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WellcomeNews ISSUE 56 OCTOBER 2008

Happy returns Career Re-entry Fellows profiled Heart of the matter Ethnicity and cardiovascular disease Striking a chord Guitarist’s recovery from brain tumour The Glasgow Spy A tale from the Wellcome archive

Wellcome News


Wellcome News is published four times a year and is available free of charge. To subscribe, contact: Publishing Department Wellcome Trust FREEPOST RLYJ-UJHU-EKHJ Slough SL3 0BP T +44 (0)20 7611 8651 F +44 (0)20 7611 8242 E or go to: We positively encourage letters to the Editor and suggestions for future articles. Please contact: The Editor Wellcome News Wellcome Trust Gibbs Building 215 Euston Raod London NW1 2BE E Editor Chrissie Giles Writers Chris Beckett, Craig Brierley, Chrissie Giles, Chris Newstead, Michael Regnier Design Cosima Dinkel Assistant Editor Tom Freeman Photography David Sayer Publisher Hugh Blackbourn All images, unless otherwise stated, are from the Wellcome Library. Copies of images can be obtained through Wellcome Images (

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 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. 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, 2008. © The trustee of the Wellcome Trust. The Wellcome Trust is a charity registered in England, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England, no. 2711000, whose registered office is at 215 Euston Road, London NW1 2BE, UK. PU-4235.2/13K/10-2008/CD Cover: Dr Jennifer Rohn, a Wellcome Trust Career Re-entry Fellow. See page 5.


This document was printed on material made from 25 per cent post-consumer waste & 25 per cent pre-consumer waste.

WellcomeNews | Issue 56

Biology is always fascinating, but there is a particular mystery to neuroscience that captivates and charms. Watching a real-time video of a nerve cell growing, sending out its tiny growth cones as it searches for the correct path to take, gives us a glimpse at how the remarkable wiring of the nervous system is laid down during development. When a bee works out the best route to take as it flies between flowers with just 1 million neurons, it is solving problems that a supercomputer could take a week to answer. And yet such delights are tempered by brain images from people with Alzheimer’s disease – seeing the destruction wreaked in the brain by this neurodegenerative disease brings home the devastating impact it has on the lives of those afflicted and on their relatives, friends and society at large. At the Wellcome Trust, we are fortunate to be able to fund so many talented neuroscience researchers in the UK and internationally. We fund research that includes molecular and cellular neuroscience, cognitive, neuropsychological and imaging studies, and clinical studies investigating neurological and psychiatric conditions. And, as a browse through the news section of our website ( shows, this research is bringing many new insights. In the last few months, for example, we have seen studies of the chemicals that send messages between nerve cells showing that acetylcholine is vital for our brain cells to pay attention to a demanding task, and that serotonin plays a critical role in regulating emotions such as aggression during social decision making. Meanwhile, new retinal ganglion cells have been discovered that control our levels of sleepiness according to the brightness of our surroundings.

Other researchers are using scanners to identify the parts of the brain that become activated when we perform particular tasks. Such approaches have shown that the ventral striatum encourages us to be adventurous – it becomes activated when we choose unfamiliar options – and that the brain regions responsible for stopping habitual behaviour are underactive in people with obsessive–compulsive disorder and their unaffected close relatives. The challenge for neuroscience – as in all areas of biomedical science – is to find ways of taking basic research forward to help people. Some areas have seen considerable success: for example, a modern look at psychology has been developed by a cadre of talented researchers into highly successful cognitive behavourial therapies for mental illnesses such as bulimia nervosa, post-traumatic stress disorder and panic disorder. But in other areas there is still much to do, particularly for dementia and neurodegenerative diseases. Indeed, as reported on page 10 of this issue, previous estimates of levels of dementia in developing countries may have substantially underestimated the problem – the 10/66 Dementia Research Group has found that the prevalence of dementia in urban settings in Latin America is comparable with rates in Europe and the USA. As part of our commitment to invest in this area, in October 2007 we awarded £1.3 million funding to a collaboration of leading UK experts to investigate the genetics underlying late-onset Alzheimer’s disease. The team is scanning the entire human genome in search of the genes that predispose people to or protect them from developing the disease. Now, in a joint activity with the Medical Research Council, we have launched a new scheme of Strategic Awards in Neurodegenerative Diseases. Such diseases take several different forms, and include Alzheimer’s disease, frontal temporal dementia, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. We hope that this £30m scheme will help to bring greater understanding of the biological processes underlying these diseases, and will catalyse the development of early diagnostic approaches and new, effective therapies. Mark Walport Director of the Wellcome Trust

in this issue news






features Back to the bench


Vive la différence


Finding Pat Martino


The Glasgow Spy




Unravel the strange case of the Glasgow Spy (top), learn about the relationship between maternal diet and child health (above left), discover how jazz guitarist Pat Martino regained his music after losing it to amnesia (above right), meet Liverpool’s lambanana leishmaniasis sculpture (right), and more… WellcomeNews | Issue 56


Flu fighters

Wellcome to India

On the record

Wellcome Trust-funded researchers are to examine what is preventing the H5N1 avian influenza virus from causing a human pandemic, and what mutations are required to realise its deadly potential. The research could hold the key to early identification of a potential influenza pandemic, and to developing drugs and a vaccine. Professor Ten Feizi at Imperial College London believes one reason that H5N1 has not yet evolved into an effective pathogen capable of widespread transmission between humans lies in how the virus attaches itself to the respiratory tract. She is leading an international research project, which has received over £720 000 from the Trust, to identify the receptor molecules in the human respiratory tract to which viruses attach. The researchers will also look at how changes in the binding protein on the surface of the virus might increase its ability to attach to the tract and cause infection. For this project, Professor Feizi will work with Professors Menno de Jong and Jeremy Farrar from the Wellcome Trust Southeast Asia Programme in Vietnam, Dr Alan Hay and Dr Steve Gamblin at the Medical Research Council National Institute for Medical Research, London, and Dr Mikhail Matrosovich at the Philipps University of Marburg, Germany.

We are launching a new partnership with the Government of India’s Department of Biotechnology to fund biomedical research in India. Operated as an independent, public charitable trust based in New Delhi, the new alliance will deliver a programme of research fellowship schemes aimed at supporting current and future leaders of Indian biomedical science. Both partners have committed £40 million over the next five years to the venture, through which three new fellowship schemes – at the early, intermediate and senior stages – will be administered. The early and intermediate awards will be launched in late 2008, the senior in spring 2009. Jimmy Whitworth, Head of International Activities at the Trust and one of the venture’s founding trustees, says: “India produces thousands of talented young biomedical researchers with PhDs each year, but the opportunities for them to continue postdoctoral work in their home country is limited, with many only returning to fill research leader roles far later in their careers. The aim of the new funding is to build credible career pathways in India for Indian scientists at all stages.”

We have been working with GPs to create guidance for the use of patient records in research. These guidelines should outline best practice for how patient data – invaluable for guiding research to develop tomorrow’s treatments – can be used by researchers without compromising patient confidentiality.

