ELOETUTANA EIW1Otbr20–0Spebr2006 ANNUAL REVIEW 1 October 2005–30 September

ANNUAL REVIEW 2006

The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk THE WELLCOME TRUST The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world.

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CONTENTS BOARD OF GOVERNORS 2 Director’s statement 4 Advancing knowledge Chairman 16 Using knowledge Martin Bobrow Deputy Chairman 24 Engaging society 30 Developing people 36 Facilitating research Patricia Hodgson 40 Developing our organisation 41 Wellcome Trust 2005/06 Ronald Plasterk 42 Financial summary 2005/06 Alastair Ross Goobey 44 Funding developments 2005/06 Peter Smith 46 Streams funding 2005/06 Jean Thomas 48 Technology Transfer Edward Walker-Arnott 49 Wellcome Trust Genome Campus As at January 2007 50 Public Engagement 51 Library and information resources 52 Advisory committees

Images 1 Surface of the gut. 3 Zebrafish. 5 Cells in a developing This Annual Review covers the 2 Young children in 4 A scene from Y fruit fly. Wellcome Trust’s financial year, from Kenya. Touring’s Every Breath. 6 Data management at the Sanger Institute. 1 October 2005 to 30 September 2006. CONTENTS 1

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EXECUTIVE BOARD MAKING A DIFFERENCE Developing people: To foster a The Wellcome Trust’s mission is research community and individual Director to foster and promote research with researchers who can contribute to the advancement and use of knowledge Ted Bianco the aim of improving human and Director of Technology Transfer animal health. During 2005–2010, Facilitating research: To promote the our aims are: best conditions for research and the John Cooper use of knowledge Director of Resources Advancing knowledge: To support research to increase understanding Developing our organisation: To use David Lynn of health and disease, and its our resources efficiently and effectively. Head of Strategic Planning and Policy societal context Clare Matterson Using knowledge: To support the Director of Medicine, Society and development and use of knowledge History to create health benefit David Phillipps Engaging society: To engage with Director of Finance society to foster an informed climate Sohaila Rastan within which biomedical research Director of Science Funding can flourish John Stewart Head of Legal and Company Secretary Danny Truell Chief Investment Officer Other senior management Director of the Wellcome Trust Sanger Institute Susannah Randall Head of Communications

As at January 2007

Strategic Plan updates, summarising progress in achieving specific objectives during 2005/06, can be found at www.wellcome.ac.uk/strategicplan. DIRECTOR’S STATEMENT 2

WORKING WITH RESEARCHERS We are working to achieve ever closer relationships with the best researchers to fund work that will have important impacts in improving human and animal health.

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This Annual Review illustrates some of Parkinson’s disease. Research we • Austin Smith and Fiona the many ways in which the work we have funded has led to both national Watt were awarded £7 million to support or carry out ourselves is and international changes in health establish an international centre of making a difference. policy. The World Health Organization excellence in fundamental stem This year’s stories of the discovery and now recommends artemisinin research. The Wellcome Trust Centre application of new knowledge illustrate combination therapies for treatment for Research at the how outstanding researchers are of malaria and the Kenyan Ministry University of will explore the gaining insight into biological processes of Health is continuing its Hib genetic and biochemical mechanisms at all scales, from the atomic structure immunisation programmes. that control how stem cells develop into particular types of cells. of medically important to the Partnerships global impact and treatment of malaria. We can only achieve this kind of • Professors Ray Dolan and Karl Our understanding of the human impact through working closely with Friston, at the Wellcome Trust Centre genome continues to grow, with yet the research community. Through for Neuroimaging, University College another surprising discovery from the supporting the best people with the London, received an award of Wellcome Trust Sanger Institute – that best ideas and providing flexible £6.7m. This will enhance their genetic variation between individuals funding, we hope to support the research programme into the neural is far higher than previously thought. generation of new knowledge to basis of human cognition, work has benefited enormously underpin future discoveries and that is extending our understanding from high-throughput sequencing their subsequent application. of common neurological and and other technologies, which have psychiatric diseases, such as A key issue for all funding agencies is schizophrenia and dementia. transformed the way research is to balance bottom-up and top-down carried out. Structural is less approaches to the support of research. • Paul Luzio received a easy to scale up, but the Structural Who drives the process of discovery? £4m award for the Cambridge Institute Consortium has made Who asks the research questions? for Medical Research. The Institute excellent progress in its production Is it the researchers or the funding explores the underlying molecular and of structures of medically important agencies? We take a flexible approach, cellular mechanisms behind disease proteins, and many valuable discoveries and have an open door for the best and it has led key research into how are being made about function researchers to bring us their best evade our immune system, on the basis of structural information. ideas. However, we also work with genetic susceptibility to diabetes, and Such studies complement research the research community to identify progress towards novel treatments for into the threats to health we face in areas where there is unmet research Alzheimer’s and Huntington’s disease. this country and globally. The global need and to provide catalysis to ensure Our strategy will continue to create a impact of malaria, for example, is now that vital research is not overlooked. framework that can support, but not much clearer. Wellcome Trust-funded Last year we introduced Strategic constrain, those that look to us for researchers are world leaders in the Awards to ensure we could support funding. Our Strategy Committees fight against this insidious disease. the best ideas wherever they are found. are key to helping us identify our Application of new knowledge has The scope of these awards is really future research priorities and this year seen trials of new dipstick diagnostic only limited by the imagination of the we published an ‘à la carte’ menu of tests for trachoma, trials of new research community. This year we areas identified as important for and diagnostics for made our first three awards, providing future research activity. , and trials for new outstanding research groups with To ensure we can support the best treatments for the symptoms of significant and flexible support: people, our portfolio of careers DIRECTOR’S STATEMENT 3

HIGHLIGHTS OF THE YEAR

schemes has been reviewed and as anticancer agents. Creative a number of new schemes were approaches to the discovery of new launched this year. The new Sir Henry medicines like this are vital to help Wellcome Postdoctoral Fellowship society address the growing burden Awards, worth £250 000 over of disease. four years, will allow researchers Improving healthcare for patients was unprecedented freedom early in their the aim of a further consortium formed careers to pursue their own research. this year. This consortium, led by the Our new Flexible Travel Awards will Wellcome Trust, provided £84m to also support collaboration-building and boost experimental medicine in the the transfer of ideas and skills through UK and the Republic of Ireland. This support for sabbaticals and travelling major investment aims to develop and fellowships. Other new initiatives were strengthen Clinical Research Facilities, also launched this year, notably the which bring together laboratory and £91m Seeding Drug Discovery clinical patient-based research in initiative, aiming to provide funding order to answer important questions • Whole-genome map uncovers for the early stages of drug discovery, about health and disease. Under the unexpectedly high levels of which often struggle to attract funding umbrella of the UK Clinical Research copy number variation. for commercial development. We hope Collaboration, this initiative brought this initiative will create a stronger together the major health research • Functional imaging reveals synergy between academia and charities, the government funding brain centres involved in industry and capitalise on the powerful bodies and health departments. decision-making. resources that are spread across the academic, biotechnology and A research funder’s work does not • Nanog identified as key pharmaceutical sectors. end with the award of a grant. What pluripotency factor in stem cells. matters is what is discovered and that In areas of unmet research need, knowledge about these discoveries can • Impaired innate immunity such as drug discovery, a key role be freely accessed around the world. revealed as potential cause for the Trust is acting as a catalyst, of Crohn’s disease. bringing together partners to help This year we led a major new initiative, tackle pressing research problems. with a nine-strong group of UK • Structures of several important research funders, to establish an Public–private partnerships are an human proteins determined by effective model for developing new online digital archive of peer-reviewed research papers in the medical and Structural Genomics Consortium drugs for important but hitherto and others. neglected diseases and we have life sciences. UK PubMed Central, formed a number this year. a partnership between the British • UK Biobank successfully Library, the European completes pilot phase. We have formed an alliance with the Institute and the University of Novartis Institute for Tropical Diseases, Manchester, will allow everyone with • Studies in India highlight the Economic Development Board access to the internet to access a vast depression as a serious health of Singapore and the Medicines for collection of biomedical research at the issue for women. Malaria Venture to jointly initiate touch of a button, promoting the free research on malaria drug discovery. transfer of ideas in a bid to speed up • Research in Kenya demonstrates Malaria continues to kill millions of scientific discovery. value of Hib immunisation people around the world and this new and informs Government partnership will investigate the potential I hope that this Annual Review health policy. for development of new treatments from illustrates our excitement about the existing compounds that have already outcomes and impacts of the work • Artemisinin combination therapies that we support. Our doors are shown antimalarial activity, and from recommended by WHO and open to excellent researchers with novel compounds. I hope this initiative adopted globally. will produce the next generation of excellent ideas. drugs to treat malaria. Mark Walport • National Science Learning Centre A new alliance was also formed Director formally opened. between the Wellcome Trust, The January 2007 Institute of Research and GlaxoSmithKline to discover, develop and commercialise novel small- Images molecule inhibitors of BRAF, a key 1 Dr Mark Walport. 3 Trachoma treatment , for use 2 Embryonic stem cells. in Tanzania.

ADVANCING KNOWLEDGE Supporting research to increase understanding of health and disease, and its societal context. ADVANCING KNOWLEDGE 6

DECISIONS, ON REPEAT DECISIONS The balancing of emotion and reason can now be Humans are genetically more followed through the labyrinthine anatomy of the brain. diverse than previously thought.

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What is happening in our brains emphasising the importance of Genetically speaking, humans when we decide on a course of emotional processing. are almost identical. But those action? Using functional imaging, Finally, we often face a dilemma differences that do exist can affect Professor Ray Dolan’s group at between acting on what we already our health. With the sequencing of the Wellcome Trust Centre for know and trying something new the human genome and global Neuroimaging at University College that might be better for us. In a efforts to map genetic variation, London (UCL) is unpicking the collaboration with the UCL Gatsby many surprising findings have neural circuitry underlying different Computational Unit, emerged – not least the importance contributions to decision-making. which integrated computational of copy number variation. One important influence comes from models of decision-making with Copy number variation refers to blocks ‘reward’: the benefits we expect from neuroimaging data, the group of DNA throughout the genome, which an action. In theory, decisions are discovered that different brain areas can be anything from 1000 to 5 million affected by experience – whether, are active in these two situations. This nucleotides long; the number of copies previously, a reward was more or suggests that harvesting a safe option at a given location in the genome can less than we expected. In animals, involves distinct neural processing vary from zero to tens or even hundreds. dopamine pathways have been systems from those associated with These variations have been implicated implicated in reward learning, and trying a less certain alternative. in several human genetic diseases, Professor Dolan and colleagues have This work emphasises how complex and are known to affect susceptibility now shown the same is true in people. human decision-making is. There to HIV and malaria . Agents that alter dopamine signalling is not one ‘analytical centre’ that Now, a multinational team, including also affect subjects’ ability to choose determines choice but a host of Dr Matthew Hurles and colleagues the most rewarding option. interconnected systems influencing the from the Wellcome Trust Sanger A striking feature of human decision- way we think – and the way we act. Institute, has constructed the first map making is its susceptibility to the Pessiglione M et al. Dopamine-dependent of copy number variation across the context in which choices are prediction errors underpin reward-seeking entire human genome. Surprisingly, presented: the so-called framing behaviour in humans. it affects 12 per cent of the genome – 2006;442(7106):1042–5. effect. This is a challenge to much more than suspected. Affected De Martino B et al. Frames, biases, and rational assumptions of ‘rational’ human decision-making in the human brain. Science areas spanned known genes and behaviour, such as those used 2006;313(5787):684–7. disease loci, emphasising the in economics. Functional imaging Daw ND et al. Cortical substrates for importance of copy number variation has revealed a central role for the exploratory decisions in humans. Nature in both disease and genetic diversity. amygdala in framing effects, 2006;441(7095):876–9.

Images 1 Professor Ray Dolan. 3 Young children. 5 Three-dimensional 2 Functional magnetic 4 An early embryo reconstruction of resonance imaging of broken open to mouse blastocyst. the brain in action. reveal stem cells. ADVANCING KNOWLEDGE 7

MORE POTENT RESEARCH What makes an embryonic stem cell pluripotent – able to create all types of cell?

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Dr Nigel Carter’s group, also at The embryonic stem (ES) cell is Research from Professor Austin Smith1 the Sanger Institute, is one of special. If we knew what gave it the and colleagues at the Institute for several teams that have identified power to create all the cell types of Stem Cell Research in Edinburgh specific copy number variations on the body (pluripotency), we might suggests that Nanog has a central chromosome 17 as causes of a be able to create new ES cells role in pluripotency. mental retardation syndrome. The and use them to repair damaged When ES cells are fused with other deletion affects two genes, CRHR1 tissues. Two lines of research cells, the resulting cell may be and MAPT, which are likely candidates have added significantly to our converted to a pluripotent state. for the syndrome, as they are active understanding of the molecular Broadly speaking, the more in the brain and known to be involved basis of pluripotency. differentiated the cell, the less likely in degenerative disorders. Dr Magdalena Zernicka-Goetz it is to become pluripotent after fusion. In other research (funded by the and colleagues at the Wellcome When ES cells containing higher than Wellcome Trust and others), Professor Trust/Cancer Research UK Gurdon normal levels of Nanog were used, Tim Aitman of Imperial College and Institute of Cancer and Developmental however, the efficiency of conversion others discovered that a low copy Biology in Cambridge have located a of part-differentiated cells was number of the Fcgr3 gene increased master switch that controls one of the greatly increased. susceptibility to a kidney disease, earliest choices a cell can make. They So, although not the only player, glomerulonephritis, in rats and humans. identified a crucial molecular difference Nanog is clearly a powerful driver Copy number variations are between cells in the four-cell mouse of pluripotency. embryo, much earlier than expected. that are likely to have a profound Torres-Padilla ME et al. Histone arginine impact on phenotypic differences This difference is a chemical tag (a methylation directs cells towards pluripotency between individuals. The whole- methyl group) added to the histone in the early mouse embryo. Nature [in press]. genome map will greatly aid studies proteins, which package DNA in Silva J et al. Nanog promotes transfer exploring the impact of genetic of pluripotency after cell fusion. Nature the chromosomes. Tagging just one 2006;441(7096):997–1001. variation on health. amino acid in a particular histone 1 Now at the Wellcome Trust Centre for Stem Redon R et al. Global variation in copy number (H3) switches on genes that establish Cell Research, . in the human genome. Nature [in press]. and maintain pluripotency. When this Shaw-Smith C et al. Microdeletion encompassing modification was introduced into MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. embryonic cells, their daughter cells Nat Genet 2006;38(9):1032–7. were pluripotent – showing dramatic Aitman TJ et al. Copy number polymorphism in activation of pluripotency-associated Fcgr3 predisposes to glomerulonephritis in rats genes, such as Nanog. and humans. Nature 2006;439(7078):851–5. ADVANCING KNOWLEDGE 8

TOUCHING TARGETING THE A NERVE TRYPANOSOME We all need help with directions sometimes, Research is revealing weak points and nerve cells are no exception. in the parasite’s defences.

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The wiring of nerve cells is a known primarily as a gene regulator – No exists for human complicated process. The cerebral Engrailed-2 – was also found to African trypanosomiasis (sleeping cortex alone contains at least affect growth cones when present sickness), and few drugs are 10 billion , with 60 trillion outside the cell, again by stimulating available. But the recent publication synapses linking them. Connecting new protein synthesis. Interestingly, of the genome sequence for up these cells is thus finely extracellular Engrailed-2 repels some Trypanosoma brucei, the parasite controlled. Gradually, though, neurons but attracts others. responsible, has increased our understanding of the parasite’s research – including that of Other morphogens, including two biology and has boosted the Professor Christine Holt (University members of the Wnt family of proteins, search for drug targets. of Cambridge) and colleagues – are also known to guide axon growth. is identifying key mechanisms in With colleagues in Spain, Professor One promising target is the flagellum – axon guidance. Holt has shown that a probable the ‘tail’ that propels the parasite Axon growth is guided by ‘push and inhibitor of Wnt signalling, SFRP1 through the bloodstream. Professor pull’ mechanisms. The growing tips (secreted Frizzled-related protein 1), Keith Gull at the of axons (growth cones) are repelled acting through a receptor known as and colleagues have shown that the from certain areas and attracted Frizzled-2 (Fz2), also plays a role in flagellum plays a critical role in cell towards others. axon guidance. division and is, therefore, essential for parasite survival. They have A protein called Slit2, for example, So, as well as patterning the body, identified flagellar proteins that, repels growth cones of frog retinal morphogens may also be important in being unique to the trypanosome, axons. Professor Holt’s group wiring the developing nervous system. have potential as drug targets. found that Slit2 led to a burst of Piper M et al. Signaling mechanisms underlying protein synthesis in the growth Slit2-induced collapse of Xenopus retinal growth Other studies have revealed further cone, increasing levels of an actin cones. 2006;49(2):215–28. chinks in the trypanosome’s armour. regulatory protein, cofilin. This led Brunet I et al. The Trypanosomes use an unusual Engrailed-2 guides retinal axons. Nature mechanism to regulate gene activity, to the dismantling of actin filaments, 2005;438(7064):94–8. suggesting that changes to the in which messenger RNAs are held Rodriguez J et al. SFRP1 regulates the growth by RNA-binding proteins until they internal skeleton of the cell are of retinal ganglion cell axons through the Fz2 important in controlling the direction receptor. Nat Neurosci 2005;8(10):1301–9. are needed. By interfering with this of axon growth. system, Dr Ed Hendriks and Dr Keith Matthews were able to alter a specific Other work has focused on links step in differentiation – the first time between morphogenesis and axon this process has been genetically guidance. For example, a protein modified in trypanosomes.

Images 1 Retinal growth cone. 3 A malformed 5 Key amino acids in the 2 Staining of a single trypanosome after 5-HT3 receptor. retinal ganglion cell, cell division has showing its long been disrupted. thread-like axon. 4 A normal trypanosome. ADVANCING KNOWLEDGE 9

FORM AND FUNCTION The newly discovered structures of key proteins have revealed valuable insights into their functioning.

