network Summer 2005 News, views and information from the Medical Research Council

In this issue MRC announces plans for Funding schemes review strengthening UK clinical research A look at year one of the new grant schemes page 4 The Spring edition of Network referred to how the MRC’s scientific strategy is shifting in Regulatory emphasis towards a more translational approach. Now, following publication of the MRC’s Delivery statement Plan in May and the Government’s 2004 Spending MRC publishes policy Review allocations, Network is able to report on on research regulation the practical steps that the MRC is taking to page 8 implement its clinical research agenda.

Research Increased investment governance In recent years the MRC has spent around a third working group of its funds on clinical and public health research Units pool resources and training – around £127m per annum. But from to develop practical 2005 onwards this amount is set to rise, to about £162m by 2007/08, following the MRC’s allocation guidance for use in the 2004 Spending Review (see table overleaf). MRC-wide This significantly increased commitment results page 9 from £25m new money from the spending review specifically earmarked for clinical and public health Unit profile research during 2006-08, and from the MRC’s special redeployment of a further £37m of its existing MRC units and centres funds from 2005 onwards. The importance of partnership working in public The MRC’s ambitions for clinical research make health science When drawing up its Delivery Plan, the MRC close partnership working more important than page 10 took care to listen to the views of the scientific ever. For example, the MRC/Health Departments community and other key stakeholders. The plan Joint Health Delivery Group that was set up in Global research stresses the need to speed up the rate at which 2004 to enhance partnership working across medical science generates health benefits, so public funders of medical research, and the MRC’s ethics clinical and public health research feature work with government agencies and funders in Addressing key issues strongly, as does the importance of translating the charity, public and industrial sectors through with our African basic research findings. For although the MRC the UK Clinical Research Collaboration research partners funds a vast range of scientific activities, all share (UKCRC). These initiatives will help to ensure page 14 one central aim – the need to improve and that all the UK’s public funders of clinical and maintain human health.Achieving this goal relies translational research achieve maximum synergy on clinical research and its related disciplines to in the science they support. Plus translate discoveries from basic research into New faces, research new and improved treatments, and to feed clinical MRC objectives for clinical research centre news, board research findings back to the laboratory.The • Increased support for clinical trials and their and award MRC has funded 10 new clinical trials since development, including evaluation of public deadlines, research November 2004 – evidence that its translational health interventions. roundup, MRC drive was already starting to gather momentum • Calls for proposals in experimental and people and more… last year. translational medicine. For example, as part >> page 2 2 MRC | network Summer 2005

<< Clinical research

of an initiative with its UKCRC partners, the MRC has allocated 2004 Spending Review – MRC allocation £15m for a call for proposals in experimental medicine in September The MRC’s allocation under the 2004 Spending Review (SR2004) rises from a baseline 2005. (including non-cash items) of £478.8m in 2005/06 to £546.5m in 2007/08. The 2005/06 • Capacity building, particularly by financial year is the last year of the previous Spending Review period (SR2002) and is the increasing the numbers of clinical base year for SR2004. The table below shows the resource (non-capital) allocations for training fellows at pre- and post- 2005/06, 2006/07 and 2007/08. doctoral level, and encouraging more applications from allied health A proportion of the MRC’s extra resource allocation (£42.4m) is to meet additional costs professionals and those in following introduction of full economic costing (FEC) in universities. An additional £7.9m underpinning non-clinical disciplines. has been provided to help the MRC to implement the recommendations of the Roberts Also building capacity in population Review. The remainder (£5m extra in 2006/07 and £20m in 2007/08) will be used to take health sciences to strengthen public forward the clinical research agenda. The MRC’s capital allocation also increases during the health research capacity, and SR2004 period from £34.6m to £41.9m. developing a cadre of research translators. Resource allocation £m 2005/06 2006/07 2007/08 • Increased support for large-scale epidemiological studies. Resource allocation 444.2 465.2 504.6 • More focus on co-ordination of Less funds for FECs1 14.4 27.9 existing investments: building Less Roberts funds2 1.5 6.4 methodological networks across MRC Less non-cash items 16.1 16.1 22.1 units, and establishing an MRC Net cash funding 428.1 433.13 448.13 institute for population health sciences Increase over 2005/06 5.0 20.0 to draw together existing MRC

investments and create a focus for 1 FECs = full economic costs. new research and support for public 2 Allocated to Research Councils in response to the Roberts Review, SET for Success, 2002. 3 health elements of the UKCRC. Totals do not agree due to rounding errors.

Translational research About a third of the MRC’s current to disease.All of these activities will be Training expenditure is on research linked to clinical co-ordinated with the MRC’s plans for To address the current shortage of practice or population studies.To help other areas of research, including clinical researchers, the MRC is working strengthen translation of basic research infections, biomarkers, regenerative closely with the DoH Research Capacity findings into health benefits for people, the medicine and translational brain sciences. Building Programme and the MRC will be increasing its support for And in order to promote new and existing implementation group for the experimental medicine, and for clinical approaches to translational research, the UKCRC/Modernising Medical Careers trials and other population-level studies – MRC will be encouraging the exchange of Subcommittee.The additional funds for example, on interactions between ideas, methods and people between the received in SR2004 will enable the MRC environment, behaviour and predisposition basic and clinical areas. to increase the number of clinical

Population sciences Clinical research glossary Investigation undertaken in populations (e.g. descriptive epidemiology, cohorts, randomised trials, and case-control designs involving people) Clinical research to identify mechanisms of health or disease, or to test the validity and Research based on humans and designed to answer questions about importance of new discoveries, interventions, or treatments. health and disease. In addition to direct examination of individual patients and populations, it includes the study of biological samples and personal Translational research data deriving from the individuals concerned. It also includes research on The process of the bidirectional transfer of knowledge between basic volunteers, or on populations of apparently healthy individuals, where work (in the laboratory and elsewhere) with that in the whole patient. such study relates to a disease process being investigated. Translational research ranges from exploring fundamental scientific questions and applying the resulting knowledge to the patient, to Experimental medicine bringing insights from studies in the patient back to the laboratory Investigation undertaken in humans, relating where appropriate to in model systems for further exploration.These efforts will lead to model systems, to identify mechanisms of pathophysiology or disease, better understanding of the mechanisms of disease and the or to demonstrate proof-of-concept evidence of the validity and maintenance of health, as well as to new methods of diagnosing, importance of new discoveries or treatments. treating and preventing disease. Summer 2005 MRC | network 3

Key concepts in medical research research fellowships it can award at Discovery Science for Health PhD level – from the current level of 30 per year to 50 by 2007. Implementation & The MRC will also be providing funds Delivery to enhance research capacity in nursing Translational Research and allied health professions, and to Clinical Research increase training in the disciplines that underpin clinical, health services and Experimental Population public health research, such as health Medicine Sciences economics and statistics.

Implementing strategy Basic Research The MRC has set up two Council subgroups to oversee the implementation of the strategic aims The term “medical research” encompasses “translational research”.“Experimental outlined in the Delivery Plan – the a broad range of activities within basic and medicine” crosses the boundaries Clinical Research Oversight Group, clinical research, all aimed at improving or between basic and clinical research; there chaired by Professor John Savill, and maintaining human health. In simple terms, is also the analogous discipline of the Public Health Research Oversight “clinical research” involves research on “population sciences” which likewise Group, chaired by Dr David human participants, while “basic research” draws on basic and clinical research but Armstrong. Both groups include refers to underpinning research from areas studies much larger groups of people.The representatives of the relevant MRC such as animal studies, psychology, ultimate aim of both disciplines is to apply research and training boards and of statistics, economics, physics, chemistry, etc. the knowledge gained to improve the academic community, the MRC’s healthcare delivery, which itself may be Advisory Group on Public Clinical research involves a number of the subject of research – for example, Involvement, the Health Departments interrelated concepts:“clinical research”, studies of health services and and the Academy of Medical Sciences. “experimental medicine” and organisation.