International news The remit of our biomedical ethics funding in developing countries has recently broadened, and now includes support for research on the ethical issues arising at any point in the development and delivery of healthcare in developing or restructuring countries. Prospective applicants are invited to discuss any ideas for funding in biomedical ethics with the grants team (email; tel. +44 (0)20 7611 8536). We have also launched our International Engagement Awards, which fund projects that encourage public engagement with health research in developing countries. After an impressive response to the first round, 15 awards have been made. internationalengagement

Improved access

H5N1 avian flu has not spread from birds to cause a human pandemic. iStockphoto

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As part of our open access policy, grantholders are required to make their research papers available through UK PubMed Central (UKPMC) within six months of publication. Now, we and other UKPMC funders have announced further support for UKPMC over the next three years, to enhance information retrieval, provide access to additional content, and develop grantreporting functionality.


War and Medicine Don’t miss War and Medicine, the third major special exhibition at Wellcome Collection, which runs from 22 November 2008 to 15 February 2009. Devised in collaboration with the Deutsches HygieneMuseum, Dresden, the exhibition will assess the impact and influence that war and medicine have had on one another. warandmedicine

A military radiographer in protective gear. Photograph by H J Hickman, c.1918.

London’s medical history November 2008 sees the launch of Medical London, a unique publication that charts the role of disease, treatment and cure in London’s history. Written by historian and poet Richard Barnett and edited by author Mike Jay, the publication comprises three elements. Sick City is a book of essays that explores 2000 years of life and death in London and the role of medicine in the city’s life. Anatomy of the City is an illustrated gazetteer that guides you around London’s medical landscape and the tales that lie behind it. Lastly, there are six elegantly designed maps for self-guided walks on a range of topics – from Daniel Defoe’s Plague Year wanderings to the naval surgeons of maritime Greenwich. This stunning guide to London’s medical past is published by Strange Attractor Press, in association with Wellcome Collection, host to a series of events celebrating the book’s publication. It is also being marked by a series of walks based on the sites featured in Medical London, taking place during October. To find out more see and

Literarily speaking

Launched at the 2008 Cheltenham Literature Festival, the Wellcome Trust Book Prize is a new annual competition to recognise and reward the best in fiction and non-fiction writing centred on medicine. The £25 000 prize will be awarded for high-quality literature that explores the human experience of health or illness, or else promotes interest in medicine. An independent panel of judges – chaired for this year by comedian Jo Brand – will decide on a shortlist of six books for the prize, from which the winning title will be chosen in 2009. Among other events at the 2008 Cheltenham Literature Festival was ‘Writers and Remedies’. These five events explored the part played by medicine in the lives and works of writers from the 18th, 19th and 20th centuries, including Jane Austen, Charlotte Brontë, Marcel Proust and Thomas Mann. Building on the success of the ‘Writing Medicine’ events at last year’s festival, ‘Bodies’ was a series of six events for the 2008 festival that were funded through a Wellcome Trust People Award. This series united medical experts and contemporary writers to examine how the two groups consider biomedical issues and how these issues are expressed on the page.

In perspective The first of a series of perspectives on UK science education, Perspectives on Education: Primary Science, was published in September. In it, leading voices in primary education look at primary science in England over the 20th century and give their views on its place in the National Curriculum and on trends in attainment, attitudes and teaching approaches. Download the PDF at

Picture perfect Harriet Foyster, 15, who attends The Priory LSST in Lincoln, is the winner of the Wellcome Image Awards competition, in which entrants described their favourite image from the 2008 Awards in fewer than 100 words. Her choice was an image of a ruptured blood vessel by Anne Weston, which can be seen (along with the other images) at wia. Harriet wins prints for herself and her school, and the chance to be a judge for next year’s Awards.

Top draw The Big Draw 2008, the national campaign to get people drawing, was launched at a unique festival, ‘Drawing on Life’, at Wellcome Collection and University College London on 26–28 September. Over 1000 venues are expected to get involved in The Big Draw, which runs throughout October.

One of Steven Appleby’s cartoons for The Big Draw.

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Superlambanana Liverpool School of Tropical Medicine played host to a very special visitor over the summer: Super‘kalazar’banana, one of 118 ‘lambanana’ sculptures on display across Liverpool as part of the Capital of Culture celebrations. The statue’s distinctive decoration was designed and painted by LSTM staff and is an interpretation of the lifecycle of the Leishmania parasite, which is responsible for 60 000 deaths per year. On the statue, images to represent the parasite, the sand flies that transmit the parasite and human hosts were fused with symbols inspired by Australian aboriginal art. The rear and side of the statue show the insects’ stomachs containing a blood meal with the purple parasites flowing out. The front features a woman, and the white wings and brown eyes of the deadly insect rise in the tail. Super‘kalazar’banana recently sold for £6000.

The Liverpool Super‘kalazar’banana. Shape by Taro Chiezo, design by Rod Dillon and Ektor Diaz.

Prizes for grantholders

Building on broadcast As part of our broadcast activities, a series of ‘Crossover Labs’ are planned for late 2008 and early 2009. These week-long, intensive events bring together professionals from audiovisual production (including TV, web and games) with professionals from other

Charles Darwin, by Franz Carl Muller.

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fields to develop new media projects. We are funding three Crossover Labs – the first to involve scientists – which will be themed around games, documentaries and content for children. This programme follows on from the success of another unique collaborative project: Science on Film. Taught by leading broadcast professionals and scientists, and run in partnership with the Documentary Filmmakers Group, this project brought together eight film makers and eight biomedical scientists on an intensive film production and training scheme. You can watch the resulting films online at A number of broadcast projects to celebrate Darwin 200 (the bicentenary of Charles Darwin’s birth) are also in development. These include Evolution Matters, two programmes about good practice in teaching evolution in primary and secondary schools. We have joined with Channel 4 to fund an alternate reality game for 14- to 19-year-olds around genomics and evolution. Finally, we are commissioning a four-minute animated fly-through of the Tree of Life to form part of David Attenborough’s BBC1 special on Darwin’s birthday.

Funded through a Broadcast Development Award, the film Fireworks by Jonathan Hall and Hannah Robinson was the grand prize winner at the 11th Annual American Screenwriters’ Association International Screenplay Competition. Professor Harold Cook, director of the Wellcome Trust Centre for the History of Medicine at University College London, has won a gold medal in the 2007 ForeWord Magazine Book of the Year Awards for his book Matters of Exchange. Also at UCL, Professor Eleanor Maguire, Senior Research Fellow at the Wellcome Trust Centre for Neuroimaging, has won the 2008 Royal Society Rosalind Franklin Award, given in recognition of an individual’s contribution to the promotion of women in science, engineering and technology. Dr Daniel Freeman from the Institute of Psychiatry, King’s College London, has received the 2008 May Davidson Award from the British Psychological Society’s Division of Clinical Psychology. This award is given in recognition of a clinical psychologist who has made an outstanding contribution to the profession within his or her first ten years of qualifying.

Wellcome Trust Career Re-entry Fellowships provide support for postdoctoral scientists who want to resume their research career after a break of two years or more. Chrissie Giles meets two of the three scientists awarded fellowships this year to find out what they’ve been doing away from science, and how it has been for them getting back to the lab.

Dr Wendy Gaisford, research scientist at the University of Cambridge.