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Exploiting a naturally occurring To function properly, proteins must of Cancer Research) and colleagues, parasite transporter, Professor Ian adopt particular three-dimensional has revealed a complex set of Gilbert and colleagues showed that structures. By elucidating protein rearrangements that enable Hsp90 nitroheterocycle compounds attached structures, or even just the to bind and activate its target proteins. to melamine were effective against conformation of single amino acids, Since Hsp90 is needed to activate the parasites that give rise to human researchers can often deduce how proteins driving proliferation in many African trypanosomiasis. proteins work in the body – and cancer cells, drugs that block Hsp90 therefore begin designing or refining hold promise as anticancer therapies. Lastly, Professor Alan Fairlamb, drugs to modify protein activity and, whose Wellcome Trust Principal Finally, among much research facilitated hopefully, treat or prevent disease. Research Fellowship was renewed by the Structural Genomics Consortium, this year, is searching for candidate Dr Sarah Lummis (University of Dr Udo Oppermann and colleagues molecules to screen in a dedicated Cambridge) and colleagues, for have discovered how anti-osteoporosis drug discovery programme at the example, have discovered how a drugs, bisphosphonates, bind to their University of Dundee. He and his neurotransmitter receptor (5-HT3), target – opening up the team are focusing their search on an ion channel, is opened and closed. prospect of more finely tailored drugs. a molecule called trypanothione – The mechanism depends on the Ali MM et al. Crystal structure of an Hsp90- unique to trypanosomes and conformation of a single proline in a nucleotide-p23/Sba1 closed complex. Leishmania parasites – and its ‘hinge’ region of the receptor. In one Nature 2006;440(7087):1013–7. associated enzymes. conformation the channel is open; Lummis SC et al. Cis-trans isomerization at a proline opens the pore of a Broadhead R et al. Flagellar motility is required in the other it is closed. neurotransmitter-gated ion channel. for the viability of the bloodstream trypanosome. Myosin 5 transports material around Nature 2005;438(7065):248–52. Nature 2006;440(7081):224–7. the cell, by ‘walking’ along actin fibres. Thirumurugan K et al. The cargo-binding domain Hendriks EF, Matthews KR. Disruption of the Dr Peter Knight at the University of regulates structure and activity of myosin 5. developmental programme of Trypanosoma Nature 2006;442(7099):212–5. brucei by genetic ablation of TbZFP1, Leeds and colleagues have found that, Kavanagh KL et al. The molecular mechanism a differentiation-enriched CCCH protein. without any bound cargo, myosin 5’s of nitrogen-containing bisphosphonates as Mol Microbiol 2005;57(3):706–16. long tail domains fold up with its motor antiosteoporosis drugs. Proc Natl Acad Sci Baliani A et al. Design and synthesis of a series domains, and this globular form binds USA 2006;103(20):7829–34. of melamine-based nitroheterocycles with activity weakly to actin. When its cargo binds, • The Structural Genomics Consortium is a against Trypanosomatid parasites. J Med Chem not-for-profit organisation that aims to 2005;48(17):5570–9. the structure unfolds, the motor domains attach to actin, and the determine the three-dimensional structures University of Dundee Tropical Disease Initiative. of proteins of medical relevance, and place www.drugdiscovery.dundee.ac.uk/tropical/overview/. myosin 5 begins its walk. them in the public domain without restriction. The structure of Hsp90, determined It is supported by the Wellcome Trust and a range of public and private sources in the by Professor (Institute UK, Canada and Sweden. ADVANCING KNOWLEDGE 10

GUT INNATE FEELING INVOLVEMENT Understanding the hormonal control of appetite may Two unexpected facets of innate be the key to effective anti-obesity treatments. immunity have been identified.

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Obesity is thought to cause 1000 Control of energy balance, eating, The recent renaissance of interest premature deaths a week in the metabolism and physical exercise in innate immunity – a nonspecific UK. By focusing on the way the is complex. Nevertheless, Professor form of defence common across body controls appetite, Professor Bloom’s group has identified several the animal kingdom – has yielded Steve Bloom and colleagues at key players in this system, and shown a number of interesting findings. are that gut can influence Now, research has highlighted the investigating anti-obesity therapies appetite. Indeed, injections of potential significance of innate based on naturally occurring oxyntomodulin, a released immunity in two areas: Crohn’s hormones and neurotransmitters. by the small intestine after eating, disease and breast milk. not only reduced energy intake All current methods of weight control Currently, it is thought that Crohn’s but also increased subjects’ have significant problems. Surgery disease results from an overactive spontaneous activity. can be effective for severe obesity, immune system, which treatments but carries a 3 per cent mortality The team is now working on a are designed to ‘damp down’. But rate. Anti-obesity used drugs have formulation of the hormone that Professor Tony Segal and colleagues unpleasant side-effects. More can be injected once a day or less, at University College London have generally, dieting suffers a high as well as investigating the therapeutic put forward a different hypothesis – failure rate. potential of other factors, including that impaired innate immunity is neuromedin, neuropeptide S and A major challenge is understanding responsible for the disorder. PYY3-36. the body’s own physiology. The body The team showed that the immune has homeostatic set points to maintain Wynne K et al. Oxyntomodulin increases response of people with Crohn’s energy expenditure in addition to decreasing body weight, but it is more sensitive energy intake in overweight and obese humans: disease was much lower than that to weight loss than weight gain. a randomised controlled trial. Int J Obes (Lond) of healthy people when challenged So when we lose weight, we have 2006 [Epub ahead of print]. by exposure to weakened E. coli or a powerful drive to eat more to put Wynne K et al. Subcutaneous oxyntomodulin trauma to the rectum, ileum or skin. weight back on. reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled They suggest that bowel contents Control of appetite is therefore likely trial. Diabetes 2005;54(8):2390–5. that breach the mucosal barrier to be key to weight-control strategies. may not be cleared as effectively The Imperial group is investigating in people with an impaired immune the hormonal and neural systems response, which could lead to the underpinning appetite control – and chronic inflammation characteristic developing new interventions based of Crohn’s disease. upon them.

Images 1 A typical modern 3 Surface of the gut. 5 Malaria parasite within Western diet. 4 Examining a premature red blood cells. 2 Cells within the brain’s baby in Kilifi, Kenya. appetite control centre. ADVANCING KNOWLEDGE 11

KNOW YOUR ENEMY New modelling techniques are providing a clearer picture of the extent of malaria across the globe.

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In separate work, Dr Mario Labéta Information on the prevalence, To create a global map of malaria and colleagues at University distribution and likely future risk worldwide, the researchers from have shown that breast milk can spread of malaria is vital for Kenya and Oxford use information regulate the activity of the innate a number of reasons: giving from satellites orbiting the Earth, immune system in babies. affected countries an idea of population censuses and other The team has been investigating the disease burden, providing a electronic forms of information on mechanisms controlling the activity baseline from which to measure factors that affect the distribution of of Toll-like receptors (TLRs), which the success of intervention malaria mosquito vectors and how recognise parts of microbial pathogens programmes, and facilitating often they are likely to infect humans. and activate the innate immune effective disease-control planning. Statistical approaches will be used response. They found that as yet In a series of studies, Professor to fill in the ‘gaps’, based on unidentified proteins present in early Bob Snow, Dr Simon Hay and comparisons between areas where breast milk (but not formula milk) colleagues at the Kenya Medical information exists and those where boosted the immune responses Research Institute–Wellcome it is lacking. triggered by some TLRs, while Trust Research Programme have Applications of early versions of inhibiting those triggered by others. developed tools to collect and these models estimate that, in 2002, analyse data on the distribution 515 million people developed a As well as demonstrating a novel of malaria in affected regions. activity of human milk, the work has clinical episode of Plasmodium also identified a possible new target Across the world, malaria scientists falciparum malaria – many more for modulating innate immune collect information on how many than previously thought. responses. people are infected with malaria Hay SI and Snow RW. The Malaria Atlas Project: parasites. This information is developing global maps of malaria risk. PLoS Marks DJ et al. Defective acute inflammation Med 2006;3(12):e473. in Crohn’s disease: a clinical investigation. sometimes more widely accessible, Lancet 2006;367(9511):668–78. but not always. To date, such data Snow RW et al. The global distribution of clinical episodes of Plasmodium falciparum malaria. LeBouder E et al. Modulation of neonatal have never been gathered into a Nature 2005;434(7030):214–7. microbial recognition: TLR mediated innate single source and linked to a map • In 2005/06 Professor Snow was awarded immune responses are specifically and of the world. The Malaria Atlas differentially modulated by human milk. a Wellcome Trust Principal Research J Immunol 2006;176(6):3742–52. Project (www.map.ox.ac.uk) has Fellowship and Dr Hay a Senior so far assembled information from Research Fellowship. 3126 communities in 79 countries – the single largest repository of contemporary information on malaria risk yet produced. ADVANCING KNOWLEDGE 12

ALLERGIES AND MEET THE MODERNITY CHALLENGE An acclaimed social history of allergy highlights dramatic The UK health system is facing two changes in our perceptions of this common condition. growing health concerns.

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Allergy, argues Professor Mark The reasons for this increase are The National Health Service in Jackson in his acclaimed new book controversial. The finger of blame the UK may be regarded as Allergy: The history of a modern has been pointed at environmental one of the best in the world, but malady, is not just a collection of pollutants and even an obsession with with improvements in diagnosis, symptoms. Perceptions of allergy cleanliness. Indeed, argues Professor treatment and prevention, and have changed markedly over time. Jackson, Director of the Wellcome altering social circumstances, Understanding these changes tells Trust-funded Centre for Medical healthcare priorities are constantly us much about the changing face History at the University of Exeter, changing. Liver cirrhosis and of public health and society more allergy is not just a medical condition autism are two conditions that are generally. but also an “index of cultural anxiety”, throwing up significant challenges encapsulating fears about our lifestyles to public health. The term ‘allergy’ was coined 100 and environment. Allergies have years ago by an Austrian paediatrician, Professor David Leon and Dr Jim become a powerful and pervasive Clemens von Pirquet. Hay fever, McCambridge, a Wellcome Trust metaphor for the “pathology of though, was first described in 1819 Health Services Research , progress”. Once seen as exclusive by British physician John Bostock. looked at the rate of cirrhosis mortality to the ultra-civilised, allergies are He suggested it was a disease of in 12 European countries between now viewed as a by-product of the middle and upper classes, and it 1955 and 2001. While a decline in civilisation itself. was soon widely accepted that only the mortality rate was seen in most ‘persons of cultivation’ suffered from The book was positively reviewed in countries from the 1970s onwards, allergies. Professor Jackson notes that historical, medical and popular press. the rate in the UK increased, and in E M Forster’s Howard’s End (1910), Publishers Weekly described it as continues to rise steeply. The problem hay fever appears as the “embodiment “a masterful overview of the evolution is most acute in Scotland, where the of innate cultural refinement”. of allergy as a public health problem”. mortality rate more than doubled According to , “this The last century witnessed a surge between the periods 1987–1991 and fascinating study is undoubtedly an in allergies. In the inter-war years, 1997–2001. The most likely cause is important contribution to the social just one in 30 people suffered allergic the UK’s rising consumption of alcohol. history of medicine”. Its first print reactions: that figure was one in Prompted by reports suggesting a rise run sold out within five months. three by the turn of the century. in the prevalence of autism and autistic Allergies now cost the NHS more Jackson M. Allergy: The history of a modern spectrum disorders (ASDs), Professor malady. London: Reaktion Books; 2006. than £900 million a year. Gillian Baird and colleagues studied nearly 57 000 nine- and ten-year-olds from South Thames, UK.

Images 1 Detail of a poster 2 Testing cognitive skills 4 Women in India. held in the Wellcome in a boy with autism. Library. 3 Modern drinking culture. ADVANCING KNOWLEDGE 13

WELL WOMEN Women’s mental health is a major but neglected issue for developing countries.

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ASDs were present in around The World Health Organization sexually transmitted infection, 1 per cent of the children studied, (WHO) estimates that, by 2020, and could mean that depression one-third of whom had autism as neuropsychiatric disorders will and/or social issues affecting defined by World Health Organization be the second greatest cause of them are overlooked. As such, criteria. It is unclear whether these loss of quality of life because of the researchers suggest that findings represent an actual increase disability or death globally. One treatments for gynaecological in autism, better detection of the in four people attending primary problems should target both disorder or changes in the way it care in developing countries is infection and psychosocial factors. is diagnosed. thought to have a mental illness, A separate study showed that mental Accurate data on disease prevalence yet mental health support is often illness during pregnancy was linked to are vital for effective public health extremely limited. low-birth-weight babies, who are at an planning and the development of Working with women from Goa, increased risk of neonatal death. education programmes to try to India, Dr Vikram Patel from the Dr Patel is now leading another avert greater problems in the future. London School of Hygiene and Wellcome Trust-funded study to Leon DA, McCambridge J. Liver cirrhosis Tropical Medicine and colleagues develop an effective, affordable and mortality rates in Britain from 1950 to 2002: found that women with gynaecological sustainable healthcare programme an analysis of routine data. Lancet symptoms were at an increased risk of 2006;367(9504):52–6. that integrates management of depression. Conversely, women who Baird G et al. Prevalence of disorders of the depression into routine primary care. were depressed were more likely to autism spectrum in a population cohort of Patel V et al. Gender disadvantage and children in South Thames: the Special develop gynaecological symptoms. reproductive health risk factors for common Needs and Autism Project (SNAP). Both gynaecological symptoms and mental disorders in women: a community Lancet 2006;368(9531):210–5. survey in India. Arch Gen Psychiatry depression were associated with • Professor David Leon received programme 2006;63(4):404–13. grant funding in 2005/06 to study alcohol use social issues, including economic Patel V et al. The burden and determinants and low life expectancy among Russian men. problems and ‘gender disadvantages’ of dysmenorrhoea: a population-based survey (such as sexual violence, low family of 2262 women in Goa, India. BJOG support and being widowed). 2006;113(4):453–63. Patel V, Prince M. Maternal psychological Current WHO guidelines – which morbidity and low birth weight in India. assume that gynaecological Br J Psychiatry 2006;188:536. symptoms indicate reproductive tract – could lead to women with gynaecological problems being incorrectly classified as having a ADVANCING KNOWLEDGE 14

NEW FUNDING

Wellcome Trust Centres and core supportSanger Institute Influenza research

Nearly £20 million has been The Wellcome Trust Sanger Two important new projects invested in core support for world- Institute was awarded £340 million have been funded on human leading research centres in vibrant for 2006–11, following a review of and avian flu. areas of research. its achievements over the past The Wellcome Trust’s Major Overseas five years. Strategic Award funding is a Programme in Vietnam, led by mechanism to provide outstanding The Wellcome Trust Sanger Institute Professor , has been at research groups with significant is the only research centre directly the forefront of efforts to understand levels of support. funded by the Wellcome Trust. In the impact of H5N1 avian flu in A new Wellcome Trust Centre October 2005 it was awarded £340m people. A new award of £385 000 to for Stem Cell Research has been to support its activities over the five- Dr Cameron Simmons in Vietnam will established at the University of year period 2006–11. support a collaboration with groups in Cambridge following a £7.0m During this period the Sanger Institute Switzerland and the USA, which aims Strategic Award to Professor Austin will drive forward its revised scientific to investigate whether monoclonal Smith and Professor Fiona Watt. The strategy. Under Professor Allan antibodies derived from people who Centre will also run a new four-year Bradley, who took over as Director in survived H5N1 infection (including Hn, PhD programme dedicated to stem 2000, its emphasis has shifted from the girl pictured above) can provide . genome sequencing to large-scale protection against this strain of . The Wellcome Trust Centre for studies aimed at understanding This grant was ‘fast-tracked’ through Neuroimaging at University College the function of genes and their the grant appraisal process, in London, funded through a £6.7m contributions to health and disease. recognition of the great threat posed Strategic Award, builds on its earlier The new strategy will see a further by H5N1 influenza. success as the Functional Imaging refinement of this approach, with Support is also being provided for an Laboratory. It will be led by Professor an enhanced focus on the Sanger influenza virus genome-sequencing Ray Dolan and Professor Karl Friston. Institute’s core strengths: large-scale pipeline. The pipeline, a collaboration A Strategic Award of £4.0m was studies of natural and engineered between the Medical Research made to the Cambridge Institute for variation in genome sequence, in Council’s National Institute for Medical Research for the renewal of humans, pathogens and model Medical Research, the University of its core support and to establish two organisms (see pages 38 and 49). Cambridge, the Health Protection new training programmes operating Underpinning these major Agency, the Veterinary Laboratory at the interface between clinical and programmes will be the Sanger Agency and the Wellcome Trust basic research. Institute’s unique skills in informatics Sanger Institute, will allow researchers and high-throughput technologies to track viruses affecting animal and An existing Wellcome Trust Centre, human populations. the Wellcome Trust Centre for Cell such as sequencing and large-scale Biology, University of Edinburgh, engineering of gene knockouts in The sequence data will provide was awarded £3.3m renewal of its the mouse. valuable information about the core funding. spread of different strains of virus and identify strains that need to be targeted by vaccination. ADVANCING KNOWLEDGE 15

Major awards in the history of medicine A selection of notable grants awarded in 2005/06.

PROGRAMME GRANTS PROJECT GRANTS MOUSE MODELS DEVELOPMENTAL BIOLOGY Professor Elizabeth Fisher (Institute of Professor Sir John Gurdon (University Neurology) and Dr Victor Tybulewicz of Cambridge) Nuclear reprogramming: (National Institute for Medical Research) searching for factors that can revert frog Down’s syndrome: identifying the causes nuclei to early developmental stages. of brain and heart defects in an engineered MALARIA mouse model. Dr Balbir Singh (University Malaysia Sarawak) WOUND HEALING and Dr David Conway (London School of Professor Paul Martin (University of Bristol) Hygiene and Tropical Medicine) Effect of Inflammatory response in wound healing: cell Plasmodium knowlesi (seen mainly in biological and genetic analysis in mice and monkeys) in humans in the Far East. zebrafish. POPULATION STUDIES Dr Marjan van der Woude (University of Dr Eliya Zulu (Africa Population and York) Salmonella enterica: understanding Health Research Centre, Kenya) Impact how variation in S. enterica helps it evade Unpicking the complex political, of urbanisation and poverty on health in the host response in humans and livestock. cultural and environmental forces sub-Saharan Africa. MENTAL HEALTH that have influenced health, disease CELL BIOLOGY Dr Ed Watkins (University of Exeter) and medicine over the last 250 Professor (University of Rumination: its role in increasing susceptibility years is the goal of two major Oxford) Mechanisms of chromosome to depression and possible therapeutic history of medicine awards. segregation in meiosis. approaches. A Strategic Award in the History of TRANSCRIPTION VISUAL SCIENCE Professor Nicholas Proudfoot (University Dr Joshua Solomon (City University) Medicine was made to the Centre for of Oxford) Transcription termination: molecular Effect of context on visual perception (jointly the History of Science, Technology mechanisms and links to RNA processing. funded with the Biotechnology and Biological Sciences Research Council as part of the the and Medicine at the University of DIABETES Cognitive Foresight Programme). Manchester. This five-year award Professor Stephen O’Rahilly (University will strengthen the group’s position of Cambridge) resistance: identifying NEUROSCIENCE as one of the UK’s leading centres patients and analysing potential genetic Dr Patricia C Salinas (University College for research into the history of contributions. London) The role of Wnt signalling in synapse formation in the central nevous system. 19th- and 20th-century medicine. PHYSIOLOGY Professor Malcolm Parker (Imperial College MEDICAL HUMANITIES As well as analysing economic data London) Energy homeostasis and ovulation: PROJECT GRANTS on healthcare, the Manchester group function of ligand-dependent nuclear receptor HISTORY OF MEDICINE will explore the many NHS changes corepressor RIP140. Professor Peter Harper (University of ) Preserving the history of human of the last 30 years. Another strand STATISTICAL GENETICS and medical genetics. of research will focus on the impact Professor Lon Cardon (University of Oxford) of the Cold War, as military-derived Genome association studies: development of BIOMEDICAL ETHICS new statistical methods focusing on multiple Dr Paula Saukko (University of Exeter) technologies were deployed in interacting loci in complex human diseases Nutrigenomics: an analysis of claims made medical research and practice. (e.g. Crohn’s disease). for nutrigenomics products in marketing materials and the media. A key aim is to provide useful INFECTIOUS DISEASE information for patients, medical Dr Neil French (London School of Hygiene HISTORY OF MEDICINE professionals and policy makers to and Tropical Medicine) Karonga Prevention Dr Vanessa A Harding (Birkbeck College) Study, Malawi: impact of retroviral rollout on Health in early modern London, 1550–1750: help inform future healthcare policy- HIV and associated TB and pneumococcal creating a detailed database of residents to making, as well as to preserve the infections in local community. assess the environmental and other factors record of the past. affecting health. VETERINARY MEDICINE A five-year Enhancement Award Professor Mark Woolhouse (University of was jointly awarded to the University Edinburgh) Disease burden in East African of Ulster in Northern Ireland and cattle: characterising the full range of infections affecting animals in first year of life. University College Dublin in the Republic of Ireland to enable AGEING Professor Martin Prince (Institute of researchers to work together on Psychiatry) Ageing and dementia: identifying Details of all grants made can be found in common themes. Research will focus the risk factors for dementia in ageing Grants Awarded 2005/06, available on the particularly on medical developments populations in Latin America and China. Wellcome Trust website. in Ireland, north and south.