50th anniversary of the MRC cyclotron

On Friday 3 June the MRC Clinical explained the developments that have led Sciences Centre brought together over to increasingly detailed brain imaging; Dr 200 people to celebrate 50 years of Eric Aboagye described the use of PET research following the installation of the techniques in diagnosis and prognosis of world’s first medical cyclotron at cancers, and Dr Anne Lingford-Hughes Hammersmith Hospital in 1955. Old linked PET’s contribution to brain friends and collaborators in research, research on addiction and craving to clinicians and policy-makers heard a clinical practice to help addicts change fascinating series of talks on the history their behaviour. of the MRC Cyclotron Unit, key turning points in positron emission tomography The event buzzed with an atmosphere of (PET) research and predictions for the people renewing friendships and future. identifying new collaborations. It ended with a reception and the unveiling of the Professor Jack Fowler reminded the Vonberg Suite in the Cyclotron Building, audience about the vagaries of early named after Derek Vonberg who guided computing techniques, the first the MRC Cyclotron Unit through the investigations which meant carrying early years of its pioneering work. anaesthetised pigs up to the top of the building, and various ingenious engineering Find out more online solutions to push forward the frontiers of For full details of talks, including the new science. The other speakers Professor Jack Fowler renewing old friendships presentations, visit: described the legacy of the pioneering outside the Wolfson Conference Centre, www.livegroup.co.uk/cyclotron work – Professor Richard Frackowiak Hammersmith Hospital campus. 4 MRC | network Summer 2005

New MRC funding schemes: review of year one

In February 2004 the MRC introduced major changes to its funding schemes, to provide fewer, simpler and more flexible options for researchers.A year on, Network takes a look at the new grant schemes in action.

Response from researchers term five-year programmes. However, the intention-to-apply form and use of The MRC is pleased to report that the vast majority of applications in the first triage to hasten decisions about new Research and Collaboration Grant year of the Research Grant scheme proposals with the lowest scores. schemes have been well received by the were for lower cost, short-term However, the very substantial increase scientific community, with the number of proposals. The MRC hopes that in the experienced meant these measures had applications received increasing future scientists will start to take fuller a limited impact. significantly with each round of research advantage of the flexibility that the board meetings in 2004/05. Compared scheme offers, to maintain a balance of The need to develop effective strategies with figures for May 2004, the number of short- and long-term grants. Of course, for managing demand, including applications, including those for Trial this may sometimes result in a short- encouraging higher-quality applications, Grants, had risen by 73 per cent by term grant of one or two years, but only is clearly a key priority for the MRC. It October 2004 and by 126 per cent by where it is the scientifically appropriate will therefore be monitoring the volume May 2005. More grants were awarded – option for the research in question. and quality of applications closely during 180 compared with 161 in 2003/04 – and the next year and publishing figures for the total value of grants increased from Impact on peer reviewers success rates and quality of applications £85.4m to £99.2m. Network readers will not be surprised to by university. learn that the dramatic increase in the As the MRC anticipated, the Research number of applications presents some One solution to the problem lies with Grant scheme was the most popular major challenges, both for the MRC and the scientific community. The overriding choice for applicants (see Figure 1). It for its expert reviewers (see Figure 2). determinant of an application’s success was introduced to enable applicants to Before introducing the new schemes in will always be its core scientific quality tailor the length of support they request 2004 the MRC had anticipated a fairly and importance, particularly in view of to the actual needs of the proposed modest increase in volume. Given that the fierce competition for funds. This research, rather than them being the review community was already at full means that the MRC is unlikely to fund restricted to the traditional model of stretch, the MRC introduced measures applications that are not of an focused three-year projects or longer- to help manage this increase – an online internationally competitive standard. So

Figure 1 – Application types and numbers received 2004/05 Figure 2 – Number and quality of applications by MRC research board cycles 2004/05

Research Collaboration Trial Total no. of Total no. of internationally Total no. of IC Research grants include Research, Strategic, Programme and Co-operative Group Component applications competitive (IC) applications awarded Collaboration grants include Collaborative and Co-operative Group (parent & development) applications Summer 2005 MRC | network 5

researchers can avoid placing an total annual number and value of awards, unnecessary burden on their colleagues and average size of grant. As these trend in the peer review system by only data show, cheaper short-term submitting high-quality proposals that applications are not more likely to be request an appropriate amount of money funded than more expensive, longer-term for the research described. proposals – the decisive factor is always scientific quality. In 2005/06, the MRC received extra money to maintain the current volume of As the MRC’s Director of Research new awards at full economic cost. Management, Dr Diana Dunstan, told However, if the resources requested Network,“We want to be fair to “ … we are keen to within applications increase significantly, applicants and to ensure that the best maintain a balance of then the number of awards that the MRC science continues to get funded. But we can make at full economic cost will fall. also want to avoid over-burdening long-term and short-term reviewers. Our increased transparency programmes within the A word about timing about trends in applications and awards Research Grant scheme.” Before submitting applications, the MRC will help to achieve this.” When asked to recommends that applicants look at the comment on the increase in applications Dr Diana Dunstan, Director of funding section of the MRC website to in 2004/05, Diana said “We welcome the Research Management gauge the level of very positive response to the new competition for Research Grant scheme. But as many of funds in their the applications were for shorter-term Figure 3 – Success rate of internationally competitive scientific area. grants, I would like to stress that we are applications by MRC research board cycles 2004/05 They can then keen to maintain a balance of high-quality decide whether long-term and shorter-term programmes or not to within the scheme.” postpone their application until a More data about 2004/05 future research applications board cycle. • The overall success rate for Other useful internationally competitive information applications for the new funding available on the schemes was 68 per cent and the site includes success rates for internationally success rates by competitive applications for each of research board the research boards ranged from and university, >> page 6

Figure 4 – Internationally competitive (IC) applications by duration Figure 5 – Overall success rates and success rates by duration 2004/05 of application 2004/05

IC <3 years IC >3 years as % Total IC as % of all Success rate of Success rate of General success rate as % of all of all >3 years applications <3 years as % of >3 years as % of <3 years all <3 years all >3 years 6 MRC | network Summer 2005

<< New funding schemes MRC Research Boards

51 per cent to 88 per cent. The success rate of longer-term applications was Health Services & Public Health higher than for short-term applications. Research Development and evaluation of healthcare • There has been a significant shift in the proportion of short-term (three years interventions (with particular emphasis on or less) and longer-term applications submitted. Short-term applications Phase III trials); population-based studies increased from 51 per cent in May 2004 to 84 per cent in January 2005, but of the aetiology of disease (with particular were generally of a lower quality than the longer-term applications (see emphasis on the role of psychosocial Figures 3-5) factors); research methodologies in health services and public health research; • The average value of awards was £320k for proposals of three years or less translating research into practice; studies and £963k for proposals of more than three years. However, many proposals of public understanding/involvement in received contained costs that could not be justified and these grants needed health research. to be pruned at the peer review stage (see Figures 4 and 5). Infections & Immunity • There was no significant change in the proportion of applications received and Transmission and control of infectious awarded within clinical/non-clinical, principal investigator aged 40 or under, agents and their interaction with the and gender. However, the introduction of the New Investigator Award immune system, pathogenesis, competition has led to a significant increase in awards to early career development and control of the immune scientists. system, parasitology, virology, bacteriology and tropical medicine. Budgets for 2005/06 The MRC received increased funding in the 2004 Spending Review, but still has Molecular & Cellular Medicine some challenging decisions to make about allocation given the growing strategic All aspects of molecular and cellular importance of clinical and translational research – see article on page 1. The table research including: cancer biology, genetic below shows the MRC’s proposed budgets for its research boards and its strategic mechanisms, methodology development budget; the actual distribution across MRC units and grants will depend on peer for gene therapy, bioinformatics, review. The strategic budget, which funds strategic initiatives, cross-board research biotechnology and structural studies, and MRC institutes and centres, is £67.2m for 2005/06. This money will be targeted nanotechnology, cell biology, and at experimental medicine, health services research and public health research. Also, developmental and stem cell biology the strategic budget may be allocated to the research boards following response to excluding neurobiology. calls for proposals in strategic areas, e.g. experimental medicine. Neurosciences & Mental Health All aspects of research into the Proposed funds for new awards in 2005/06 compared to neurosciences and mental health. Including funds available in 2004/05 basic neurobiology (e.g. molecular and cell biology, developmental neurobiology);

Research board/strategic budget 2005/06* £m 2004/05 £m systems based research; senses and cognition; behavioural neuroscience; HSPHRB 28.2 16.4 medically relevant psychology; IIB 20.4 15.5 neuroimaging; dementia, neurodegenerative MCMB 31.4 23.8 disease, transmissible spongiform NMHB 31.9 26.1 encephalopathies and other areas of PSCSB 19.8 14.2 neurology; and mental health and psychiatry. Strategic including 2004 Spending Review 67.2 67.0 New Investigator Awards (NIA)** 11.0 5.0 Physiological Systems & Clinical TOTAL 209.9 168.0 Sciences Function and pathophysiology of the major organ systems, molecular medicine, * Including an uplift to account for the introduction of full economic costs during 2005/06. ** Merged with Career Establishment Grant scheme for the annual NIA competition, from September 2005. genetics of disease and genomic epidemiology, inflammation, pharmacology, human reproduction, fetal and infant development, nutrition and energy Find out more online metabolism, toxicology, environment and For information on the MRC’s overall funding allocation and funding opportunities health. PSCSB has a lead role in promoting including calls for proposals, visit www.mrc.ac.uk/funding.htm translational and clinical research. Summer 2005 MRC | network 7