Back to the bench Dr Wendy Gaisford is a research scientist working on autoimmunity and type 1 diabetes at the University of Cambridge. She returned to the lab in March 2008 after 14 years out of science. “I took a break from my job in immunology at the National Institute for Biological Standards and Control to have children. While they were growing I had a number of jobs, including freelance medical writing and working for a science-based computing company. I realised that I didn’t want to be sitting at a computer for the rest of my life and that I wanted to be in the lab again. “I started looking around and found that it was virtually impossible to get back into science – people just don’t want you if you’ve been out for a while. Science moves on very quickly and so the longer you’re out, the harder it is for you to prove that you can get back up to date. “I had been applying for jobs but got rejection after rejection. Then I did an Open University course, T160, which helps women to return to technical jobs. They put me in touch with Cambridge AWISE [Cambridge Association for Women in Science and Engineering], who recommended the Wellcome Trust grant. This grant was the best option, particularly as it pays both the researcher and the lab expenses. “The biggest change since I last worked in science is the technology – it’s just amazing, particularly the way you can identify and sort particular cells. It’s all so much easier now that everything is automated.

“I don’t know where I’m going next but I know this grant has given me the chance now either to stay in academia or get into industry – it’s been brilliant coming back to the lab.” Dr Jennifer Rohn is a postdoctoral researcher working on cell shape at the MRC Laboratory for Molecular Cell Biology at University College London. “I got my PhD at the University of Washington in Seattle and came to London to do a postdoc. After that I joined a small biotech start-up company in The Netherlands. I was there for about four years and it was going really well, but after 9/11 the whole biotech industry in Europe collapsed. I ended up stuck in Amsterdam on the dole for nine months, doing freelance science writing and unable to find a research position. I ended up returning to Britain to go into scientific publishing. “I worked at BioMed Central for 18 months and then moved on to a society journal. I really loved the work but the whole time I had the feeling that I had only left science because I was forced out. The job market was looking better but I didn’t think it was possible to go back to science as I’d been out for four years. “At a party I met Buzz Baum, who runs the lab I’m working in now. He said there might be something in his lab I could do, but could offer only one year’s salary. So I left my cushy, permanent job in publishing and took this in the hope I would get something. I was really lucky to get the Wellcome Trust grant.

“Coming back to the lab was hard – I was really rusty. All the things I knew, I’d forgotten, and it took almost a whole year to get back into everything. “In my spare time I write, and I’ve recently got a book deal for my first novel, so I know if it all went horribly wrong I’d be OK, but I really hope I get a permanent lab position. I don’t regret anything though. My time on the ‘other side’ in science publishing has been really useful. Now colleagues come to me for help with journal submissions – it’s great being a scientist who knows how to write a paper and get it published.”

For more on our Career Re-entry Fellowships, see careerreentry.

Dr Jennifer Rohn, postdoctoral researcher at UCL.

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Unravelling neurodegeneration

Digital artwork representing Alzheimer’s disease. Adrian Cousins

In partnership with the Medical Research Council, we are calling for proposals for Strategic Awards in Neurodegenerative Diseases. The £30 million strategic initiative aims to stimulate high-quality, collaborative research that will advance knowledge of neurodegenerative diseases through interdisciplinary approaches. By addressing key gaps in our knowledge of these debilitating and distressing diseases, this initiative should catalyse the development of much-needed new approaches for early diagnosis and effective therapies. Consortia of leading research groups from the UK and the Republic of Ireland are invited to apply for five years’ funding (up to £5m), which will support the development of collaborative and innovative

interdisciplinary research programmes to investigate the biological processes underlying neurodegenerative diseases, including Alzheimer’s disease, frontal temporal dementia, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Partners may include international researchers and those from the pharmaceutical industry. Preliminary applications must be received by 12 December 2008. More details of the call can be found at neurodegen/wn. Prospective applicants should contact Dr Shewly Choudhury ( or Dr Joanna Latimer (joannalatimer

Enhanced funding for clinicians New support for clinicians, particularly those in the early stages of their careers, comes in the form of several new funding schemes we have launched in September 2008. In collaboration with the Academy of Medical Sciences (who will administer the scheme), we are supporting research-active clinical lecturers who have recently completed their MD or PhD through funding that will allow them to maintain research momentum. The crucial pilot data that will be generated should ensure that this important group of investigators enhance their competitiveness for applications for longer-term funding. Starter Grants for Clinical Lecturers will provide between £15 000 and £30 000 over two years, to contribute to the costs of research consumables. Our Postdoctoral Training Fellowships for MB/PhD graduates provide a unique opportunity for the most promising newly qualified MB/PhD graduates to make an early start in developing independent research careers. The fellowships, which are for up to four years, are open to individuals who have graduated as an MB/PhD or who have achieved a high-quality PhD in a relevant subject either during or before commencing their initial medical, veterinary or dental degree. As part of our commitment to supporting and nurturing excellence in clinical research across disciplines and at all career stages, we have changed our eligibility criteria, meaning that clinical psychologists are now welcome to apply for our range of clinical schemes. Biomedical-science/Grants/Fellowshipsand-personal-awards/

Research evidence in policy making We understand the importance of using evidence from health research in policymaking. As part of our commitment to build capacity in this area, we are making a joint call for proposals with the Alliance for Health Policy and Systems Research (HPSR) for a new initiative, on enhancing capacity to apply research evidence in policy making. 6 | WellcomeNews | Issue 56

Teams based in low-income countries are invited to make brief expressions of interest to the Alliance for HPSR by January 2009. We and the Alliance will then fund the most promising proposals. In total, US$1 million (£550 000) is available for the scheme. For more details see

Clinical scientists can apply for a range of Trust schemes.


Technology Transfer

Infectious ideas

Translation Awards provide funding for applied research and development projects that address an unmet need in healthcare. Who can apply? Wide eligibility – open to both academic researchers and companies. What’s available? Funding to develop the project to the point where there is a realistic expectation that the innovation will be developed further by the market. What's the deadline? Preliminary applications should be received by 17 November 2008. More info: Funding/Technology-transfer/Awards/ Translation-Awards/ Seeding Drug Discovery awards are made as part of a five-year, £91 million initiative to develop drug-like small molecules in an area of unmet medical need. Who can apply? Wide eligibility – open to both academic researchers and companies. What’s available? Funding for two to three years to develop early-stage small molecules to the point where they are attractive to third-party funders – typically at the stage of selection of an optimised pre-clinical candidate. What's the deadline? Preliminary applications should be received by 7 November 2008. More info: seedingdrugdiscovery

South Africa demographic surveillance support Professor Stephen Tollman at the University of Witwatersrand, South Africa has received core funding for his research at the Agincourt demographic surveillance site. This funding follows earlier Wellcome Trust support for the research, which focuses on the health and socioeconomic changes affecting a rural population in transition, near South Africa’s Mozambican border.

Large Arts

Penicillium mould. David Gregory and Debbie Marshall

Two project grants have been awarded to researchers at Imperial College London through the Immunology and Infectious Disease stream. Dr Maria-Gloria Basanez will explore how the differences in cattle and human density affects the spread of onchocerciasis (river blindness), which is transmitted by a black fly. Dr Matthew Fisher and colleagues will study Penicillium marneffei, the only Penicillium fungus to cause serious disease in humans, to find out what makes this particular fungus pathogenic.

We have made three large Arts Awards. One goes to Bridget Nicholls of Animal Alchemy for the 2009 International Arts Pestival, a festival to celebrate insects in art and the art of being an insect. Anna Ledgard has received funding for ‘For the Best’, a performance project with young people attending the Evelina Children’s Hospital Renal Unit at Guy’s and St Thomas’, London. Simon Pummell will work on ‘Shock Headed Soul’, a project to create a film and publication based on Daniel Paul Schreber’s 1903 book Memoirs of my Nervous Illness.