USING KNOWLEDGE Supporting the development and use of knowledge to create health benefit. USING KNOWLEDGE 18

LIFE-SAVING TAMING TB NUMBERS Clinically relevant, practical findings from studies in Kenya are leading A new vaccine and diagnostics will directly to health policy changes – and saving children’s lives. aid the fight against TB.

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Research led by Dr Anthony Scott District Hospital between 2000 and About 1.7 million people die from at the Kenya Medical Research 2005. Hib immunisation reduced the tuberculosis (TB) annually; 500 Institute–Wellcome Trust Research number of cases of Hib disease by children die of it every day. As Programme in Kilifi, Kenya, has 88 per cent, on the basis of which the such, new tools to control TB are helped ensure that Kenyan children Kenyan Ministry of Health committed urgently needed. will continue to receive vaccinations itself to funding the ongoing Dr Helen McShane of the University against Hib – a disease that causes immunisation programme. of Oxford has been developing and 400 000 deaths per year globally – Other work supports the introduction testing a ‘prime–boost’ vaccine for as part of standard immunisation of pneumococcal vaccines into TB. The existing vaccine, BCG, programmes. immunisation programmes. In a similar is not always fully protective against Hib (H. influenzae type b) infection is surveillance study of children attending TB disease, particularly in adults. expensive and difficult to diagnose, the hospital in Kilifi, the incidence of However, it may be more effective and can lead to pneumonia and pneumococcal bacteraemia – blood when used as a ‘prime’ in combination meningitis. Although a Hib vaccine poisoning caused by bacterial infection with a second ‘boost’ immunisation exists, a lack of available data on its – was four times greater than based on the new vaccine. previously estimated from inpatient effectiveness and on Hib disease The combination has been shown to studies, suggesting that bacterial burden means that Hib immunisation be safe and immunogenic in phase I infections have a much greater is a low priority for many developing and phase II clinical trials in adults. impact on child health than had countries. With recently agreed Technology been appreciated. In 2001, a five-year programme Transfer funding, further phase II trials, (sponsored by the Global Alliance Cowgill AD et al. Effectiveness of Haemophilus first in adults then in children and influenzae type b Conjugate vaccine introduction for Vaccines and Immunization) into routine childhood immunization in Kenya. infants, are planned for South Africa’s was launched to provide free Hib JAMA 2006;296(6):671–8. Western Cape – where TB is rife. vaccine to Kenya and 11 other Brent AJ et al. Incidence of clinically significant Professor Ajit Lalvani, whose Senior African countries; but from 2007, bacteraemia in children who present to hospital Research Fellowship in Clinical these countries are being asked in Kenya: community-based observational study. Lancet 2006;367(9509):482–8. Science was renewed this year, has to contribute financially to identified another possible benefit of the programme. BCG. BCG has been thought to work To assess the impact of Hib by preventing TB disease rather than vaccination, researchers at Kilifi by blocking initial infection. Use of a examined Hib infection rates in new diagnostic test by Professor 38 000 under-fives admitted to Kilifi Lalvani showed that BCG did seem

Images 1 Young children in 3 Samples held in the Kenya. Manchester CRF. 2 Mycobacterium 4 Nursing care in the tuberculosis. Manchester CRF. USING KNOWLEDGE 19

CARE IN THE CLINIC Fascinating insights into the brain have been obtained thanks to research support and patient care facilities at the Cambridge Clinical Research Facility.

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to protect children from infection as Research on people is a vital The CRFs support high-quality well as disease. BCG may therefore part of work to understand human research funded by a range of be more useful in disease control biology and disease processes, bodies. A notable example in 2006 than once thought. and the impact of new medicines. was the study of an individual in a It calls for the highest possible persistent vegetative state, who Sadly, advanced TB diagnostics are levels of care and support. The showed specific neural responses not an option for resource-poor Wellcome Trust Clinical Research to stimuli, suggesting that she retained countries, while the low-cost methods Facilities (CRFs), the UK’s first sites conscious awareness. This study, promoted by the WHO lack sensitivity dedicated to research on people, funded by the Medical Research and give no information about drug provide an environment uniquely Council, depended on both the resistance. But a new test, the MODS tailored to clinical research. expertise and equipment at the assay (microscopic observation drug Wolfson Brain Imaging Centre and susceptibility), developed in Peru by The Cambridge CRF, based at the CRF’s accommodation and Addenbrooke’s Hospital, has Professor Bob Gilman and evaluated intensive clinical and nursing care. and refined by Dr David Moore and strengths in areas such as nutrition, energy balance and obesity, Chamberlain SR et al. Neurochemical modulation colleagues at Imperial College London of response inhibition and probabilistic learning in and in Lima, Peru, is an affordable, endocrinology and metabolic humans. Science 2006;311(5762):861–3. defects, and brain function. sensitive and rapid test for TB and Owen AM et al. Detecting awareness in the drug-resistant TB. The speed can With Wellcome Trust support, vegetative state. Science 2006;313(5792):1402. save lives – a patient with multidrug- Professor Barbara Sahakian, Professor resistant TB may be dead before drug Trevor Robbins and colleagues have resistance has been identified by used the CRF to study cognitive conventional methods. function in healthy volunteers – McShane H et al. Recombinant modified specifically, their ability to suppress vaccinia virus Ankara expressing antigen 85A impulsive behaviours and to learn boosts BCG-primed and naturally acquired from complex input. antimycobacterial immunity in humans. Nat Med 2004;10(11):1240–4. They were able to distinguish effects Soysal A et al. Effect of BCG vaccination on mediated through two key pathways in risk of Mycobacterium tuberculosis infection in the brain: noradrenaline and serotonin children with household tuberculosis contact: systems. This work will shed light on a prospective community-based study. Lancet 2005;366(9495):1443–51. conditions in which these behaviours are disrupted, including depression, Moore DA et al. Microscopic-observation drug- susceptibility assay for the diagnosis of TB. N drug addiction and attention deficit Engl J Med 2006;355(15):1539–50. hyperactivity disorder. USING KNOWLEDGE 20

IN ON TACKLING THE ACT TRACHOMA Artemisinin combination therapies are now the recommended A new dipstick diagnostic test for World Health Organization treatment for malaria. trachoma has been successfully trialled.

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A rare success story in the fight organisations and developed Trachoma, eye damage resulting against malaria has been the countries would have to contribute from Chlamydia trachomatis development and use of therapies up to US$300–500 million per year infection, is a major cause of based on artemisinin, originally to reduce the cost of ACTs to 10 blindness across the world. isolated from the sweet wormwood cents per course or less, in line with Although the condition can plant. Professor Nick White and the price of the cheapest single-drug be cured by a single dose of colleagues at the Wellcome Trust’s artemisinin-derived therapy. antibiotics, identifying who should South-east Asia Major Overseas Development of a new drug for be treated has been difficult. Programme have pioneered the malaria has been a remarkable Now, a team headed by Professor use of artemisinin combination scientific and technical achievement. David Mabey (London School of therapies (ACTs), which have An equally committed and concerted Hygiene and Tropical Medicine) proved extraordinarily effective effort is now needed to ensure that and Dr Helen Lee (University at controlling malaria in Vietnam all vulnerable people – mostly young of Cambridge) has evaluated and Thailand. ACTs are now children in Africa – can benefit a cheap, simple and quick the recommended World Health from ACTs. diagnostic dipstick for Organization treatment for malaria. C. trachomatis, developed by WHO Guidelines for the Treatment Dr Lee and colleagues. Following Artemisinin derivatives are potent, of Malaria. Geneva: World Health successful trials, the test is being well-tolerated, rapidly acting drugs that Organization; 2006. www.who.int/malaria/docs/ TreatmentGuidelines2006.pdf [accessed 23 fine-tuned for use in areas of carry a low risk of resistance, as long November 2006]. different trachoma prevalence. as they are used in combination with Institute of Medicine, Board on Global Health. other antimalarial drugs. ACTs are, Saving Lives, Buying Time: Economics of In eradication campaigns, whole however, more expensive than other malaria drugs in an age of resistance. communities must be treated for treatments. Nearly all countries have Washington, DC: National Academies Press; trachoma because it is spread 2004. http://newton.nap.edu/catalog/ now in principle adopted ACTs as their 11017.html?onpi_newsdoc07202004 extremely easily. Currently, clinical first line of defence against malaria. In [accessed 23 November 2006]. signs are used to diagnose trachoma, practice, however, ACTs do not always so treatment can be targeted reach the people that need them. effectively – but clinical observation The Institute of Medicine, one of the is not an accurate guide to infection. US National Academies, has called Dr Lee’s laboratory has developed for an annual global subsidy to make technologies that have been used in ACTs more affordable. The Institute a new generation of robust and simple estimates that international diagnostic tests for a range of

Images 1 Testing for malaria in 3 Using the trachoma South-east Asia. diagnostic in Tanzania. 2 Malaria-transmitting 4 Real antimalarial drugs. mosquito. USING KNOWLEDGE 21

COSTS OF COUNTERFEITING Researchers fear that Africa is next in line for the influx of fake antimalarials.

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infections. Teaming up with Professor The swamping of South-east The situation is exacerbated by Mabey, the group has evaluated a test Asia with fake antimalarials is increasingly sophisticated counterfeits, for trachoma. A trial in Tanzania (where a massive threat to health that with highly realistic holograms on trachoma is rife) showed that the is likely to spread to Africa, says the fake packaging. High prices, dipstick was more than twice as good Dr Paul Newton of the Wellcome high demand and a shortage of raw as clinical signs at predicting trachoma Trust–Mahosot Hospital–Oxford material mean that an epidemic of fake cases, identifying over 97 per cent of Tropical Medicine Research artesunate in Africa is highly likely. cases correctly. The work was Collaboration in Laos. This illegal The World Health Organization is captured in a BBC documentary and pernicious trade could be set to launch IMPACT (International aired in more than 100 countries. responsible for thousands of Medical Products Anti-Counterfeiting In new research funded by the deaths, as fake drugs often Taskforce), which is expected to work Wellcome Trust, the team will test contain no active ingredients, with pharmaceutical manufacturers the effectiveness of the dipstick in subtherapeutic levels of active to make drugs harder to fake, and The Gambia, Senegal and Ethiopia ingredient and even toxic easier to trace from factory to (areas with high, medium and low substances. consumer. IMPACT will also tackle levels of trachoma, respectively). In Dr Newton has worked with the under-reporting of fake drugs addition to evaluating its performance colleagues in South-east Asia, by consumers, healthcare providers in the field, they will use mathematical Europe and the USA to raise and pharmaceutical companies. modelling to determine the most cost- awareness of this growing threat. Dr Newton and colleagues hope effective strategies for using the At least eight of the 14 main types to set up a network to detect and dipstick to identify communities of antimalarial drug are being analyse counterfeit antimalarials, to needing treatment. counterfeited, including artesunate, assist drug regulatory authorities and Michel CE et al. Field evaluation of a rapid point- a highly efficacious treatment for to pinpoint where fakes were made. of-care assay for targeting antibiotic treatment for potentially fatal falciparum malaria Newton PN et al. Counterfeit anti-infective trachoma control: a comparative study. Lancet and a key component of ACT 2006;367(9522):1585–90. drugs. Lancet Infect Dis 2006;6(9):602–13. (artemisinin combination therapy). Newton PN et al. Manslaughter by fake Recent studies have found that about artesunate in Asia – will Africa be next? PLoS Med 2006;3(6):e197. half of all ‘artesunate’ packs bought in South-east Asia are fake, with the majority sampled in some research containing no artesunate. USING KNOWLEDGE 22

WIDE BREATHE SCREEN EASY With its first drugs entering clinical trials, DanioLabs Clinicians and patients will both is making the transition from small fry to big fish. benefit from a new laryngoscope.

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Two compounds developed by DanioLabs has continued to grow Keeping a patient’s airways clear DanioLabs Ltd, a spin-out from since its launch in 2002 – attracting is vital during anaesthesia or the University of Cambridge and £3.2 million in venture capitalist emergency treatment. Usually the University of California, San funding in 2005. Currently, two doctors use a laryngoscope, to Francisco, have entered clinical compounds (novel combinations of assist placing a flexible tube trials for the treatment of established drugs) are undergoing through the vocal cords and into Parkinson’s disease symptoms. phase I trials for the treatment of the windpipe. Laryngoscope design drooling and excessive sweating in has changed little since the 1940s. The company uses in vivo assays in Parkinson’s disease. There is also a Great skill is needed to use them zebrafish to look for new clinical uses further compound under investigation safely and they can damage of either established drugs or those for seborrhoea (excessive sebum patients’ teeth, vocal cords and that dropped out of the research secretion), an additional feature soft tissue. and development pipeline, alone of Parkinson’s disease but also a or in combination. Matt McGrath, a former John Logie pathogenic factor in acne and the Baird Young Innovator of the Year, DanioLabs has pioneered the use skin condition seborrhoeic dermatitis. of zebrafish in compound screening. founded Aircraft Medical Ltd in The company is also researching The fish are vertebrates that model 2001, having started designing his treatments for several other human systems closely; they have laryngoscope two years earlier as part conditions, with compound screens transparent embryos, it is possible of his degree course. With the support currently underway for epilepsy, to work with single cells, and the of a Wellcome Trust Translation Award, Alzheimer’s disease, Parkinson’s genome is easy to manipulate and his company developed Mk 4 and disease and multiple sclerosis. is currently being sequenced. Mk 5 prototypes, which led to the ® www.daniolabs.com 2006 launch of the McGrath The company, which developed Series 5 laryngoscope. with Wellcome Trust Technology Transfer funding, focuses on Thanks to an integrated camera and treatments for ophthalmic and screen, the portable battery-powered ® neurological disorders. The company McGrath Series 5 provides a clearer operates an in-house drug discovery view of the airway. As a result, it is process that re-screens existing drugs easier to manoeuvre – good for patient and also offers screening services to and for doctor. The laryngoscope is pharmaceutical companies. size-adjustable and also features disposable blades to prevent cross- infection between patients.

Images 1 Adult zebrafish. 3 Intubating a patient in 2 Matt McGrath and his the operating theatre. laryngoscope. USING KNOWLEDGE 23

NEW FUNDING

A selection of notable grants New malaria drugs awarded in 2005/06.

TECHNOLOGY TRANSFER AWARDS Dr Richard Marais and Dr Caroline Springer (Institute of Cancer Research) Research into drug-like inhibitors of BRAF kinase for the treatment of malignant . The Wellcome Trust and the Institute of Cancer Research have also established an alliance with GlaxoSmithKline to discover, develop and commercialise novel small-molecule inhibitors of BRAF. Dr James Hamilton (University of Keele) Pheromone-based sand-fly traps: sex 3 pheromones will lure disease-transmitting sand flies to insecticide-laden traps. Dr Andrew Gee (University of Cambridge) The McGrath® laryngoscope has The Wellcome Trust, the Singapore Mathematical manipulations to improve ultrasound imaging. been described as the “most Economic Development Board significant advancement in and the Medicines for Malaria Professor Sir (University of Cambridge) Fragment-based inhibition of laryngoscope design since the Venture (MMV) have pledged over protein interactions. 1940s” (Dr Gary Enever £10 million to a new partnership of the Royal Victoria Infirmary, dedicated to malaria drug Professor Paul Addison (CardioDigital Ltd, East Lothian) Software enhancements to Newcastle). In a recent study on development. predict responsiveness to cardioversion 150 patients at the Royal Infirmary The new programme, which received therapy in atrial fibrillation patients. of Edinburgh, the McGrath® £6.4m from the Wellcome Trust, will Professor Paul Sharp (Odontis Ltd) Using demonstrated 94 per cent grade 1 be led by Professor Alex Matter of the stem cells to regrow teeth: moving from views, whereas current equipment animal studies to human application. Novartis Institute for Tropical Diseases achieves under 70 per cent. (NITD) in Singapore – a partnership Dr Lorenzo Frigerio (University of Warwick) LMA North America has been Engineering plants to produce higher yields between Novartis and the Singapore of secretory IgA than are currently possible. appointed exclusive distributor Economic Development Board. in the USA, in a five-year contract The NITD will conduct research jointly with potential value of US$50 million to with several institutions, including the Aircraft Medical. With laryngoscopes Genomics Institute of the Novartis being used in 60 million Research Foundation and the Swiss anaesthetisations each year, the Tropical Institute. product has a chance of making a significant impact on health. Scientists at the NITD will investigate Shippey B et al. Rapid sequence intubation using the potential of existing compounds the McGrath videolaryngoscope. Eur J Emerg with some antimalarial activity, as well Med 2006;13(5):A12–13. as exploring novel compounds. The research will focus on two main goals: a one-dose cure for Plasmodium falciparum, the most dangerous form of malaria; and new treatments for P. vivax, the most widely distributed cause of malaria. Development of the most promising Details of all grants made can be found in candidate drugs will be taken forward Grants Awarded 2005/06, available on the by MMV. Wellcome Trust website.

ENGAGING SOCIETY Engaging with society to foster an informed climate within which biomedical research can flourish. ENGAGING SOCIETY 26

SCHOOL AIRING THE REPORT ISSUES Better teachers using a better curriculum: the ‘Real’ characters can breathe life prospects for UK science education are looking up. into ethical debates.