Research centre news

New Institute for Radiation Biology Research at Oxford Upstate building honours A new centre for research in radiation biology and oncology is planned at Oxford grandfather University, under the leadership of Professor Gillies McKenna. Jointly funded by the of protein MRC, Cancer Research UK and the University of Oxford, the Institute for Radiation Biology Research will be an amalgamation of the MRC Radiation and Genome phosphorylation Stability Unit, Harwell, and the Gray Cancer Institute, London. Professor McKenna returned from the USA in April to take up the post of Professor of Radiation On 8 March US life sciences Oncology and Biology at the University of Oxford. For the past 16 years, while at the company Upstate opened a University of Pennsylvania, his main research interest has been how to make cells new building in Dundee to more sensitive to radiation by blocking mechanisms that control cell survival.Areas house its European of research at what promises to be a world-class centre include delivering radiation operations, including work in more sophisticated and precise ways, using new imaging techniques to restrict stemming from a pioneering radiotherapy to tumours and finding new ways to make tumours more sensitive to collaboration with the MRC radiation. Professor McKenna said,“The new centre is designed to foster Protein Phosphorylation collaboration between scientists from quite distinct areas of expertise, and I’m Unit. More than eight per confident it will be the source of many groundbreaking discoveries.” cent of Upstate’s products, which are used to develop therapies for cancer, diabetes and other critical diseases, NIMR update originate from reagents developed at the MRC Unit As reported in the Spring edition of Network, in February 2005 the MRC’s Council directed by Sir Philip Cohen. chose University College London (UCL) as the preferred partner for the renewal of The new building is named the MRC National Institute for Medical Research (NIMR). Since then, the project group the Fischer Building after has been preparing the full science and business case for the NIMR’s re-location. Professor Edmond Fischer, who with Edwin Krebs won The project group has been supported by eight workstream groups with members a Nobel prize for his drawn from MRC head office, the NIMR and UCL.The groups covered the following discovery of reversible areas, five of which relate to research and three to more general requirements: protein phosphorylation in genetics and development; infections and immunity; neuroscience; structural biology; the 1950s. Professor Fischer translational opportunities and training; building and facilities requirements; the – who celebrates his 85th provision of biological research facilities; and the new site’s scope for enhancing public birthday in 2005 – was the engagement by the NIMR and the wider MRC. guest of honour at the opening and the keynote The workstream groups provided important information for inclusion in the business speaker at a symposium held plan for the renewal of the NIMR in partnership with UCL, including examples of two days later by the Protein potential research collaborations within the partnership.The plan was presented to Phosphorylation Unit to the MRC’s Council on 18 May and approved, although the Council recognised that celebrate the 50th further work needed to be done on the biological research facility. In June, the UCL’s anniversary of his discovery. Council also approved the business plan. The MRC will now present its case to the Office of Science and Technology and seek financial support from the Large Facilities Capital Fund. It will also be considering ways in which the enthusiasm and momentum that the workstream groups have generated can be continued over Find out more online the coming months. The science case for the renewal of the NIMR and the final papers The project group also provided MRC, UCL and NIMR input into the process for of the five research workstream recruiting the new Director of the NIMR in anticipation of Sir John Skehel’s retirement groups are available at next year.A paper setting out the principles for the recruitment process and the www.mrc.ac.uk. implementation plan was approved by the MRC’s Council at its May meeting. 8 MRC | network Summer 2005

MRC policy on research regulation The MRC’s recently published position statement acknowledges the challenge of balancing ethical requirements with the public’s need for speedy research delivery.

Over the last couple of years MRC- experimental work. The MRC expects the Tony went on to describe current MRC funded scientists have been voicing scientists it funds to comply with the activities to address the problem, starting concerns about the amount of regulation regulations relevant to their areas of with more dialogue with the public and surrounding their work. This growing research. Some of these will be contained media to understand public concerns concern reflects the impact of recent in primary legislation, which can however about areas of medical science and to major developments in regulation: the be a blunt instrument for guiding human explain the rationale for such research. incorporation of the EU Clinical Trials behaviour and difficult for non-lawyers to Secondly, the MRC keeps in touch with Directive into UK law, the passing of the understand. This is why the MRC provides active researchers to learn about the Human Tissue Act (2004), the increasing additional, publicly available guidance for issues that concern them, and ensures that requirements of Research Ethics researchers to help them put their daily scientists have clear, up-to-date Committees (RECs) – arising in part work into the appropriate legal context. information about regulation and ethics. from new legislation, and the wide The internet is an increasingly useful variation in implementation of regulations Challenges for researchers medium for disseminating such by RECs, universities, NHS Trusts and Despite the clear benefits of regulation, information. For example, in October 2004 R&D departments and other bodies. the MRC is well aware that it presents the MRC and the DoH launched a ‘clinical challenges for researchers. Compliance trials toolkit’ website, which uses a The MRC has responded by developing a involves additional bureaucracy, costs and routemap approach to help researchers position statement on research regulation time. In theory – and in practice – it negotiate complex new EU clinical trials and ethics, which summarises the MRC’s could create so many difficulties as to legislation and attracts around 3,000 views about the need for such regulation. discourage an important programme of visitors a month.The MRC also keeps It also acknowledges how this ethical need research from taking place, or it could abreast of developments in broader must be balanced with scientists’ desire to lead to barriers to participation that aspects of regulation, including law and proceed quickly and efficiently with introduce bias. Unfortunately, there is no political science. Thirdly, the MRC research to benefit human health, and easy answer to finding the right balance maintains the highest standards of peer outlines what the MRC is doing to help between regulation and researchers’ review to ensure reliable research findings, achieve this balance. wishes. Obstacles to progress here which helps to prevent unnecessary include the fact that aspects of the duplication of research – a potential cause The MRC’s role in research regulatory process may not be well of public concern. regulation controlled, as with EU legislation, or the The MRC is a leading national source of balance may need to be very different for Equally importantly, the MRC continues to guidance and advice on medical research apparently similar situations, or it will engage with the Government and other regulation. It was the first research need to change over time to reflect public regulators over problems presented by organisation to publish ethical guidelines attitudes or significant events. existing and proposed regulation. As a concerning investigations on human preliminary to this, it will be working with participants. Produced in the early 1960s, Working to achieve a balance the UK Clinical Research Collaboration these pre-dated the first version of the Dr Tony Peatfield, the MRC’s Head of (UKCRC) to review regulation that Declaration of Helsinki (1964).The MRC Corporate Governance and Policy, told involves unnecessary bureaucratic continues to set standards of good practice Network: “Although a key part of the procedures and other counterproductive in all aspects of medical research, including MRC’s mission is to promote and elements. The MRC and its UKCRC patient safety and the use of animals, safeguard good practice in medical partners will then develop proposals for personal information and human tissue. research, we realise that implementing new regulation in the context of existing regulation can present very real regulation, taking account of the likely The need for regulation challenges for hard-pressed researchers. level of risk to participants. Regulation protects both participant – Understandably, scientists are keen to human or animal – and researcher. It sets progress their science as quickly and Find out more online out clearly what is acceptable and what is cost-effectively as possible and increasing not, providing a protective framework that levels of regulation can sometimes MRC position statement on research regulation and ethics is appropriate to the level of risk involved. frustrate this aim. The trust of the public www.mrc.ac.uk/pdf-mrc_statement_ In addition, effective regulation helps to and media is a key factor in preventing regulations_ethics_may_2005.pdf ensure that the reputation of funding excessive regulation and the MRC is MRC/DoH EU Clinical Trials Directive bodies and employing organisations is not continuing to increase its work to website: www.ct-toolkit.ac.uk damaged by misjudged or unethical promote such trust.” Summer 2005 MRC | network 9