Gaining knowledge At the Wellcome Trust Centre for Neuroimaging at University College London, Dr Dharshan Kumaran has been awarded an Intermediate Clinical Fellowship. The neurologist and chess grandmaster will study knowledge acquisition in the human brain.

Neuroscience and Mental Health

Henry Wellcome Fellowships

Three grants have been made through our Neuroscience and Mental Health stream. At the Institute of Education, Professor Ian St James Roberts has been awarded a project grant to explore the relationship between crying and sleep–wake patterns in infants in the first 18 months of life. Professor Philippa Garety and colleagues at the Institute of Psychiatry, King’s College London will use project grant funding to explore how jumping to conclusions and anxiety-related processes are linked in psychosis. Lastly, an equipment grant has been made to Professor Brian Day at the Institute of Neurology, University College London. This funding will be used to upgrade and expand a 3D motion analysis system.

The prestigious Sir Henry Wellcome Postdoctoral Fellowship scheme is now taking applications for its third year of awards. Who can apply? Talented researchers who are in the final year of their PhD or who have less than one years’ postdoctoral experience. What’s available? £250 000 for a four-year, full-time fellowship to develop an independent research career in the best labs in the UK and overseas. What’s the deadline? Preliminary applications must be received by 3 November 2008. More info: New research will relate babies’ crying to their sleep patterns. Anthea Sieveking

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Humanities resources We have made three significant awards to support the interdisciplinary field of medical humanities. King’s College London will receive about £2 million over five years, and Durham University around £1.8m. The grants will be used to establish centres of excellence in medical humanities. At King’s, Professor Brian Hurwitz and colleagues will study ‘The Boundaries of Illness’, looking at personal and cultural representations of health and illness and the boundaries between them. Professor Martyn Evans and colleagues at Durham University will examine ‘Medicine and Human Flourishing’ – a programme of research aimed at understanding the human side of medicine.

The Glasgow Centre for the Social History of Health and Healthcare – a joint venture between the University of Strathclyde and Glasgow Caledonian University – has received the largest award ever made for the history of medicine in Scotland. The £375 000 Enhancement Award will be used to employ new researchers over the next five years and assist with outreach activities. Dr James Mills, Director of the Centre, said: “Many of the illnesses we associate with today – binge drinking, obesity and non-prescription drug use – are nothing new. By looking at the policies of the past, we can help inform how we can deal effectively with the same problems now, and just as importantly, which policies should be avoided at all costs.”

Fruit fly. Audio Visual, LSHTM

In development Among the awards made through the Molecules, Genes and Cells stream is a programme grant to Wellcome Trust Principal Research Fellow Professor Elizabeth Robertson at the University of Oxford to study the networks of genes that control development in the early mammalian embryo. Meanwhile, at the University of Glasgow, Dr Stephen Goodwin plans to use a genome-wide approach to explore how a gene called fruitless acts with other genes in male fruit flies to coordinate events that lead to sex-specific behaviours and physiology.

Sound approach A Technology Development Grant has been awarded to Professor Brian Derby and colleagues at the University of Manchester. The team will optimise scanning acoustic microscopy, a technology usually used in engineering, for use in medical applications, matching tissue features to its mechanical properties.

Glasgow grants Funding for the Wellcome Trust Centre for Molecular Parasitology at the University of Glasgow has been renewed. Also at the Centre, malariologist Professor Andy Waters was awarded a Principal Research Fellowship.

Translational research A man seeks medical help after “going rather too far in the Pursuit of Pleasure and Amusement”. Lithograph by George Cruikshank.

Malawi renewal

Road to discovery

We have renewed funding for the Malawi–Liverpool–Wellcome Trust Programme for Research in Tropical Medicine, one of our four Major Overseas Programmes. The £8.8 million award includes £800 000 for a new training and learning centre. The Programme also has a new Director, Professor Rob Heyderman from the University of Liverpool.

A Strategic Award of £4.7 million has been made to the European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI) to make a number of databases from the drug discovery company Galapagos NV part of EMBL-EBI’s open access resources. The databases contain details of the properties and activities of drugs and drug-like small molecules, and should prove invaluable for researchers developing new drugs.

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Dr Jillian Baker and colleagues at the University of Nottingham have received a Seeding Drug Discovery award to develop highly selective ß1-antagonists. Unlike other ß-blockers, which cause airway narrowing and so can’t be given to patients with respiratory diseases, these drugs would be suitable for patients with both heart and lung diseases. Dr Liam Marnane and colleagues from University College Cork have been given a Translation Award to develop a signal processing system, based on EEG and ECG, to help medical staff to identify seizures in newborn babies without the need for complicated equipment.

The SABRE study will examine links between health and ethnicity. SABRE

Vive la différence Ethnic differences seem to play a major role in a person’s susceptibility to cardiovascular disease. Chrissie Giles talks to Professor Nishi Chaturvedi, who has been at the forefront of this research for over 20 years, about a major new study, SABRE. Some 20 years ago researchers scouring routine mortality statistics from the UK came across something strange. They found that first-generation migrants of Indian Asian descent had significantly more heart attacks and strokes than white European people. In contrast, African Caribbean people, although also at higher risk of stroke, seemed to be at a significantly lower risk of coronary heart disease – particularly men, whose risk was half that of their European counterparts. Nishi Chaturvedi – now Professor of Clinical Epidemiology at the International Centre for Circulatory Health, part of Imperial College Healthcare NHS Trust – was intrigued. To try to unpick this apparent ethnic aspect to susceptibility to heart disease, she and her colleagues performed two surveys of 4000 Londoners between 1989 and 1991: the Brent study, which looked at an African Caribbean population, and the Southall study, which looked at an Indian Asian group. These studies found that, although both ethnic minority groups had higher rates of

diabetes than Europeans, the profiles of fats (lipids) in the bloodstream varied. Indian Asians tended to have ‘unhealthy’ blood lipid profiles, which are linked to an increased risk of heart disease, while the African Caribbeans had ‘healthy’ lipid profiles. Although the variation in lipid profile appeared to be behind the ethnic differences in susceptibility to heart disease, it was not clear why diabetes affected lipid profiles differently in the two groups. The study follow-up confirmed that adverse lipid profiles and diabetes contributed to the high rate of heart disease in Indian Asians, but did not explain it completely. In addition, the studies also showed that the greater risk of stroke in both ethnic groups was strongly related to their higher rates of diabetes, even though blood pressure, the most important risk factor for stroke, differed substantially. So, in 2008, Professor Chaturvedi and colleagues embarked on SABRE (Southall and Brent Revisited). This study, funded by the British Heart Foundation and us, revisits the