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School students have been The Twenty First Century Science A mum tries to calm the blazing clamouring for more meaningful GCSE, launched in September 2006 row between her vegetarian science education. Teachers agree following a successful pilot, will help animal-loving son and his medical and, given training and resources, prepare 14–16-year-olds for a rapidly researcher sister. Sonny opposes are keen to deliver it. The opening changing world. Its modular approach research on animals, sister Anita of the National Science Learning is designed to cater both for the believes it is justified, while mum’s Centre at York and the launch academically gifted destined Buddhist boyfriend provides an of the Twenty First Century Science for a career in science and for non- interesting commentary. Later, curriculum are important steps specialists who will nonetheless be Sonny’s principles are tested when towards this goal. living in a science-dominated world. asthma puts him into hospital. The Wellcome Trust has provided The GCSE aims to give essential Funded by a Wellcome Trust Society £25 million for the National Science factual education while also conveying Award, Every Breath, written by Learning Centre, in York, to support the nature of science and rooting Judith Johnson and produced by teachers’ continuing professional science in the world experienced Y Touring Theatre Company, is a development, with the Department by today’s young people. It will thought-provoking yet balanced for Education and Skills contributing also challenge science teachers, production. It does not attempt to £26m funding for nine regional technicians and teaching assistants push any particular argument, but centres. to keep themselves updated with a helps the audience to see all sides rapidly developing subject and to In March 2006, the Prime Minister, of a complex and emotive issue. make use of innovative techniques Tony Blair, opened the National A live debate follows the that engage students – for example, Centre, saying: “At school we all knew performances, encouraging students through the national network of the one thing that made a difference to explore the issues. Y Touring’s . was if the teacher felt personal website has downloadable lesson enthusiasm for their subject, then it www.sciencelearningcentres.org.uk resources to help teachers and was communicated to their students.” students. In the first year, more than 1000 Aimed at 14-year-olds and upwards, teachers and technicians attended the play has been seen by more than courses in York, a figure that will rise 14 000 youngsters this year. Although to 5000 teachers annually from 2013.

Images 1 Trainee teachers at 2 A scene from Every 3 A speaker at one the National Science Breath. of the ‘wellbeing’ Learning Centre. events. ENGAGING SOCIETY 27

SHARED EXPERIENCE Members of the public and a range of experts engaged in thoughtful discussions about the nature of wellbeing.

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showing predominantly in schools, Naturally, we all value our population boom, could we ‘cure’ Y Touring has taken the production to health and wellbeing. Scientific ageing to live a longer life? As lifestyle a young offenders’ centre as well as discoveries impinge on our sense makes more demands on medicine, the Edinburgh Fringe Festival, where it of ‘wellness’, but so too do our we may see a new relationship won the best production award. social circumstances – our between medicine and culture Every Breath is specifically designed relationships, environment, developing. for cross-curricular learning. One family and so on. A series of Feeling close to the speakers, 14-year-old said: “It was good to public events organised by the audiences raised points easily in a see drama and science mixed Wellcome Trust featured a range non-academic, friendly environment. together like that. It’s better than of perspectives on a topic close More than 200 people attended sitting in the classroom and reading to our hearts. the three July events, which were about it in a book.” The first event, ‘What Makes us oversubscribed several times over. www.ytouring.org.uk Happy?’, brought insights from As a result, the events were run science, philosophy and gritty again (and were again sold out) • The Every Breath project also received funding from the Association of Medical street reality to explore the concept later in 2006. Research Charities. of happiness. These sell-out events augur well for Music has always been important the opening of in self-expression and scientists are in 2007 (see page 41), which has now beginning to understand how a similarly intimate ‘forum’ space. it affects us. ‘Exploring the Rhythms of Life’ combined science and psychology with live performance to demonstrate what happens when music meets mind. ‘Full Life, Long Life?’ used philosophy and science to explore the choices and consequences of the lives we lead. Faced with an over-60s ENGAGING SOCIETY 28

THE RHYTHM YOUNG OF LIFE CITIZENS How do you get young people interested in a subject as alien as ‘Young citizens’ have had a chance epigenetics? Or psychotherapies? Dance and drama may be the answer. to have their views heard.

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At first sight, the idea that project, which featured at a special The new world of genetic dance could be used to interpret event at the European Science Open technology will affect young epigenetics – the chemical Forum in Munich in July 2006 and people more than the older modification of DNA or its later played at the Barbican. generation. But what do they proteins – seems far-fetched. By helping a frozen pea diagnosed think about the application of Yet to see young dancers perform with a personality disorder undergo these technologies to reproductive so exuberantly, and to hear how CBT, Baker manages to be both decision-making? Dr Rachel Iredale discussion of the dance’s fluid thought-provoking and entertaining. and colleagues at the University choreography led to sophisticated “Charming, eccentric, thoughtful,” of Glamorgan’s Genomics Policy discussion of DNA and inheritance, said The Financial Times; “Farcical Unit ran a ‘citizens’ jury’ for young is to appreciate the power of and dark, and as Bobby promises people between 16 and 19 years old artistic approaches to engage at the outset, makes you feel better,” to find out where they would draw people with biomedical science. thought the Guardian. the line with ‘designer babies’. The intricate moves of the young • A DVD of IMPACT Danscience is available Fourteen young people from Wales dancers in IMPACT Danscience’s at: www.impactdanscience.co.uk. were chosen as jurors; they cross- project draw upon both classical examined experts on topics such ‘How to Live’ also received support from Indian dance and the dynamics Calouste Gulbenkian Foundation and as preventing genetic disease, of cells, nuclei and chromosomes. Arts Council England. It is due to tour in sex selection and ‘saviour siblings’. The project is the result of a series of 2007 (see http://bobbybakersdailylife.com They also heard from non-experts for details). workshops run by the choreographers who had personal experience of the Mayuri Boonham and Subathra issues before reaching their verdict. Subramaniam of ANGIKA Dance The organisers concluded that the Company, and biomedical scientist first citizens’ jury with this age group Dr Sheila Ochugboju. demonstrated the validity of the If dance and epigenetics seems method in terms of engaging young like a strange combination, how people with current issues in science, about cognitive behavioural therapy and that they have important and (CBT) and frozen peas? Acclaimed useful things to say about genetic performance artist Bobby Baker, who technologies. has herself undergone CBT and other As well as writing their report, psychotherapies, raises important and the young jurors presented their challenging issues in her ‘How to Live’ conclusions to the Human Genetics

Images 1 Epigenetics dancers. 2 The group who sat on the citizens’ jury. ENGAGING SOCIETY 29

NEW FUNDING

A selection of notable grants Generation Genome awarded in 2005/06.

PUBLIC ENGAGEMENT INTERNATIONAL PUBLIC ENGAGEMENT Seven projects were awarded a total of £933 000 through the Livestock for Life initiative, which aimed to forge closer links between researchers, policy makers and livestock owners in developing countries. WEBSITE Dr Sue Ziebland (University of Oxford) Living with autism: establishing a web resource combining factual information with video and audio material from affected families; part of 2 the ongoing DIPEx (Database of Individual Patient Experiences) project. VISUAL COMMUNICATION Commission, the Human Fertilisation At-Bristol has been awarded a Shirley Wheeler (University of Sunderland) Visual design: discussions with scientists, and Embryology Authority, and the £1.5 million Capital Award to designers and the public about ways to Health and Social Services Committee produce a five-year national portray molecular biology and science of the Welsh Assembly Government. touring exhibition on genomics. information visually. They included agreement that it is At the heart of the Generation Genome INTERACTIVE EXHIBITS acceptable to use genetic technology Martin J Freeth (Windfall Digital Ltd) project is a vast 350 m2 travelling to prevent genetic disorders being Development of interactive genetics exhibits. exhibition aimed at 14-year-olds and passed on, or to save a sibling. But above, to engage them in the science SCIENCE AND ART the jury opposed sex selection for Cambridgeshire County Council of the human genome, genomics social reasons. Genetics-inspired art on the Great Shelford research, and related social and ethical to Addenbrooke’s Hospital cycle path. The They also declared that ‘designer issues. It will be hosted by science path features 10 000 stripes representing babies’ is not a useful term – and centres and museums in the UK. the genetic code for the BRCA2 gene, which that the Human Fertilisation and was sequenced at the nearby Wellcome Trust The travelling exhibition will feature a Sanger Institute, and celebrates the 10 000th Embryology Authority should have continuously updated News and Views mile of the National Cycle Network. some members under 20. area and a Dialogue Zone, as well as HISTORY OF MEDICINE Iredale R et al. What choices should we be able multiple opportunities for visitors to Dr Tilli Tansey (Wellcome Centre for the to make about designer babies? A Citizens’ Jury engage with topical ideas and ethical History of Medicine, University College of young people in South Wales. Health Expect London) Dr Tansey and Professor Les 2006;9(3):207–17. issues at ‘opinion stations’. Iversen will video interviews with 12 Six smaller replicable ‘exhiblets’ – leading neuroscientists. satellite mini-exhibitions, featuring HISTORY OF MEDICINE basic introductory material, the Justin Hardy (Hardy & Sons Ltd) updated News and Views area A docudrama based on the medical relief operations at the liberated Belsen and opinion stations – will visit smaller concentration camp. The same team museums and shopping centres. made the award-winning drama The project also includes an Trafalgar Battle Surgeon. education dimension, such as RESEARCH teachers’ resources and workshops, Professor Sarah Franklin (London School as well as informal engagement of Economics and Political Science) How new approaches in public engagement events, including debates and have impacted on biomedical scientists. meet-the-scientists opportunities. Generation Genome is being produced by At-Bristol on behalf of Ecsite-UK, Details of all grants made can be found in the UK’s network of science centres Grants Awarded 2005/06, available on the and museums. Wellcome Trust website. DEVELOPING PEOPLE Fostering a research community and individual researchers who can contribute to the advancement and use of knowledge. DEVELOPING PEOPLE 31

SECRETS OF ROYAL SOCIETY THE CILIA FELLOWSHIPS Studies of a rare genetic condition are revealing Royal Society recognition for unexpectedly important roles for cilia in development. Wellcome Trust-funded scientists.

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Wellcome Trust Senior Research and interacts with most BBS proteins. Professor Nick White, Chairman Fellow Professor Philip Beales Symptoms thus depend not only on of the Wellcome Trust’s Major (Institute of Child Health) and which BBS gene is affected, but also Overseas Programme in South-east colleagues have discovered that on any other BBS gene alterations Asia, was elected a Fellow of the cilia – tiny hair-like structures on present, and on the effects exerted Royal Society in 2006. the surface of cells – may be by mutations within other, non-disease Two researchers associated with new involved in a range of fundamental (so-called ‘modifier’) genes, such as Wellcome Trust Centres – Professor developmental pathways. The MGC1203. Austin Smith (Wellcome Trust Centre researchers have identified several The group also uncovered a for Stem Cell Biology, University of genes causing a rare genetic connection with ‘planar cell polarity’, Cambridge) and Principal Research condition, Bardet–Biedl syndrome which controls aspects of cell function Fellow Professor Karl Friston (BBS), and discovered that these such as cell orientation and polarity. (Wellcome Trust Centre for can interact with each other to In mice, mutations in BBS genes Neuroimaging, University College influence disease severity. Each disrupt cell polarity. Furthermore, BBS London) – were made of appears to affect the function genes were shown to interact with cell the Royal Society this year. of cilia. polarity genes, suggesting a novel role Several researchers with major for cilia in this process. BBS is an inherited complex disorder, Wellcome Trust grants were also causing obesity, vision defects, Other aspects of the syndrome, such recognised: Professor cognitive impairment, kidney failure as obesity and extra digits, cannot be (University of Oxford), Professor and other problems. Several genes readily explained by dysfunctional cilia Richard Jackson (University of mutated in the condition have been but it is likely that further study of the Cambridge), Professor discovered; one of the latest is BBS genes will eventually explain (University of Hong Kong) and BBS10, identified in studies of families these links. Professor Helen Saibil (Birkbeck from an isolated Lebanese village Ross AJ et al. Disruption of Bardet–Biedl College London). particularly affected by the condition. syndrome ciliary proteins perturbs planar • A list of other researchers receiving cell polarity in vertebrates. Nat Genet In a separate study, Professor Beales notable awards this year can be found 2005;37(10):1135–40. at www.wellcome.ac.uk/annualreview06. and colleagues showed that a single Badano JL et al. Dissection of epistasis in nucleotide polymorphism in an oligogenic Bardet–Biedl syndrome. Nature interacting gene, MGC1203, does not 2006;439(7074):326–30. itself cause BBS, but can have a novel Stoetzel C et al. BBS10 encodes a vertebrate- effect on its severity. The MGC1203 specific chaperonin-like protein and is a major BBS locus. Nat Genet 2006;38(5):521–4. protein was found at the base of cilia

Images 1 Cross-section through 2 Professor Nick White. cilia showing their distinctive microtubule rings. Left: Professor Philip Goulder, a Senior Research Fellow at the University of Oxford. DEVELOPING PEOPLE 32

AVATAR CONDENSATION AID REACTION Virtual reality could unlock the A key component of chromosome secrets of paranoia. condensation has been discovered.

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Paranoid thoughts, arising from an the virtual reality system to assess Every human cell contains nearly exaggerated or unfounded distrust patients’ responses and behaviour in 2 m of DNA crammed into a of others, regularly affect one in three a fully immersive but totally controlled nucleus just 6 µm across. The people in the UK, but are particularly environment. For example, it will be pinnacle of this extraordinary feat problematic in psychotic conditions possible to compare the responses of packaging is the winding of such as schizophrenia. A team of patients with those of non-clinical chromatin into the chromosomes from the Institute of Psychiatry has individuals in the general population, visible during cell division. Now, developed a virtual reality system to to identify behaviours characteristic work by Wellcome Trust Principal investigate the processes behind this of paranoid thinking. Research Fellow Professor Bill kind of thinking, and to develop It is hoped that in the future, this Earnshaw at the Wellcome Trust treatments for it. system could be adapted to become Centre for Cell Biology in Edinburgh In a Wellcome Trust-funded pilot study, part of cognitive behavioural therapy, has revealed a key player in this the group pioneered the use of virtual a form of psychotherapy. process of condensation. reality – already shown to help people Freeman D et al. The psychology of persecutory Two protein complexes, condensin to overcome phobias – to develop an ideation II: a virtual reality experimental study. I and II, contribute to chromosome understanding of paranoid thoughts. J Nerv Ment Dis 2005;193(5):309–15. condensation, but are not the Now, one of the original researchers, Freeman D et al. Acting on persecutory delusions: the importance of safety seeking. complete picture – in some types Dr Daniel Freeman, has been awarded Behav Res Ther 2007;45(1):89–99 [Epub ahead of cell, chromosomes can condense a Research Career Development of print]. without them. So Professor Earnshaw Fellowship to continue this work. Freeman D et al. Psychological investigation and a team led by Dr Paola Vagnarelli of the structure of paranoia in a non-clinical looked for factors that were needed Paranoia arises from abnormalities in population. Br J Psychiatry 2005;186:427–35. for chromosome condensation in social cognition – understanding how Freeman D. et al. Can virtual reality be used to people interact with one another and investigate persecutory ideation? J Nerv Ment the absence of condensins, using interpreting interpersonal behaviour in Dis 2003;191(8):509–514. genetically modified chicken cells. particular social situations. People with Freeman D. Suspicious minds: the psychology of persecutory delusions. Clin Psychol Rev They identified an activity – probably paranoid thinking patterns interpret [in press]. a protein or protein complex – that social signals abnormally – believing The group has also produced a self-help could maintain chromosomes in a that everyone on a bus is looking at book, Overcoming Paranoid and Suspicious condensed form during mitosis. This them, for example. Thoughts. See www.paranoidthoughts.com. activity, which they named ‘regulator As well as undertaking various studies of chromosome architecture’ (RCA), exploring these aberrant ways of only functioned when a protein called thinking, Dr Freeman is also using Repo-Man (discovered in the lab of

Images 1 An image from 2 Left pair: ‘bridged‘ 3 Dr Sumantra Chattarji. a virtual reality chromosomes, where 4 Effects of stress underground tube chromatin has not on a pyramidal environment used in remained condensed. amygdala neuron. studying paranoid and Right: normal suspicious thinking. condensed chromosomes. DEVELOPING PEOPLE 33

STRESSFUL MEMORIES After severe stress or trauma, we may remember things we would prefer to forget. Stress-induced changes to the amygdala could explain why.

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Professor Angus Lamond, another Wellcome Trust International factor, for example, can simultaneously Wellcome Trust Principal Research Senior Research Fellow heighten anxiety by strengthening Fellow) was inhibited. Blocking Repo- Dr Sumantra Chattarji and his connections in the amygdala, but Man probably prevents an associated team at the National Centre for reduce depressive symptoms by enzyme, protein phosphatase 1 Biological Sciences in Bangalore, protecting the hippocampus. (PP1, which is involved in many India, are studying how the wiring The amygdala has received less cell processes), from removing of the brain changes under stress. attention than the hippocampus, key phosphate groups needed for A better understanding of the but Dr Chattarji’s research has RCA activity. cellular mechanisms that imprint identified stress-induced changes in RCA and condensins probably act emotional memories in our brains the amygdala that underlie sensitivity together to condense chromosomes, could lead to better treatments for to emotional experience. Ultimately, suggests Professor Earnshaw. One severe anxiety or post-traumatic this work will provide a clearer picture interesting possibility is that RCA stress disorder. of the neural changes that leave drives condensation and condensin Stress intrigues memory researchers people susceptible to flashbacks of stabilises the compacted forms. because of its contrasting impact highly stressful events, and lead to Vagnarelli P et al. Condensin and Repo-Man-PP1 on different types of memory, and new approaches to understanding co-operate in the regulation of chromosome opposite effects on different parts of and treating conditions such as architecture during mitosis. Nat Cell Biol the brain. Prolonged stress impairs stress-induced depression and 2006;8(10):1133–42. recollection of facts and events, by chronic anxiety. causing damage to the hippocampus. Mitra R et al. Stress duration modulates the By contrast, it greatly amplifies spatiotemporal patterns of spine formation in the emotional memories, by enhancing basolateral amygdala. Proc Natl Acad Sci USA 2005;102(26):9371–6. the wiring of neuronal circuitry in Vyas A et al. Prolonged behavioral stress the amygdala. enhances synaptic connectivity in the basolateral amygdala. Neuroscience 2006 [Epub ahead With collaborators in the USA, of print]. Dr Chattarji has begun to identify the Govindarajan A et al. Transgenic brain-derived biochemical and electrophysiological neurotrophic factor expression causes both changes in single neurons that affect anxiogenic and antidepressant effects. Proc the hippocampus and amygdala – Natl Acad Sci USA 2006;103(35):13208–13. and, through them, mouse behaviour. Raising levels of the signalling chemical brain-derived neurotrophic DEVELOPING PEOPLE 34

THE BILINGUAL CITATION BRAIN STARS A small area of the brain helps to control Wellcome Trust-funded scientists choice of language in bilingual people. are highly influential in malaria.

