ISSUE 64 SEPTEMBER 2010
Pick of the postdocs What’s on the cards for our Sir Henry Wellcome Fellows?
Picture this Using comics to explain medicine
Bad science? The dual-use dilemma
Wellcome News
Editorial
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The Wellcome Trust
We are a global charity dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. www.wellcome.ac.uk This is an open access publication and, with the exception of images and illustrations, the content may, unless otherwise stated, be reproduced free of charge in any format or medium, subject to the following constraints: content must be reproduced accurately; content must not be used in a misleading context; the Wellcome Trust must be attributed as the original author and the title of the document specified in the attribution. The views and opinions expressed by writers within Wellcome News do not necessarily reflect those of the Wellcome Trust or Editor. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. ISSN 1356-9112. First published by the Wellcome Trust, 2010. © The trustee of the Wellcome Trust. The Wellcome Trust is a charity registered in England and Wales, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England and Wales, no. 2711000 (whose registered office is at 215 Euston Road, London NW1 2BE, UK). PU-4737.3/14.5K/09-2010/JS Cover: Playing cards of Sir Henry Wellcome Postdoctoral Fellows. See page 4. 50%
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WellcomeNews | Issue 64
At the heart of our Strategic Plan are the five research challenges that will shape much of our work over the coming decade. Each challenge is a theme that brings together the many different activities of the Trust – including research in biology and medicine, the translation of research into healthcare products, public engagement, history of medicine and the ethics of research. For both our Strategic Awards and Investigator Awards, we are asking applicants to consider how their research will address one or more of these challenges. This is particularly important because each challenge comes with intent – that the work we fund should make a difference. For example, ‘maximising the health benefits of genetics and genomics’ makes clear that if we and our partners are to be successful, genetics research must feed through into important improvements in the lives and health of patients and others. The last few months have seen the launch or funding of a number of projects that address our challenges directly. In the field of genetics, alongside the celebration of the human genome sequencing’s ten-year anniversary in June came the launch of the ambitious UK10K project. As its name suggests, UK10K will decode the genomes of 10 000 people over the next three years and is expected to uncover many rare genetic variants that are important in human disease. The project will studying 4000 people from TwinsUK and the Avon Longitudinal Study of Parents and Children – two extremely fruitful studies that the Trust supports – as well as 6000 people with extreme obesity, neurodevelopmental disease and other conditions. In our challenge area of ‘understanding the brain’, two projects looking at stroke – the leading cause of adult disability in the UK – aim to help us to understand and reduce the devastating effects it can have on the lives of those affected. At the University
of Oxford, Dr Heidi Johansen-Berg has recently had her Senior Research Fellowship renewed; she is looking at how the structure of the brain changes when we learn new skills and when the brain recovers from damage such as stroke. Meanwhile, Dr Parashkev Nachev at University College London has been funded to produce a system that marries automated brain imaging, to capture patterns of brain damage, with computers that can infer the relationship between the damage and the outcome in the patient. This will help doctors to determine the best treatment for the patient. In our challenge on ‘combating infectious disease’, a Strategic Translation Award to Professor Andrew Pollard at the University of Oxford will help to take a new vaccine against meningitis B from preclinical studies to phase I clinical trials in humans. Meningitis B is the leading cause of bacterial meningitis in the UK, causing 1500–2500 cases each year, and is also a major infectious cause of death in childhood. Meanwhile, Professor Kaspar Althoefer at King’s College London and colleagues are developing a way to combat the emerging problem of counterfeit medicines. In low-to-middleincome countries, 10–30 per cent of medicines are fake, placing patients at extreme risk. Professor Althoefer’s system uses radio waves to detect signals from medicines (or their imposters), even through packaging. Under our challenge on ‘investigating development, ageing and chronic disease’ we have awarded £3.8 million to a team at the University of Bristol to develop a new painkiller for the severe chronic pain associated with diabetes, for which there are currently limited effective treatments. The new analgesic is based on galanin, a small protein that is made by nerve cells and that can reduce neuropathic pain. Finally, in our challenge on ‘connecting environment, nutrition and health’, I was very pleased that we could announce £10m of funding, through the Insect Pollinators Initiative, for nine projects investigating the decline of honeybees and other pollinating insects in recent years. These projects will be exploring the causes and consequences of threats to these insect populations.
Sir Mark Walport Director of the Wellcome Trust
In this issue Funding
2
African genomics studies
7
Investigator Awards open
8
Capital funds for UK universities
8
20 News New biomedical research centre
2
Wellcome Collection’s millionth visitor
2
Giant trypanosome in Glasgow
3
Research
18 Features Sir Henry Wellcome Postdoctoral Fellows
Malaria-carrying lizards
12
Dopamine and willpower
13
Blood donors’ views
17
Genes linked to diabetes
18
Noticeboard
21
4
Picture this: comics and medicine
10
The dual-use dilemma
14
Illuminating Florence Nightingale
20
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News Visions of new biomedical research centre
Impression of UKCMRI seen from Eurostar Terminal. Justin Piperger/Wadsworth3d. Inset: UKCMRI entrance atrium. Glowfrog
These are the latest artist impressions of how one of the biggest centres for biomedical research in Europe will look. The designs and a video fly-through for the UK Centre for Medical Research and Innovation (UKCMRI), at St Pancras in London, were released alongside the Centre’s scientific vision and research strategy. UKCMRI, to be headed by Nobel Laureate Sir Paul Nurse, is founded by the Wellcome Trust, the Medical Research Council, Cancer Research UK and University College London. www.ukcmri.ac.uk
Wellcome Collection reaches 1 million visitor milestone On 20 July 2007 Wellcome Collection opened to the public. Just three years later, one million people have passed through its doors. Yaphet Berihoun, a student and regular user of the Wellcome Library, was the milestone visitor and received a goodie bag to mark the event. Wellcome Collection’s latest temporary exhibition, Skin, wrapped up in September.
Yaphet Berihoun, Wellcome Collection’s 1 millionth visitor.
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A summer of related events included sessions on the science of healthy skin (audio recording available at www. wellcomecollection.org), the history and cultural significance of tattoos and the ‘Skin: Exposed’ symposium, which explored nakedness in different periods, cultures and contexts. High Society, which opens in November, will look at mind-altering drugs in history and culture. The exhibition will explore everything from apothecary to laboratory studies, self-experimentation, collective intoxication and the drugs trade. An accompanying series of events will include a two-day symposium and discussion events curated by cultural historian Mike Jay. Also in November, free Friday-night extravaganza ‘Hand’ will celebrate the functional organ that allows us to make, touch and hold. Finally, a new app for the iPhone and iPod Touch gives you your very own multimedia Medical London guide in your pocket. Produced in association with City Stories Walks, the free app ‘Blood, Guts, Brains and Babies’ leads you through the streets of London, bringing together film, audio and photographs from our archives. Download the app from iTunes, or find the app and more at www.citystorieswalks.com.
Trust embarks on new education strategy We have recently completed our new education strategy, which was agreed at the Wellcome Trust Governors meeting in June. The strategy will focus on four key areas: playing a leading role in science education; embedding continuing professional development for teachers; building our reputation as a trusted deliverer of contemporary science resources; and strengthening research and development in primary science and the transition to secondary school, informal learning, and understanding the links between neuroscience and learning. More immediately, we will be publishing the findings of an investigation into pupil and parent attitudes to assessment at Key Stage 2 (age 11). This innovative study incorporated children aged 10 and 11 into the research team, providing fresh insights into children’s views of assessment. We will also publish the outcomes of a seminar, held in July, marking 21 years since the National Curriculum was introduced. These reports are timely, given that the new UK government is currently outlining its proposals to revise the curriculum and school assessment in England.
Pacific Health Summit held in the UK
Sir Mark Walport addresses the Summit.
In June the Pacific Health Summit, the world’s most prestigious health policy summit, came to London for the first time. The annual meeting brings together key leaders from science, industry, health systems and government to discuss how scientific advances and appropriate policy can be combined to make dramatic health improvements around the globe. This year’s topic was maternal and newborn child health. The Summit was co-presented by the Wellcome Trust, the Fred Hutchinson Cancer Research Center, the Bill & Melinda Gates Foundation and the National Bureau of Asian Research. www.pacifichealthsummit.org
Meetings explore medical futures As the drug development industry looks for alternative ways to find new medicines, ‘open source’ partnerships between academics and pharmaceutical companies are increasingly common. But challenges remain. These were explored in a two-day Frontiers meeting hosted at the Trust and attended by representatives from both public and private sectors. The conclusions include the development of a cross-sector working group for the identification and validation of drug targets, and agreement on the need for common repositories for drug targets, failed drugs and key compounds.