original participants from the Southall and Brent studies, a unique and large population that has been followed for a long period of time. “We’re trying to explore the idea of ‘diabetes toxicity’,” says Professor Chaturvedi. “Why does diabetes seem to be particularly bad for an Indian Asian or African Caribbean in terms of cardiovascular disease?” The researchers have begun seeing the individuals from the original studies again, a process expected to take three years. The Southall and Brent studies captured only mortality data since the baseline studies, so now the researchers are studying the participants’ medical records to see what cardiovascular events have occurred since the first studies. They are also looking at early signs of cardiovascular disease that are not apparent to the individual. Professor Chaturvedi hopes that understanding these risk factors better will lead to a change in the way that people are diagnosed and treated for cardiovascular diseases. “We know a lot about how to prevent disease occurring in the first place if you’re European, and we know a lot about how to treat people who are at high risk of cardiovascular disease,” she says. However, the story isn’t so clear for Indian Asians and African Caribbeans. “Given the differences in risk, we don’t think the same cut-off points should apply,” she says. This kind of research should benefit everyone, not just those from the populations studied. For example, understanding how African Caribbean men are ‘protected’ from heart disease could provide information relevant to the health of people in other ethnic groups. What are the ethical implications of this kind of work? “Sometimes there are criticisms that you’re compartmentalising groups that can’t be compartmentalised,” says Professor Chaturvedi. “People ask, ‘What do you mean by “Indian Asian” or “African Caribbean”? Is this a genetic or a racial thing?’” She explains that ‘ethnicity’, the definition they use to group individuals, may appear somewhat heterogeneous, being based on a number of factors including lifestyle, religion, language, cultural beliefs and behaviour – which can differ substantially between groups. “Nevertheless, whether you’re talking about a Punjabi Sikh, a Muslim or a Bangladeshi, all those groups share a predisposition to heart disease and diabetes… It does go back to an underlying biological explanation rather than one based on lifestyle,” she says. “In order to reduce that risk you have to appreciate why it occurs in the first place. This comparative epidemiology will help us to understand that difference.” WellcomeNews | Issue 56 | 9


Switching off to sound

Stutter risk

Children with autism pay less attention to speech sounds. Don Bayley/iStockphoto

Oxford researchers have shown that children with autism ‘switch off’ to repeated speech sounds. Findings such as these could ultimately help to guide how people teach and communicate with children affected by the disorder, although the researchers stress that more research in this area is required. In autism, children often don’t pay attention to speech sounds, but it is not clear why. Professor Dorothy Bishop and Dr Andrew Whitehouse from the University of Oxford studied 15 children with autism and 15 without. To avoid any external distractions or stressors, the researchers used their Wellcome Trust-funded mobile lab – a well-equipped soundproof van.

The researchers found that children with autism were able to respond to a speech sound (such as ‘ah’) when it was presented in a sequence of nonverbal sounds (beeps). However, when a beep was presented in a series of speech sounds, the brains of the children with autism did not respond as expected – they had ‘switched off’. “Although in its early stages, this kind of research could change educational practices,” says Dr Whitehouse. “If children with autism switch off to speech sounds then you might want to teach them in a different way, so you’re not always talking or so you’re using more pictures.”

Bilingual children have a greater risk of stuttering than monolingual children, particularly if they do not wait until they start school to learn their second language, Professor Peter Howell from University College London and colleagues have found. Their study provides evidence for the link between bilingualism and stuttering – long hypothesised but poorly supported by data – and also shows that bilingual stutterers tend to stutter in both languages they speak. The researchers studied 317 children aged eight to 12 years who stuttered, looking at their stuttering history, school test results and stuttering recovery/persistence. Of the 38 children who used a language other than English at home, 23 spoke both English and the non-English (minority) language from birth. The remaining 15 learned English only once they started school. The results suggest that the risk of stuttering can be reduced if children who speak a minority language at home wait until they are five to start learning English. Deferring the time bilingual children learn English also improves the chance of recovering from a stutter later in childhood. School performance was not affected by whether a child had a stutter or not, nor did it depend on whether a bilingual child learned English alongside or after a minority language. Howell P et al. The effects of bilingualism on stuttering during late childhood. Arch Dis Child 2008 [Epub ahead of print].

Whitehouse AJ, Bishop DV. Do children with autism ‘switch off’ to speech sounds? An investigation using event-related potentials. Dev Sci 2008;11(4):516–24.

Developing-country dementia Levels of dementia in developing countries could be much closer to those in developed countries than previously thought. New research, conducted by the 10/66 Dementia Research Group, an international collaboration part-funded by us, suggests that policy makers in low-income and middleincome countries may need to re-examine the burden of dementia on their health services. The researchers assessed almost 15 000 people over the age of 65 in 11 countries, including India, China, Cuba and Peru. The assessment consisted of interviews with the affected individual and, typically, a family member, as well as a physical examination and a blood test. According to the study, the prevalence of dementia in urban settings in Latin America is comparable to rates in Europe and the USA, though the prevalence in China and India is lower. 10 | WellcomeNews | Issue 56

The team found evidence that people in developing countries were less likely to perceive or report that their elderly relatives were experiencing difficulties, even with clear evidence of disability and memory impairment. “Our data suggest that, even if it is not recognised as dementia, the illness places a heavy burden on both the elderly patient and their relatives,” says Professor Martin Prince from the Institute of Psychiatry, King’s College London, who leads the group. “Being able to estimate accurately the true population of people living with this burden is the first important step towards putting into place appropriate health and social care systems.” Llibre Rodriguez J et al. Prevalence of dementia in Latin America, India, and China: a population-based crosssectional survey. Lancet 2008;372(9637):464–74.

Prof. Peter Howell carries out a motor assessment on a participant.

Building brains Size isn’t everything when it comes to brain power, scientists working at the Wellcome Trust Sanger Institute, the University of Edinburgh and Keele University have found. They suggest that increasing sophistication in the molecular processing of nerve impulses during evolution allowed complex brains – including those of humans – to evolve. Emes RD et al. Evolutionary expansion and anatomical specialization of synapse proteome complexity. Nat Neurosci 2008;11(7):799–806.


On your nerves

Regional variation

Baby face

Trouble concentrating? Research by Professor Alex Thiele from Newcastle University and colleagues has revealed that the nervous system chemical acetylcholine is vital for preparing our brain cells to pay attention to a demanding task. Another neurotransmitter, serotonin, has been shown by Professor Trevor Robbins at the University of Cambridge and colleagues to play a critical role in regulating emotions, such as aggression, during social decision making.

A trio of publications has boosted our knowledge of the function and activity of different parts of the brain. Research at the University of Cambridge – led by Wellcome Trust Senior Research Fellow Professor Paul Fletcher – has shown how patterns of brain activity in healthy participants may help to predict symptoms of psychosis in people with schizophrenia. Also at the University of Cambridge, Dr Sam Chamberlain and colleagues have found that the brain regions responsible for stopping habitual behaviour are underactive in people with obsessive–compulsive disorder and their unaffected close relatives. Dr Bianca Wittmann from the Wellcome Trust Centre for Neuroimaging at University College London and colleagues have identified a key region located in a primitive area of the brain that encourages us to be adventurous.

Babies as young as four months old can recognise nonverbal communication signals, suggesting that infants’ brains may have an innate capacity for social communication. Using two imaging techniques, researchers at Birkbeck College and University College London studied the brain activity of infants in response to dynamic faces on a screen. The faces either established eye contact or averted their gaze, then raised their eyebrows and smiled. Two brain areas – the prefrontal cortex and the temporal cortex – responded to the face that established eye contact. These areas, part of the cortical network, are the same as those implicated in nonverbal communication in adults. This suggests that the cortical network specialises early or may even be hard-wired to perceive facial communication cues – essential for an infant’s ability to interact with, and learn from, others.