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The ability of bilingual people to responding just to the meaning of Thomson Scientific’s Essential read or hear a particular language, the words or were also sensitive to Science Indicators tracked more and respond using that language a change in language in which they than 14 500 authors in 134 alone, suggests some kind of were presented. countries to identify the most language-specific system in the Using functional imaging techniques, influential malaria researchers – brain. But the same areas of the the team detected one area that those whose work (published brain are active no matter what responded to both the switch in during 1995–2005) was cited most language someone is using. language and the meaning of the often by their peers. Wellcome Now, though, Wellcome Trust words – the head of the left caudate. Trust-funded researchers occupied Senior Research Fellow Professor Researchers think that this area could five of the top ten places in their Cathy Price and colleagues at be important in telling the brain which independent citation ‘league table’. the Institute of Neurology have language to respond in. The Wellcome Trust has historically identified an area of the brain that been a major supporter of research is active when a person switches Interestingly, bilingual people with in developing countries generally from one language to another. damage to this area of the brain are known to have problems switching and on malaria specifically. It has In the group’s study, 25 German– between languages. The team will established programmes in South-east English speakers and ten Japanese– now to try to piece together this Asia and sub-Saharan Africa, and has English speakers were shown pairs language-sensitive circuit in the brain identified and supported leading of words and told to ignore the first by examining individuals with damage individuals to drive their research one (the primer). The words were either in this and other brain areas. forward. This long-term commitment related (e.g. bathtub–SHOWER) or not to excellence is reflected in the malaria Crinion J et al. Language control in the bilingual (e.g. bathtub–SPOON). When the brain. Science 2006;312(5779):1537–40. research indicators. words were related, brain activity in Professor Kevin Marsh, Director of language areas was typically lowered, the KEMRI (Kenya Medical Research as the brain had been ‘primed’ to be Institute)–Wellcome Trust Research thinking about that subject. Programme in Kenya, made second Sometimes the related pairs were place. As well as leading the Research in the same language (e.g. trout– Programme, Professor Marsh has SALMON) and sometimes in different made major contributions to our languages (e.g. forelle–SALMON). understanding of the host immune The researchers could thus identify response to the malaria parasite. whether areas of the brain were

Images 1 An English–French 2 Professor Cathy Price. 4 Malaria studies in dictionary. 3 Professor Kevin Marsh. Kenya. DEVELOPING PEOPLE 35

NEW FUNDING

A selection of notable grants Principal Research Fellows awarded in 2005/06.

SENIOR RESEARCH FELLOWSHIPS GENETIC DISEASE Professor David Rubinsztein (University of Cambridge) Possible therapies for codon repeat diseases such as Huntington’s disease. METABOLISM Dr Alexander Gourine (University College London) Cardiorespiratory control: chemosensing and the role of brain plasticity. TROPICAL MEDICINE 4 Dr Alison Elliott (London School of Hygiene and Tropical Medicine) Helminth infection: effects on immunisation and disease in Ugandan children. In third spot was Professor Nick White, Four Principal Research NEUROSCIENCE Chairman of the Wellcome Trust’s Fellowships, the most senior Professor Michael Hausser (University College London) Understanding network South-east Asia Major Overseas of the Wellcome Trust’s personal dynamics and plasticity in the cerebellar Programme in Thailand and Vietnam. support schemes, were awarded cortex. Professor White has pioneered the use or renewed this year. Professor Angus Silver (University College of artemisinin combination treatments Professor Chris Fairburn, University London) The links between vesicle dynamics for malaria (see page 20). He was and synapse behaviour. of Oxford, has pioneered the use of recently awarded an OBE and made cognitive behavioural therapies for INTERNATIONAL SENIOR a Fellow of the Royal Society. RESEARCH FELLOWSHIP eating disorders. He is now attempting MOLECULAR MOTORS Professor Marsh’s colleague Professor to adapt a successful treatment for Dr Roop Mallik (Tata Institute of Bob Snow also made the top five. bulimia nervosa for use in other Fundamental Research, Mumbai, India) Professor Snow has carried out a eating disorders. Using optical trap technology to study series of landmark studies on global individual molecular motors. Professor Bob Snow (above), disease burden and risk of malaria RESEARCH CAREER who works at the KEMRI–Wellcome (see page 11 and right), and promoted DEVELOPMENT FELLOWSHIPS Trust Research Programme, will be the use of research findings to drive NEUROANATOMY taking forward his work on mapping Dr Heidi Johansen-Berg (University of policy making. malaria risk to predict its likely Oxford) Premotor networks in the human Two other Trust-funded researchers distribution in ten and 25 years’ brain: their anatomy, physiology and modulation in disease. Dr Johansen-Berg made the top ten: Professor François time. A complementary programme was formerly a Wellcome Trust Four-year Nosten, Director of the Shoklo Malaria of research will identify the best PhD Student and a Research Training Research Unit in Mae-Sot, Thailand, approaches for national malaria Fellow in Mathematical Biology. who has overseen some of the largest control programmes. BIOMEDICAL ETHICS FELLOWSHIPS drug trials ever undertaken in malaria; STEM CELL BANKING Infectious disease is also the focus and Professor Adrian Hill at the Dr Helen Busby (University of Nottingham) of Professor Alan Fairlamb’s Wellcome Trust Centre for Human Cord blood stem cell banking: ethical aspects research at the University of Dundee. of its commercial application. Genetics, University of Oxford, He is searching for weak points in who is developing and testing HISTORY OF MEDICINE the defences of trypanosome RESEARCH LEAVE AWARD malaria vaccines. parasites and developing drugs MILITARY MEDICINE targeted against them. Dr Mark Harrison (University of Oxford) British military medicine in the First World At the Wellcome Trust Centre for War. Dr Harrison’s last book was the award- Cell Biology, University of Edinburgh, wining Medicine and Victory: British military Professor David Tollervey is studying medicine in World War Two. the function of two large multiprotein Details of all grants made can be found in cellular structures, the exosome and Grants Awarded 2005/06, available on the the ribosome. Wellcome Trust website. FACILITATING RESEARCH Promoting the best conditions for research and the use of knowledge. FACILITATING RESARCH 37

ALL SYSTEMS RIGHT ARE GO HOOKE After a successful pilot study, UK Biobank The Royal Society has regained got the green light to roll out nationally. Robert Hooke’s notebook.

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UK Biobank will gather, store and An independent review panel judged Study of the past relies heavily protect the world’s largest bank proposals for UK Biobank to be on historical documents. This of blood and DNA samples, and excellent, praising its planning and means ensuring that important health information, collected from handling of potential ethical problems, documents and other materials 500 000 volunteers in the UK aged as well as its ability to recruit enough are in repositories where they between 40 and 69. People in this volunteers and assess them can easily be accessed and are age group are at risk of developing extensively within budget. As a protected for future generations. a wide range of fatal and disabling result, in August 2006, the funders Wellcome Trust funding helps to illnesses such as heart disease, announced that the study will be achieve both these aims. diabetes, cancer, mental illness rolled out nationally. Robert Hooke is a neglected figure and joint diseases. By following Over the next four years, UK Biobank in science history – partly because this group over many years, UK will start recruiting 500 000 adults – of a feud with Isaac Newton, who Biobank will provide researchers nearly 1 per cent of the UK population downplayed his achievements. But with a unique resource for studying – who will attend one of a network of Hooke did become secretary of the the roles of genes, lifestyle and 35 assessment centres across the UK, Royal Society. environment in disease. each open for about six months. Strangely, his records of Royal Society To test procedures, a three-month www.ukbiobank.ac.uk meetings went missing – but turned pilot study was held from March to • The £61 million UK Biobank project is funded up this year, having lain in a dusty May 2006 in the Altrincham district by the Wellcome Trust, the Medical Research Hampshire attic for half a century. of Manchester. Some 3800 men and Council, the Department of Health, the Donations from the Wellcome Trust women were recruited in the pilot Scottish Executive and the North West Regional Development Agency. and others enabled the Royal Society phase. They each spent about 90 to buy the manuscript. minutes at an assessment centre, answering questions about their health The donation to the Royal Society and lifestyles, and giving blood and was a one-off, in recognition of the urine samples. All agreed to allow their huge importance of the material to health to be followed by UK Biobank the nation’s scientific heritage. The for many years, through routine medical ongoing Research Resources in and other health-related records. Medical History scheme helps to preserve and open up key resources. Some 90 projects have been funded to date, covering material such as the archives of Broadmoor Hospital, the papers of R D Laing and César Milstein, and records at Great Images Ormond Street Hospital. 1 Taking blood during 2 Stored biological the pilot phase of samples. UK Biobank. 3 Robert Hooke’s notebook. FACILITATING RESEARCH 38

BRED FOR BUILDING SUCCESS SIGHTS When it comes to modelling human biology, the mouse remains the organism Several new biomedical research of choice. A host of shared resources is accelerating mouse research. facilities opened in 2005/06.

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The sequencing and annotation Meanwhile, the Sanger Institute The Joint Infrastructure Fund of the mouse genome, by the continues to develop its mouse (JIF) and the Science Research Wellcome Trust Sanger Institute resources. Mouse sequence data, Investment Fund (SRIF), run and others, created a powerful extensively annotated, are available in partnership with the UK resource for researchers exploring through the Ensembl Mouse website Government between 1998 mouse biology. Now new biological (www.ensembl.org/Mus_musculus). and 2003, saw substantial sums tools and the results of genetic Biological tools include MICER and invested in the UK research experiments are offering even ‘gene-trap’ resources, which provide infrastructure. Recently, several more help to mouse researchers. the means to generate genetically facilities funded through these altered mice. schemes have opened. A major challenge in biomedical research is to disentangle the The Sanger Institute has also been JIF and SRIF funding was restricted effects of multiple genes on complex awarded major funding from the US to the UK, but the Wellcome Trust biological traits, including common National Institutes of Health and the has also funded facilities outside the diseases. Mice have similar biology to EU to generate a resource of mouse UK to support research at its Major humans but can be bred and analysed knockouts of 13 500 genes, as part Overseas Programmes. This year in ways impossible in humans. of two international collaborations saw the opening of new labs at (KOMP and EUCOMM) aiming to Professor Jonathan Flint, Dr Richard Kilifi General Hospital, Kenya, mutate 95 per cent of mouse genes Mott and colleagues at the Wellcome housing research carried out at the by 2011. As many as 2500 of these Trust Centre for Human Genetics in KEMRI–Wellcome Trust Research will be converted into mice to examine Oxford have been carrying out Programme (see pages 11 and 18). the role of single genes. All of these genome-wide analyses of complex In the UK, the excellent science resources will be available to the traits in genetically mixed mice (as base in Scotland has been reflected scientific community. opposed to the ‘pure’ inbred strains in a range of infrastructure awards. usually used). As well as shedding Valdar W et al. Genome-wide genetic association This year saw the opening of the of complex traits in heterogeneous stock mice. light on the environmental and genetic Nat Genet 2006;38(8):879–87. Sir Graeme Davies Biomedical influences on these traits, the results Valdar W et al. Genetic and environmental Research Building, to which the Trust are also being made freely available effects on complex traits in mice. Genetics contributed £8 million. The building on the web for researchers to explore 2006;174(2):959–84. will house the Glasgow Biomedical particular traits in more detail (see Cunningham F et al. TranscriptSNPView: Research Centre. In Edinburgh, the a genome-wide catalog of mouse coding http://gscan.well.ox.ac.uk). The variation. Nat Genet 2006;38(8):853. Ashworth Building Extension, funded methods also illustrate the potential in part by a £4.7m grant from the for high-throughput genetic analysis Trust, was opened in November 2005. in mice.

Images 1 Labs at the Wellcome 3 New laboratories at Trust Sanger Institute. Kilifi, Kenya. 2 Data storage at the Sanger Institute. FACILITATING RESARCH 39

NEW FUNDING

A selection of notable grants Clinical research facilities awarded in 2005/06.

RESOURCES DEVELOPMENTAL BIOLOGY Dr Mathew Guille (University of Portsmouth) Xenopus Stock Centre: a central repository storing and distributing genetically modified Xenopus. Professor So Iwata (Imperial College London) Establishing a membrane protein laboratory at the Diamond synchrotron. EQUIPMENT 3 DEVELOPMENTAL BIOLOGY Dr Stephen Wilson (University College London) New aquarium and other equipment for the UCL zebrafish facility. London saw several new and Some £84 million has been BONE AND JOINT DISEASE refurbished facilities opened, including committed by ten UK funding Professor Stuart Ralston (University of Edinburgh) A variety of equipment for the University College London Centre agencies to strengthen and extend analysing animal models of human bone for Auditory Research (£9m grant), the the UK’s Clinical Research Facility and joint disease. Department of Medical and Molecular (CRF) network. The initiative is MASS SPECTROMETRY Genetics at Guy’s Hospital campus founded on the success of the Dr Kevin Brindle (University of Cambridge) (£6.4m) and the Department of first five CRFs, funded by the A 500 MHz NMR spectrometer for high- Optometry and Visual Science, Wellcome Trust. throughput metabolomics to examine City University (£1.5m). multifactorial diseases in animal models. CRFs provide sites for patient-oriented Dr Catherine H Botting (University of St Some 78 buildings in 29 institutions research in a hospital setting. Andrews) A MALDI-TOF mass spectrometer received JIF/SRIF funding from the Specialised facilities and staff make and associated equipment to support several Trust, whose total investment CRFs ideal sites for research on groups studying infectious diseases. exceeded £500m. The University people, and they act as local beacons CRYO-EM of Sheffield received several awards, of good clinical research practice. Professor Helen R Saibil (Birkbeck College) including funding for the Wellcome Cryo-electron microscopy equipment to With Wellcome Trust support, Trust and the Wolfson Foundation determine the structure of various large CRFs have been established in assemblies within the cell. Facility for Molecular Life Sciences Birmingham, Cambridge, Edinburgh, (£16.3m from the Trust), which CONFOCAL AND OTHER IMAGING Manchester and Southampton. In an Dr Andrew M Fry (University of Leicester) opened in November 2005. unprecedented joint venture, ten UK Dr Craig A McArdle (University of Bristol) The University of Cambridge was also funding agencies joined forces to fund Dr Eric C Schirmer (University of Edinburgh) successful with several applications, Dr Helen le Breton Skaer (University of eight new bench-to-bedside initiatives Cambridge) and opened its – in London (Imperial College, King’s Building, housing the Leverhulme RESEARCH RESOURCES College London, the Institute of IN MEDICAL HISTORY Centre for Human Evolutionary Studies Cancer Research and University ARCHIVES (and 18 000 skeletons), in 2006. College London), Oxford, Belfast Dr Knight (Royal College of Surgeons of and Newcastle in the UK, and Dublin England) Conservation of the College’s Following these substantial cash manuscripts and archives. injections, the Trust does not routinely in the Republic of Ireland. Peter Harper (National Cataloguing Unit for support new building projects. Clearly, Four existing CRFs will also receive the Archives of Contemporary Scientists) though, facilities are important to the support for further development. The Cataloguing the medical physics papers of research enterprise and requests for final sums to be awarded to each Sir Joseph Rotblat FRS. such support will be considered under centre are currently being negotiated. exceptional circumstances. • The competition was managed by the Details of all grants made can be found in Wellcome Trust on behalf of the UK Clinical Grants Awarded 2005/06, available on the Research Collaboration. Funders included Wellcome Trust website. the Wolfson Foundation, the Medical Research Council, the British Heart Foundation, Cancer Research UK and various health departments. DEVELOPING OUR ORGANISATION Using our resources efficiently and effectively.

BOND ISSUE GRANTS ONLINE FINANCIAL PLANNING An innovative bond issue has An upgraded version of the Good financial management has enhanced the Wellcome Trust’s Wellcome Trust’s ‘eGrants’ online enabled the Wellcome Trust to investment portfolio. grants application system has increase its spending projections. been launched – and an enhanced The Wellcome Trust derives the vast The Wellcome Trust’s expenditure successor is in the pipeline. majority of its income from a diverse is linked to the size of its investment portfolio of investments, valued at A review of the eGrants system base. It has a long-term target rate of £13.9 billion (as at 30 September in 2005/06 revealed high levels return for its investments of 6 per cent 2006). An innovative bond issue of satisfaction – 93 per cent of a year in real terms, and aims to launched in 2006 will add to the respondents declared themselves distribute, on average, about 4 per cent Wellcome Trust’s funding power ‘very satisfied’ or ‘fairly satisfied’. of its assets each year. To smooth over the coming years. Some 79 per cent preferred the annual fluctuations, expenditure is In effect, the Wellcome Trust is using eGrants approach to Word templates. based on a weighted rolling average the bond to borrow money from other Useful feedback was obtained from spanning several years. With its financial institutions. It undertakes to respondents, and several new features investments performing strongly, it has pay a fixed amount of interest to the were introduced as a result. been able to increase significantly the lender over the period of the bond Meanwhile, development work began funding it plans to make available over and reinvests the sums borrowed. on an ambitious new web-based the next five years. As the interest rate is relatively low, system that will handle not just the Charitable expenditure in 2005/06 was investment returns should comfortably grant application process but also £484 million. The total expenditure exceed the interest paid. refereeing and ongoing management budget available for 2006/07 has been Because of the Trust’s strong financial of awarded grants. increased to £540m. Levels of funding basis and long-term perspective it is This new system will provide are anticipated to increase in future judged to be a low-risk option for convenient online access for years, dependent on continuing good investors. The Trust received the grant applicants, grantholders and performance of the investment portfolio. highest possible bond credit ratings, referees, helping to streamline both The additional funds will be used to Aaa from Moody’s and AAA from the application and review process support major new initiatives, and are Standard & Poor’s. and the financial management of unlikely to impact on funding rates for The bond issue proved highly popular, grants. It is due to launch in late 2007. existing grant schemes. enabling the Trust to increase the Communication with grantholders value of the bonds issued to £550m. and potential grantholders remains a high priority. A revised version of the Wellcome News newsletter has been launched and a periodic e-bulletin introduced for grantholders. These and other methods will be used to keep the research community up to date with the status of the new grants system. OVERVIEW 41

WELLCOME TRUST 2005/06 A brief overview of corporate activities over the year.

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Governors and senior staff Manchester and the European The Trust and the MRC have jointly Sir William (‘Bill’) Castell took over Bioinformatics Institute. UKPMC published an informational booklet as Chairman of the Wellcome Trust’s will provide free online access to the on non-human primate use. Board of Governors in May 2006, digital archive of published articles Buildings succeeding Sir Dominic Cadbury, resulting from research paid for by New research facilities at the Wellcome who retired from the Board. Bill was any of the funding consortium. Trust Genome Campus, Cambridge, formerly President and CEO of GE The Trust also reached agreement were opened by HRH The Princess Healthcare, the medical diagnostics with a range of science publishers, Royal in October 2005. and biosciences business of the ensuring that material can be Significant work was undertaken General Electric Company of the USA, deposited in UKPMC by authors during the year to convert the and also a Vice-Chairman at General according to the Trust’s Grant Wellcome Building, the Trust’s former Electric. Before that, he was Chief Conditions without infringing headquarters, into a public space. Executive of Amersham plc. He publishers’ copyright. has a wealth of experience in global The venue, to be known as Wellcome healthcare and has also been involved Several submissions to Government Collection, is due to open in 2007 and in many not-for-profit activities. consultations were made during will house a range of permanent and the year, including responses to the temporary exhibitions, a forum space, Professor Sir Leszek Borysiewicz, Department for Education and Skills’s a Conference Centre, a bookshop Deputy Rector of Imperial College consultation on the reform of higher and café, as well as the Wellcome London and an expert in education research assessment Library and researchers from the and viral infections, joined the Board and funding, and to the Department Wellcome Trust Centre for the History of Governors in January 2006. of Health’s consultation on the of Medicine at UCL. In January 2006, Susannah Randall regulations to be made under the The Trust’s current headquarters, was appointed the Trust’s Head of Mental Capacity Act 2005. The Trust the Gibbs Building, 215 Euston Communications. also contributed to the Cooksey Road, London, was again a major Review, which has been considering Contributions to policy-making attraction during Open House the nature of the UK’s unified health The Trust continued to play an active weekend in September 2006. Its research fund. role in the drive towards open access eclectic window displays are a talking models of science publishing. A nine- With the Academy of Medical point for passers-by, while guided strong group of UK research funders, Sciences, the Royal Society and tours are given for visitors keen to including the Trust, awarded a the Medical Research Council (MRC), see Thomas Heatherwick’s sculpture contract to run UK PubMed Central the Trust supported an in-depth study, ‘Bleigiessen’, a 30-metre installation (UKPMC) to a partnership of the by an independent committee chaired composed of 150 000 specially British Library, the University of by Sir David Weatherall, on the use processed glass spheres. of non-human primates in research. Images 1 The new Chairman. 3 Sanger Institute 2 Thomas Heatherwick buildings. Studio’s ‘Bleigiessen’. FINANCIAL SUMMARY 2005/06 42

FINANCIAL SUMMARY 2005/06 In the year ending 30 September 2006, the Wellcome Trust’s total charitable expenditure was £484.1m.

