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
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).
CURRENT MRC PROGRAMMES
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
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
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
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,
- 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
- 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
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
- 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
- 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.