Making history
A separate workshop at the Trust looked at hospital-associated infections, such as MRSA and Clostridium difficile, and the patient pathway. Some 40 delegates, including scientists, healthcare workers, industry representatives, policy makers and patients, highlighted the many facets of the problem, such as detection and surveillance, hospital design and disease transmission. Among the conclusions were the need for standard operating procedures, new diagnostics and a national surveillance database.
Comics and comics
A new book charts the history of the Trust, from Sir Henry Wellcome’s interest in medicine and the challenges of establishing a medical research charity, to the shaping of the organisation it is today. Written by former Trust Director Peter Williams, The Story of the Wellcome Trust is published by Quiller Press and priced at £16.95. www.countrybooksdirect.com
Students win Galápagos trip
From left: Eleri Morgan, Jessica Woodfield, Charlotte Woodfield and Rebecca Hill.
The giant trypanosome is marched through Glasgow. Stewart Cunningham, Great Scot Photography
There was an unusual addition to the Glasgow West End Festival parade this summer: a giant trypanosome. The 7-metre model, 500 000 times the size of the actual parasite, was created to raise awareness of research on human African trypanosomiasis (sleeping sickness), a devastating disease that affects 70 000 people and countless animals on the continent. The work was the brainchild of Jamie Hall, a PhD student at the Wellcome Trust Centre for Molecular Parasitology in Glasgow. He and artist Edward Ross created a comic book to accompany the parade (download it at www.wellcome.ac.uk/
parasites). Comics of another kind, Timandra Harkness and Matt Parker, brought the maths of death to Edinburgh Fringe Festival with the People Award-funded comedy act ‘Your Days are Numbered’. As they put it, “You have a 0.000043 per cent chance of dying during this show. You will at least die laughing.”
Read our feature about comics and medical education on pages 10–11.
Four lucky students from St Cyres School in Penarth, Wales, have won the Survival Rivals competition and received their prize at the British Science Festival in Birmingham. Jessica Woodfield, Becky Hill, Eleri Morgan and Charlotte Woodfield will be packing their bags in October for the trip of a lifetime to the Galápagos Islands, 175 years after Charles Darwin was there himself. The students won the prize for producing a film called Bacteria: The future, in which they explain to Darwin how science has progressed since the publication of On the Origin of Species and show him evolution in action using the Wellcome Trust X-Bacteria kit produced as part of the Darwin200 year celebrations. www.survivalrivals.org
Wellcome Image Awards Judging for the next Wellcome Image Awards takes place very soon. A panel of expert judges from the world of science and media will consider all images acquired before 15 October 2010. If you produce images as part of your research we want to hear from you. Contact Dr Laura Pastorelli: l.pastorelli@wellcome.ac.uk.
WellcomeNews | Issue 64 | 3
Carving a niche In 2006, the Wellcome Trust launched the Sir Henry Wellcome Postdoctoral Fellowships, which give newly qualified postdoctoral researchers £250 000 to pursue research questions and establish an independent research career. Chrissie Giles caught up with some of these pioneering postdocs to hear how they’re getting on.
You’ve got your BSc, maybe an MSc too. A year or four chained to the laboratory bench, the long days of experiments and even longer nights of thesis writing behind you and you’ve earned your PhD. So what now? For many researchers, the next step is to find a postdoctoral position in a lab. But not all postdocs are the same. In 2006, the Wellcome Trust introduced a scheme unlike any other available in the
UK. Every year since, up to 20 researchers each receive £250 000 over four years to launch their independent research careers. Fellows can divide their time between different institutions across the world, giving them the chance to get experience in the best labs for their field, gain independence and make contacts. We spoke to some of the current Fellows to find out about their experiences and research so far, and the best ways to secure one of these Fellowships. Inspired? It’s not too late to apply for this year’s competition; visit www.wellcome.ac.uk/ shwpf for details.
Dr Shane Herbert Dr Shane Herbert was one of the first 20 researchers to be awarded a Sir Henry Wellcome Postdoctoral Fellowship, in late 2007. Having completed a PhD and a year of postdoc research at the University of Leeds, Shane headed to the USA to undertake his Fellowship. “The best place in the world to do what I wanted to do was California, so I’ve based my Fellowship at the University of California, San Francisco. There’s such a large network here that I’ve had multiple collaborations with other researchers within the faculty,” he says. Shane is investigating how new blood vessels form, on a molecular level. Insufficient or excessive growth of blood vessels plays a role in many different kinds 4 | WellcomeNews | Issue 64
of disease, including cancer, blindness and stroke. The ultimate aim of his work is to identify the molecules that affect how blood vessels behave and try to use them to design drugs to combat these diseases. He had planned to split his four-year Fellowship between working on two models: zebrafish and mouse. However, when the zebrafish work proved particularly promising early on, his plans changed. “The flexibility of the award allows me to stick with this model for now and then pick up the mouse later on in my career,” he says. He appreciates the greater autonomy
“I don’t think I’d be in the position I’m in currently without my mentor” and independence that this Fellowship gives, compared with some other postdoctoral schemes. “The salary is included in the Fellowship, but then so is money for consumables [the everyday items needed for lab research],” he says. “When you’re working in somebody else’s lab as an independent fellow, this is critical, because it means that you can direct your own research and do the experiment you want to do.” Fellows are asked to find a mentor, someone’s who’s independent of their work, as part of the scheme. Shane has found this invaluable: “I don’t think I’d be
in the position I’m in currently, looking at future jobs, without my mentor, Steve Watson at the University of Birmingham. He’s helped with job negotiations, putting together offers etc. You have tons of questions, so it’s vital you choose someone you feel comfortable with.”
Dr Tim Hallett Like Shane, Dr Tim Hallett received one of the inaugural Fellowships. Currently based in Seattle at the University of Washington, he’s studying interventions to stop the spread of HIV and how these could be tailored for different populations and different epidemics. “So far, my Fellowship’s been really, really busy, but productive,” he says. “The best thing has been being able to switch focus and follow my nose a bit – following up developments in the field, for instance, as they arise.” An example of this is the ‘test and treat’
number of places including Qatar, Kenya, Zimbabwe and Thailand. Most recently, he’s been working with researchers from Karachi, Pakistan to develop evidence-based recommendations on how to help injecting drug users there.1 “The travel was one of the big draws for me,” he says. “The field I’m in is very international and there are groups working all over the world that I’d always wanted to work with. The Fellowship let me do that. “It was quite a big step, particularly as I’ve got two children who came with me – but they’re enjoying their holiday out here!”
Dr Marie-Jo Brion
In a paper Travel has played a large part in Dr Marierecently Jo Brion’s Fellowship. Her PhD involved published in looking at the factors that influence Pediatrics,2 Marie-Jo and colleagues showed that childhood blood pressure in the ALSPAC while socioeconomic predictors of cohort, made up of children born to over maternal smoking in pregnancy differed 14 000 mothers living in the Bristol area between ALSPAC and Pelotas, there was in the early 1990s. For her Fellowship she’s remarkable consistency in the association expanded this work by also looking at a second cohort, consisting of 5000 children born in the Brazilian city of Pelotas in 1993. She is comparing both groups to try to understand what factors are involved in different aspects of child health. While it’s not new to compare populations, researchers tended to use similar populations, with most research between maternal smoking and child coming from cohorts based in highbehavioural problems, strengthening the income countries, Marie-Jo says. For her likelihood that these problems are due to Fellowship, she’s comparing high- and intrauterine effects of fetal exposure to middle-income groups. tobacco smoke. “When you compare two cohorts Around halfway through her Fellowship, that are as dissimilar as ALSPAC and she’s already spent six months working Pelotas you get a better idea of whether something is causing a particular condition or not,” she says. “We can compare and contrast, for example, predictors of maternal smoking in pregnancy and then use this to explore how maternal smoking relates to aspects of child health in both populations. These comparisons can then give us a better idea of whether biological A meeting of Sir Henry Wellcome Postdoctoral Fellows at the Trust. intrauterine factors are in Brazil and 12 months at the University likely to be driving these associations, or of Western Australia’s Centre for Genetic if it’s more likely to be due to wider social, Epidemiology and Biostatistics. Here, psychological or environmental factors.”