Total charitable expenditure, BREAKDOWN OF WELLCOME TRUST £484.1 million, was broadly in line CHARITABLE EXPENDITURE 2005/06 with 2004/05’s figure (£485.9m). Grants expenditure dipped slightly, while support for direct activities rose by a small amount, reflecting additional work at the Wellcome Trust Sanger Total:£484.1m Institute and preparation for the GRANTS opening of the new public venue, £324.7M Wellcome Collection, in 2007. Support costs increased slightly, principally due DIRECT ACTIVITIES £119.3M to planned expansion at the Sanger Institute, which now employs more SUPPORT COSTS than 800 people. £40.1M Careers support Total expenditure on careers support across all funding areas amounted to £100m in 2005/06, an increase on last GRANTS: £324.7M year’s figure (£92m). The bulk of this Competitive grant schemes are support is for Principal, Senior and run in the Wellcome Trust’s areas intermediate-level fellowships, along of interest: biomedical science; Biomedical science with Four-year PhD Programmes and Technology Transfer; and Medicine, £295.7m Research Training Fellowships for Society and History (history of Technology Transfer £13m medically qualified researchers. medicine, biomedical ethics and Medicine, Society public engagement with science). and History International support £16m Some £26.3m was awarded directly to researchers at overseas institutions. A further £46.2m was awarded to DIRECT ACTIVITIES: £119.3M researchers at UK locations for Direct activities are those managed research overseas. Most international Biomedical science by the Wellcome Trust itself or in support is targeted at developing and £9.5m partnership with others. These include: Technology Transfer restructuring countries. The total figure £4.2m of £72.5m includes some funding in • Wellcome Trust Genome Campus Genome Campus developed countries, such as the (including Sanger Institute) £83.8m Medicine, Society Structural Genomics Consortium, • and History which carries out research in Canada. £21.8m • Directly managed public Infrastructure engagement activities Awards for buildings, refurbishment and • Scientific conferences. equipment amounted to £15.7m. This figure does not include infrastructure costs awarded as part of project, SUPPORT COSTS: £40.1M programme or fellowship grants. Support costs include expenditure Biomedical science required to run the Wellcome £18.9m Trust and Genome Campus. Technology Transfer £2.5m These include costs associated with Genome Campus administering grants and the wide £8.9m range of other activities carried out Medicine, Society and History by the Trust. £9.8m

The expenditure values used here are audited figures taken from the Wellcome Trust’s Annual Report and Financial Statements, which include a detailed breakdown of the Trust’s expenditure and investments during the year. The Annual Report is available at www.wellcome.ac.uk. FINANCIAL SUMMARY 2005/06 43

FUNDING HIGHLIGHTS INVESTMENTS 2005/06 £19.4m £4.1m The value of the Trust’s investment Rollout of UK Biobank. Ensembl genome browser portfolio ended the year at £13.9 billion. This figure included £18.4m (European Informatics £539m raised through the bond New and renewed Principal Institute). issue (see page 40). The net value Research Fellowships. £4.0m of £13.4bn represents an increase of £1.1bn on last year. £16m Cambridge Institute for Medical Research core The Trust maintains a diversified portfolio Phase 2 Structural Genomics of investments, encompassing equities Consortium funding. support. (stocks and shares) in UK and other markets, cash and bonds, venture £7.0m £3.3m Renewal of core support for capital investments, and property Wellcome Trust Centre investments. All sectors performed well for Stem Cell Research, Wellcome Trust Centre for during the year, particularly private equity, University of Cambridge. Cell Biology, University of with buyout funds benefiting from strong Edinburgh. market conditions. In property, the South £6.7m Kensington estate made significant gains Wellcome Trust Centre for £3.0m on the back of strong demand for Neuroimaging at UCL. Renewal of core support premium properties in London. for Karonga Prevention The Trust took advantage of equity £6.4m Study, Malawi. market strength in the first half of the Malaria drug discovery year to sell £1bn of equities, which programme at the Novartis £1.5m was used to fund increased investment Institute for Tropical Diseases. Generation Genome in hedge funds and active currency touring exhibition. strategies. This should serve to enhance returns and to diversify risk further. The Trust also instigated a passive currency hedging strategy at the start of 2006, which helped to mitigate the impact of the strongest year for sterling since 1990.

Grants awarded 2002–06 (£m) Grant liabilities 2002–06 (£m) Market value of total portfolio at 30 September (£bn)

1185 1168 15.0 500 1200 15 13.9

419 1035 1023 1017 12.3 395 1000 11.7 12.1 400 12

344 10.4 10.5 10.2 10.1 325 800 9.3 300 9 258 600

200 6 400

100 3 200

0 0 0 2002 2003 2004 2005 2006 2002 2003 2004 2005 2006 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 FUNDING DEVELOPMENTS 2005/06 44

FUNDING DEVELOPMENTS 2005/06 An overview of strategy development, new initiatives, significant changes to funding policies, and an analysis of the year’s funding.

The Wellcome Trust’s funding is STRATEGIC AWARD PRIORITY AREAS based around funding streams, covering core areas of biomedical The following areas were identified by Strategy Committees as priorities science and the medical for Strategic Award applications: humanities. Cutting across these • mathematical biology/statistical methods – training and capacity building streams are funding programmes in Technology Transfer and Public • public health research – training and capacity building Engagement (see below). • ‘in vivo’ physiology – training and capacity building Each funding stream has associated • neuroimaging – interdisciplinary networks/programmes with it one or more Funding • emerging diseases – interdisciplinary networks/programmes Committees, responsible for most • promotion of interactions at the clinical–basic science interface. funding decisions, and a Strategy Committee, which advises the Trust on the needs and opportunities within PRIORITY AREAS STRATEGY DEVELOPMENT its area of interest. Mathematical biology/statistical At its annual strategy meeting in June The funding streams offer a variety methods: all the Strategy Committees 2006, the Board of Governors outlined of forms of support, such as project highlighted the need to build expertise ‘vision statements’ for the future. and programme grants, and career in statistics, study design, data More focus on the best people development awards. analysis and mathematical biology. While support has always been Technology Transfer funding comprises The Populations and Public Health focused on individuals with the best Translation Awards and Strategic Strategy Committee identified a need ideas, there will be a greater emphasis to address training of and interactions Translation Awards. A special initiative, on identifying the most successful between clinicians, basic scientists Strategic Translation Awards in Drug researchers, or those with the greatest and practitioners in public health Discovery, was launched in 2005. potential, and encouraging them to research. Public Engagement is supported come up with bold applications for The Physiological Sciences Strategy support. primarily through the Engaging Committee expressed concern Science programme, which includes about a potential skills gap in Larger, longer, braver awards Society Awards and People Awards. in vivo research. Huge medical challenges remain. Occasional large Capital Awards are To take full advantage of the UK’s At the same time, new technological made to support nationally or strengths in neuroimaging, the opportunities are emerging. To achieve internationally important developments. Strategy Committee more in the future, ambitious plans are Strategic Awards and some identified a need for increased needed, which may call for imaginative other large or unusual awards are networking between major imaging funding solutions. considered by a Strategic Awards centres, and interdisciplinary An enhanced international funding Committee, comprising Governors, programmes involving mathematicians, and advocacy profile senior staff and other representatives, physicists and engineers. The priority will be to build upon on a one-off basis. The Immunology and Infectious the Major Overseas Programmes, Disease Strategy Committee saw in the context of the new international research into rapid, accurate diagnosis and response to emerging strategy (see right). The potential for diseases as crucial. Networks of an increased presence in India and Immunology and in continental Europe will also be Infectious Disease epidemiologists, molecular biologists, clinicians and veterinarians, and linking explored. Populations and Public Health surveillance data with research, are Reputation as a trusted and a priority. Neuroscience and important partner of choice Mental Health Several Strategy Committees Highly successful partnerships Physiological highlighted the need for more have been forged with governments, Sciences interactions between basic and other funding agencies and charities. Molecules, clinical science. Genes and Cells Possible collaboration in areas such as clinical research, public health Medical Humanities and interdisciplinary research will be explored. Wellcome Trust funding streams. FUNDING DEVELOPMENTS 2005/06 45

STRATEGIC INITIATIVES FUNDING ANALYSIS

Funding opportunities Funding policies Total no. of grant applications: 2666 Following strategic reviews, funding Significant changes to funding policy Total no. of grants awarded: 790 opportunities were overhauled, or new were implemented in the following areas: Value of applications considered: £923.6m or revised schemes were launched, in • eligibility (UK and Europe) the following areas: Value of grants awarded: £333.9m • international eligibility No. of programme grants awarded: 64 • careers support • open access publication. No. of PRFs awarded/renewed1: 8 • global health research No. of SRFs awarded/renewed: 27 • drug discovery research. No. of intermediate fellowships awarded: 63 No. of training (junior) fellowships awarded: 26 No. of PhD studentships supported: 133 CAREERS SUPPORT Technology Transfer funding will also FUNDING RATES The suite of Wellcome Trust personal be available to tackle neglected By no. By amount support schemes was overhauled diseases. Funding is also provided for Project grants 24% 22% during the year. A significant research into the ethical issues raised introduction was the Sir Henry by studies in developing countries, Programme grants 41% 43% Wellcome Postdoctoral Fellowship and the potential for more international New PRF (full app.) 40% 45% scheme, with awards worth £250 000 public engagement is being explored. SRF (full app. basic) 11% 10% over four years, providing fellows with SRF (full app. clinical) 17% 16% unprecedented freedom early in their DRUG DISCOVERY RESEARCH SRF (full app. tropical) 60% 60% career to pursue their own research. A Technology Transfer initiative, Seeding Drug Discovery, was SRF (full app. international) 11% 11% Among other innovations, Research launched in October 2005. It provides Intermediate fellows 19% 19% Career Development Fellowships were funding for the early stages of drug Training (junior) fellows 14% 16% extended to five years and discovery, which struggle to attract competitions were launched for new funding for commercial development. Biomedical Ethics 50% 27% Four-year PhD Programmes and The £91 million, five-year initiative is History of Medicine 46% 29% Clinical Research Training open to researchers at public or Programmes. Finally, new Flexible private institutions, including Livestock for Life 19% 18% Travel Awards will support commercial companies, in the Research Resources in collaboration-building and skills UK and the Republic of Ireland. the History of Medicine 62% 41% transfer, through sabbaticals and Small public engagement travelling fellowships. FUNDING POLICIES awards (< £30 000) 19% 26% Eligibility rules for researchers in the GLOBAL HEALTH RESEARCH Large public engagement UK were relaxed during the year, awards (> £30 000) 9% 10% The Wellcome Trust’s new global enabling scientists employed at health research strategy builds on its Research Council units or charity- long-standing commitment to research Total no. of institutions funded institutions to apply for receiving funding in 2005/06 (UK): 84 in developing countries. funding. Internationally, current or Total no. of institutions receiving The Trust plans to increase its past International Senior Research funding in 2005/06 (non-UK): 74 support in this area, building on Fellows, or other overseas researchers 2 the Major Overseas Programmes in receipt of major Trust grants, can ONGOING LIABILITIES Total grants liabilities: £1.017bn in South-east Asia and Africa. The now apply for support through most priority will be to identify key people funding schemes. No. of countries receiving funding: 54 Fellows currently supported: 825 to take forward research in high- As part of the Trust’s drive to promote quality and supportive environments, open access publishing, submission Researchers currently supported: 3493 tackling important local medical of published papers to repositories Total no. of institutions receiving issues. Capacity-strengthening and such as PubMed Central was made funding (UK): 92 putting research into practice will be mandatory during the year. Initially, Total no. of institutions receiving central to future activities. this grant condition applied to newly funding (non-UK): 123 awarded grants. From 1 October 1 Includes PRF programme grant renewals. 2 2006, it has applied to all grants. As at 30 September 2006. PRF: Principal Research Fellowship SRF: Senior Research Fellowship STREAMS FUNDING 2005/06 46

STREAMS FUNDING 2005/06 1 October 2005 to 30 September 2006.

IMMUNOLOGY AND Total number of grants awarded 115 INFECTIOUS DISEASE Total value of grants awarded £54m The Immunology and Infectious Number of programme grants awarded Disease stream supports research 13 that will further our knowledge Value of programme grants awarded £14m and understanding of the infectious organisms that cause disease in MAJOR PERSONAL SUPPORT AWARDS humans and animals, and of the • 2 renewal Principal Research Fellowships immune systems that fight these • 2 renewal Senior Research Fellowships in Clinical Science • 3 new (and 1 renewal) Senior Research Fellowships in Basic Biomedical Science organisms. OTHER NON-FUNDING/INTERVIEW COMMITTEE ACTIVITIES DURING YEAR • £0.7m to establish a consortium to sequence genomes of influenza strains • Frontiers Meeting on ‘Emerging Zoonotic Infections: Integrating research, diagnosis and surveillance’ • Vaccinology Frontiers Meeting on ‘Bringing Industry and Academia Together for the Next Generation of Vaccines’

POPULATIONS AND Total number of grants awarded 50 PUBLIC HEALTH Total value of grants awarded £19m The Populations and Public Number of programme grants awarded Health stream supports research 5 to improve understanding of the Value of programme grants awarded £7m determinants of disease and quality of life in populations, and MAJOR PERSONAL SUPPORT AWARDS to provide a sound evidence base • 1 new Principal Research Fellowship to inform decisions in public health • 1 new Senior Research Fellowship in Basic Biomedical Science and healthcare delivery. OTHER NON-FUNDING/INTERVIEW COMMITTEE ACTIVITIES DURING YEAR • £19.4m for UK Biobank project • £3.0m core funding for the Karonga Prevention Study in Malawi (focusing on HIV and antiretroviral therapy roll-out with population-based epidemiological and demographic studies) • Joint meeting with the European Commission: ‘From Biobanks to ’

NEUROSCIENCE AND Total number of grants awarded 85 MENTAL HEALTH Total value of grants awarded £40m The Neuroscience and Mental Number of programme grants awarded Health stream supports high-quality 7 research into the function of the Value of programme grants awarded £8m nervous system in health and disease. MAJOR PERSONAL SUPPORT AWARDS • 1 renewal Principal Research Fellowship • 2 renewal Senior Research Fellowships in Clinical Science • 2 renewal Senior Research Fellowships in Basic Biomedical Science OTHER NON-FUNDING/INTERVIEW COMMITTEE ACTIVITIES DURING YEAR • £6.7m Strategic Award for core support for Wellcome Trust Centre for Neuroimaging at University College London • Pilot scheme supporting Masterclasses in Clinical Neuroscience to catalyse collaboration between basic and clinical neuroscientists STREAMS FUNDING 2005/06 47

PHYSIOLOGICAL Total number of grants awarded 66 SCIENCES Total value of grants awarded £23m The Physiological Sciences Number of programme grants awarded stream supports high-quality 5 basic and clinical research relevant Value of programme grants awarded £6m to the understanding of biological processes at the cell, organ, MAJOR PERSONAL SUPPORT AWARDS system and whole-animal levels • 1 new Senior Research Fellowship in Clinical Science in health and disease. • 1 new Senior Research Fellowship in Basic Biomedical Science

MOLECULES, GENES Total number of grants awarded 102 AND CELLS Total value of grants awarded £72m The Molecules, Genes and Cells Number of programme grants awarded stream supports high-quality 15 research that will further our Value of programme grants awarded £24m understanding of the fundamental biology and specialist functions MAJOR PERSONAL SUPPORT AWARDS of molecular, cellular and genetic • 1 new (and 3 renewal) Principal Research Fellowships processes, and their role in health • 4 renewal Senior Research Fellowships in Basic Biomedical Science • 4 new International Senior Research Fellowships and disease. OTHER NON-FUNDING/INTERVIEW COMMITTEE ACTIVITIES DURING YEAR • £7.0m Strategic Award to establish Wellcome Trust Centre for Stem Cell Research • £4.0m Strategic Award for renewal of core support to Cambridge Institute for Medical Research (and to establish two new training programmes at the interface between clinical and basic research) • £3.3m renewal of core support for Wellcome Trust Centre for Cell Biology, University of Edinburgh • £16m for phase 2 funding of Structural Genomics Consortium (conditional on additional funding being secured)

MEDICAL HUMANITIES Total number of grants awarded 171 The Medical Humanities stream Total value of grants awarded £8m aims to enhance understanding of Number of programme grants awarded the historical and social context of 0 medicine and biomedical science. Value of programme grants awarded – It supports research in history of medicine and biomedical ethics, MAJOR PERSONAL SUPPORT AWARDS and encourages use of findings, • History of Medicine Strategic Award to for example to inform public • History of Medicine: 2 University Awards • Biomedical Ethics: 1 University Award policy making. OTHER MAJOR AWARDS • First University Award in Biomedical Ethics • £1.2m award for core support of Nuffield Council on Bioethics OTHER ACTIVITIES DURING THE YEAR • Biomedical Ethics Summer School, September 2006 • ‘Practices and Representations of Health’ conference at Warwick University, June 2006 TECHNOLOGY TRANSFER 48

TECHNOLOGY TRANSFER Technology Transfer at the Wellcome Trust seeks to maximise the impact of research innovations on health by facilitating the development of early- stage technologies to a point at which they can be further developed by the market.

The major award of the year was the £6.4 million grant to Professor Alex Matter at the Novartis Institute for Tropical Diseases in Singapore, for a programme of drug discovery research in malaria. This complements last year’s £8.1m award to Professor Michael Ferguson and colleagues, who are establishing a neglected disease drug discovery programme at the University of Dundee. With the £91m Seeding Drug Discovery Initiative launched in 2005, the Trust has developed a range of ways of supporting the early stages of drug development in tropical and other diseases.