Exploring practical solutions In conversation to regulatory challenges with Dr James Watson An MRC unit-led working group is pooling experience and ideas to develop a resource base of ‘tried-and-tested’ good A lively public discussion practice… between DNA discoverer Dr James Watson and As shown in this edition’s article on the MRC’s policy on research regulation, an Professor Colin important aspect of the MRC Council’s work is the support and guidance it gives scientists over implementing research governance legislation and guidance. To help Blakemore… involve scientific staff more directly in this area, the MRC has recently set up a unit- led working group to look at governance of research involving human participants, On 18 May Dr James Watson treated their tissues or data. The group are identifying, documenting and sharing the good an audience of 150 people to candid practice they follow, with the aim of developing good practice documents, illustrated and enthralling reflections on his life in with working examples, for publication on the MRC portal. science. The eminent biologist, who with Francis Crick won a Nobel prize Encouraging in-depth discussion for unravelling the secrets of DNA in Each MRC unit that carries out research involving human participants has nominated 1953, was the guest of Colin Blakemore a representative for the working group. To ensure that all the relevant issues are at an ‘In Conversation With….’ event at discussed in sufficient depth, the group’s remit has been split into three main areas, the Dana Centre in London’s Science each led by unit representatives: Museum. The wide-ranging conversation • Collection and management of human tissues and biological samples. touched on the difference between • Risk assessment, management and monitoring. science now and 50 years ago. James • Sponsorship and agreements. Watson welcomed the huge increase in the pace of discovery but regretted The project is led by Dr Sarah Dickson, who is on secondment from her role as that this means less time for scientists Clinical Studies Manager at the MRC Human Reproductive Sciences Unit at to stop and think – he remembered Edinburgh. Sarah told Network,“The changing legislative environment poses challenges how in 1952 he had been able to take for researchers and we feel it is important that unit staff have the opportunity to off the whole of the summer to do so. share problems and work together to develop effective, reliable solutions that work On a more personal note he talked on the ground. What’s more, this will enable the MRC to develop a resource base of about the impact of his son’s mental practical,‘tried-and-tested’ approaches to meeting governance standards, to illness and how it drives his continuing complement the formal guidance produced at a corporate level.” interest in neuroscience, and offered some controversial opinions on the Interested in joining the group? UK’s role in stem cell research If you work in research that involves human participation in any way, and are following recent announcements from interested in joining one of the subgroups or in contributing advice or ideas, please Newcastle University. email the relevant contact below:

• Collection and management of human tissues and biological samples: patient or volunteer recruitment (information and consent); management of sample storage and tracking through databases. Catherine Elliott, [email protected]

• Risk assessment, management and monitoring Randomised controlled trials: Jane Armitage, [email protected] Social, public health, observational or questionnaire-based studies: Catherine Ferrell, [email protected] Studies involving human tissue or sample collection: Sarah Dickson, Dr James Watson and Professor Colin [email protected] Blakemore discussing scientific issues at the Dana Centre. • Sponsorship and agreements: roles and responsibilities of sponsors under Research Governance Framework; production of generic agreements for You can follow the whole collaborative studies and transfer of human material. Tony Hodge, conversation on the webcast archive [email protected] for “DNA, Genes and the Brain” at www.danacentre.org.uk/Default.aspx? • All other enquiries: Sarah Dickson, [email protected] DanaMenu=_WEBCASTARCHIVE 10 MRC | network Summer 2005

Science for public health In this edition of Network we expand our regular Unit Profile to include a number of MRC units united by their work in public health science...

Providing the scientific foundation for all current cases of type 2 diabetes are still individuals to reduce the likelihood of public health action is an important part undiagnosed, which opens up the possibility them developing diabetes, while primordial of the MRC’s mission, and one which of earlier detection and treatment through interventions are designed to reduce the involves the work of a variety of screening to help minimise the risk of likelihood of an individual becoming high- Cambridge-based units. All share an complications at a later stage. risk in the first place. Studies in the USA, interest and expertise in population Finland and India have shown that primary science and an ambition to harness the The National Screening Committee is prevention can be effective, but have full potential of collaborative effort to currently considering whether or not focused on groups with the pre-diabetic tackle some of today’s major health screening for diabetes should be state of impaired glucose tolerance (IGT). problems. For example, the current introduced as a public health intervention. Detecting IGT in the wider population is epidemic of obesity and its metabolic But until now there has been uncertainty difficult so researchers from the MRC consequences, particularly type 2 diabetes, about its cost-effectiveness, principally Epidemiology Unit have been investigating which the World Bank and the World because of the difficulty of measuring the more practical ways of identifying people Health Organization say are now global reduction of heart disease risk after who are at high risk. Using data from the public health challenges. intensive combined treatment to reduce large MRC-funded population-based study glucose levels, lipids and blood pressure in EPIC, undertaken in collaboration with the Cutting complications people with screen-detected diabetes. MRC Dunn Human Nutrition Unit and Type 2 diabetes is not only a major cause Most trials have assessed the effects of University of Cambridge, the team has of premature death – including through single agents rather than the real-life demonstrated that people with a family associated conditions such as situation of combined therapy. To provide history of diabetes were more likely to cardiovascular disease – but it is also the a more reliable indication of the value of develop diabetes if overweight or leading single cause of preventable screening, researchers from the MRC sedentary. This group is a good target for blindness, amputation and kidney disease. Epidemiology Unit, MRC Biostatistics Unit preventive efforts because they are To reduce the occurrence of these and the University of Cambridge General relatively easy to identify and stand to devastating complications, public health Practice Research Unit (GPRU) recently benefit considerably if they can avoid scientists focus on prevention at different modelled its impact on heart disease risk. weight gain. A key question for the team levels. Secondary prevention aims to As a result, they have estimated the was whether there was evidence that diminish the likelihood of people with combined risk reduction for heart physical activity could help to prevent diabetes going on to develop disease, which can now be probed by weight gain and what could be done to complications, and tertiary prevention research such as the ADDITION trial, a help people change their activity patterns. helps to reduce the impact of any such large multi-centre study that is being The team went on to develop an complications by improving the conducted by the Epidemiology Unit and intervention (see box) that has been effectiveness of treatments. Evidence from the GPRU. Within the intensively treated trialled in the ProActive study, the results studies such as the MRC Epidemiology group, the team is also assessing ways of of which are expected later this year. Unit’s Ely Study suggests that up to half of helping people make key changes to their lifestyles, including increasing All in the genes? physical activity, stopping So what is it about the interaction smoking, changing their diet between family history and obesity that and taking medication as gives rise to increased risk? Well firstly, prescribed.Trials such as families share genes and environments. ADDITION will contribute Understanding how genes, early life directly to decisions made development and lifestyle behaviours about public policy in the interact to affect risk is a major part of the future. MRC Epidemiology Unit’s programme. Using data from individuals with extreme Focus on prevention phenotypes, together with case-control It is becoming increasingly studies and cohorts, the Unit is evident that primary or even collaborating with Professor Steve primordial prevention is also O’Rahilly of the University of Cambridge Measurement of supine length in children is essential for studies possible. Primary interventions and Dr Ines Barosso of the Wellcome Trust investigating appropriate early growth and weight gain. are aimed at high-risk Sanger Institute in the Genetics of Energy Summer 2005 MRC | network 11

