Appendix 1: Research Councils UK response
Research Councils UK is pleased to be able to respond
to the above report on behalf of all of the seven research councils.
This response has been shared and discussed with the Department
of Health to complement the Government response by expanding on
the research issues raised within the report.
The research councils strongly endorse the Committee's
recommendations and strong emphasis on research-based practice.
This response will, firstly, highlight the significant research
activity across the councils and, secondly, specifically respond
to some of the recommendations made by the Committee.
Cross-council research activity
The Antimicrobial Resistance Funders Forum[1]
The UK research base in antimicrobial resistance
(AMR) is supported by a range of funders, including public sector
organisations, charities and industry. However, as highlighted
in the report, a single body needs to "take action and corral
the efforts". To this end, the Antimicrobial Resistance Funders'
Forum (AMRFF) has been established to provide a forum for the
sharing of information on activities relating to AMR by the various
member organisations, with a particular focus on anti-bacterial
resistance in humans and farm animals. The AMRFF provides a framework
for a more coordinated approach to tackling AMR research to maximise
impact on national and international policies and activities.
Specifically, the key aims of the AMRFF are to:
- Take a strategic view of the
UK AMR research base with an understanding of its output, skill
base, resources and impact
- Create a common vision for the future of AMR
research and its implementation
- Add value to existing programmes of work through
coordination, synergy of activities and gap awareness
- Coordinate and/or support the initiation of unilateral,
bilateral or multilateral funding and delivery programmes
- Raise the understanding and profile of AMR research
base in the UK and internationally through proactive communication
with all stakeholders
The AMRFF is led by the MRC and membership includes
all of the research councils, UK Health Departments, governmental
bodies, as well as charities that have a direct or indirect interest
in AMR and provide significant R&D budgets in the area.
- Arts and Humanities Research
Council (AHRC)
- Biotechnology and Biological Sciences Research
Council (BBSRC)
- Department of Business, Innovation and Skills
(BIS)
- Defence Science and Technology Laboratory (Dstl)
- Department for the environment, food & rural
affairs (Defra) & Veterinary Medicines Directorate (VMD)
- Department for International Development (DFID)
- Department of Health (DH)
- Economic and Social Research Council (ESRC)
- Engineering and Physical Sciences Research Council
(EPSRC)
- The Food Standards Agency (FSA)
- HSC R&D Division, Public Health Agency, Northern
Ireland
- Medical Research Council (MRC)
- Natural Environment Research Council (NERC)
- National Institute of Health Research (NIHR)
- Science and Technology Facilities Research Council
(STFC)
- Technology Strategy Board (TSB)
- Wellcome Trust
Forum members held a number of workshops and discussions
throughout 2013 and 2014 to identify the research challenges and
opportunities as well as needs. There was a very strong call for
research to be multidisciplinary, calling on the expertise of
a broader range of expertise than may currently be involved—for
example, bacteriologists working alongside clinicians, veterinarians,
engineers, chemists, environmental scientists, geneticists, social
scientists and more. It was also considered essential that research
is relevant to humans and animals under a "one health"
agenda.
The research councils have also developed strong
international links in AMR. The MRC leads, on behalf of the UK,
on a Joint Programming Initiative (JPI) with EU member states—"The
microbial challenge—an emerging threat to human health".
We have developed and launched a Strategic Research Agenda (SRA)
as well as call to fund research proposals. We have established
two research consortia in partnership with the Canadian Institute
of Health Research (CIHR). The MRC is the BIS appointed UK representative
on the State Representative Group for the EU and European Federation
of Pharmaceutical Industries and Associations (EFPIA) "Innovative
Medicines Initiative (IMI)". To date €431m has been
committed to five AMR consortia across Europe with UK researchers
involved in a number of these. BBSRC is contributing to the Animal
Health and Welfare ERA-Net, an EU wide funding programme as well
as an international Veterinary Vaccinology Research Network. The
research councils are currently developing links with China, India
and Brazil in the AMR area to answer research questions globally.
Addressing the challenges - a thematic approach
Through the work of the AMRFF, four key themes have
emerged that require a multidisciplinary approach and are considered
essential to tackling AMR.
THEME 1: UNDERSTANDING RESISTANT BACTERIA IN CONTEXT
OF THE HOST
Despite a strong basic bacteriology portfolio across
the UK, funded through a number of sources, there are still many
gaps in our understanding of the molecular and cellular biology
of bacterial resistance, especially how bacteria evolve, acquire
and transmit antibiotic resistance and how they adapt to life
in human and animal hosts. This theme will aim to take a multidisciplinary
approach to understand how resistance develops and is transmitted.
THEME 2: ACCELERATING THERAPEUTIC AND DIAGNOSTICS
DEVELOPMENT
This theme will cover the discovery of new antibiotics
as well as revisit old antibiotics with new scientific approaches
to enhance their usefulness. It will also look to developing new,
non-traditional antibiotic treatments. The science will build
on discoveries made as part of theme 1 as well as on existing
research programmes. This theme also emphasises the importance
of developing new technologies for identifying resistant bacteria,
to underpin diagnostics development and so better target any new
therapies. Finally, the research in this theme may provide a real-life
test bed studying the impact of different economic and business
models, or development of novel business models, related to the
process and drivers of innovation in the development of new antibiotics
and diagnostics.