Technology Transfer funding One award was made to support treatment for falciparum malaria and concentrates on projects that are workshops on intellectual property a new therapeutic option for vivax too early either to attract venture in sub-Saharan Africa. Additional malaria. Promising compounds will capital or to be seen by industry as workshops were supported on be channelled into the Medicines credible in-licensing opportunities. vaccine research, including a frontier for Malaria Venture for further Two forms of translational research meeting to facilitate greater integration development. support are available: Translation between industry and academia. The Seeding Drug Discovery Awards and Strategic Translation Strategic Translation Awards initiative, launched in November Awards. support translational research in areas 2005, received 86 applications for Translation Awards are a response- of key importance to the Wellcome funding, of which eight were taken to mode form of support, used to Trust. Nine applications have been the final application stage. Shortlisted support a diverse array of considered to date, in diagnostics, applicants from academic institutions technologies from the physical vaccination, regenerative medicine, were awarded small grants to engage sciences and mathematics as genotyping technology and drug industry experts to advise on project well as biology. They are open discovery. The mean value of awards design and outsourcing options. The to academic institutions and has been £3 million (ranging from first awards will be made in financial early-stage companies. £1.1m to £8.1m). New awards were year 2006/07. Based on the quality of made to: Professor Paul Sharpe for the first wave of applications, Seeding In the third full year of funding, work on the development of natural Drug Discovery has been rolled out as 44 applications were received from replacement teeth using stem cell a five-year initiative with a grants 29 institutions; 20 per cent were technology; Dr Helen McShane for budget of £91m. awarded. The mean value of awards work on a new tuberculosis vaccine has been £445 545 (ranging from Several projects supported through (see page 18); and Professors Richard £74 000 to £1 022 854). The average Technology Transfer funding have Marais and Caroline Springer for time from application to decision is made encouraging progress (see research into the discovery of drug-like around three to four months. page 22). In addition, several small inhibitors of BRAF kinase for the companies that received support The projects address a wide range treatment of malignant melanoma. during early validation of their of potential applications, including An award of £6.4m was made to technology have raised further funds. therapeutics, vaccines, diagnostics Professor Alex Matter at the Novartis These include: the University of Leeds and medical devices. Others are in Institute for Tropical Diseases in spin-out, Syntopix Ltd, which floated support of new platform technologies, Singapore for drug discovery research on the Alternative Investments Market such as: fragment-based into malaria. The research consortium (AIM); Paradigm Therapeutics Ltd, with a focus on protein–protein includes investigators from across which successfully completed a fourth interactions; T-cell therapy for the Novartis Foundation institutes, professional funding raising round; immunodepressed patients; ultrasonic together with the Swiss Tropical Celltran Ltd, which raised further elasticity imaging for tumour detection; Institute and the Biomedical Primate finances to extend its business and pheromone-baited traps for vector Research Centre. The five-year operations; and CardioDigital Ltd, control in visceral leishmaniasis. programme aims to discover which received the first down-payment compounds for use in a single-dose on a future investment round. WELLCOME TRUST GENOME CAMPUS 49

WELLCOME TRUST GENOME CAMPUS The Wellcome Trust Genome Campus at Hinxton, near Cambridge, is home to the Wellcome Trust Sanger Institute, the Wellcome Trust Conference Centre and Wellcome Trust Advanced Courses.

The official opening of the new laboratory space for the Wellcome Trust Sanger Institute in October 2005 symbolised its shift into new scientific territories. It is now a centre driven by the need to understand biological function, underpinned by unique high-throughput sequencing and genetic manipulation techniques. Other parts of the Genome Campus continue to develop their programmes of activities, and building work began on the £8.6 million extension to the European Bioinformatics Institute.

Wellcome Trust Sanger Institute 2006. Study of human genetic variation Extra courses are planned for The Sanger Institute passed three was enriched by the completion of the 2006/07, both at the Genome major milestones in 2005/06: in first phase of the International HapMap Campus and overseas, starting with October 2005, the extension to the Project, in which the Sanger Institute a workshop at the KEMRI– was opened by was a major participant. It has also led Trust Research Programme in Kenya HRH The Princess Royal; in December efforts to map copy number variation in December 2006. 2005, the Wellcome Trust announced (see page 7). Wellcome Trust Conference Centre the award of £340 million funding for In pathogen research, significant and Meetings Programme 2006–11; and, in September 2006, results include the genome sequences A total of 14 scientific meetings were the Sanger Institute proposed a new of Clostridium difficile and the held as part of the Wellcome Trust strategic focus on natural and capsule genes of the pneumococcus Meetings Programme at Hinxton this experimental genetics. bacterium, both current issues for year. These included two meetings The Genome Campus extension healthcare. The Sanger Institute is held jointly with University of California includes new laboratory space for also involved in a project analysing the San Diego and Cell, several in 140 staff, accommodation for model spread of influenza virus (see page 14). partnership with Cold Spring Harbor organisms and a Data Centre housing The Sanger Institute produces more Laboratory, and a conference on some of the UK’s most powerful DNA sequence than at any time in vaccine adjuvants held jointly with computers. These new facilities its history, but its outputs are now the World Health Organization and underpin a major drive to make data focused on the medical and biological the Malaria Vaccines Initiative. and resources available to scientists context of sequence data. A review of the Meetings Programme around the world. was carried out in conjunction with Wellcome Trust Advanced Courses The funding award will enable the Keystone Symposia. The results The programme expanded significantly Sanger Institute to drive forward its were positive. Overall, 98 per cent in 2005/06, doubling the number of new strategic focus, based on large- of respondents said that the meeting courses run for PhD students and scale studies of the effects of variation they had attended had been good postdoctoral scientists. New courses in DNA sequence in humans, model for them. included ‘The Molecular Basis of organisms such as mice and Infection: Basic and applied research The Wellcome Trust Conference zebrafish, and pathogens. approaches’, a laboratory-based Centre operates as a semi-commercial The Sanger Institute has also attracted course on new molecular techniques entity. It completed its first three-year major awards from the European used to study bacterial infection. business plan in 2005/06, meeting Union and the US National Institutes its efficiency, quality and standards A new initiative this year has been of Health (see page 38). targets. Over 60 major scientific the expansion of courses overseas. meetings and courses were held at The Sanger Institute led the Two human bioinformatics workshops the Conference Centre, generating sequencing of the first human were held in Mexico and Brazil, and an revenue of £1.7m. Most meetings chromosome sequence – IT suite has been set up in the Institute were scientific and research-focused, chromosome 22 – and, fittingly, of Hygiene in Uruguay, as a base for so qualified for extensive discounts. it was also behind the final report, the Advanced Courses training on chromosome 1, published in May programme in South America. PUBLIC ENGAGEMENT 50

PUBLIC ENGAGEMENT The Wellcome Trust’s Public Engagement activities aim to raise awareness and understanding of biomedical science, its social and ethical implications, and its historical context.

This year saw the official opening of the National Science Learning Centre at York and the first widespread use of the innovative new Twenty First Century Science GCSE curriculum, the development of which was part-funded by the Wellcome Trust. Educationalists were among the groups represented at the Trust’s Engaging Science conference, which highlighted the stimulating diversity of individuals and groups involved in public engagement in its broadest sense, who collectively are helping to ensure science is integrated into and respected within wider society.

Grants Grants worth £2.2m for public Gender and Thinking. Full text and A total of 59 grants were awarded engagement were made through classroom facilities are available online. under the £3 million Engaging the Wellcome Trust’s Strategic Awards Supporting researchers Science funding scheme. Committee to At-Bristol to develop a The Wellcome Trust hosted two touring exhibition, Generation Genome Society Awards: Seven of these events designed to facilitate interaction (see page 29), and to the Science large awards (over £30 000) were between broadcasters and senior Museum to digitise parts of Henry made for a range of nationally Trust-funded researchers. In addition, Wellcome’s collection (the Science important activities. A notable award pilot training sessions were run by the Museum has many of Wellcome’s was to Professor Keith Roberts at the National Science Learning Centre to collection of objects on indefinite loan). John Innes Research Centre, for the provide an introduction for researchers installation of a city exhibition entitled Livestock for Life, a one-off grant wanting to work in schools. The ‘Making Faces’ as part of the British scheme to strengthen links between Wellcome Trust renewed its partnership Association Festival of Science in livestock keepers, researchers and with the UK Research Councils to run Norwich. Two awards were made to policy makers in developing countries, the Researchers in Residence scheme, support academic research about made 19 awards. Fifteen exhibitions with the contract awarded to the public engagement. opened across the UK thanks to University of Edinburgh. ReDiscover funding – a joint initiative People Awards: Ever popular, 26 of Public participation these small, flexible, rapid-turnaround with the Millennium Commission and the Wolfson Foundation. The Wellcome Trust organised several awards were made to a variety of events to offer a foretaste of the public organisations, supporting diverse The Wellcome Trust held a two-day programme in Wellcome Collection activities including performances, conference in April to mark the past opening in 2007. These included exhibitions, talks, conferences, five years of its public engagement ‘wellbeing’ discussion events (see debates and documentaries. funding. This was followed by the page 27) and a one-day extravaganza Arts awards: In the Sciart strand publication Engaging Science: in the British Library Piazza of funding, nine grants were made Thoughts, deeds, analysis and action, showcasing nine talented young UK for small Research and Production setting out Wellcome Trust funding designers, who created remedies for Awards, as well as three Production highlights over ten years with essays modern-day ailments and peddled Awards (of up to £120 000). One from experts on the state of public them to the public in the style of a award was for film-maker Ian Knox, engagement in the UK. Wild West medicine show. producer Rebecca O’Brien and Education In February 2006, the Wellcome Trust neuropsychologist Paul Broks to The National Science Learning Centre hosted a discussion evening to mark make a documentary film based at the University of York opened to the publication of Better Humans? The on the experience of jazz guitarist teachers in October 2005 with a formal politics of human enhancement and Pat Martino, who lost his memory opening by the Prime Minister, Tony life extension in partnership with the following brain surgery for an Blair, in March 2006 (see page 26). think-tank Demos. The publication aneurysm. The Pulse scheme Two issues in the Big Picture series, received extensive media coverage. (performing arts for young people) a publication for teachers and post-16 also received record numbers of students, were published, on Sex and applications, with 12 being awarded. LIBRARY AND INFORMATION RESOURCES 51

LIBRARY AND INFORMATION RESOURCES The Wellcome Library provides free public access to more than a million items related to the history of health, disease and medicine. The Wellcome Trust also works to enhance access to key information resources and publishes material in a range of formats for a variety of audiences.

This year’s award of the contract to run UK PubMed Central, to a partnership between the British Library, the University of Manchester and the European Bioinformatics Institute, reflects the central place of the web in providing access to information. Use of the Wellcome Library website continues to grow and considerable resource material is now published on the Wellcome Trust’s main site. The major exception is developing countries, where, for the time being at least, there is still a role for alternative resources such as CD-ROMs.

The Wellcome Library Biomedical Information Full text for Wellcome Science and In October 2005, the Wellcome On 27 July 2006, the contract to run Wellcome Focus is now available Library collections were awarded UK PubMed Central (UKPMC) was online, along with all articles from ‘Designation’ status by the Museums, awarded (see page 41). As part of the Trust’s quarterly magazine, Libraries and Archives Council (MLA), the drive towards open access, the Wellcome News. in recognition of their outstanding Medical Journals Backfiles Digitisation The Trust’s Human Genome website national and international importance. project was launched in May 2006. was relaunched with: an updated Among many notable acquisitions was Through the project, complete back design; in-depth sections on topics a portrait of an 18th-century Dorset issues of significant biomedical such as diabetes, cancer and gene farmer, Benjamin Jesty, who, in 1774, journals – eventually some three million therapy; and new articles on the used cowpox inoculations to protect pages covering nearly 200 years – are science of the human genome, its his wife and children against smallpox being made freely available online. role in health and medicine, and the – 20 years before Edward Jenner’s The £1.3 million initiative is jointly broader social impact of genetic famous ‘first’ vaccination. funded by the Wellcome Trust and the knowledge. In January 2006, the Wellcome Joint Information Systems Committee The Publishing Group – International Library co-organised (with the Digital (JISC), and was developed through Health underwent an extensive Curation Centre) and hosted a two- a partnership between the Trust, JISC, evaluation of its educational and day workshop on future-proofing the US National Library of Medicine training CD-ROMs, which are now institutional websites. Websites are and medical journal publishers. in use by more than 50 000 people key repositories of information, but In April 2006, the Wellcome Trust in over 80 countries worldwide. The their transience may mean important won the first Scholarly Publishing evaluation revealed very high levels material is lost, without suitable and Academic Resources Coalition of user satisfaction; nearly half of all archiving procedures – such as the (SPARC) Europe Award for its users reported improvements in Wellcome Library’s web-archiving work on open access publishing. professional or clinical practice, or programme. improved healthcare delivery. A third Publishing edition of the best-selling CD-ROM on Two INSET training days for teachers The second and third issues of malaria was published during the year. were held in 2006, to encourage Wellcome Science were published, teachers to use historical approaches showcasing notable Wellcome Trust- A collaboration with Fiocruz, the (and Wellcome Library materials) in funded projects and providing insight Brazilian national research their teaching. into the latest scientific discoveries. organisation, will see Topics in The winning images in the Wellcome Subjects covered included the International Health CD-ROMs Trust Biomedical Image Awards 2006 placebo effect, clinical use of stem translated into Portuguese for the went online and on show at the cells, body clocks and the Brazilian and Portuguese-speaking Wellcome Library foyer in July 2006. neuroscience of social interactions. African markets. The project promises An additional display opened at the Wellcome Focus on Ageing to bring the CD-ROMs to countries National Science Learning Centre summarised scientific, medical with a combined population of over in York. and social developments in ageing. 200 million. ADVISORY COMMITTEES 52

ADVISORY COMMITTEES

Basic Immunology Professor L H Pearl Professor M Maze Professor S King and Infectious Disease Institute of Cancer Research, Imperial College School Oxford Brookes University London of Medicine, London Funding Committee Professor H Marland Professor A C Hayday Dr H Skaer Professor S H Sacks University of Warwick (Chair) Guy’s, King’s and St University of Cambridge Guy’s, King’s and St Thomas’ Dr T Tansey Thomas’ School of Medicine, School of Medicine, King’s Professor D F Smith University College London King’s College London College London University of York Dr B Arnold Professor A J Silman Professor P J Van Der Eijk Professor C M R Turner University of Newcastle upon Tyne German Cancer Research Centre, University of Manchester Heidelberg, Germany University of Glasgow Professor P Woodruff Immunology and Infectious Professor M J Whitaker Professor G S Besra Disease Strategy Committee University of Newcastle upon Tyne University of Birmingham Dr R M Atlas Cognitive and Higher Professor M Duszenko Professor M Yaniv (Chair) University of Louisville, University of Tübingen, Germany Pasteur Institute, Paris, France Systems Funding Kentucky, USA Committee Professor L Borysiewicz Professor R M Elliott Biomedical Ethics Funding Professor J N P Rawlins University of St Andrews Committee (from February 2006) Governor, (Chair) University of Oxford Wellcome Trust Professor N L G Eastman Professor G Griffiths Professor J P Aggleton University of Oxford (Chair) St George’s Hospital Professor P Smith Medical School, University Governor, Wellcome Trust Professor P D Griffiths of London Professor D V M Bishop Professor J O Thomas Royal Free and University College University of Oxford Medical School, London Dr R Ashcroft Governor, Wellcome Trust (from June 2006) Queen Mary Professor A Brice Professor V S Chauhan Dr M J Keeling College, Pitié-Salpêtrière Hospital, University of Warwick International Centre for Genetic Dr C Barton Paris, France Engineering and Biotechnology, Dr B Luisi Professor R J Dolan New Delhi, India University of Cambridge Professor A V Campbell (to May 2006) Centre Institute of Neurology, Professor D G Colley Professor R M Maizels for Ethics in Medicine University College London University of Georgia, USA University of Edinburgh Dr D Coles Professor P A Garety Professor G Dougan Professor K H G Mills European Commission, Institute of Psychiatry, (from December 2005) Wellcome Trinity College Dublin, Ireland Brussels, Belgium King’s College London Trust Sanger Institute, Cambridge Professor B P Morgan Professor P Kaufert Professor P B Jones Professor C C Goodnow Cardiff University University of Manitoba, Canada University of Cambridge Australian National University, Canberra, Australia Professor F C Odds Dr P Martin Professor E M Joyce University of Aberdeen University of Nottingham University College London Professor A C Hayday King’s College London Professor D O’Connor Professor S McLean Professor R A Kauppinen (from January 2006) University University of Glasgow University of Birmingham Professor K P Klugman of Southampton Emory University, Atlanta, USA Professor N Nevin Professor M J Morgan Professor C E Rudd Queen’s University Belfast City University, London Professor H R P Miller Imperial College of Science, Professor R Salmelin University of Edinburgh Technology and Medicine, London Professor D Wassenaar University of KwaZulu-Natal, Helsinki University of Professor A B Rickinson Dr R E Sockett Pietermaritzburg, South Africa Technology, Finland University of Birmingham University of Nottingham Professor S Wilkinson Professor W Schultz Professor M E J Woolhouse Professor D Soldati-Favre Keele University University of Cambridge University of Edinburgh University of Geneva, Switzerland Professor A Thapar Professor J A Vazquez-Boland Clinical Interview Committee Cardiff University Library Advisory Committee Professor D M Turnbull Ms J Wilkinson University of Bristol Professor J M Wardlaw (Chair) University of Newcastle (Chair) The British Library, London Western General Hospital, upon Tyne Basic Science University of Edinburgh Mr E Walker-Arnott Interview Committee Professor M R Bennett Governor, Wellcome Trust Professor G Banting University of Cambridge History of Medicine (Chair) University of Bristol Funding Committee Dr P Ayris Professor C G Fairburn University College London Library Professor N J Buckley University of Oxford Professor M A Jackson University of Leeds (Chair) University of Exeter Ms A Fleming Professor R Franklin Mr N Hopwood Professor T J Elliott University of Cambridge Dr J Andrews Southampton General Hospital University of Newcastle upon Tyne (from April 2006) University Professor J A Franklyn of Cambridge Professor P W Ingham University of Birmingham Dr J M T Ford Mr N Kingsley (in abeyance 2005/06) University Dr M Harrison of Sheffield Professor D P Kelleher (to April 2006) The National Trinity College Dublin, Ireland University of Oxford Archives, Kew Professor A R Mayes Mr J N P B Horden University of Liverpool Royal Holloway, University of London ADVISORY COMMITTEES 53

The Wellcome Trust is committed to the principles of peer review. We are indebted to the many researchers who gave up their time to sit on our advisory committees, and to the thousands of scientific referees, in the UK and overseas, who provide comments on grant applications. The following pages list the membership of our advisory committees during 2005/06.