“It’s about taking forward the conventional approaches for studying health and disease and trying to improve it and get more reliable answers”
debate, when a group working on HIV said that to stop the disease they should treat everyone who had the infection. “This created an enormous debate in the international research community,” Tim says. “I switched focus for a little while to work on that, and published a paper quite quickly to add to the discussion. That was really satisfying.” He’s been part of many collaborations as part of his Fellowship. As well as keeping close links with Imperial College London, where he did his PhD, he’s also worked with agencies including UNAIDS, the US Centers for Disease Control and Prevention and the World Health Organization. He’s travelled to a
WellcomeNews | Issue 64 | 5
This year’s Fellows Congratulations to the 2010 Sir Henry Wellcome Postdoctoral Fellows: • Oliver Bannard, University of Oxford – The regulation of B-cell responses during malaria infections. • Ross Chapman, CRUK London Research Institute – Defining the role of BRCA1 and associated proteins in suppressing 53BP1dependent toxic DNA repair. • Molly Crockett, University College London – Automatic and analytical altruism: neurobiological foundations of human prosocial behaviour.
she’s been gaining experience in the latest techniques for using genetic information in epidemiological studies, something new to her for the Fellowship. “I’m looking to use genetic information as proxies for maternal exposures in
“Four years of research funding, a generous amount of travel and opportunities to work abroad. It’s a gift – if you can get it, go for it!” pregnancy,” Marie-Jo says. For example, there are genetic variants related to whether or not mums stop smoking during pregnancy, and how effectively people’s bodies break down the ethanol in alcohol. You can use these genetic variants as a means to tease out to what extent mothers’ smoking or drinking in pregnancy might biologically affect components of development in children. “It’s about taking forward the conventional approaches for studying health and disease and trying to improve it and get more reliable answers,” she says. Do it yourself So what do these researchers think is the secret to securing one of these prestigious Fellowships? Shane is emphatic about getting the right people behind you. “The most important thing to do is to identify the key people in the field doing what you want to do, then approach them about being sponsors for your application,” he says. “Finding the best people is critical.”
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For the application itself, you must identify a niche within your field of interest that you can develop into. “This will give you the best opportunity to develop an independent research career in the future. If you want a chance to become one of the top three people in the world in your field, then you need to be a competitive researcher.” Marie-Jo agrees about finding a unique question: “I tried to think of a project that pushed the boundaries a little bit. It was exciting and interesting to try and come up with things that might extend conventional approaches and improve the way we’re able to get answers.” “It is a big jump from PhD,” she says, “but a big learning curve, which is excellent. It’s great knowing that how things turn out is, by and large, a function of what you do with your time, how well you liaise with people and how well you work.” “I have very warm and fuzzy feelings for the Wellcome Trust for giving me this opportunity and for filling this gap in the market,” Tim laughs. “What would I say to prospective applicants? Well, you’ve got nothing to lose by applying. It’s one of those really rare opportunities: four years of research funding, a generous amount of travel and opportunities to work abroad. It’s a gift – if you can get it, go for it!” References 1S trathdee SA et al. HIV and risk environment for injecting drug users: the past, present, and future. Lancet 2010;376(9737):268–84. 2B rion M-J et al. Maternal smoking and child psychological problems: disentangling causal and noncausal effect. Pediatrics 2010;126(1):e57–65. For more information on the scheme and to watch some of the current Fellows, including Marie-Jo Brion, talk about their experiences, visit www.wellcome.ac.uk/shwpf
• Samuel Dean, University of Oxford – The trypanosome flagellar pocket functions and adaptations in differentiation, pathogenicity and immune evasion. • Helge Dorfmueller, University of Dundee – Mechanism and inhibition of chitin synthesis. • Daniel Fazakerley, University of Dundee – Use of proteomics and systems biology to dissect the molecular adaptability of metabolism in muscle and fat cells. • Demis Hassabis, University College London – Understanding the episodic memory system and its critical role in future thinking. • Nerea Irigoyen, University of Cambridge – Ribosomal frame-shifting and read-through in virus gene expression. • Benjamin Judkewitz, London School of Hygiene and Tropical Medicine – Optofluidic microscopy for portable low-cost malaria diagnostics. • Line Löken, University of Oxford – Feelings of pain and pleasure: delineating hedonic sensation in the brain. • Andrew MacAskill, University College London – Spine-specific targeting of ion channels in striatal neurons. • John Perry, University of Exeter – Identifying low-frequency and rare genetic variation involved in type 2 diabetes using nextgeneration sequencing data. • Sridharan Rajagopalan, University of Oxford – Proteases as next-generation therapeutics for influenza A. • Oliver Ratmann, Imperial College London – Unravelling the dynamics of rapidly evolving infectious diseases in humans with approximate Bayesian computations. • Anthony Roberts, University of Leeds – Mechanisms regulating movement and force generation by cytoplasmic dynein. • Aleksandra Watson, University of Cambridge – The structural basis of the interactions of the NuRD co-repressor complex. • Elton Zeqiraj, University of Dundee – A structural and biochemical approach to understand the molecular mechanism of glycogen synthesis. • Kaixin Zhou, University of Dundee – Heritability and pharmacogenetics in patients with type 2 diabetes.
Funding Trust partnership to fund African genomics studies
The H3 Africa Project will support research across the continent.
A new $38 million (£24m) partnership will be studying thousands of people in Africa to discover how genes and the environment interact in the development of cancer, heart disease, malaria and other diseases. The Human Heredity and Health in Africa Project (H3 Africa), which we have established with the US National Institutes of Health, will see African researchers leading studies of population-wide diseases on the African continent. These will cover both non-communicable diseases and disorders, such as diabetes and mental health, and infectious diseases such as tuberculosis. Previous research suggests that there
is greater genetic diversity in African populations than those in Europe and Asia. The project may help researchers to identify rare genetic variations that affect people all over the world. And as new genetic factors are identified, this may open up new ways to diagnose disease and develop treatments. “H3 Africa will build the capacity for African researchers to study African populations to solve African problems, and will create strong collaborations between African researchers and those in Europe, the United States and other parts of the world,” said Dr Charles N Rotimi, President of the African Society for Human Genetics.
Scheme for global health trials launched
Ethicists meet to consider community
In partnership with the UK Medical Research Council and the UK Department for International Development, we have committed up to £12 million per year for the next three years to fund late-stage trials of health interventions that, by addressing major causes of mortality or morbidity, will help to improve health in low- and middle-income countries. The scheme focuses on late-stage (phase III/IV) efficacy and effectiveness trials, and its scope includes behavioural interventions, disease management, drugs, vaccines, and hygiene and diagnostic strategies. Applications are now closed for 2010, and final decisions on who will receive support are expected in May 2011.
We supported a one-day meeting on the concept of community in bioethics in the run-up to the World Congress of Bioethics in Singapore in July. Convened by our Biomedical Ethics team with the help of Dr Angus Dawson and Dr David Hunter from Keele University, the meeting brought together some 50 ethicists, philosophers, social scientists and scientists from around the world. They discussed philosophical and cultural positions on how we define ‘the community’ when thinking about the ethical aspects of different areas of research and healthcare practice, such as genomics research, research in disaster settings and vaccination.
UK researchers gear up for 10 000 genomes Over the next three years, scientists will be decoding the genomes of 10 000 people in one of the largest DNA-sequencing programmes ever undertaken. It is hoped that the Trust-funded £10.5 million UK10K project will help to uncover many rare genetic variants important in human disease. Researchers from the Wellcome Trust Sanger Institute, working with clinical researchers from around the UK, will sequence the complete genomes of 4000 people from the TwinsUK and ALSPAC (Avon Longitudinal Study of Parents and Children) studies, who have been studied for many diseases and traits over many years. They will also look at the gene-containing regions of the genomes of 6000 people with extreme obesity, neurodevelopmental disease and other conditions.