Herrero JL et al. Acetylcholine contributes through muscarinic receptors to attentional modulation in V1. Nature 2008;454(7208):1110–4. Crockett MJ et al. Serotonin modulates behavioral reactions to unfairness. Science 2008;320(5884):1739.

Honey GD et al. Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo. J Neurosci. 2008;28(25):6295–303. Chamberlain SR et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science 2008;321(5887):421–2. Wittmann BC et al. Striatal activity underlies novelty-based choice in humans. Neuron 2008;58(6):967–73.

Grossman T et al. Early cortical specialization for face-toface communication in human infants. Proc Biol Sci 2008 [Epub ahead of print].

Controlling sleepiness

Aggression is regulated by serotonin. Craig Wactor/iStockphoto

Sharing memories Our visual memory can be used more flexibly than previously thought, according to Trustfunded research carried out at University College London. For almost 50 years, scientists have believed that when we look at a visually ‘busy’ scene, we are only able to store a very limited number of objects in our visual short-term or working memory, the memory that we hold for a few seconds after looking at a scene. Now researchers have shown that this is not the case: our visual working memory can be shared out across the whole image, with more memory being allocated to objects of interest and less to background detail. Bays P, Husain M. Dynamic shifts of limited working memory resources in human vision. Science 2008;321(5890):851–4.

A set of nerve cells in the eye controls our levels of sleepiness according to the brightness of our surroundings, University of Oxford researchers have discovered. In the study, supported by Wellcome Trust and European Commission funding, the researchers showed that retinal ganglion cells directly regulate the activity of sleep centres in the brain, providing a new target for the development of drugs to control sleep and alertness. “We have discovered a new pathway that modulates sleep and arousal,” says Professor Russell G Foster of the Nuffield Laboratory of Ophthalmology. “If we can mimic the effect of light pharmacologically, we could turn sleep on and off.”

Professor Foster and colleagues have previously shown that the eye contains a group of retinal nerve cells that are sensitive to light. Working on mouse models in which these retinal ganglion cells have been turned off genetically, the research team found that the effects of light on sleep and alertness were completely abolished. The researchers were able to track this sleep pathway to the brain, where two sleepinducing centres are directly activated by the cells, turning sleep on or off. Lupi D et al. The acute light-induction of sleep is mediated by OPN4-based photoreception. Nat Neurosci 2008 [Epub ahead of print].

Certain retinal cells make us sleepy depending on how bright it is. Dianne Harris

WellcomeNews | Issue 56 | 11


Counting Crohn’s New research has trebled the number of genetic regions known to be implicated in Crohn’s disease, a form of inflammatory bowel disease, to over 30. The study also identified a number of potential targets for drug development, and revealed surprising new links between Crohn’s and other common diseases, including asthma. The first two Crohn’s susceptibility genes were discovered in 2001, followed by a third in 2006. The Wellcome Trust Case Control Consortium and parallel studies took that number above ten the following year. Now researchers have linked 32 genetic regions to susceptibility to Crohn’s. The team of scientists and clinicians involved used DNA samples from almost 12 000 people. Many were from UK patient collections and analysed originally in the Case Control Consortium. Others came from European and North American collections. “We now know of more than 30 genetic regions that affect susceptibility to Crohn’s disease,” says Dr Jeffrey Barrett from the Wellcome Trust Centre for Human Genetics at the University of Oxford, lead author of the study. “These explain only about a fifth of the genetic risk, which implies that there may be hundreds of genes implicated in the disease, each increasing susceptibility by a small amount. “While this study shows the power of genome-wide association studies to reveal the genetics behind common diseases, it also highlights the complexity of diseases such as Crohn’s.” Barrett JC et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 2008;40(8):955–62.

Q&A For the immune system, preventing an inappropriate response to a harmless antigen is just as important as responding to one that poses a genuine threat. We asked Sir Henry Wellcome Fellow Dr Robert Snelgrove about his recent Nature Immunology paper, which showed the importance of a protein called CD200 receptor (CD200R) in controlling the immune response in flu. Why study CD200R? In the airway, the primary type of immune cell is the alveolar macrophage, which is important in judging the environment and whether an immune response should be made or not to a particular antigen. These cells have high levels of CD200R on their surface, and when this binds to CD200 on the surface of other cells in a healthy lung the macrophage is switched off. This switching off can be overridden when a real threat is detected.

What goes wrong in flu? A lot of the symptoms of flu – like breathlessness, fever and weight loss – are worsened by an excessive immune response. One of the reasons this might happen is because the immune cells that invade the airways to fight the infection reduce the number of CD200 proteins on their surface. This means that they can’t deliver an inhibitory signal through CD200R, so you have a problem switching off inflammation.

What did your study show? A granuloma of the kind often seen in cases of Crohn’s disease.

12 | WellcomeNews | Issue 56

When we gave mice a mimic of CD200 to replace that which is lost in flu, they

showed fewer symptoms and a huge reduction in lung inflammation. We concluded that CD200 is important in controlling if an immune response is initiated, as well as the amplitude and duration of any such response.

What’s next? We’re now looking at other ways we can alleviate the inflammation caused by flu by targeting the excessive immune response. This is very early-stage research, but we hope that this kind of treatment could be progressed into humans, where it could have broad ramifications for the many diseases in which an excessive immune response is the problem.

What difference has your fellowship made? It was a fantastic opportunity because of the amount of flexibility it gave. I could choose the area I was passionate about and then do cutting-edge research in any lab I liked around the world – I’m currently in Alabama. Already, at an early stage in my career, it’s given me a taste of being an independent researcher.

What do you do outside of the lab? I’m a massive Tottenham Hotspur fan but trying to keep in contact with football from Alabama is a bit of a challenge. Everyone’s so friendly here though – we managed to find a pub that would open especially for us at lunchtime so we could watch the European Championship before we went back to work. Snelgrove RJ et al. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat Imm 2008;9(9):1074–83.


Class findings

A sticky end for malaria?

Kenyan children receiving intermittent preventative treatment for malaria. Sian Clarke

Intermittent treatment with antimalarial drugs can reduce anaemia and improve classroom attention in Kenyan schoolchildren, says research by a multidisciplinary team of Kenyan and British researchers. While many African children have developed partial immunity to malaria by school age, the disease still accounts for a fifth of all deaths among school-aged children. Asymptomatic infection also causes problems, including anaemia and absenteeism. A new method of tackling malaria, intermittent preventative treatment (IPT), involves mass administration of a full therapeutic course of antimalarial drugs at specific intervals. In this study, the researchers examined the effects of IPT at 30 primary schools in a rural area of high malaria transmission in western Kenya. Nearly 5000 children were given either IPT (sulfadoxine-pyrimethamine with amodiaquine) or a placebo once a term for a year. The children were surveyed six weeks

after the last treatment and the researchers found that the IPT had reduced the occurrence of anaemia and asymptomatic malaria infection, and increased the children’s attention in class. IPT had no effect on educational achievement. The authors conclude: “The pronounced effects of the IPT intervention…highlight the issue of the continued, and often unrecognised, malaria burden among school-aged children in Africa and the potential of school-based programmes for tackling the problem.” We are funding future work to explore the effectiveness of the approach through Career Development Fellowships to study authors Dr Simon Brooker, currently based in the Kenya Medical Research Institute in Nairobi, Kenya, and Dr Siân Clarke, who will work in Senegal.