Metabolism Collaborative. This programme point, researchers need has detected rare gene mutations that give substantial, long-term rise to early-onset obesity or extreme evidence of an interaction insulin resistance, one of the main factors between genes and lifestyle leading to type 2 diabetes. The team is behaviours. Collecting such now investigating whether variation in data is the aim of the UK these genes causes less severe and more Biobank project which the common forms of disease. They have MRC co-funds. It is a shown that polymorphisms in genes formidable task because of impacting on beta-cell function are the scale of the project and associated with type 2 diabetes and that the time required before some rare gene variants interact to cause results are available – subjects are been developing expertise in less disease. The next step, to move beyond followed from the age of 40 to 69. expensive, more practicable population testing genes we already know about to The Epidemiology Unit is therefore measures such as objective monitoring finding new ones, will come about through using resources currently available and instruments. The Epidemiology Unit’s new developments in typing whole areas of a modified scientific approach (see Fenland Study, for example, uses a newly chromosomes and the entire genome. This box overleaf), to research how genes designed combined heart rate and area of work is particularly important and lifestyle influence the incidence movement sensor to provide detailed because understanding how genes impact of diabetes. energy expenditure and physical activity on disease risk can have implications for data. In collaboration with HNR, they have prognosis. For example, some patients with Tracking pathways to diabetes been evaluating how well these sensors rare mutations in a beta-cell gene have a The links between dietary patterns, specific compare with the stable isotope method, relatively indolent form of hyperglycaemia, food groups and nutrients with obesity and with all age groups including children. which means that they can be reassured diabetes have yet to be well established. about long-term risks and targeting of MRC Human Nutrition Research (HNR) Ultimately, the greatest impact on the pharmacological treatment. On the other conducts intervention studies to determine growing public health burden of obesity hand, some patients respond better to a the effects that changes in nutrients, foods and diabetes may well come from particular glucose-lowering therapy. or dietary habits have on obesity, insulin collective interventions that impact on the resistance and related cardiovascular risk very infrastructure of society, rather than In the future, genetic risk prediction may factors. One such study, RISCK, is the UK’s constantly focusing on individuals at high improve to the extent that it surpasses largest ever dietary intervention study. risk and targeting them for intensified the relatively crude information, such as Funded by the Food Standards Agency, it intervention. family history, that is currently being used involves manipulating the proportion of in trials. But before we can reach that mono-unsaturated fat in the diet and the Getting society on the move glycaemic index of participants. RISCK also Obesity and inactivity are now so includes the first community-based trial of prevalent that public health scientists are The ProActive approach the effect of wholegrain consumption on starting to think in terms of sick to prevention risk of cardiovascular disease, in populations rather than sick individuals. collaboration with the University of This is likely to lead to a movement away Newcastle. These intervention studies are from focusing on intensified intervention The MRC ProActive trial is based on the closely linked into the Government’s public for high-risk individuals towards collective EPIC observation that obesity and reduced physical activity contributed to the higher health nutrition agenda, and the scientists interventions that impact on society as a prevalence of type 2 diabetes in those with involved are actively engaged in policy whole. An important part of the a family history of the disease. In the trial discussions related to the government Epidemiology Unit’s work is to identify sedentary people from such families are White Paper Choosing Health. what determines lifestyle behaviours. For encouraged to increase their physical example, declining physical activity – in activity, which is then measured objectively. The link between physical activity and part influenced by the changing nature of The trial, which is being conducted in collaboration with Cambridge University metabolic disease is also much less certain work and transport – and its association General Practice Research Unit, is part of than is generally realised, largely because with ill-health. More research is needed the MRC co-operative group on the of the difficulty of measuring physical into the variation of physical activity development and evaluation of complex activity precisely in population-based between individuals and other social and interventions. It provides a model of how studies. HNR has an international environmental determinants, which is one information concerning inherited risk could reputation in measuring energy reason why the unit’s researchers often be used to identify individuals for expenditure using stable isotopes, though collaborate with sociologists, preventive interventions, and how to get patients actively engaged in prevention and these methods are too expensive to be psychologists, geographers and maintain their motivation. used in large cohorts. To help tackle this environmental scientists. The unit is problem, the MRC Epidemiology Unit has >> page 12 12 MRC | network Summer 2005

<< Science for public health

currently working with the London Public Health Observatory and the School of Hygiene and Tropical Medicine University of Cambridge Department of Investigating gene– and the University of East Anglia School of Public Health and Primary Care. The environment interactions Environmental Science to investigate the Epidemiology Unit is collaborating extent to which physical activity, including increasingly with other MRC groups One way of pinpointing the genes that access to sports and recreational facilities involved in population science, such as the cause diabetes is through cross-sectional and public transport, is geographically new MRC Epidemiology Resource Centre case-control studies, such as the Norfolk Diabetes Study involving 10,000 patients determined. in Southampton. From 2007 the unit will with type 2 diabetes and 20,000 controls. be located within the new Cambridge The EPIC-Norfolk study of 25,000 The MRC’s contribution to public health Institute for Diabetes, Endocrinology and participants is another example and part science in Cambridge and beyond Metabolism, which will also house groups of a larger EPIC study involving 500,000 continues to evolve with a range of new undertaking basic cellular and molecular people in 10 European countries. The research projects and partnerships. For research. These burgeoning links between MRC Epidemiology Unit is leading efforts example, the establishment of the epidemiology, basic science and public to find new onset cases of diabetes in this cohort and to investigate how genes, Cambridge Institute of Public Health, health have a vital role to play in providing physical activity and diet interact. which includes the MRC’s Epidemiology the scientific base needed to underpin UK Unit and Biostatistics Unit, the NHS public policy and practice.

New faces Dr Middleton completed his training in record of delivering drug candidates into neurology in France and at Columbia the clinic. Dr Bryans’ previous positions University, New York. He became a include Senior Chemist at Xenova, Dr Lefkos T Fellow of the Royal Society of Medicine Associate Director of Chemistry at Middleton has been in 1987. His work in Cyprus during Parke-Davis and Senior Principal appointed to the 1982–99 centred on gene mapping Scientist at Pfizer. He has led projects in MRC's Council as an studies and preventative genetic a wide range of therapeutic areas and is industry member. He programmes for highly prevalent a co-inventor in over 50 patents.The will join in August for a neurogenetic diseases. new Drug Discovery Group builds on term of just under four existing strengths within MRCT, which years until 31 March Dr Justin Bryans already has a group of scientists who 2009. Dr Middleton is Head of joined MRC Technology screen potential drugs at its laboratories Translational Medicine and Genetics at (MRCT) in June as in Mill Hill, north London. MRCT is GlaxoSmithKline R&D, where his role is Head of the Chemistry recruiting a group of medicinal chemists to support drug discovery and division of its new and expanding the biology group.The development through genetic, biomarker Drug Discovery Group. aim is to enhance screening capability and imaging research initiatives, and He brings a wealth of and chemistry to help accelerate the experimental medicine.A graduate in commercial drug translation of MRC biology into medicine at the University of Strasbourg, discovery experience and a proven track innovative new therapies.

Infowatch Biomedicine and the Human Condition: Challenges, Risks, and Rewards

This new book by Michael Sargent of the MRC National Institute for Medical Research explores many issues that have perplexed mankind throughout history – such as the powerful influence of infectious disease on human society, the burden of our genetic legacy and the lottery of procreation. It discusses how prospects for human life might continually improve as biomedicine addresses these problems.

Cambridge University Press,April 2005, £18.99, ISBN 0521 541 484 Exclusive offer for Network readers: Cambridge University Press is offering a 20 per cent discount off the paperback edition until 31 October 2005.To order a copy for £15.00, telephone 01223 326050 and quote the ISBN and promotional code 'MRC2005'. If you have any questions please email Hannah Proctor ([email protected]). Summer 2005 MRC | network 13

Opportunities Programme leader From 1 September 2005, the MRC will only accept track forum applications costed on a full economic cost (FEC) basis. The EAA application form has been adapted accordingly. On 19 March more than 40 MRC researchers from all over the Research board applications 2006 UK gathered together at head office for a networking forum. The first of its kind for the MRC, the event gave up-and-coming scientists the opportunity to rub shoulders with their Infections and Immunity contemporaries, share scientific ideas and develop contacts for Intention to apply Full application Board meeting* future collaborations. And although networking was the focus 5.8.05 2.9.05 22/23.2.06 of the day, participants were also able to increase their corporate knowledge through presentations by Chief Executive Physiological Systems and Clinical Sciences Colin Blakemore, programme managers from their respective Intention to apply Full application Board meeting* research area and other key head office sections. 5.8.05 9.9.05 20/21.2.06 The forum attracted scientists from a variety of disciplines and Neurosciences and Mental Health at different stages in the programme leader track development Intention to apply Full application Board meeting* scheme (see box). All had submitted a brief abstract of their 5.8.05 16.9.05 1/2.3.06 research portfolio in advance, which were then used as a springboard for informal discussions throughout the day. Judging Health Services and Public Health Research by the lively and sustained conversations taking place in all Intention to apply Full application Board meeting* directions during breakout sessions, some mutually beneficial 5.8.05 23.9.05 9/10.3.06 collaborations may soon be in the offing!