UK10K will draw on a twins database.
UK10K follows on from the 1000 Genomes Project, an international collaboration to build the most detailed map of human genetic variation to date. The consortium behind the project recently announced the completion of three pilot projects, the data from which are now freely available in public databases. The pilot studies have helped to optimise the sequencing technology for the full-scale effort, which will build a database from the genomes of 2500 people from 27 populations around the world.
WellcomeNews | Issue 64 | 7
Funding Investigator Awards to open in October
Neil Leslie
Our brand new Investigator Awards open for applications on 1 October. These aim to give exceptional researchers the flexibility and support they need to innovate and pursue bold ideas. The scheme extends the successful model of fellowship support to researchers in established academic posts – that is, those who have permanent, open-ended or long-term rolling contracts
of employment salaried by their university or research institution. There are two categories: New Investigator Awards, for world-class researchers who are no more than five years since appointment to their first established academic position; and Senior Investigator Awards, for exceptional researchers who hold an established academic position and already have an outstanding track record. We’ll be making the first Awards in May 2011. “This scheme furthers our focus on supporting the most outstanding scientists and providing the flexibility needed to best enable them to ask the most challenging questions,” says Alan Schafer, Director of Science Funding at the Trust. We strongly advise potential applicants to contact us so we can review their eligibility and provide advice. www.wellcome.ac.uk/investigators
Trust hails first Senior Fellow in Public Health and Tropical Medicine Professor Hector H Garcia from the Universidad Peruana Cayetano Heredia, Lima, Peru has become the first ever Wellcome Trust Senior Fellow in Public Health and Tropical Medicine (for researchers from low- and middle-income countries). He will continue his work on the brain disease neurocysticercosis. The disease is the major cause of acquired epilepsy in low-income countries, and occurs when the larvae of the pork tapeworm Taenia solium enter the brain. Although the parasites die eventually, they can become calcified brain scars (above), and people can suffer seizures years later. Recent research led by Prof. Garcia at the Institute of Neurological Sciences in Lima has shown that some scars become inflamed 8 | WellcomeNews | Issue 64
when patients have a new seizure, raising questions about the role of these scars in causing seizures. Prof. Garcia (below) will investigate the contribution of neurocysticercosis to the burden of seizures in Peru, where the disease is endemic. He will also explore the characteristics of the inflamed brain scars and conduct a clinical trial to see whether steroids can reduce seizures in people with these scars.
UK universities receive millions in capital funding Over £30 million is being invested in large-scale university infrastructure projects courtesy of the Wellcome– Wolfson Capital Awards initiative. The scheme is intended to facilitate internationally competitive, leading-edge biomedical research in a way that would not otherwise be possible. Building on our Capital Awards initiative launched in 2007, the new partnership with the Wolfson Foundation has awarded funding of between £3m and £5m to seven universities from across the UK. Professor Simon Duckett at the University of York has secured funding for the York Centre for Hyperpolarisation in MRI. Hyperpolarisation enables imaging measurements that were previously impossible to be made in a few seconds. The Centre’s ten-year programme of interdisciplinary work will turn this important scientific discovery into specific clinical applications. “World-class science needs to be supported by world-class infrastructure, which requires significant investment,” said Sir Mark Walport, Director of the Trust. “The Capital Awards partnership between the Wellcome Trust and the Wolfson Foundation will provide an important injection of cash into our universities at a time when they face uncertainty about future capital funding.”
Brand new way to ask: who am I? The refurbished Who Am I? gallery is now open at the Science Museum in London. Funded in part through a £2.5 million Wellcome Trust capital award, the gallery presents the latest in biomedical research, from neuroscience to genetics, exploring how science is transforming our understanding of what it means to be human.
National Institutes of Health Director Francis Collins and Nobel Laureate John Sulston at the Who Am I? gallery. TNR/Science Museum
Recent biomedical sciences awards Among the new awards made through our Neuroscience and Mental Health funding stream is one to Professor Phil Maguire, a psychiatrist at King’s College London who will be researching psychosis at an early outreach clinic in south London. He will investigate why individuals develop the condition using a combination of neuroimaging methods. Prof. Andrew Wilkie has been awarded a programme grant through our Molecules, Genes and Cells stream to explore the consequences of ‘selfish mutations’, which confer a growth advantage to cells in the testes that produce sperm. He and colleagues at the University of Oxford will investigate whether these mutations are more common than thought and whether they contribute to cancers and other complex diseases in the offspring.
Trust renews support for Centres
Kidney anatomy. Medical Art Service, Munich
Prof. Dario Alessi from the University of Dundee will use a project grant awarded through the Physiological Sciences stream to investigate a kidney protein that’s targeted in the first-line treatment for high blood pressure. His work, in conjunction with researchers in Mexico, should improve our understanding of hypertension, which could ultimately lead to new treatments.
‘I’m a Scientist’ celebrates best year yet
Science’s answer to The X Factor – ‘I’m a Scientist, Get Me Out of Here!’ – took place in June, bigger and better than before. For two weeks, over 5000 students from 150 schools read about the work of the 100 scientists involved, asked them questions and joined them in live online chats. They then voted for the scientist they wanted to win, with those with the fewest votes evicted, until a single winner from each of 20 zones was crowned. The event inspired everyone who took part: students formed fan clubs, scientists stayed up all night making videos, and one participant even responded to questions from the toilet queue at Glastonbury. Sophia Collins, co-producer of the event, said: “I think the reason ‘I’m a Scientist’ is so successful is because it makes young people feel empowered – by letting them vote and having their vote count, it gives them a reason to engage with the science,
and shows them that their opinion matters. The fact that the event is real – real scientists, real science, real prize money – makes it a far more vivid experience.” The event will run again next year, with core funding from the same Welcome Trust Society Award. The team is also looking to run similar events in other countries and is seeking local partners. imascientist.org.uk
A participant in the Avon Longitudinal Study of Parents and Children being tested.
Our Strategic Award Committee recently renewed funding for a number of our best-known Centres. The Wellcome Trust Centre for Cell Biology at the University of Edinburgh was awarded £5 million over five years to continue its work into the molecular principles that underlie cellular function. Professor David Tollervey will replace Prof. Adrian Bird as Director there in 2011. The Wellcome Trust–Cancer Research UK Gurdon Institute, Cambridge, which promotes research at the interface of developmental biology and cancer biology, was awarded £10m funding over five years. Researchers there study normal animal development, including cell differentiation, morphogenesis and cell proliferation, and aim to understand how cancers may develop when these processes fail. We awarded just under £8m over five years to the Wellcome Trust Centre for Neuroimaging at University College London and its Director, Prof. Ray Dolan. Plans include the development of a model-based framework to better address fundamental questions in systems neuroscience and the breakdowns in function that characterise common neurological and neuropsychiatric disorders. With the Medical Research Council’s Molecular and Cellular Medicine Board, we approved the renewal of core funding for the Avon Longitudinal Study of Parents and Children, at a total of £6m over three years. Running for nearly 20 years, the study has collected, among other information, genome-wide data from over 20 000 mothers, children and fathers.
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Picture this In June, the Wellcome Trust sponsored the first ever conference on comics and medicine at the Institute of English Studies in London. Mun-Keat Looi, science writer and comic aficionado, went along to see out how the graphic medium is helping doctors and patients alike. Comics and medicine may seem like strange bedfellows. The former you may dismiss as a frivolous medium for children, while the latter is a critically important, serious endeavour. But graphic stories are hugely popular among all age groups and are today seen as a legitimate form of literature. And not just fiction: graphic novels have dealt with all kinds of medical and scientific subjects: substance abuse, depression, HIV, diabetes, epilepsy, mental illness. ‘Graphic pathographies’ provide powerful, personal insights into medical conditions. The visual format can communicate the personal experience of conditions such as depression and help to destigmatise and demystify an illness. As Paul Gravett, a writer and lecturer on comics says, creating autobiography and first-person fiction allows graphic novelists to explore aspects of coping with illness, as patient, professional, carer and relative. Researchers have found how combining pictures and text enhances understanding. The activities of reading and viewing activate different information-processing systems within the brain, and the 10 | WellcomeNews | Issue 64
combination fosters connections between new information and existing knowledge. Comic artist and former journalist Brian Fies says comics have the capacity for powerful visual metaphors and universality. The spare and stylised use of text and art allows readers to project themselves into the story. “These powerful images illustrate the patient’s and family member’s experience in a way that standard clinical reportage could never achieve with such economy,” says Dr Michael Green, a physician and bioethicist at Penn State University. Green runs a course for fourth-year medical students at Penn State College of Medicine. This uses comics to enhance observational and communication skills and improve understanding of patients’ experience of illness. The novel approach helps students to consider discrete elements more efficiently than if they’d been assigned a whole book to read. Further evidence comes from Professor Keith Stevenson, Stella Williams and Dr Paula Nunes of the University of the West Indies, who have used cartoons to make the
For the 2010 Glasgow West End Festival, the Wellcome Trust Centre for Molecular Parasitology produced a comic to raise awareness of the parasitic disease trypanosomiasis.
