Issue 66, spring 2011 Wellcome NEWS INVESTING IN POLLINATOR RESEARCH Protecting insect pollinators’ health – and our food supply. Technology Transfer

Technology 14 Beautiful creatures: Transfer: Lainson and his parasites

Pushing the CONTENTS Designed and manufactured by Aircraft Medical Designed and manufactured by Aircraft The McGRATH® Series 5 video laryngoscope, developed with Trust funding. Series 5 video laryngoscope, developed with Trust The McGRATH® boundaries INSIDE THIS ISSUE

In brief of medical Message from the Director 4 Funding news 6 We are a committed funder of Research news 8 translational R&D, bridging the gap between fundamental research In depth innovation and the development of new health products. How I Got Into… cancer genetics: Prof. Mike Stratton 10 We work with world-class Beautiful creatures: Prof. Ralph Lainson 14 investigators in academic institutions The dirty truth: Dirt at 20 and companies alike, in pursuit of YouTube and blog update 24 solutions for unmet medical needs. Q&A: Dr Beau Lotto 25 Protecting the pollinators 28 Opinion Museums need more compelling games 13 Appliance of Science: bringing real life into art 34 Picture features Wellcome Image Awards 2011 22 Nuts and Bolts: primary cilia 26 From the Archive: Nuremberg Chronicle 32 www.wellcome.ac.uk/technologytransfer 2 | WELLCOME NEWS SPRING 2011 | 3 WellcomeNEWS MESSAGE FROM THE DIRECTOR Telling the stories of the ’s work SIR MARK WALPORT UKCMRI plans approved

Editor Chrissie Giles Plans to build a world-leading medical research institute at St Pancras in Assistant Editor Tom Freeman London have been approved by Camden councillors. The UK Centre for Writers Craig Brierley, Chrissie Giles, Mun-Keat Looi, Jen Middleton Medical Research and Innovation (UKCMRI), designed by the architects Design Malcolm Chivers, Marianne Dear HOK with PLP Architecture, will have around 1500 staff , including 1250 Photography David Sayer scientists. The Development Control Committee voted in favour of the Publisher Hugh Blackbourn £500 million project on 16 December 2010. Contributors: Sir David Cooksey, Ch airman of UKCMRI, says: “UKCMRI Mike Stratton illustration Bret Syfert will harness the talent and potential of doctors, nurses, biologists, Primary cilium illustration Lucy Farfort mathematicians, physicists, chemists, computer scientists and engineers Ideas, comments, suggestions? Get in touch: to understand the underlying causes of disease. This will accelerate our Wellcome News ability to treat disease – bringing benefi ts to patients through the NHS Wellcome Trust Gibbs Building and to the economy by developing a sector in which the UK already 215 Euston Road excels.” We are co-founders of UKCMRI, in partnership w ith the Medical London NW1 2BE Research Council, Cancer Research UK and University College London. E [email protected] www.wellcome.ac.uk/wellcomenews Construction is expected to begin this year, and to be completed by 2015.

To subscribe: www.ukcmri.ac.uk T +44 (0)20 7611 8651 E [email protected] www.wellcome.ac.uk/subscribe Impression of the UKCRMI entrance atrium. Wadsworth3d

