical work on a newly circulating strain.

  5.  We are working with BBSRC, the Wellcome Trust, the Health Departments and the Health Protection Agency to survey the UK's main influenza research programmes. The survey will be resource for all the partners and contribute to MRC's strategy development in influenza. We anticipate the survey will be placed in the public domain.


  6.  The Department of Health published a National Pandemic Influenza Contingency Plan in March this year. It subsequently established a Scientific Advisory Group on Pandemic Influenza, on which MRC is represented. MRC officials are in regular informal contact with counterparts from the Health Departments, the Department for International Development, the Department for Environment, Food & Rural Affairs, the Health Protection Agency, the BBSRC and ESRC, the OST, the Wellcome Trust, and the Academy of Medical Sciences.

  7.  Professor Blakemore (MRC Chief Executive) has regular contact with senior officials of the Chinese Academy of Sciences. Together with the Chairman and Deputy Chairman of the MRC's Infections & Immunity Board, he recently met Dr Jeremy Farrar, Director of the Oxford Clinical Research Unit in Vietnam. The meeting informed plans for the MRC's Emerging Infections mission to Vietnam and China, when Professor Blakemore will also be in China.

  8.  Research issues in the field are also reviewed by Heads of International biomedical Research Organisations (HIROs). This informal grouping, which meets six-monthly, brings together the heads of MRC, the USA National Institutes of Health, and counterparts from Canada, Australia, New Zealand, several European national funders and China (represented by a Vice President of the Chinese Academy of Sciences).


    i.    The MRC currently invests £1.6 million per annum on flu research.

    ii.  The MRC's principal investment in influenza research is at the National Institute for Medical Research (NIMR). The NIMR programme was recognised as being internationally outstanding in a recent a quinquennial review.

    iii.    Sir John Skehel's programme focuses on the structural and functional characteristics of the virus surface that enable it to infect cells; and on the mechanism by which anti-haemagglutinin antibodies neutralise viral infectivity. His team recently explained how the haemagglutinin (HA) of the 1918 virus both retained receptor binding site amino acids characteristic of an avian precursor HA, and was able to bind to human receptors and how, as a consequence, the virus was able to spread in the human population. The programme has produced other major insights into the molecular basis of host range, pathogenicity and human-to-human transmission and into the pandemic potential of different influenza subtypes.

    iv.    Dr Alan Hay leads the World Influenza Centre at the NIMR, monitoring changes in the virus that have significance for human health and protection as those changes occur: this work makes an important contribution to public health internationally. Dr Hay works closely with the HPA and with WHO Collaborating Centres in the USA, Japan and Australia and the global network of National Influenza Centres. Dr Hay also leads a programme of basic research on the mechanisms of action of resistance to antiviral drugs, including the structural basis of M2-channel activity. Dr Hay also participates in international and EU networks concerned with viral drug resistance.

    v.  The NIMR has ACDP Category 4 facilities and the Council is keenly aware of the need to make appropriate high containment arrangements in renewing the Institute in partnership with UCL. The renewal and partnership strategy offer significant advantages over current arrangements at Mill Hill in terms of strengthening translational research and integration with world-class physical sciences.

    vi.    The Council also funds a programme of research at the University of Oxford (Professor George Brownlee) to study transcription and regulation of influenza A virus. This is fine-grained, basic molecular work on how the segmented RNA viral genome is copied in a regulated manner, and has the potential to lead in the longer term to production of novel influenza antivirals and vaccines.


  Based on input from the community and expert discussion, the Infections & Immunity Board will formally define its emerging infections priorities early in 2006. Until then, the following questions - as applied to influenza - describe the Board's interim priority research themes:

    -   What is the current risk posed by avian flu to the human population? How robust are the data and systems on which risks are being estimated? What are the specific modes of transmission? What do ecology, epidemiology and clinical research reveal about the critical points for preventive (pre-pandemic) or responsive (pandemic) action?

    -   Some flu strains are more readily transmitted from non-human species to people than are others; and strains differ in their transmissibility between people. What are the mechanisms that determine viral strain transmissibility and individual susceptibility? What are the strategies to reduce transmission effectively? What are the critical research issues?

    -   People with H5N1 influenza reported to the World Health Organisation in the current outbreak have a high mortality rate. But what is the full spectrum of illness? What makes people infected with H5N1 influenza become seriously ill and die? What are the genetic, molecular and cellular and immune mechanisms determining virulence, pathogenicity and protection? What are the contributions of the virus and the host and the interplay between them to clinical outcomes of infection? How can collaborative research on clinical and pathological manifestations, and the effectiveness of interventions to control and treat infection, be promoted?

    -   Current vaccines for seasonal flu are strain-specific. There are few effective drugs, and resistance is a threat. What characteristics do we need vaccines and drugs to exhibit to achieve effective prevention and control? What are the opportunities and strategies for innovation to develop better and new vaccines and drugs - (a) in the short term; (b) in the longer term?

    -   Were a pandemic to emerge, the timescale could be very rapid. How can biomedical and health research contribute to rapid and reliable collection, analysis and evaluation of surveillance data and samples? What might be the opportunities for effective intervention in the early stages of an outbreak of a dangerous flu strain, so as to prevent a pandemic?

    -   Similarly, what research is required to ensure that public health intervention strategies and technologies in an epidemic can be effective in healthcare and community settings? What contributions can public health modelling and behavioural research make?

  The Board recognises that:

    -   Some crucial research questions are urgent now; others can be addressed only over a longer time-scale. Some can be addressed only at the moment a serious outbreak occurs - in which case a research protocol needs to be enacted then, without delay. MRC will consider proposals for such ­preparedness protocols";

    -   A broad range of disciplines and technologies need to be brought to bear on these questions;

    -   The MRC's remit and capacity is such that it's most effective contribution is likely to be to basic biomedical and health research on aetiology and mechanisms; and generalisable clinical, behavioural, public health and field research;

    -   Human infections that are also zoonoses require complementary and coordinated human and veterinary research strategies;

    -   Access to specialised models, expertise and infrastructure is critical;

    -   Large and small scale research have important roles to play: some questions will be best addressed through goal-oriented, research networks, collaborations or consortia; and others through focused, individual grants;

    -   There is strong rationale for collaborating internationally, especially with countries at high endemic risk from emerging virulent infections;

    -   Influenza research outputs need to be translated efficiently into implementable benefits for patients and public health globally.

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