‘mundane’ topic of communication skills – which medical science students rarely take seriously – ‘come alive’. Reading graphic stories may enhance students’ observational and interpretive skills, as well as raising awareness of broader social and political issues associated with medicine. The comic series Depresso by Nottingham-based artist Brick, for example, has been used to train student mental health workers and is recommended by GPs to patients. M K Cserwiec, a nurse and graphic artist, has found that the graphic medium can circumnavigate the professional detachment that comes from wearing a ‘white coat’. She has asked caregivers to draw their experience of an illness from the point of view of a professional and a patient. Those drawn from a patient
perspective were full of emotion and empathy, but that was lost when taking on a professional capacity. Obstacles remain in challenging people’s preconceptions and biases against comics: presenting comic-form information may seem flippant to some. But challenging these preconceptions has its benefits. As Fies said: “It gives people information they didn’t have before in a way they hadn’t seen before. That a comic could do that come as a surprise to people.” For a longer version of this article see: www.wellcome.ac.uk/comics References Green MJ, Myers KR. Graphic medicine: use of comics in medical education and patient care. BMJ 2010;340:574–7. Graphic Medicine: www.graphicmedicine.org
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Research Researchers probe lizard malaria parasites
Ameiva ameiva lizard. Dario Sanches
Trust-funded researchers in Brazil have published the first description of the malaria species Plasmodium carmelinoi, which infects the Ameiva ameiva lizards common in South and Central America. Professor Ralph Lainson, who led the research, says that as the parasite does not cause disease to its hosts, this suggests that the two have an ancient and wellbalanced relationship. This contrasts to other Plasmodium species (such as P. falciparum, the most common cause of
malaria in humans), which provoke a violent reaction in the host, often leading to disease and the death of both organisms. The researchers have encountered a wide variety of malarial parasites in a range of lizard species and have yet to find any evidence of disease.
Poverty linked to mental health disorders, review finds Over the last 20 years, researchers have been debating whether common mental disorders, such as depression and anxiety, are linked to poverty in low- and middle-income countries. Now, a systematic review funded by the UK Department for International Development has strengthened evidence for such a link, and added weight to calls to include mental health on the agenda of development agencies and international targets such as the Millennium Development Goals. Researchers, including Wellcome Trust Senior Research Fellow Professor Vikram Patel from the London School of Hygiene and Tropical Medicine, looked at 115 studies, most of which reported positive associations between a range of poverty indicators and common mental disorders. Some factors, notably education, food
Lainson R et al. Plasmodium carmelinoi n. sp. (Haemosporida: Plasmodiidae) of the lizard Ameiva ameiva (Squamata: Teiidae) in Amazonian Brazil. Parasite 2010;17:129–32.
Antibiotics offer ‘vaccine-like’ immunity to malaria Antibiotics could help to generate ‘vaccinelike’ immunity against malaria – an alternative to traditional immunisation that uses weakened pathogens. Researchers from the KEMRI–Wellcome Trust Research Programme in Kenya and colleagues found that if mice were infected with malaria parasites and given preventative antibiotics, they developed immunity against reinfection. If proved to work in human clinical trials, this could help to control or eliminate malaria in high-risk populations, particularly young children. The researchers showed that two antibiotics – clindamycin and azithromycin – caused a defect in the malaria parasites when they entered the liver. This didn’t prevent them from multiplying, but it did stop them from changing into the disease-causing form that 12 | WellcomeNews | Issue 64
enters the bloodstream. This buys the immune system time to mount a defence – a response robust enough to protect against subsequent infections 40 days after the ‘immunisation’, even without the presence of antibiotics. Friesen J et al. Natural immunization against malaria: causal prophylaxis with antibiotics. Sci Transl Med 2010;2(40):40–9.
Clindamycin capsules. sparktography on Flickr
Children in rural Pakistan. N Durrell McKenna
insecurity, housing and financial stress, were strongly associated with mental health issues. Others, including income and employment, were less strongly linked. Concluding, the researchers warn that development policies aimed at economic growth may not necessarily carry mental health benefits: “It is interventions that promote security, education, social welfare and health safety nets that are more likely to protect the mental health of populations, and allow for the full development of human potential.” Lund C et al. Poverty and common mental disorders in low and middle income countries: a systematic review. Soc Sci Med 2010;71(3):517–28.
Impulsive, weak-willed, or just too much dopamine?
stockcam/iStockphoto
Scientists at the Wellcome Trust Centre for Neuroimaging at University College London have shed light on the brain processes that underlie our willpower and impulsive action. The study shows that increased levels of dopamine, a chemical in the brain involved in mediating reward, motivation
and learning through reinforcement, make us more likely to opt for instant gratification, rather than waiting for a more beneficial reward. Professor Ray Dolan and colleagues tested 14 healthy volunteers given either a placebo or a small dose of L-dopa, a dopamine-like drug. Subjects were asked to make a number of choices consisting of either a ‘smaller, sooner’ option (for example receiving £15 in two weeks) or a ‘larger, later’ option (such as receiving £57 in six months). The researchers found that every subject was more likely to behave more impulsively – choosing the smaller, sooner option
– when levels of dopamine in the brain were boosted by L-dopa. The findings may help to explain why people affected by conditions such as attention deficit hyperactivity disorder tend to show extremely impulsive behaviour. Similarly, this highlights why such behaviour is a potential negative side-effect of L-dopa, used to help to alleviate the symptoms of Parkinson’s disease Pine A et al. Dopamine, time and impulsivity in humans. J Neurosci 2010 [Epub ahead of print].
Research reveals brain cells’ role in breathing
Teen antisocial behaviour shows in the brain
Astrocytes (green) in culture. Yirui Sun
parema/iStockphoto
The onset of severe antisocial behaviour in teenagers may be more than just ‘falling in with the wrong crowd’. A new study reveals that young adults with conduct disorder display an abnormal pattern of brain activity compared with their peers. Scientists from the Medical Research Council Cognition and Brain Sciences Unit and the University of Cambridge used functional magnetic resonance imaging to measure and analyse the brain activity of 75 teenage boys while they were shown images of angry, sad and neutral faces. The scans showed lower activity in the areas of the brain responsible for processing emotions in those with either childhoodonset or adolescence-onset conduct disorder. This may explain why teenagers
with conduct disorder are insensitive to the distress of others and to social signals of aggression. The scientists also found that the more severe the aggression and antisocial behaviour in the teenagers, the greater the level of brain abnormality. “There are few effective conduct disorder treatments, so collaborative research like this, which really sheds light on the brain processes behind why and how these disorders emerge, is really important if we’re to help sufferers and their families,” said Dr Andy Calder, who led the research. Passamonti L et al. Neural abnormalities in early-onset and adolescence-onset conduct disorder. Arch Gen Psychiatry 2010;67(7):729–38.
Astrocytes – brain cells named after their characteristic star shape and previously thought to act only as the ‘glue’ between neurons – have a central role in the regulation of breathing, research suggests. Dr Alexander Gourine, a Wellcome Trust Senior Research Fellow at University College London, and colleagues have shown that brain astrocytes can sense the levels of carbon dioxide in the blood. These then activate neuronal respiratory networks that increase our breathing in line with prevailing metabolism and activity. The finding may help to explain the causes of devastating conditions associated with respiratory failure such as sudden infant death syndrome. “This research identifies brain astrocytes as previously unrecognised crucial elements of the brain circuits controlling fundamental bodily functions vital for life,” said Dr Gourine. “It indicates that they are indeed the real stars of the brain.” Gourine A et al. Astrocytes control breathing through pHdependent release of ATP. Science 2010 [Epub ahead of print].