THEME 3: UNDERSTANDING THE REAL WORLD INTERACTIONS
It is clear that the environment, and the way people
and communities interact with the environment, hugely influences
the way bacteria behave and the transmission of genes within and
between bacterial species. A greater understanding of how differing
environments and their uses influence the evolution, acquisition
and spread of antibiotic resistance and reservoirs of resistance
is therefore needed. Here the "environment" is seen
in its broadest sense from host tissues to man-made settings and
natural environments. This would encompass, for example, human
and animal intestinal tracts, wounds in humans and animals, hospitals,
care homes and transport systems, all the way through to waste
water, agricultural and natural environments (freshwater, marine,
soil, air, etc. and their interfaces). Understanding these environments
and their role in resistance will help identify and target better
prevention measures and management practices.
THEME 4: BEHAVIOUR WITHIN AND BEYOND THE HEALTH CARE
SETTING
This theme will aim to elucidate the underpinning
motivations for human behaviours relating to AMR, and how behaviour
can affect development and spread of antibacterial resistance.
It will also explore how to best enable effective behaviour change
interventions in a variety of settings, relevant to both humans
and animals. It may also serve as the basis for research into
the economics of AMR.
The research councils are now launching initiatives,
ring fencing funds from current headroom, to address these themes.
MRC and BBSRC are investing £20m in themes 1 and 2 and calls
have now been launched. EPSRC, recognising the important role
that engineering and physical sciences can play in this challenge,
are investing £5m to encourage universities to build capacity
and understanding through multidisciplinary networks focussed
on the four key themes identified. Themes 3 and 4 are in development
and NERC and ESRC are playing a key role in shaping future calls
in consultation with other potential partners, including BBSRC,
MRC, EPSRC and AHRC. All funding will be reviewed for scientific
excellence by expert panels, consisting of both international
leading academics and relevant industry. The initiative will be
overseen by a specialist steering group of national, international
and private sector experts.
Response to specific report recommendations:
5. Diagnostics are a key tool in limiting and
targeting use of antibiotics. The Government should indicate in
its response to this report how it intends to ensure better use
of current diagnostic facilities, how it intends to speed up diagnostic
provision and how it will ensure that the Catapult for Precision
Medicine delivers diagnostics for infectious diseases.
In recognition of the importance of diagnostics,
theme 2 of the AMRFF initiative specifically calls for research
proposals to develop new diagnostics. This will build on the expertise
of the academic sector but is also expected to link strongly with
the private sector.
The research councils have developed strong working
relationships with TSB and their position on the AMRFF will ensure
alignment of their activity with the research councils. The research
councils have worked closely with TSB on the development of the
Precision Medicine Catapult to accelerate diagnostics development.
The research councils also look forward to working with NESTA
on the Longitude Prize which will be focussed on new diagnostic
tools for antibiotics.
The report already recognises the cutting edge work
of the EPSRC interdisciplinary research collaboration, i-Sense,
in UCL to create a new generation of early-warning sensing systems
for diagnosis, monitoring and prevention of the spread of infectious
diseases. Elsewhere, the MRC has worked in partnership with TSB,
BBSRC and Defra to fund research on the detection and identification
of infectious agents.
One other important aspect is the detection of genes
which confer anti-microbial resistance. Advances in next-generation
sequencing at BBSRC, MRC and NERC centres will allow for more
rapid identification of resistance genes and the ability to attribute
these genes to a potential source.
9. "The Government recognises that there
is a lack of information concerning environmental drivers of antimicrobial
resistance. We recommend that the Government publish, in its Action
Plan, a research programme that will recruit expertise across
the UK to fill the knowledge gaps on how antimicrobial resistance
exists and may be transmitted via environmental routes. Hoping
that research grant applications to research councils will serendipitously
gather this necessary information leaves too much to chance. Research
council funding should be, in this important field of study, complementary
to Government directed, and funded, research programmes."
The research councils fully endorse the necessity
of understanding the impact of the environment on antimicrobial
resistance and have funded work through response mode mechanisms.
For example, NERC have funded a study "Finding hidden AMR
in the environment" at the University of Warwick that examines
the link between the environment, bacteria and human health by
looking at the impact of sewage treatment on AMR bacteria in a
river. Another example is a BBSRC-funded study at the University
of Exeter to determine whether the low levels of antibiotics in
the environment, from both humans and animals, could be contributing
to AMR.
We agree too that there should be better coordination
of research and more investment into environmental factors. To
highlight this, the AMRFF has identified this as one of their
key themes for future research. The role of the environment in
AMR will be comprehensively addressed through multidisciplinary
research plans being developed by the research councils to "Understand
the real world interactions". There is an expectation that
funding will be ring fenced from current headroom to fund environmental
science in areas that have also been highlighted by the Committee.