Molecular and Cellular Medicine The afternoon was headlined by Colin Blakemore’s concise yet comprehensive overview of the MRC’s corporate strategy for Intention to apply Full application Board meeting* the next few years and its 10-year vision for the future. Specific 5.8.05 30.9.05 15/16.3.06 topics included the 2004 Spending Review and the MRC’s * Normal decision point research priorities, the various advisory bodies involved in MRC Note: Start date for all awards is 1.7.06 or later decision-making, external partnerships and their importance to the MRC’s goal of advancing clinical research, and results of interest from the MRC’s recent reputation audit. Colin MRC awards identified the key challenges for the MRC, discussing their implications for future MRC programme leaders. Questions from the audience included queries about career opportunities Institutional Discipline Bridging Award within the MRC and funding for scientific collaborations with Intention to apply Closing date Panel meeting external partners. 31.8.05 2.12.05 Interview Mar-06 Participants told Network that they particularly appreciated the Discipline Hopping Awards event’s dual perspective: the mutually supportive and stimulating Intention to apply Closing date Panel meeting experience of networking with peers, coupled with the 22.9.05 25.11.05 Feb-06 opportunity to meet their programme board managers and receive useful corporate information. One participant saw it as * Normal decision point a “move by the MRC towards greater transparency and clearer Note: Start date for all awards is 1.7.06 or later guidelines and expectations.” Certainly many expressed enthusiasm for more events of this type, seeing it as a winning formula for developing the programme leaders of the future. FP6 final call The programme leader track scheme is open to researchers who The fourth call for Framework Programme 6 is have shown the potential to lead and sustain independent research 9 November. This final call is for Thematic Priority 1 – programmes of international standing. The scheme offers participants the opportunity to combine further development of their research Life Sciences, Genomics and Biotechnology for Health. programme with structured personal development, including For further details, see www.cordis.lu/lifescihealth,or performance management and training in transferable skills. contact Rosa Parker ([email protected]). For further details visit www.mrc.ac.uk/about-careers/ about-careers_with_mrc.htm 14 MRC | network Summer 2005

Research ethics – the global perspective Medical research in the developing world can pose particular ethical challenges. The MRC and other European funders are working with their African research partners to address the key issues…

6th Global Forum on Bioethics in Research

March 2005 saw 150 people from more than 40 nations gathering together in Blantyre, Malawi, to discuss one of the burning ethical questions arising from research in developing countries – what happens when the research is over? This 6th Global Forum on Bioethics in Research was, as in previous years, designed to encourage free and frank debate, with emphasis on the perspectives of developing countries. Participants examined the ethical issues Participants deep in discussion during refreshments at the Global Forum in Blantyre, Malawi. surrounding post-research access to drugs, devices and vaccines for study REC members is also essential. Delegates et de la Recherche Médicale (France), the volunteers and their wider communities, were asked to take these messages back European Commission, the European and focusing on the roles and responsibilities home and urged to continue working Developing Countries Clinical Trials of investigators, research sponsors and towards solutions appropriate for their Partnership, the Council on Health research ethics committees (RECs). countries. Research for Development, and the Aga Khan University (Pakistan). A series of thought-provoking Forum facts introductory lectures, followed by case The Global Forum on Bioethics in studies and breakout groups, ensured that Research is an informal partnership the debate was challenging, lively and founded by a number of organisations wide-ranging. So what should happen with a shared interest in the ethical when the research is over? There are no conduct of research involving human easy answers but the consensus was that beings in developing countries. It meets plans to make the benefits of research annually to debate a chosen topic and the available to participants and local great majority of participants come from communities must be in place before the developing countries; other Forum research begins and revisited as it partners contribute funds to enable these progresses. Researchers cannot participants to attend. African countries launch implement the results of their research in ethics network isolation; they need to work with policy- The MRC has a long-standing investment makers. Furthermore, they need help to in medical research in Africa through its In April the MRC Laboratories in The do so, as few researchers are natural units in The Gambia and Uganda. It was Gambia hosted the first meeting of negotiators. Sustainable local capacity- one of the Forum’s founding partners in Networking for Ethics on Biomedical building and improved research facilities 1999, along with the Fogarty International Research in Africa (NEBRA).A are of key importance to developing Center and other institutes of the US collaboration of West African countries, countries.And the role of RECs has National Institutes of Health, the World NEBRA is funded by the European expanded vastly.They now frequently face Health Organization, the South African Commission under its Science and Society applications ranging from genetic risk MRC, and the Pan American Health programme. It involves four factors to huge epidemiological surveys. Organization. Over the years many other co-ordinating countries – Benin,The In developing societies it is especially organisations have joined, including the Gambia, Gabon and Mali, and 11 important to provide opportunities for Wellcome Trust – the main organisers of participating countries – Burkina Faso, RECs to share experiences and learn the 6th Forum – the Rockefeller Cameroon, Central African Republic,The from one another. Ongoing training of Foundation, Institut National de la Santé Congo, Côte d’Ivoire, the Democratic Summer 2005 MRC | network 15

Republic of the Congo, Ghana, Guinea, Nigeria, Senegal and Togo. €533m available to support NEBRA came about because these life sciences research African countries wanted to improve their ethics review procedures to fulfil international requirements and so Update on valuable funding opportunities for UK biomedical attract more clinical research scientists through the EU Framework Programmes… addressing their own health priorities. Together they approached the European Commission for support, As the current Framework Programme theme with a greater emphasis on along with the MRC, the World Health (FP6) draws to a close, the fourth and translational research, new therapies and Organization, the University Eberhard final round of calls for Thematic Priority healthcare systems. Other promising Karls (Tübingen, Germany) and project 1 – Life Sciences, Genomics and areas for the UK biomedical community co-ordinators the French Institut Biotechnology for Health has recently include diet and nutrition, environmental National de la Santé et de la been announced. The call, which closes in factors relating to health and diagnostics Recherche Médicale. November 2005, has a budget of €362m, and applications.There are also significant with a further €171m allocated to opportunities for mobility and career NEBRA’s primary aims are to: proposals led by small and medium-sized development under the People area and • Draw up an inventory of the enterprises (SMEs). Details of the topic for basic research delivered through a people and resources involved in areas for which proposals are invited are European Research Council under Ideas. research ethics review in West available from the EU’s CORDIS website. Africa. Throughout 2005 the MRC will continue • Acquire a real understanding of Help with the application process to contribute to the development of FP7 their needs and gaps in the ethics The MRC and the Department of Trade through Research Councils UK, the review infrastructure. and Industry act as the UK National Government and directly to the • Increase understanding of the Contact Point for Thematic Priority 1 European Commission. And to help particular ethical issues raised by (TP1). They can assist on all aspects of ensure that the views of the UK research in the area. the application process, including biomedical research community are fully • Develop a strategy for improving guidance on application procedures, one represented, the MRC is asking that its ethics review capacity in West to one meetings, proposal screening, help scientists engage in Government and EU Africa. in finding partners and identifying consultations on the development of FP7 • Strengthen networking to ensure potential sources of funding to support wherever possible. the dissemination of results and submission. The MRC, for instance, continued development of NEBRA. provides funding to support the MRC and UK submission of proposals involving MRC success in FP6 At the plenary meeting in April, units, institutes, centres and research representatives of the 15 member professors, which can cover networking For the first three calls for TP1 – Life countries discussed and agreed the first and planning meetings, proposal writing, Sciences, Genomics and Biotechnology for stage of the NEBRA initiative.This will business plans, etc. The closing date for Health – UK co-ordinators lead 16 per involve each country using interviews such funding is 29 July 2005 – for further cent of all projects funded, and UK and a questionnaire survey to identify information and an application form, partners are involved in 70 per cent of all its existing ethics review capacity and contact [email protected] awards. The success rate is also substantial at 28 per cent for UK participants overall needs.African and European experts and 36 per cent for proposals involving with a particular interest in the social FP7 update MRC scientists. science issues raised, and four trained In April 2005 the European Commission African interviewers, worked with published plans for the next Framework NEBRA on developing the Programme, FP7. The plans show a questionnaire, which is now being significant extension in scale and Find out more online piloted in The Gambia and Mali. ambition from previous programmes, EU CORDIS website: with a budget of €73bn for the seven www.cordis.lu/lifescihealth years from 2006 to 2013 to support four Fourth call for TP1 proposals and MRC Find out more online areas of activity: Co-operation, People, support for proposals: please contact Rosa Capacities and Ideas. These proposals Parker at [email protected] Global Forum meeting reports: www.gfbronline.com herald exciting opportunities for the Other FP6 calls: fp6uk.ost.gov.uk development of research across Europe. Programme of the 6th Forum: Development of FP7: www.wellcome.ac.uk/doc_ europa.eu.int/comm/research/ WTD003178.html Key features of FP7 include a broadening future/themes/index_en.cfm of thematic areas; an expanded Health 16 MRC | network Summer 2005 research roundup research roundup research roundup