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“ Events, dear boy, events” The biotechnology revolution is seeing an explosion of new knowledge, materials, skills and technologies, nearly all of them produced with the benign aim of improving public health. But those same scientific findings and products could also be used in bioterror or, worse, biowarfare – a problem known as the dual-use dilemma. How real is the threat and what can we do about it? Penny Bailey talks to Trust-funded researchers who are investigating. In June 2000, biologist Professor Matthew Meselson wrote: “Every major technology – metallurgy, explosives, internal combustion, aviation, electronics, nuclear energy – has been intensively exploited, not only for peaceful purposes but also for hostile ones. Must this also happen with biotechnology, certain to be the dominant technology of the twenty-first century?” This potential for scientific findings produced to improve public health to be used for malign ends, such as war or terrorism, is known as the dual-use dilemma. While biosecurity experts are increasingly concerned about the possible hostile misuse of biotechnology, scientists have tended to see the threat as either remote, or outside their responsibility, and 14 | WellcomeNews | Issue 64
few bioethicists have focused on the issue. In 2009, a collaboration of researchers at the Universities of Bradford, Exeter and Bath, and the Australian National University in Canberra, was awarded a Wellcome Trust Enhancement Award, to build sustainable capacity among bioethicists globally to explore the dualuse dilemma. Although the threat may not be large at the moment, it is real. That has already been demonstrated by the series of large-scale offensive biological warfare programmes carried out by major states such as Japan, France, the USA, the USSR and the UK in the last century, and by recent bioterrorist attacks such as the 2001 anthrax letters in the USA.
Controlling weapons Clearly, if biological weapons were to become a routine part of states’ armed forces, the consequences for international security and global health could be devastating. The Biological and Toxin Weapons Convention, signed and ratified by 163 states to date (with 13 additional signatories), came into force in 1975, to deter state-level assimilation of such weapons. The Convention commits all parties to prohibiting the development, production, and stockpiling of biological and toxin weapons. However, it has no organisation to look after it and no system of formal verification, such as onsite inspections, to ensure compliance. This means that countries could, in practice, stockpile biological agents for offensive ends. Moreover, although it bans research for offensive purposes, the convention permits research into biological agents or toxins for medical and defensive purposes, in small quantities. And faced with the shadowy threat of bioterrorism, many states have thriving biodefence industries. Such research, as Dr Tom Douglas at the University of Oxford points out, could be used to enable biological attack capacities as well. “There’s a thin line between
defence and offence.” In the USA, the biodefence industry has grown tenfold in the wake of the anthrax letter bombs in 2001 – ironically, expanding the pool of potential terrorists. “So there are now ten times as many people who could defect, or become deranged in some way, and decide they have a grudge they want to follow,” says Dr Douglas. Indeed, the perpetrator of the 2001 anthrax attacks was later revealed to have been a scientist employed in the US government’s biodefence laboratories. Sceptics counter that we still don’t really know how to make a pathogen dangerous or to disseminate it widely, and that to do so requires state-of-the-art technology. However, Dr Douglas points out that what is state-of-theart now probably won’t be in ten or 20 years time. “Amateur biologists could make weaponised agents in a garage or basement lab. You could argue there are enough crazy people in the world, and it’s only a matter of time before someone does.” A few high-profile cases have illustrated how easy it could be to create such agents. In 2001, scientists accidentally created a highly virulent mousepox strain, simply by inserting one extra gene into the viral genome – and published the information, albeit with a warning to scientists to be aware of the potential consequences of research. And in 2006 a Guardian reporter purchased a 78-nucleotide sequence of DNA based on the smallpox genome from a commercial company with alarming ease – bearing in mind the fact that the full-genome smallpox sequence is readily available on the internet. Those cases can be disregarded to some extent. The mousepox strain was eventually shown to be less virulent than at first feared, and reconstructing the 185 000-base-pair smallpox genome from such a small sequence would be extremely challenging, if not impossible. However, Dr Brian Rappert at the University of Exeter believes that the more problematic issue is the general development, proliferation of knowledge and expertise in science, which open up huge new possibilities, and are widely published in journals and on the internet. “Basic blue skies research, which is so needed for public health issues, is the same kind of proliferation that security people look at and think, ‘oh dear’,” he says.
Protecting freedom One of the difficulties is finding a way to prevent hostile misuse of science, without impeding scientific progress and the freedom to publish. Policy makers and biosecurity experts have advocated downstream regulation, such as export controls and laboratory security requirements, to prevent dangerous agents and technologies from falling into the hands of possible hostile users. But, says Dr Rappert, they generally
While biosecurity experts are increasingly concerned, scientists have tended to see the threat as remote or outside their responsibility
convention, nationally implemented, attempting to prevent the misuse of their work. And they’ve got some responsibility for maintaining and developing the convention. For instance, they should make sure that their students are educated about these dangers and what might be done.” On a practical level, engaging the scientists is essential. “Without scientists involved I don’t think there are going to be effective or sensible policies,” says Dr Rappert. “Oversight and codes of conduct can’t be put in place by security and policy people who have no connection to how life science research is practised. So until scientists are aware of this problem, and thinking about it, it’s difficult to see anything meaningful being done.”
haven’t thought deeply about the wider implications of scientists conducting and publishing work. The problem is compounded by the fact that many scientists have tended to believe that knowledge in itself is intrinsically valuable and ethically neutral, and that how it is used is the responsibility of politicians.
Culture change The need to think about their work in terms its potential for harm is likely to be counterintuitive for many scientists, who see their research as something of immense value for society – a means of enhancing health and lives. Getting them to think about the possible ways that the new knowledge
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Krakozawr/iStockphoto
However, ethics work by the researchers funded by the Trust Enhancement Award has concluded differently. “The question is, what can you reasonably ask of a scientist?” says Professor Malcolm Dando at the University of Bradford. “It’s not reasonable to ask people to have responsibility for things that are way outside their control. But you can reasonably suggest to them that they should be aware of the possibility of misuse, and that there is an international
they generate could be misused is not something that can happen overnight. “We’re looking for cultural change,” says Dr Judi Sture at the University of Bradford, who is overseeing the development of an ethical framework with which to approach the dual-use dilemma. “We want to see the community of life scientists undertaking the transformation that medics undertook after WWII. As I understand it, it’s very difficult now for a medical student to graduate without being aware that there WellcomeNews | Issue 64 | 15
Rowena Dugdale
are ethical issues in almost everything they do. And that they have a responsibility to think about these things and to act in an ethical way. It’s going to go through a process of professionalisation and become part of professional identity.” To set the ball rolling, in 2004 Professor Dando and Dr Rappert began delivering interactive workshops, which they have since taken to 13 countries, including Argentina, Uganda and Japan, to engage scientists with the issue. “As we went to all these seminars, we were becoming more and more wide-eyed at the fact that we could hardly find anybody who knew anything at all about how their work could potentially be misused,” says Professor Dando. They realised they needed to start earlier, by educating science PhD students on the dual-use dilemma. “People with advanced degrees should have some more meaningful training or education and at least have thought about these things,”
says Professor Dando. To this end, the group have developed an online educational module resource, in collaboration with Japanese colleagues. It can be incorporated into life science and associated teaching modules and is freely available online (see below). The Bradford group has also developed a Master’s-level distance learning module, to be rolled out in October 2010, which offers students two hours of lectures on the dualuse dilemma per week, and a seminar and discussion group requiring them to think about a range of ethical dilemmas, such as whether they would undertake or publish a piece of work, based on ethical analysis using the principles and underlying ethical themes developed within the Bradford group’s framework. The group will be presenting its educational module and ethical framework, along with findings from international surveys exploring existing thinking on the dual-use dilemma, at the
2011 Review Conference of the Biological and Toxin Weapons Convention. “We’re hoping that the state parties will agree that scientists should have a legal obligation to train young scientists in these issues, and show that they’ve thought about them in relation to their work. That’s the holy grail,” says Dr Simon Whitby at Bradford. There are signs that things are changing. In a significant development in the USA, the National Science Advisory Board for Biosecurity recently recommended that all federally funded institutions should be required to provide ethics education, including biosecurity and the dual-use dilemma. However, the researchers believe that ultimately the spur to get scientists deeply engaged with the possible misuse of their work will be when they actually see it happen, in an event such as a bioterrorist attack. Says Professor Dando: “It’s down to what Macmillan said: ‘Events, dear boy, events’!”