10: "There is circumstantial evidence
that antimicrobial resistance can be transmitted from animal pathogens
to human pathogens although the evidence base is incomplete. The
Government needs to ensure that this is addressed. We recommend
that this is an additional focus of research in the action plan
and that in the meantime, the Government takes action to ensure
the use of antibiotics in farm animals is strictly required for
therapeutic use."
The research councils and AMRFF agree that this is
an important area to study. The research themes developed all
fall under the "One Health" umbrella and collaboration
between human and animal researchers will be essential. The BBSRC
brings strong expertise in basic animal bacteriology and veterinary
medicine, and there will be close alignment with Defra and Veterinary
Medicines Agency through the AMRFF. Research into animal pathogens
will be included in the first two themes of the cross council
initiative highlighted above.
12: "As the development of new antibiotics
and new technologies is dependent on private enterprise working
closely with academia, we were disappointed to find that the membership
of the Government's High Level Steering Group for the Strategy
did not incorporate voices from industry or learned societies.
We recommend that the membership of the High Level Steering Group
be expanded to include those voices."
The research councils are actively encouraging engagement
with private sector partners and the involvement of the private
sector will be essential at all stages of research and development.
There is now a wealth of experience within the research councils
in working with companies, from small one-to-one initiatives through
to larger, multi-sector, multi-partner consortia and networks.
The addition of the TSB to the AMRFF brings the ability to fund
directly into smaller companies, which will allow us to develop
public/private partnerships. The review mechanisms for funding
research through our four themes above will include expertise
from the private sector as will the top level governance group.
Many of the key learned societies (Biochemical Society,
British Society for Antimicrobial Chemotherapy, Royal Society
of Chemistry, Society for Applied Microbiology, Society for General
Microbiology and Society of Biology) have formed their own AMR
group and a number of AMRFF members attend these to ensure a joined-up
approach. We will continue these discussions as we develop our
plans. We will also continue our close engagement with senior
academic colleagues across the disciplines and ensure through
working closely with DH that communicate advice and opinion from
academic, industrial and learned societies are communicated to
the HLSG.
13 & 14: "Antimicrobial resistance
has the potential to send medicine back to the early 20th century,
severely limiting the use of what are now considered basic and
routine surgical procedures. The best current defence against
this scenario is a strong global pipeline of new drugs, possibly
using a range of solutions as described above. But that is dependent
on the infrastructure that provides financial incentive to the
industries that deliver these technologies including means of
compensating for the uncertainties inherent in research and development.
We agree with the Prime Minister that, if there
is no change to the economic landscape for developing new antimicrobials,
the pipeline of new antimicrobials will run dry. We also agree
that the Government needs to work with researchers, investors,
small and medium sized enterprises, large pharmaceutical companies
and other Governments to urgently identify appropriate economic
models that might encourage the development of new antimicrobials.
We hope that the review, which will take almost two years to report
back with recommendations, will not delay work on any pricing
alternatives that could be agreed with the pharmaceutical industry
over a shorter timescale."
The research councils fully support the work being
done on economic models to encourage development of new antibiotics
- it is essential to address these issues. The ESRC will work
with the recently announced commission, and themes 2 and 4 of
the research councils' initiative will also address some elements
of the business and economic modelling.
The pull-through generated by these economic models
is one essential part of the fight against AMR but the pipeline
of new treatments also needs to be restocked. This will be driven
by a range of factors such as better understanding of how resistance
occurs and is spread, identification of new "druggable"
targets in bacteria, better ways of screening new compounds, targeted
delivery mechanisms, new treatment paradigms and beyond. The thematic
approach taken by the research councils aims to tackle many of
these questions. Theme 1—Understanding resistant bacteria
in context of the host—will focus on deeper understanding
of bacterial resistance with the aim of identifying new ways to
beat antibiotic resistance. Theme 2—Accelerating therapeutic
and diagnostics development—will address some of the important
questions around developing these treatments, be they small molecule
antibiotics or novel treatment regimes. As discussed above, this
theme will also look at developing novel diagnostics to identify
the infection and target the best treatment.
By utilising the latest chemistry and engineering,
the advent of new synthetic biology techniques, advances in industrial
biotech, coupled with the detailed understanding of bacterial
cells, there has never been a better time to address the challenge
of discovering new antibiotics. Building on the advanced knowledge
in the research base, the research councils will work closely
with TSB and the pharmaceutical industry to help improve the pipeline
of new antibiotics.
Summary
The research councils welcome the Science & Technology
Committee's report and the opportunity to highlight the action
that is already or soon to be put in place to address some of
the concerns. All seven of the research councils are investing
in this area and we are co-ordinating our efforts with other funders
through the AMRFF. We are strongly aligned with the Department
of Health, Defra and devolved equivalents to ensure join-up of
our research with other Government agencies and pull-through to
policy and practice, while also engaging the private sector at
the earliest opportunities for maximum buy in.
1 www.mrc.ac.uk/amr Back
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