Smoke gets in your eyes Benefits of drug reviews Age-related macular degeneration (AMD) is a condition in which the retina’s light- questionable capturing cells are gradually destroyed; it is the most common cause of blindness in Providing home-based medication review the UK. Research led by Professor Astrid Fletcher has now shown that smoking for elderly people may increase hospital doubles the risk of AMD and may account for almost 30,000 cases in the UK.The admissions, shows a study at the population-based study at the London School of Hygiene and Tropical Medicine University of East Anglia.These assessed over 14,000 elderly people from 49 general practices.The participants had unexpected findings raise questions detailed eye tests and were asked about their past and present smoking habits.After about NHS recommendations to taking into account other possible risk factors, the results showed that current introduce regular medication reviews smokers were twice as likely as non-smokers to be visually impaired because of into primary care. MRC fellow Dr AMD. Better news was that people who stopped smoking more than 20 years earlier Richard Holland and colleagues identified were not at risk. By using current estimates of the number of people in the UK who 872 elderly patients discharged from are blind or partially sighted as a result of AMD, the researchers calculated that hospital after an emergency admission. smoking was likely to have caused 28,000 cases. Professor Fletcher commented:“An Half of the patients received two home increased risk of AMD is yet another reason for people to stop smoking and for visits by a pharmacist, while the other governments to develop public health campaigns against this hazard.” half continued with usual care.The Br J Ophthalmol 89: 550-553 pharmacists educated the patients and carers about their drugs, removed out- of-date medicines, reported potential Deaf mice hold hearing clues side effects and drug interactions to the MRC and University of Hong Kong scientists have pinpointed the gene responsible general practitioner (GP), and informed for sensory development in the inner ear.Their discovery may lead to major the local pharmacist if a compliance aid advances in developing treatments for the deaf and severely hearing impaired.The was needed. During six months, there team studied two types of mice – one completely deaf and the other with severe were 30 per cent more hospital hearing impairment – and compared the gene activity of sensory and associated admissions among patients visited by the supporting cells. In the deaf mice, with no sensory hair cells and severe inner ear pharmacists than patients who were not. malformation, Sox2 gene activity was absent. However, in the hearing impaired Having a home-based medication review mice, which had abnormal inner ear development with disorganised and few also led to a 40 per cent increase in GP sensory cells, expression of Sox2 was reduced, but present. Several genes are home visits and seemed to worsen implicated in making functional hair cells, but Sox2 is the first gene to be identified patients’ quality of life.The reasons for that initiates development of the entire sensory system, comprising hair and these counterintuitive results were not supporting cells. Professor Robin Lovell-Badge of the MRC’s National Institute for clear, but they may have been due to Medical Research said:“To develop treatments for deafness in the future, it is now patients understanding their conditions necessary to look at whether the Sox2 gene can play a part in bringing damaged better and so seeking more help, or from sensory hair cells back to life or in triggering new sensory cells to grow for use in them taking their prescribed medications potential stem cell therapy.” correctly, leading to more complications Nature 434: 1031-1035 from drug interactions and reactions. In addition, the intervention may simply have increased anxiety and dependence Something in the air on health services.This work, which Air pollution thickens the blood and increases the likelihood of inflammation.These suggests the need for more effective findings by University of Edinburgh researchers may help to explain why polluted air ways to review medication, has crucial is linked to worsening respiratory problems and an increased risk of heart attacks implications for the national service and stroke. Funded by the MRC, the British Lung Foundation and the Cold framework for older people. Foundation, the study focused on the effect that inhaling ultra-fine pollutants has on BMJ 330: 293 cell function. Professor William MacNee and colleagues tested the inflammatory and blood clotting responses of human macrophages, lung cells and umbilical cord cells after exposure to these tiny particles.They found that levels of blood-clotting factors were raised in most of the cell types, the death rate of immune cells increased Find out more online significantly, and inflammatory activity was boosted. One mechanism by which the Research Roundup covers only a small particles might lead to these cardiovascular effects is by entering the bloodstream selection of recent research highlights. through the lungs. Here, their effects on macrophages could lead to plaque build-up To find out about other MRC research on artery walls. If these plaques rupture they can lead to blood clots – an effect that news, please visit www.mrc.ac.uk/ is enhanced by the particles – which can then trigger a heart attack or stroke. public-news_centre.htm Occup Environ Med 65: 164-171 Summer 2005 MRC | network 17 research roundup research roundup research roundup

Vaccine saves young lives in rural Africa Minimising stroke brain Pneumococcal pneumonia and meningitis cause about 1.6 million deaths each year, damage mostly in developing countries.A large MRC trial has shown that vaccinating A stroke is caused by an abrupt children against the bacterium that causes deadly pneumonia, meningitis and sepsis interruption of the blood flow to the brain. could save the lives of up to a million children a year. Led by Professor Felicity The oxygen-deprived brain cells die Cutts, with colleagues from the London School of Hygiene and Tropical Medicine, instantly and release substances that can the four-year randomised study vaccinated over 17,000 children in the rural parts of kill surrounding cells and so cause brain The Gambia.While the vaccine is known to prevent invasive pneumococcal disease damage. For many years, researchers have in the developed world, this was the first to study its effectiveness in rural Africa, sought ways of preventing the spreading of where child mortality is high and access to healthcare is limited.The results showed this lethal effect on nearby cells. It was that the conjugate pneumococcal vaccine reduced overall child mortality by 16 per known that the excessive release of the cent. In addition, compared with children who were not vaccinated, those who neurotransmitter glutamate following received the vaccine had 15 per cent fewer hospitalisations and 37 per cent fewer nerve cell death triggers a flood of calcium cases of X-ray-confirmed pneumonia.The study is the first proof that the vaccine ions into surrounding cells, which are prevents deaths.“Vaccination can prevent many of the serious infections caused by ultimately killed by increased calcium levels. pneumococcus even in a rural African setting,” said Professor Cutts,“This is great However, the process itself was not fully news for children and parents in rural areas everywhere.” understood.A team at the MRC’s Lancet 365: 1113-1114 Toxicology Unit, with researchers in British and Italian universities, have revealed one of the key mechanisms involved. Led by Turning to the left Professor Pierluigi Nicotera, the group Some children with attention deficit hyperactivity disorder (ADHD) can behave as looked at what causes calcium overload in if the left side of the world has disappeared.Work at the MRC Cognition and Brain rat brains during stroke.They discovered Sciences Unit in Cambridge shows that this phenomenon of ‘left neglect’ is more that the initial calcium influx activates common in children than previously thought. Since left neglect is not routinely proteases known as calpains.These tested for by clinical services and it is not apparent to the children or parents, the enzymes break down the cell membrane condition often goes unnoticed. Children can have problems reading, as they ignore proteins that would normally pump the first letters of words, yet the cause of this problem is not always picked up and calcium out of the cell – revealing that the may be attributed to dyslexia. Dr Tom Manly and colleagues found that children fault lies in the mechanism to remove with ADHD particularly stop noticing things to their left when doing unstimulating calcium ions.“These findings may explain tasks. Dr Manly said,“The right side of the brain seems to be heavily involved in why stroke therapies aimed solely at keeping us awake and alert, particularly when we are bored. Because the right side blocking the entry of calcium into nerve is interested in what is going on to the left, and vice versa, as this alertness declines cells have been unsuccessful,” explained over time or with boredom, it takes some of our awareness of the left with it. Professor Nicotera,“The research Children with ADHD appear to reach this point more quickly than other children.” identifies novel targets for stroke and Routine assessment of children’s ability to attend to the left and right could be other neurodegenerative diseases, and may useful to help identify children with ADHD and other learning difficulties. lead to new drugs to treat these J Child Psychol Psychiatry (online doi:10.1111/j.1469-7610.2005.00421.x conditions successfully.” and doi:10.1111/j.1469-7610.2005.01432.x), Brain and Cognition 57: 264-275 Cell 120: 275-285 18 MRC | network Summer 2005

An engaging week of science

A key focus of the MRC’s mission is to promote public engagement with medical research. But how can more MRC scientists become involved in communicating their work? National Science Week in March showcased a selection of effective and adaptable approaches.