Want to know more? • • • • •
Biological and Toxin Weapons Convention: www.opbw.org Disarmament at the UN Office at Geneva: www.unog.ch/disarmament The Life Sciences, Biosecurity, and Dual Use Research: projects.exeter.ac.uk/codesofconduct/BiosecuritySeminar/ US National Science Advisory Board for Biosecurity: oba.od.nih.gov/biosecurity/biosecurity.html Bradford distance learning dual-use module: www.brad.ac.uk/bioethics
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Research More openness could boost blood banking, research suggests
NHS Blood and Transplant
The act of giving blood is associated with notions of community and contributing to the greater good. But blood services today are an increasingly complex business clouded by issues such as the use of blood for research as well as the clinic, distribution and contamination. Dr Helen Busby from the University of Nottingham interviewed 26 donors at
one UK blood centre as part of a wider programme of work about blood banking and biobanking. She found that donors often don’t appreciate the complex issues surrounding blood donation. There was a lack of knowledge and understanding of how their contribution would be used – few knew, for example, that just 8 per cent of blood donations in England and Wales are used in emergencies. Dr Busby found an implicit trust in the National Blood Service to use the blood and blood products as they saw fit, though there was a strong emphasis on the voluntary act of giving blood and contributing to the NHS, a service many were grateful for. She calls for blood services to be more open about how blood is used and processed, and for this to be better communicated to the public. Though such information is openly available, little effort is made to emphasise this. She suggests that a more open discussion could help modern blood services in the long run as traditional aspects of blood banking fail to attract the donations needed to sustain demand. Wynne Busby H. Trust, nostalgia and narrative accounts of blood banking in England in the 21st century. Health 2010;14:369–82.
Researchers find new role for matrix molecule in memory Once regarded as an inert scaffold or ‘glue’, the extracellular matrix – the molecules that surround and support animal cells – has been shown to have crucial roles in the function of organisms. Now, an international team of researchers has identified a new role for an extracellular matrix molecule in memory and learning. Hyaluronic acid is a key part of the extracellular matrix. The team, co-led by Wellcome Trust Senior Research Fellow Professor Dmitri Rusakov from the University College London Institute of Neurology, looked at the role of this molecule in the activity of synapses in the brain. They studied slices of mouse and rat hippocampus, a brain region involved in memory and learning. The researchers conclude that hyaluronic acid regulates a particular kind of calcium channel found in nerve cells, and so affects use-dependent changes in the strength of synaptic connections (plasticity) – in particular, long-term potentiation, a mechanism thought to underlie learning and memory. The researchers also showed that removing hyaluronic acid from the brains of mice impaired their ability to learn to fear a particular stimulus, further linking this molecule to memory and/or learning. Kochlamazashvili G et al. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels. Neuron 2010;67:116–28.
Pregnancy, vision and ageing: latest Trust films online
Should pregnant women eat for two? Why do we age? How do we see things? These are just some of the questions posed by the latest films from the Wellcome Trust and Wellcome Collection. The phrase ‘eating for two’ is often used when talking about the diet of pregnant women. But how does the mother’s diet determine her child’s future health?
In these two new films, the Trust’s own Jennifer Trent Staves investigates the nutritional science aiming to help mothers build healthy babies. In ‘Blue Death’ (left), David Gems from University College London’s Institute of Healthy Ageing and his student Cassandra Coburn take us on a journey exploring the nature of ageing and explain how they are using the nematode worm to unravel its mysteries. Watch these at www.youtube. com/wellcometrust. How do we actually see things? What our brains bring to perception matters as well as what meets the eye, making our learning an essential part of making sense of the world. At ‘Seeing Myself See’, an event held at Wellcome Collection in
May 2010 (below), the audience were be able to experience the visual world in a completely new way – in sound. At www. youtube.com/wellcomecollection, join event creator and neuroscientist Beau Lotto as he talks us through the activities of this fascinating evening.
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Research High-fat maternal diet linked to birth defects
Shyman/iStockphoto
Pregnant mothers who eat a high-fat diet before and during pregnancy could be putting their unborn child at risk of congenital heart disease, according to researchers at the Wellcome Trust Centre for Human Genetics in Oxford. Their study suggests that a mother’s diet may interact with the genes of their offspring. The researchers studied mice lacking a gene called Cited2, deficiency in which leads to heart defects. The mice were fed on a high-fat diet before and throughout pregnancy, resulting in offspring with double the average risk of atrial isomerism – a serious heart defect – and a more than seven-fold increase in the risk of cleft
palate. The offspring of a control group of mice, also lacking Cited2 but fed on a balanced diet, were normal. Further analysis showed that these factors affect the expression of another gene called Pitx2, required for heart development and the body’s natural asymmetry. “We are excited by this as it suggests that congenital heart defects may be preventable by measures such as altering maternal diet,” said Dr Jamie Bentham, one of the researchers.
A study has added to the evidence that taking vitamins C and E does not lower the risk of pre-eclampsia in women with type 1 diabetes – a condition linked to reduced antioxidant levels – but vitamins may help those with low levels of antioxidants. Researchers gave vitamin or placebo pills to 762 pregnant women with type
More genes linked to diabetes An international consortium of scientists, led by researchers from the Wellcome Trust Centre for Human Genetics at Oxford, has identified 12 new genes associated with type 2 diabetes in the largest ever genetic study of the condition. Though the individual effect of each of the 12 regions is small, the findings bring the total number of genetic regions known to be associated with type 2 diabetes to 38. This could ultimately have a substantial impact on our understanding of the biology of diabetes, and on the development of therapies. Voight B et al. Nat Genet 2010;42(7):579–89.
Bentham J et al. Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects. Hum Mol Genet 2010 [Epub ahead of print].
Vitamins don’t lower pre-eclampsia risk in women with diabetes
Anthea Sieveking
Round-up
1 diabetes recruited from clinics around the UK. The rate of pre-eclampsia was similar in both groups (15 per cent in the vitamin group vs 19 per cent in the control group). However, there was a significantly lower risk in women with low levels of antioxidants who took vitamins. The authors suggest that the vitamins may be being given too late in pregnancy to affect pre-eclampsia and question whether individual vitamin supplements carry the benefits of other interventions, such as a diet high in antioxidant fruit and vegetables. However, contrary to previous research, they found no evidence that vitamin C and E supplements cause harm to mothers or babies. Antioxidant vitamins also tended to reduce the risk of having a low-birthweight baby and fewer babies were born early to women taking vitamin C.
The structure of insulin. Anna Tanczos
Cancer drug study yields first results The largest study to correlate genetics with response to cancer drugs has released its first results. The researchers behind the study, based at Massachusetts General Hospital Cancer Center and the Wellcome Trust Sanger Institute, describe in this initial dataset the responses of 350 cancer samples to 18 anticancer therapeutics. These first results, freely available on the Genomics of Drug Sensitivity in Cancer website, will help cancer researchers around the world to seek better understanding of cancer genetics and could help to improve treatment regimens. www.sanger.ac.uk/genetics/CGP/translation/
McCance DR et al. Vitamins C and E for prevention of preeclampsia in women with type 1 diabetes (DAPIT): a randomized placebo-controlled trial. Lancet 2010 [Epub ahead of print]. Lung cancer cells. Anne Weston, LRI, CRUK
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Protein shape change ensures pick-up in right places
Q&A: Cora Araújo We often have a skewed perception of how we look, particularly when it comes to weight. This can be particularly acute in teenagers, already uncomfortable with the rapid changes in their bodies. With funding from the Wellcome Trust, Dr Cora Araújo and colleagues studied this in a group of over 4400 teenagers from the Pelotas birth cohort in Brazil. What is the Pelotas birth cohort? The 1993 Pelotas (Brazil) Birth Cohort Study tracks all the 5249 children born in the city of Pelotas, southern Brazil, during 1993. These individuals were visited on several occasions from birth to adolescence. The cohort was set up to evaluate the influence of prenatal, infancy and childhood exposures on health throughout their lifespan. What was the aim of your study? To compare adolescents’ self-perceived body image with their measured body size.