Scientists have found a key mechanism that enables malaria-infected red blood cells to stick to the walls of blood vessels and avoid being destroyed by the body’s immune system. The research, funded through our Functional Genomics Development Initiative, highlights an important potential new target for antimalarial drugs. When the malaria parasite infects healthy red blood cells, it secretes a ‘glue’, known as PfEMP1, that travels to the surface of the cells, leading to the formation of knobs there. The cells stick to the walls of the blood vessels, which prevents the cells being flushed through the spleen (where the parasites would be destroyed by the body’s immune system) and also restricts blood supply to vital organs. Now, an international collaboration of scientists has identified eight proteins that transport the Plasmodium falciparum parasite’s ‘glue’ to the surface of the infected red blood cells. Removing just one of these proteins prevents the infected red blood cells from sticking to the walls of the blood vessels. “Malaria parasites are evolving, making our current treatments increasingly less effective,” says Professor Alister Craig from the Liverpool School of Tropical Medicine, who collaborated on the project. “A drug which prevents disease rather than killing the parasite might be important because it could retain natural inoculation in the patient, limiting damage caused by the parasite and providing protection from further infection.” Maier AG et al. Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell 2008;134(1):48–61.

Clarke SE et al. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial. 2008;372(9633):127–38. • This research was funded in part by the Wellcome Trust.

Fairer funding The Millennium Development Goal to halt and begin to reverse the incidence of malaria globally is unlikely to be met, warns Wellcome Trust Principal Research Fellow Professor Bob Snow. In a report in the journal PLoS Medicine, Professor Snow and colleagues call for more money to be invested in tackling malaria, and for this support to be distributed more equitably. Snow RW et al. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission. PLoS Med 2008;5(7):e142.

Professor Bob Snow. Caroline Penn

Red blood cells, vulnerable to malaria infection. Annie Cavanagh

Sex change Malaria parasites produce more sons than daughters when conditions are difficult, according to research led by Wellcome Trust Research Career Development Fellow Dr Sarah Reece at the University of Edinburgh. The change in sex ratio increases the overall chance of parasite genes being passed on and, hence, the successful spread of malaria. WellcomeNews | Issue 56 | 13


Inside the interactome Forget gene number: it’s the number of protein interactions in an organism that appears to reflect biological complexity. What’s more, it’s hoped that in the future, comparison of protein interaction networks could help researchers to understand the different effects of similar organisms – for example, why some fungal species can be used to make bread and beer while others can cause fatal fungal infections. In the study, researchers from Imperial College London worked with colleagues from the Max Planck Institute for Molecular Genetics in Berlin and the University of Aarhus in Denmark to devise a mathematical tool that allowed them to predict the size of an organism’s protein interaction network, or interactome. While humans have fewer than twice as many genes as fruit flies, the human interactome is around ten times bigger than that of fruit flies, and around three times bigger than that in the nematode worm Caenorhabditis elegans. “Understanding the human genome definitely does not go far enough to explain what makes us different from more simple creatures,” says Professor Michael Stumpf at Imperial. “Our study indicates that protein interactions could hold one of the keys to unravelling how one organism is differentiated from another.” Stumpf MP et al. Estimating the size of the human interactome. Proc Natl Acad Sci USA 2008;105(19):6959–64.

C. elegans, which has a much smaller interactome than humans. Dr David Becker

In sequence Genomic sequencing studies can uncover unexpected findings. Research by a team at the University of Bath has shown that the bacterium responsible for Lyme disease, Borrelia burgdorferi, did not originate in America as thought, but in Europe, before the Ice Age. Meanwhile, the sequence of a newly emerging superbug, ‘Steno’ (Stenotrophomonas maltophilia), completed by scientists at the Wellcome Trust Sanger Institute and the University of Bristol, has revealed that the bacterium has a high capacity for drug resistance. 14 | WellcomeNews | Issue 56

You are what your mum ate

Junk food eaten by pregnant or breastfeeding mothers can affect the child’s health. iStockphoto

Mothers who eat an unhealthy diet during pregnancy may be putting their children at risk of developing long-term, irreversible health issues, including obesity and raised cholesterol levels. The Wellcome Trust-funded research, carried out in rats, suggests that the effect is most pronounced in female offspring. Dr Stephanie Bayol and Professor Neil Stickland from the Royal Veterinary College, London compared the offspring of rats fed a diet of processed junk food during pregnancy and lactation with the offspring of those fed a healthy diet of regular feed. The offspring of the mothers fed junk food had raised levels of cholesterol as well as higher levels of triglycerides, a type of fat found in the bloodstream. Both are known to increase the risk of developing heart disease. They also had higher levels of glucose and insulin, which both increase the likelihood of developing type 2 diabetes. “It seems that a mother’s diet while pregnant and breastfeeding is very important for the long-term health of her child,” says Dr Bayol. “We always say ‘you are what you eat’. In fact, it may also be true that ‘you are what your mother ate’. This does not mean that obesity and poor health is inevitable… but it does mean that mothers must eat responsibly while pregnant.” Bayol S et al. Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females. J Physiol 2008;586(13):3219–30.

The nuclear protein UHRF1. Structural Genomics Consortium

Proofreading protein Scientists from the Structural Genomics Consortium have determined the threedimensional structure of a key protein component involved in enabling ‘epigenetic code’ to be copied accurately from cell to cell. Epigenetic code is a series of chemical switches added on to DNA to ensure that body cells can form different types of tissue, despite having identical DNA code. It is essential that the epigenetic code is copied accurately when DNA is copied from cell to cell, as a breakdown in this system might mean that a gene for cell growth is accidentally switched on, for example, leading to unregulated cell growth and the development of tumours. Research published in 2007 showed the importance of the nuclear protein UHRF1 in ensuring that the epigenetic code is accurately copied. The key element of UHRF1 involved in this ‘proofreading’ process is known as the Set and Ring Associated (SRA) domain. Now, three papers published in Nature have revealed the mechanisms by which this domain accomplishes this task. A co-author of one of the papers, Professor Sirano Dhe-Paganon from the Structural Genomics Consortium laboratories at the University of Toronto, Canada, says: “Given the increasing focus on epigenetics as a mechanism behind cancer, elucidating the structure of UHRF1 may provide crucial insights into what goes wrong.” Avvakumov GV et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 2008 [Epub ahead of print].

When Pat Martino awoke from surgery to remove a brain tumour, he had forgotten that he was a world-renowned jazz guitarist. He made a remarkable recovery from the amnesia and returned to playing seven years later. Martino Unstrung, a documentary film funded by a Wellcome Trust Sciart award and produced by director Ian Knox and neuropsychologist Paul Broks, explores his musical rediscovery. By Barry Gibb. Pat Martino, who used videos of his former self to relearn guitar playing. Ian Knox

Finding Pat Martino Pat Martino may not be a household name, but in the world of jazz his guitar playing is legendary. Indeed, the opening sequence of Martino Unstrung is in a New York guitar store, with a jazz fan in a near gibbering state of excitement, exclaiming to camera that his whole world has flipped from one of tears of hopelessness to bliss because he has just seen Martino: “it’s like finding da Vinci!” Born in 1944 and playing at a professional level since his early teens, Martino saw his career take off in the 1960s as a sideman and then leader. He created a prolific back catalogue of vinyl and gained an enviable following of fans and friends (including Les Paul, inventor of the electric guitar, and film star Joe Pesci, who appear in the film). To counterpoint this success, however, Martino’s mental state was declining, to the extent that electroshock therapy was sought as a treatment for his darker episodes. Neurosurgeon Fred Simeone removed the real cause of Martino’s mental problems in 1980: a bleeding ‘bundle of worms’ the size of an apple in the left hemisphere of his brain – a tumorous growth, or arteriovenous malformation. But the surgery also took a slab of Martino’s identity – including the knowledge that he was a world-class guitarist. Martino Unstrung explores this profound loss of identity and Martino’s long journey of personal – and musical – rediscovery.