Brainy questions diagnostics at the MRC Cognition and recent MORI survey Science in Society,for Who are “psycho people with medicines, Brain Sciences Unit open evening, the Department of Trade and Industry, curly haired and wearing glasses and Exploring the Brain and Mind.An open day indicates that trust in scientists remains labcoats”? Scientists, as perceived by at the Institute of Psychiatry in London high at around 70 per cent – a slight groups of Manchester school children. attracted 180 people; in Oxford and increase since 2003. Colin said that,“the And who are “everyday people who find Reading, 500 primary school pupils real key to public ownership of science out different things and make a change to participated in art workshops on hearing, is that scientists should be more visible the world”? Scientists, as perceived by the movement and micro-organisms; and and more willing to talk to principal same groups after collaborating with about 50 children and adults prepared stakeholders – ordinary people who will MRC researchers to devise and perform DNA, looked at cells under a microscope benefit or suffer from their actions.” an interactive event on brain sciences at and heard about how the brain works at a the Trafford shopping centre.The project, London event exploring life sciences This was clearly the case when Professor led by Dr Stuart Allan of Manchester research. Post-doctoral and PhD students Simon Lovestone used an MRC Science University, was one of many events at the MRC Radiation and Genome Week grant to fund an open day on organised by MRC scientists as part Stability Unit at Harwell presented the Alzheimer’s research at the Institute of of National Science Week – a global reality of life in the laboratory to 25 A- Psychiatry.The audience was drawn from celebration to increase public awareness level students.Together they worked on the local community and organisations, of science. practical experiments and held discussion such as the University of the Third Age, groups on genetic engineering.The MRC and charities, and many had a personal In Cambridge, there were talks on diet Human Reproductive Sciences Unit and interest in the disease. Staff gave guided and interactive exhibitions on cancer the MRC Human Genetics Unit in tours of the laboratory and demonstrated Edinburgh fielded an real experiments at 16 research stations. impressive team of The day ended with a lively panel session Present your science to Parliament enthusiastic PhD chaired by Dr Raj Persaud. students to engage family Over 250 young researchers won places to present posters on audiences in two their research at the National Science Week Parliamentary exhibitions at the MRC Science Roadshow event.This year, winners of the top two awards at the Edinburgh International Biosciences evening reception were MRC-funded scientists. Art workshops: connecting young Science Festival. Dr Rachel Batterham, a special fellow at University College people to science London, was awarded the 2005 Mendel Medal, and runner-up Katherine Sharrocks, a research student at Oxford University, Demystifying science Pupils at the Hill Primary School, won the 2005 De Montfort Medal.To find out more about the So what are the reasons Caversham, Reading, having fun during an annual event, see www.setforeurope.org and rewards for this art workshop based on topics in the impressive focus on National Curriculum linked to MRC- public engagement? In his funded research.Artist and scientist Lizzie Burns helped the children create artworks Edinburgh Medal address, based on hearing, movement and micro- Whose Science is it organisms. Anyway, MRC Chief Executive Professor Colin Blakemore set it in the context of “an inexorable, irreversible and admirable trend to openness,” but with the caution that, Biosciences prize winners with Lord Sainsbury, Minister for “transparency should

Science and Innovation. generate more trust than Anne-Marie CoriatPhotograph by suspicion.” In fact, the Summer 2005 MRC | network 19

Left: School children looking at real cells under a microscope, Events diary as part of the interactive exhibition Brain, cells and genes BA Festival of Science in London. The MRC will once again be Bottom: Postgraduates taking part in the BA Science showing how vision Festival at Trinity College can be tricked during Dublin, with a number of the You Know It stimulating events.The Medical Makes Sense Sciences Section presents a day workshop at of talks on 7 September on the Manchester theme Viruses: the Deadly Enemy? Museum. The MRC will be organising hands-on activities in the The event also engaged festival’s drop-in zone, which a younger audience. In aim to attract hundreds of collaboration with visitors of all ages. Dr Lizzie three local schools,A- Burns is holding an art/science level students worked workshop, Build Your Own Virus, alongside researchers and the resulting artworks will on a pilot experiment be judged in a competition by to test a series of Medical Sciences President, compounds on fruitflies. Professor Luke O’Neill. Their reward was some The BA Festival of Science interesting results, with 2005 takes place in Dublin findings published in a during 3 to 10 September. letter in PLoS Biology – More details are available from an exciting outcome for www.the-ba.net/FestivalofScience the students contemplating a career in science. One of the researchers invigorates her own excitement with The Battle of Ideas commented,“twelve pairs of hands and science,“There’s always someone who The MRC is one of the eager minds enabled gathering data that opens my eyes and makes me see science sponsors of the Battle of Ideas would have required some weeks of from another angle.” – a inter-disciplinary event at research time.” which hundreds of people will These activities reflect just some of the have the opportunity to get to Engaging opportunities opportunities throughout the year for grips with and discuss the key So what else motivates busy researchers MRC scientists to engage with the public. ideas of our time.This is a new to take their science to the public? The And recognising that there are barriers to initiative from the Institute of opportunity to change perceptions and taking part, the MRC is looking at ways of Ideas as part of its commitment attitudes to science is frequently enabling more researchers to be involved to robust and open debate. reported as one of the most rewarding in the future – from sharing good practice aspects. For Lizzie Burns (see box) it to increasing financial incentives. Themed discussion strands on the battle for education, community, culture, medicine Find out more online and international relations and Information on how to get started and keep A guide for anyone wanting to talk with the the battle of the books will going. public about science issues. run alongside salons,“in www.rcuk.ac.uk/documents/ conversation…” events, films Funding evaluationguide.pdf and keynote debates on Research Councils UK (RCUK) Science Week different aspects of the future. grants – see details on the website Contacts www.rcuk.ac.uk from August. See MRC Science Week grant holders at: The event will be held on www.mrc.ac.uk/public-interest/public- Publications 29/30 October at the Royal events/public-events_science_ week_ College of Art, London. For RCUK Dialogue with the Public: Practical 2005.htm guidelines more information, visit: www.rcuk.ac.uk/guidelines/dialogue/ For advice and information, email: www.instituteofideas.com/ [email protected] RCUK Practical Guidelines: Evaluation events/battle2005.html 20 MRC | network Summer 2005

MRC people

Seven MRC scientists have been right), Professor Emeritus of Your feedback elected Fellows of The Royal Immunology and Deputy Head please Society in recognition of their of the MRC Centre of Immune medical achievements and Regulation, University of MRC Network is for anyone scientific excellence: Professor Birmingham, was made a who has an interest in the Douglas Higgs (top), Director Commander of the Order of work of the MRC, including of the MRC Molecular the British Empire.They were scientists, doctors, and Haematology Unit, Professor joined by Professor Alan Jackson CBE, health professionals involved John Collinge (middle), former member of the MRC’s Physiological in medical research, Director of the MRC Prion Medicine and Infections Board, and Dr Mac government departments Unit, Professor Trevor Armstrong, a previous member of the MRC’s and parliamentarians, and Robbins (bottom), Director of Council who was made a Companion of the university staff and students. the MRC Cambridge Centre Order of the Bath. The aim is to provide a for Behavioural and Clinical quick, easy-to-read summary Neuroscience, Dr David of activities across the MRC, Spiegelhalter, senior scientist Professor Michael Alpers of from research news through of the MRC Biostatistics Unit, the MRC’s Prion Unit was to funding, grant schemes Dr Philip Evans of the MRC appointed as an Officer of the and policy issues, with Laboratory of Molecular Order of Australia in January in pointers to more in-depth Biology, and MRC-funded recognition of a lifetime of information on websites and scientists Professor Uta Frith and Professor service to tropical medicine and in other publications. Nicholas Proudfoot. public health. Professor Alpers was previously director of the Papua New Guinea We are very keen to Institute for Medical Research and has dedicated receive feedback on Professor Wendy Bickmore, his career to researching tropical diseases. Network and suggestions senior scientist at the MRC for new features from our Human Genetics Unit, has been readers. So if you have any awarded double honours, being Professor Colin Blakemore, Chief Executive comments, including on the elected to the Fellowship of the of the MRC, was awarded the 2005 Edinburgh new design format that we Royal Society of Edinburgh and Medal by the City of Edinburgh Council at the have launched with this to the Fellowship of the Edinburgh International Science Festival in April. edition, please let us know. Academy of Medical Sciences. This annual award is for outstanding scientific Just mail: newsletter@ achievements that are judged to have made a headoffice.mrc.ac.uk significant contribution to the understanding and The Academy of Medical well-being of humanity. MRC Network is produced Sciences also bestowed by the MRC Publications Fellowships on Professor Team and is available in Janet Darbyshire, Director The UK chapter of the International League print and in downloadable of the MRC Clinical Trials Unit, Against Epilepsy has presented its Lifetime pdf format at: Dr Anne O’Garra and Dr Services to People with Epilepsy Award for 2005 www.mrc.ac.uk Brigitta Stockinger, of the to Dr Tony Johnson, of the MRC Biostatistics MRC National Institute for Medical Research, Unit. Dr Johnson received the award for his life- and MRC-funded researchers Professor Jon long statistical contributions to research into Driver, Dr Roger Keynes and Professor epilepsy in the UK across observational and Hugh Perry. randomised studies and for his support in the education of generations of clinicians in clinical epidemiology and statistics. Medical Research Council The Queen’s birthday honours rewarded two 20 Park Crescent leading MRC scientists for their contributions to London W1B 1AL medical research. Nancy Jonathan Bird, MRC-funded student at Rothwell (left), MRC Research University College London, has won the first Tel:020 7636 5422 Fax: 020 7436 6179 Professor at the University of Pauline Ashley Prize for his research into the Manchester, has been made repair and regeneration of the avian inner ear. www.mrc.ac.uk Dame Commander of the Funded by the charity Defeating Deafness, the Order of the British Empire, award is aimed at encouraging young scientists and Ian MacLennan (top to undertake research into hearing conditions. © Medical Research Council 2005