Livestock for Life Awards Molecular and Cellular Professor C L Mummery Professor P W J Rigby Funding Committee Neuroscience Funding Netherlands Institute for The Institute of Cancer Professor H R P Miller Committee Developmental Biology, Research, London (Chair) University of Edinburgh Professor V H Perry The Netherlands Professor J M Thornton Dr J Claxton (Chair) University of Southampton Professor G Murphy European Bioinformatics Institute, Cambridge European Commission, Dr C D Benham Cambridge Institute for Medical Research Brussels, Belgium GlaxoSmithKline Neuroscience and Mental Professor S Neidle Professor J R Gillespie Professor P J Brophy Health Strategy Committee University of London University of California, Davis, USA University of Edinburgh Professor D Purves Professor A J Rees Dr C Heffernan Professor G L Collingridge (Chair) Duke University, University of Aberdeen University of Reading (to April 2006) University of Bristol Durham, USA Professor L M Roberts Professor K Homewood Professor V Crunelli Professor A P Bird University of Warwick University College London Cardiff University Governor, Wellcome Trust Dr D L Stemple Dr B Ilsoe Professor M Götz Professor R Plasterk Wellcome Trust Sanger Institute, Danish Ministry of Foreign Affairs, Institute of Stem Cell Research, Governor, Wellcome Trust Cambridge Copenhagen, Denmark Munich, Germany Professor D M Clark Professor C E Sunkel Dr R Kock Professor C F Inglehearn Institute of Psychiatry, King’s University of Porto, Portugal Conservation and Wildlife Health, University of Leeds College London Zoological Society of London Professor A B Tobin Professor D M Kullmann Professor D A S Compston University of Leicester Dr A McLeod University College London University of Cambridge AGAL, Food and Agriculture Professor M F Tuite Professor S H Lovestone Professor V H Perry Organization, Rome, Italy University of Kent, Canterbury Institute of Psychiatry, University of Southampton Dr C Peacock King’s College London Professor J P Waltho Professor M C Raff FARM Africa, London Professor B Robertson University of Sheffield University College London Dr S Ramdas University of Leeds Professor R J White Professor J N P Rawlins ANTHRA, Andhra Pradesh, India Dr G Schiavo University of Glasgow University of Oxford Mr C D Spencer Cancer Research UK, London Professor D I Wilson Professor A Toga African Development Bank, Research Institute University of Southampton Reed Neurological Research Tunis, Tunisia Center, Los Angeles, USA Professor K P Steel Molecules, Genes and Cells Wellcome Trust Sanger Institute, Medical Humanities Strategy Committee Professor D Turnbull Cambridge University of Newcastle upon Tyne Strategy Committee Professor B Alberts Dr D G Wilkinson Professor R A Hope (Chair) University of California, Physiological Sciences (Chair) University of Oxford National Institute for Medical San Francisco, USA Research, London Funding Committee Professor P Smith Professor A P Bird Professor I C A F Robinson Governor, Wellcome Trust Professor H J Willison Governor, Wellcome Trust (Chair) National Institute for Medical University of Glasgow Mr E Walker-Arnott Professor R Plasterk Research, London Governor, Wellcome Trust Molecules, Genes and Governor, Wellcome Trust Professor T B Bolton Professor N Britten Cells Funding Committee Professor J O Thomas St George’s Hospital Medical (from November 2005) Peninsula Professor S G Oliver Governor, Wellcome Trust School, University of London Medical School, Exeter (Chair) University of Manchester Professor D M Altshuler Professor E R Chilvers Professor N L G Eastman Dr V Allan Massachusetts General University of Cambridge St George’s Hospital Medical University of Manchester Hospital, USA Professor R Dimaline School, University of London Professor J A Armour Professor G Banting University of Liverpool Professor H M Evans University of Nottingham University of Bristol Professor A F Dominiczak University of Durham Professor P R Avner Professor A Berns University of Glasgow Professor K W M Fulford Pasteur Institute, Paris, France The Netherlands Cancer Institute, Professor D J Fitzgerald University of Warwick Professor L R Cardon The Netherlands University College Dublin, Ireland Professor M A Jackson University of Oxford Professor A Bradley Professor A T Hattersley University of Exeter Dr R M Cooke (from December 2005) Wellcome Peninsula Medical School, Exeter Trust Sanger Institute, Cambridge Professor H King GlaxoSmithKline Professor S G Hillier University of Reading Dr R Brent Dr A J Greenfield University of Edinburgh University of California, Professor G Richardson Medical Research Council Berkeley, USA Professor A J Knox King’s College London Mammalian Genetics Unit University of Nottingham Dr P N Goodfellow Professor T Treasure Professor A I Lamond Professor L Lanyon Guys’ and St Thomas’ University of Dundee Professor S G Oliver Royal Veterinary College, NHS Foundation Trust University of Manchester University of London Professor M S Marber King’s College London ADVISORY COMMITTEES 54

ADVISORY COMMITTEES

Professor P Maxwell Professor A Fontanet Public Engagement Ms K Huffman Imperial College of Science, Pasteur Institute, Paris, France Strategy Committee Cornerhouse, Manchester Technology and Medicine, London Professor K Hill Professor N J Rothwell Professor B Hurwitz Professor M Perretti Harvard Initiative for Global (Chair) University of Manchester King’s College London Barts and The London, Health, USA Ms P Hodgson Ms L Keidan Queen Mary’s School of Professor A O House Governor, Wellcome Trust Live Art Development Agency Medicine and Dentistry University of Leeds Mr A Ross Goobey Professor G A Rutter Ms L Le Feuvre Professor S J Jejeebhoy Governor, Wellcome Trust Goldsmiths College London Imperial College of Science, The Population Council, Technology and Medicine, Professor N L G Eastman Dr J Turney New Delhi, India London St George’s Hospital Medical Science writer Professor K T Khaw School, University of London Professor J Seckl Dr R J T Wingate University of Cambridge Queen’s Medical Research Ms C Fox King’s College London Institute, Edinburgh Professor M McKee Institute of Ideas, London Seeding Drug Discovery Professor A Tinker London School of Hygiene and Professor A Irwin Tropical Medicine University College London University of Liverpool Funding Committee Professor W Charman Professor A M Tomkins Professor C A Stoltenberg Professor M A Jackson (from January 2006) Norwegian (from January 2006) (Chair) Institute of Child Health, London University of Exeter Institute of Public Health, Norway Monash University, Victoria, Australia Physiological Sciences Professor R Millar Professor M Tanner University of York Strategy Committee Swiss Tropical Institute, Switzerland Professor J Allen Professor P M Stewart Dr R Persaud University College Dublin, Ireland (Chair) University of Birmingham Populations and Public Bethlem Royal Hospital Professor K Altmann Health Strategy Committee Professor A P Bird Professor K Sykes (from January 2006) Swiss Federal Professor L Peltonen-Palotie Institute of Technology, Zürich, Governor, Wellcome Trust University of Bristol (Chair) Biomedicum Helsinki, Switzerland Professor R Plasterk Finland Dr G Watts Dr P England Governor, Wellcome Trust BBC Radio 4 Professor P Smith ProXara Biotechnology Limited Professor F M Ashcroft Governor, Wellcome Trust Mr S Webster Dr F King University of Oxford Imperial College of Science, Professor F Binka Technology and Medicine, London (From January 2006) Professor K R Chien INDEPTH Network, Ghana Dr T Rink Massachussetts General Professor Lord Robert Winston Professor N Day Hospital, USA Imperial College School of Professor P Vallance (to June 2006) Strangeways Medicine, London GlaxoSmithKline Professor G Fitzgerald Research Laboratory, Cambridge University of Pennsylvania School Professor B Wynne Professor P J Donnelly Society Activity Awards of Medicine, Philadelphia, USA (from February 2006) Lancaster University of Oxford University Funding Committee Professor J Hunter Professor S B J Ebrahim Professor R Millar GlaxoSmithKline London School of Hygiene Research Resources in (Chair) University of York Medical History Funding Professor J J Mullins and Tropical Medicine Dr S Blakemore University of Edinburgh Committee Professor P Elliott (from April 2006) University Professor H King Professor I C A F Robinson Imperial College School of College London (Chair) University of Reading National Institute for Medical Medicine, London Dr S Joss Research, London Ms N Bell Professor W Graham University of Westminster The National Archives, Richmond Populations and Public University of Aberdeen Dr G Mulgan Ms Y M T Dahnsjö Health Funding Committee Professor H Jaffe Young Foundation, London South East Regional Office, University of Oxford Professor S B J Ebrahim The National Trust Professor M Parker (Chair) London School of University of Oxford Hygiene and Tropical Medcine Principal Research Mrs J Etherton Fellowship Interview Valence House Museum, Mr N Partridge Professor M Barreto Committee Dagenham Terrence Higgins Trust (from January 2006) Federal University of Bahia, Brazil Professor P W J Rigby Professor M A Jackson Dr S Preston (Chair) Institute of Cancer University of Exeter University of Durham Professor N Chaturvedi Research, London Imperial College School of Ms H Lindsay Mr M Whitby Medicine, London Professor M Bobrow London Metropolitan Archives The Red Green and Governor, Wellcome Trust Blue Company Ltd Professor C A Dezateux Professor R O Hynes Sciart Funding Committee Institute of Child Health, London Production Awards Society Awards Funding Massachusetts Institute Committee; Pulse Professor M Egger of Technology, USA Dr L Goodman University of Bern, Switzerland (Chair) SMARTlab, University Dr H Nicholson Professor T E Wellems of East London (Chair) Royal Holloway, Dr A C Ezeh National Institute of Allergy University of London African Population and Health and Infectious Diseases, USA Ms M Ellis Research Centre, Nairobi, Kenya Film London Ms H Durman Resource Base, Southampton ADVISORY COMMITTEES 55

Dr D Glaser Professor D J Porteous Dr F Sams-Dodd Tropical Interview (to May 2006) University University of Edinburgh (from February 2006) Committee College London Neurofit SAS, France Professor M J Prince Professor K P Klugman Mr S Hawkes Institute of Psychiatry, Dr M Skingle (Chair) Emory University, HQ Arts Ltd, Pontefract King’s College London GlaxoSmithKline Atlanta, USA Ms S Hill Professor R W Snow Professor C E Clayton Technology Transfer University of Heidelberg, Germany Eden Project, Cornwall KEMRI–Wellcome Trust Research Strategy Panel Programme, Nairobi, Kenya Mr R Levinson Dr T J Rink (Chair) Professor R H Gilman University of London Professor D P Strachan Johns Hopkins University, St George’s Hospital Medical Professor L Borysiewicz Baltimore, USA Ms V Reiss School, University of London (from April 2006) Governor, Arts Council England Wellcome Trust Professor P T LoVerde Professor J N Weber Southwest Foundation Mrs L Thomas Imperial College School Professor R Plasterk for Biomedical Research, Dr R Wingate of Medicine, London (to April 2006) Governor, San Antonio, USA Wellcome Trust (from April 2006) King’s Professor S Wyke Dr F Wabwire-Mangen College London University of Stirling Dr S Foden Makerere University, Kampala, (to April 2006) Uganda Society Research Awards Dr B Zaba Funding Committee London School of Hygiene Dr R G Hill (to April 2006) (established in February 2006) and Tropical Medicine Merck Sharp & Dohme UK Professor B Wynne Technology Transfer Dr J Hills (Chair) Lancaster University Challenge Committee (from February 2006) Professor S Cunningham-Burley Dr T Bianco Bristol-Myers Squibb University of Edinburgh (Chair) Wellcome Trust Dr R Parekh Ms J Cummins Dr A Boyd Abingworth Management Office for Public (from February 2006) Independent Limited, London Management, London consultant Dr A Wood Professor G Gaskell Professor W Charman (from February 2006) Eli Lilly London School of Economics Monash University, Victoria, Research Centre and Political Science Australia Tropical and Clinical Dr L Henderson Professor K Davies Immunology and Infectious Brunel University (from December 2005) University of Oxford Disease Funding Committee Professor J Leach Professor M E J Woolhouse University of Leeds Dr G Forrest (Chair) University of Edinburgh Independent consultant Ms J Lewis Professor Z A Bhutta National Centre for Social Professor B Furr The Aga Khan University Hospital, Research, London (to May 2006) AstraZeneca plc Karachi, Pakistan Professor J Osborne Professor P Ghazal Professor U d’Alessandro King’s College London University of Edinburgh Prince Leopold Institute of Tropical Medical School Dr A Stockl Medicine, Antwerp, Belgium University of East Anglia Professor D Horwell Professor D Goldblatt (to May 2006) University Institute of Child Health, London Study Design Expert Group of East Anglia Professor P J Donnelly Professor P Hagan Dr A Hudson University of Glasgow (Chair) University of Oxford Independent consultant Professor S Krishna Professor P R Burton Dr K Johnson University of Leicester St George’s Hospital Medical (from December 2005) School, University of London Professor R Collins Index Ventures Radcliffe Infirmary, Oxford Dr D G Lalloo Dr F King University of Liverpool Dr P Deloukas Dr G Lawton Dr M M Lederman Wellcome Trust Sanger (from February 2006) Lectus Institute, Cambridge Case Western Reserve University, Therapeutics Limited Cleveland, USA Professor R J Hayes Dr W Luyten Professor D U Pfeiffer London School of Hygiene IriDM, Leuven, Belgium and Tropical Medicine Royal Veterinary College, Hatfield Dr R Parekh Professor E Schurr Professor M Khoury Abingworth Management Limited Centers for Disease Control and Montreal General Hospital Prevention, Atlanta, USA Dr J Rasmussen Research Institute, Quebec, (from December 2005) Canada Professor A D Morris Independent consultant University of Dundee ACKNOWLEDGEMENTS 56

Acknowledgements The Wellcome Trust Annual All images are courtesy of pp. 34–35: 1 (iStockphoto), We are grateful to everyone Review is distributed via the Wellcome Library, except 3 and 4 (C Penn), Bob Snow who agreed to be reviewed a mailing list held by the as follows: (C Penn); pp. 36–37: 3 in this issue, everyone who Wellcome Trust. If you would Contents and p. 1: gut (© The Royal Society); pp. supplied images or gave us like to be added to this list, (Professor Alan Boyde), 38–39: 3 (Michael Chew); permission for their images or if you have a colleague children (Caroline Penn), p. 46: above left (David to be used, and the many who would like to receive Every Breath (David Gregory and Debbie members of Wellcome Trust the Wellcome Trust Annual Kampfner), fruit-fly cells Marshall), centre right staff who helped produce Review, please contact: (Dr Andrea H Brand); pp. (C Penn), below left (Dr this volume. Publishing Department 2–3: 2 (Annie Cavanagh), Steve Wilson), below right Editor Wellcome Trust phagocyte (Rob Young); (Rachel Ashworth and Ian Jones FREEPOST pp. 6–7: 1 (Mark Lythgoe William Hinkes); p. 47: above left (Professor Alan Boyde), Project Manager ANG 6754 and Chloe Hutton), 3 (Fiona Ely CB7 4YE, UK Pragoff), 4 (Yorgos Nikas), above right (D Gregory and Lucy Moore D Marshall), centre left (Oliver T +44 (0)20 7611 8651 5 (Emlyn Parfitt and Writers Magdalena Zernicka-Goetz); Burston), centre right (Dr Penny Bailey F +44 (0)20 7611 8242 Andrea H Brand); p. 48: (K E [email protected] pp. 8–9: 1 and 2 (Christine Chrissie Giles Holt), 3 (Helen Farr and Hodivala-Dilke and M Stone). Jon Turney www.wellcome.ac.uk/publications Keith Gull), 4 (SPL), 5 Cover image: Editorial staff ISBN 978 1 84129 068 3 (Sarah Lummis); pp. 10–11: Scanning electron micrograph Tom Freeman 1 (Getty Images), 2 (MRC of breast cancer cells (Annie The Wellcome Trust is a Toxicology Unit), 3 (Professor Cavanagh). Design charity registered in England, Alan Boyde), 4 (C Penn); Marianne Dear no. 210183. Its sole trustee pp. 12–13: 2 (James Design Manager is The Wellcome Trust King-Holmes/SPL), 3 Steve Russell Limited, a company (iStockphoto), 4 (Mark registered in England, no. Picture research Henley/Panos); pp. 14–15: 2711000, whose registered Anne-Marie Margetson mouse blastocyst in office is at 215 Euston Road, Manika Power diapause (Jose Silva and London NW1 2BE, UK. Jennifer Nichols), Vietnamese Photography First published by the girl (Chan Doan), mushroom David Sayer Wellcome Trust, 2007. cloud (Rex Features); pp. Comments on the Wellcome 18–19: 1 (C Penn), 2 © The trustee of the Trust Annual Review are (CAMR/AB Dowsett/SPL); Wellcome Trust, London. welcomed and should be pp. 20–21: 1 (Marcus sent to: All rights reserved. No part Rose/Panos), 2 (Audio of this publication may be Ian Jones, Publisher Visual, LSHTM), 4 (C Penn); reproduced, stored in a Publishing Group pp. 22–23: 3 (Lee retrieval system, or Wellcome Trust Snyder/SPL), malaria transmitted by any means Gibbs Building parasite (Moredun Scientific electronic, mechanical, 215 Euston Road Ltd/SPL); pp. 24–25: photocopying, recording London NW1 2BE, UK stinging nettle close-up or otherwise without the (Liz Hirst); pp. 26–27: 2 F +44 (0)20 7611 8270 prior permission of the (D Kampfner); pp. 28–29: E [email protected] Wellcome Trust. 1 (D Kampfner), 2 (University Wellcome Trust of Glamorgan/Wales Gene Gibbs Building Park/Techniquest), human 215 Euston Road chromosome 1 (Dr TJ London NW1 2BE, UK McMaster); pp. 30–31: 1 (Dr David Furness); pp. T +44 (0)20 7611 8888 32–33: 1 (Angus Antley, F +44 (0)20 7611 8545 Computer Scientist, UCL), E [email protected] 2 (Dr Paola Vagnarelli), www.wellcome.ac.uk 3 (Manoj Sudhakaran), 4 (Dr Sumantra Chattarji);

DC-3656.p/15K/01-2007/MD ELOETUTANA EIW1Otbr20–0Spebr2006 WELLCOME TRUST ANNUAL REVIEW 1 October 2005–30 September

ANNUAL REVIEW 2006

The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk THE WELLCOME TRUST The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world.

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CONTENTS BOARD OF GOVERNORS 2 Director’s statement William Castell 4 Advancing knowledge Chairman 16 Using knowledge Martin Bobrow Deputy Chairman 24 Engaging society Adrian Bird 30 Developing people Leszek Borysiewicz 36 Facilitating research Patricia Hodgson 40 Developing our organisation Richard Hynes 41 Wellcome Trust 2005/06 Ronald Plasterk 42 Financial summary 2005/06 Alastair Ross Goobey 44 Funding developments 2005/06 Peter Smith 46 Streams funding 2005/06 Jean Thomas 48 Technology Transfer Edward Walker-Arnott 49 Wellcome Trust Genome Campus As at January 2007 50 Public Engagement 51 Library and information resources 52 Advisory committees

Images 1 Surface of the gut. 3 Zebrafish. 5 Cells in a developing This Annual Review covers the 2 Young children in 4 A scene from Y fruit fly. Wellcome Trust’s financial year, from Kenya. Touring’s Every Breath. 6 Data management at the Sanger Institute. 1 October 2005 to 30 September 2006.