Usually a director of fiction, Ian Knox didn’t set out to make a documentary about Martino, but was inspired to do so when, in 2004, he went to hear the guitarist who had ‘forgotten more music than most musicians learn in a lifetime’. Knox says: “I went along, the gig was amazing, absolutely fantastic. And in between sets, when I was downstairs in Ronnie Scott’s, I spotted him sitting in the Green Room bar and I just stuck my head in…” A couple of beers later and the idea was born. Neuropsychologist and author Paul Broks joined Knox on the project: “The very fact that he [Martino] had this abnormal collection of blood vessels in a particular part of his brain would have affected brain function, it might well have shaped his personality, his musical ability even, in ways that we can only speculate wildly about.” Indeed, scanning technology reveals Martino had lost a large portion of his left temporal lobe during surgery, removing regions associated with memory and emotions – and only narrowly missing areas associated with musical interpretation. Martino rediscovered music on a primitive computer while confined to a locked ward at New York’s Mount Sinai hospital. The computer’s 127k memory contained a music program, which he began to play. It was an epiphany. After 17 years of silence,

he took up the guitar again, studying technique, via tuition videos, from a great teacher – his former self. “What he had probably lost was memory that he was a player, motivation to play, and semantic [fact-based] memory for music; when he did pick up the guitar again to play, it wasn’t with any great confidence…maybe by discovering the music, he rediscovered himself,” reflects Broks. Filmed in the USA in 2006 and 2007, the film departs from contemporary, graphically intensive approaches to science, opting instead for a lighter, more poetic visual touch. The city itself becomes a metaphor for the physical and emotional landscape of Martino’s brain, an approach more artful and abstract. Broks comments: “The idea was to use images of the city and images of machinery impressionistically…Ian would say, ‘go out and find me some brain imagery’, so I would wander round the streets, round the park and look at things that might have some connotation of brain damage or brain function.” Screenings of Martino Unstrung will be announced later in 2008. Our Sciart and Pulse funding schemes were amalgamated and relaunched in 2007 as the Arts Awards. For more details see

WellcomeNews | Issue 56 | 15

The curious case of the Glasgow Spy

Press coverage of the Glasgow Spy trial, 1918.

Chris Beckett tells a tale of espionage, forgery and astute bureaucracy from the Wellcome Foundation Archive. Armgaard Karl Graves, referred to in press reports as ‘the Glasgow Spy’, was the first person to be convicted in Scotland under the Official Secrets Act (1911). On 23 July 1912, at the High Court of Judiciary, Edinburgh, Graves was found guilty of making or obtaining a telegraphic code for the purpose of communicating information relating to the British Navy and land fortifications. The code had been concealed within the pages of a Burroughs Wellcome & Co. diary, and the firm’s headed paper had been used to cloak communication with an accomplice in Brussels. Graves went to considerable lengths to establish his identity as a doctor who had practised in Australia, and was now visiting England to undertake further training in Edinburgh and to conduct clinical experiments. His first port of call was not the Firth of Forth but the Wellcome Medical Museum in Wigmore Street, London. This was not the casual visit of a medical man with wide interests and time on his hands but a calculated move in establishing a consistent identity. The Wellcome Foundation archive contains a revealing record of this visit on 14 February 1912. After showing an interest in various Burroughs Wellcome & Co.

16 | WellcomeNews | Issue 56

products (“he would like literature re all our newest products sent to his Edinburgh address,” it was noted), Graves reinforced his credibility by association: the Medical Officer of Southern Australia was presently staying in London, he explained, and should be contacted as a valuable source of business. Graves’s final comment was to remark that he had not received a Burroughs Wellcome & Co. diary since 1909 and would greatly appreciate one (thereby pushing further back into time his fictive identity). In fact, the company had been carefully selected as a suitable source of cover for communication. Counterfeit Burroughs Wellcome & Co. envelopes and headed paper had been fabricated in advance of the mission and were used on occasion to convey coded information about Britain’s expanding naval capacity (construction of the Royal Naval Dockyard at Rosyth began in 1909), and to send payment to Graves in return. The note of his attendance at the Wellcome Museum included an observation that could not pass unrecorded, in the midst of a national mood of contagious spy fever: Graves was German. In Edinburgh and Glasgow, Graves fleshed out his identity still further. He applied for a position as a locum, and his medical knowledge was sufficiently convincing to a

Dr Leith, who interviewed him. But, as Leith was to tell the court, he did not like the German accent. “It is does not do in Leith?” quipped the Solicitor-General, to the local court’s amusement. The strict application of Post Office procedure contributed to Graves’s undoing: he was refused collection of a letter addressed to James Stafford Esq. (one of Graves’s many aliases). The letter, which bore the name of Burroughs Wellcome & Co. imprinted on the envelope, was returned to its ostensible sender. At the company’s office in Snow Hill, London, the envelope was immediately recognised as counterfeit. When Inspector Edward Parker of the Yard, who was already on the case, called at Snow Hill on Saturday 13 April he was told, somewhat proprietarily, that the matter had been placed in the hands of the company solicitor, who was not available until Monday. Parker left his card, and when he returned on Monday, he left a detailed receipt – an inventory – of everything: two letters in German and an inner envelope containing one fivepound note and one ten-pound note. In the intervening period before Parker took away the items, Burroughs Wellcome & Co. had photographed all: the set of photographs sits today in the archive, along with Inspector Parker’s calling card, and several statements, letter translations and newspaper cuttings from the trial. Graves was sentenced to 18 months’ imprisonment. If his memoir is to be believed, the unsuccessful Glasgow Spy undertook subsequent work for the British Secret Service. His life remained colourful: in 1916, he was arrested in Washington on a charge of blackmail (the charges were eventually dropped), and in 1929 he was arrested in Los Angeles for grand theft. Chris Beckett is an Assistant Archivist of the Wellcome Foundation Archive, Wellcome Library, London. A longer version of this article appered in Wellcome History 38. See

Wellcome Foundation The Wellcome Foundation Archive dates from 1860 to 1995, and covers the period from Henry Wellcome’s business partnership with Silas Burroughs (Burroughs Wellcome & Co.) to the emergence and consolidation of a highly recognised international pharmaceutical company. Wellcome established the Wellcome Foundation Limited in 1924, bringing together his non-commercial and commercial interests under a single corporate umbrella.







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Courses, conferences and workshops January 2009 25–30 Genomics and Clinical Microbiology 
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Neural stem cells. Yirui Sun

GC: Event takes place at the Wellcome Trust Genome Campus, Hinxton, Cambs. For information on Wellcome Trust Conferences, see conferences. For information on Advanced Courses and Open door Workshops, see

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