Depiction of cell membrane with different receptor types. Medical Art Service, Munich
Research has shown the complex molecular rearrangement that ensures a key cell membrane transport machine binds only to cargo proteins when in the correct environment. The discovery furthers our understanding of how membrane-embedded proteins are transported between cell membranes in vesicles, a process vital for cell signalling, homeostasis and cell–environment interactions. ‘Pinching off’ a small portion of any membrane produces a vesicle, many of which become coated with a scaffold made of the protein clathrin. Adaptors link the clathrin to the membrane and select which proteins are included into the vesicle as cargo. Researchers from the Cambridge Institute for Medical Research have found that the one of the most abundant adaptors, AP2, changes its structure radically when binding its cargo. This change unblocks AP2’s two cargo interaction sites and, at the same time, puts them on the same plane as AP2’s membrane binding sites so that all the sites can be used simultaneously. Jackson LP et al. A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex. Cell 2010;141(7):1220–9.
What were your findings? Overall, two-thirds of the adolescents we met have a self-perception of their body image that agrees with their measured body size. However, a third of them either think they are too thin when this is not true, or too fat when this is not the case. Boys are more likely to wrongly consider themselves as being too thin, whereas girls are more likely to consider themselves as being too fat, even when their body size is adequate. What impact did the parents have on this? Parents’ perceptions were a key influence on how the adolescents saw their body image. When the parents had a skewed judgement of their kids’ body image, adolescents were more likely to also have a skewed opinion. This suggests that part of the reason why kids have a distorted view of their body size is their parents’ perceptions. What are the implications of your findings for health education? Parents need to be aware of what a healthy body size is. That way, they can help reassure their children that they are not too thin or too fat when that
is not the case. Providing parents with information and guidance on these issues may aid this, and avoid parental views distorting a child’s body image. Additionally, it is important to highlight publicly that the bodies of high-performance athletes and supermodels are not necessarily examples of adequate and healthy body sizes. How does this study compare to other studies done in Europe, the USA or elsewhere? Our findings are similar to those observed elsewhere, particularly in highincome countries, which suggest that teenage girls tend to visualise models and try to copy their body shapes. Similarly, teenage boys tend to visualise sports starts and try to build similar muscles. Distortions in adolescents’ body image are an important public health issue in the developed world, and an increasing problem in low- and middle-income countries. But little data on these issues are available outside high-income countries. Further studies like this are vital in filling this gap. What do you do outside of work? I like walking outdoors with friends and drinking chimarrão [a typical hot drink in Brazil] on the weekends with friends and family. I love being by the beach and usually go on vacation along the coast of the Rio Grande do Sul state in Brazil. Araújo CL et al. Measured weight, self-perceived weight, and associated factors in adolescents. Rev Panam Salud Publica 2010;27:360–7.
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Illuminating the Lady with the Lamp Few figures in medical history have been as fascinating and enduring as Florence Nightingale, who died 100 years ago this August. The Wellcome Library’s Ross MacFarlane guides us through some of the items in the Library’s collection that shed light on her life, and how it’s been viewed ever since. Around the Wellcome Library’s main Reading Room runs a frieze containing the names of some of the most famous figures in medical history. Installed in 1962, it names 29 men but only one woman. The woman in question – Florence Nightingale – would perhaps see this imbalance as apt, as she was often characterised as a lone female bringing care to the wounded, while arguing with the male authority figures of the British Army. In the year that marks the centenary of her death, it’s particularly worthwhile to note that the Library’s materials offer a great insight into not only her pioneering life but also how she was judged by her contemporaries and reinterpreted by later generations. Our collections include a sizeable amount of Nightingale correspondence: hundreds of manuscript letters, spanning the whole of her life and many aspects of her career, including her attempts to become a nurse, her famous service during the Crimean War and subsequent work reforming nursing, through to her concerns with sanitation, cottage hospitals and medical statistics. The last of these topics is illustrated by her lengthy correspondence with William Farr, one of the leading epidemiologists of the 19th century, who collaborated with Nightingale in providing statistical evidence for sanitary reform. She became the first female member of the Royal Statistical Society in 1858 – in no small part owing to her graphical representation of statistics, mostly notably the polar area diagram (or Nightingale rose diagram), a 20 | WellcomeNews | Issue 64
form of pie chart (below). Our collections also cast a more disparaging light on Nightingale. For example, the letter book of Sir John Hall, Head of Medical Services during the Crimean War, paints a less than flattering portrait. Hall writes to his superiors defending the Army Medical Services from
her criticisms, also arguing that her intervention deprived the Army of good nurses who were working in the Crimea before her arrival. Hall pulls no punches in accusing Nightingale of arrogance and being an interfering busybody desperate for power – a “petticoat imperium”. However, the romanticised representations of Nightingale – often in object form – of the late 19th century are
mirrored in the visual representations the Library holds. Lithographs, prints and paintings, all putting a positive spin on her activities in the Crimea, show how she was objectified and romanticised. Ever since Lytton Strachey’s revisionist account of Nightingale in his classic Eminent Victorians (1910), her life has been interpreted and reinterpreted by each generation. Understandably, given the range and scale of the sources described above, many of these biographies – such as Mark Bostridge’s Florence Nightingale: The Woman and her Legend (2008) – have used our resources and, on publication, have gone on to find a space in our collections. Perhaps we can leave the last word to Nightingale herself, through her own voice in a recording made in 1890 to raise money for the impoverished veterans of the Charge of the Light Brigade (you you can hear it at catalogue.wellcome.ac.uk/ record=b1590740~S3): “When I am no longer a memory, just a name, I hope my voice may perpetuate the great work of my life. God bless my dear old comrades of Balaclava and bring them safe to shore.”
Florence Nightingale Museum 2010 has also seen the reopening of the Florence Nightingale Museum, following a £1.4 million redevelopment supported by the Wellcome Trust, Guy’s and St Thomas’ Charity and Garfield Weston Foundation. www.florence-nightingale.co.uk
Seeding Drug Discovery
A £200 million funding initiative to facilitate early-stage small-molecule drug discovery. Projects must address an unmet need in healthcare and have a realistic expectation that the product will be developed further by the market. Researchers from academia and companies are invited to apply by 19 November 2010. www.wellcome.ac.uk/sdd/wn
Courses, conferences and workshops
A gene map of the malaria-causing Plasmodium falciparum genome.
GC: Event takes place at the Wellcome Trust Genome Campus, Hinxton, Cambs. For information on Wellcome Trust Conferences, see www.wellcome.ac.uk/conferences. For information on Advanced Courses and Open door Workshops, see www.wellcome.ac.uk/advancedcourses.
January 2011 23–28 Genomics and Clinical Microbiology Advanced Course GC
February
May
14–27 Mathematical Models for Infectious Disease Dynamics Advanced Course GC
18–22 Nicotinic Acetylcholine Receptors 2011 Conference GC
20–26 Malaria Experimental Genetics Advanced Course GC
July
March 23–27 Genomic Disorders 2011: The genomics of rare diseases Conference GC 30–1 Apr Cellular Cytoskeletal Motor Proteins Conference GC
April 10–21 Computational Molecular Evolution Advanced Course GC
20–23 The Genomics of Common Diseases 2011 Conference GC 23–29 Human Genome Analysis: Genetic analysis of multifactorial diseases Advanced Course GC
August 7–22 Drosophila Genetics and Genomics Advanced Course GC
WellcomeNews | Issue 64 | 21
OPEN TUESDAY–SUNDAY (UNTIL 18.00) LATE-NIGHT THURSDAY (UNTIL 22.00)
www.wellcomecollection.org
NEW FREE EXHIBITION 12–22 OCTOBER
A CALL TO UPDATE HENRY WELLCOME’S CURIOUS COLLECTION. PLEASE GIVE US A ‘THING’ NO BIGGER THAN YOUR HEAD OR COME FOR A SNOOP! See online for details: www.wellcomecollection.org/things
A FREE DESTINATION FOR THE INCURABLY CURIOUS