All images, unless otherwise stated, are from the . You can get copies through The Wellcome Trust supports and forms partnerships with a includes events on 28 April and 5 May. Wellcome Images (images.wellcome.ac.uk). Library welcomes diverse range of people working on an equally diverse range of topics. Dirty work On 8 April, the whole building will be Wellcome Trust However, there is a common denominator that unites everyone with taken over by ‘Elements’. This event, Head of Discovery We are a global charitable foundation dedicated to achieving whom we work – a passion for their work. In this, the fi rst issue of the at Wellcome curated by chemist Andrea Sella and In January the Wellcome Library extraordinary improvements in human and animal health. We welcomed Dr Vicki Porter as support the brightest minds in biomedical research and the new-look Wellcome News, we are proud to be able to bring you some author Hugh Aldersey-Williams, will medical humanities. Our breadth of support includes public stories of these people and what drives them to succeed. Collection allow visitors to explore the Janus-like Head of Discovery and engagement, education and the application of research to improve As Mike Stratton, Director of the Wellcome Trust Sanger Institute The doors have now closed on Wellcome qualities of some elements, including Engagement. Dr Porter will be health. We are independent of both political and commercial responsible for transforming and co-leader of the , tells us, his fascination Collection’s High Society exhibition – its arsenic, mercury, oxygen and iodine. interests. www.wellcome.ac.uk audience strategy, including most successful to date – but there’s a www.wellcomecollection.org with cancer began early in his career, when as a pathologist he would fi nding new ways for people to This is an open access publication and, with the exception of look down a microscope to diagnose cancer. This fascination has driven wealth of events coming up in the spring. images and illustrations, the content may, unless otherwise stated, get involved with the work and be reproduced free of charge in any format or medium, subject to his career, and the Institute that he now heads is working to understand Replacing High Society is Dirt: The fi lthy the resources of the Library. She the following constraints: content must be reproduced accurately; the genetic changes behind the cancers he used to examine. reality of everyday life (see page 20). There joins from the J Paul Getty Trust in content must not be used in a misleading context; the Wellcome It was a similar passion for the microscopic world that took will be a series of events around Dirt, Los Angeles, where she managed Trust must be attributed as the original author and the title of the document specifi ed in the attribution. The views and opinions Ralph Lainson from his native England to Brazil. The Wellcome including – for the strong of stomach digital policy and audience strategy. expressed by writers within Wellcome News do not necessarily Trust’s longest-serving grantholder – 47 years so far – he has forged perhaps – a dirt-themed Supper Salon She has also worked at the National refl ect those of the Wellcome Trust or Editor. No responsibility a formidable reputation as a parasitologist, specialising in the on 13 April. Gallery, Tate, the Roya l Collection is assumed by the publisher for any injury and/or damage to and the National Gallery of Art in persons or property as a matter of products liability, negligence or disfi guring disease leishmaniasis. He has discovered nearly 100 new Other happenings include ‘Tell it Washington, DC. otherwise, or from any use or operation of any methods, products, parasite species, as well as the sand-fl y vectors that carry the disease. to Your Doctor’, two events that explore instructions or ideas contained in the material herein. ISSN 1356- An interest in insects also unites the researchers working as part the conversations between doctors and 9112. First published by the Wellcome Trust, 2011. Wellcome News is © the Wellcome Trust and is licensed under Creative Commons of the £10 million Insect Pollinators Initiative. Through this, nine patients, which will run on 16 and 21 New-look SPIN Attribution 2.0 UK. The Wellcome Trust is a charity registered in diverse groups are examining the pressing issue of how populations April. The ‘Born Today’ series, which England and Wales, no. 210183. Its sole trustee is The Wellcome of bees and other pollinators are collapsing and what can be done to looks at the moment of childbirth, We have relaunched our SPIN Trust Limited, a company registered in England and Wales, no. (Science Policy in the News) service reverse this trend. From neurobiologists to beekeepers, mathematical ce is at 215 Euston Road, London with a new look. A weekly email NW1 2BE, UK). modellers to nutritionists, this is a great example of people with PU-5047/12.8K/03-2011/MD,MC produced by our Strategic Planning diff erent interests coming together for a common, important cause. and Policy Unit, SPIN provides This document was printed on material 50% made from 25 per cent post-consumer Experiments with bees also feature heavily in the work of Beau waste & 25 per cent pre-consumer waste. concise digests of news stories Lotto, a neuroscientist and enthusiastic advocate for involving the Big Picture: relating to science policy. The new public in the process of discovery. He recently worked with primary- format includes direct web links to school children to help them become the fi rst in the world to plan, The Cell out now the original stories, where available. perform and publish their own scientifi c study in a peer-reviewed From the ethics of stem cell research to There’s a new dedicated website journal. Now, with Wellcome Trust support, he has taken his sculptures made of frozen blood, Big Picture: for the service at spin.we llcome. laboratory to the Science Museum, where people can take part The Cell, the latest issue of the free Wellcome ac.uk. Here, you can browse the in experiments. Trust educationa l resource for 16+ students, complete archive of SPIN, which dates back to 1992, or sign up These stories illustrate just a small proportion of the motivated explores all aspects of animal cells. Go to to receive the weekly emails. Cover: False-coloured and passionate people with whom we work, and we look forward to www.wellcome.ac.uk/bigpicture/cell to scanning electron You can also subscribe by micrograph of a bringing you the stories of many more in future issues. download a PDF of the magazine, order a honeybee (winner of a emailing [email protected]. 2011 Wellcome Image cell-themed poster, subscribe to receive all Award – see page 22). David McCarthy future issues, and browse articles, fi lms, Illustration bby and Annie Cavanagh/ image galleries and more. GlenGlen MMcBethcBeth Wellcome Images FUNDING NEWS Rare disease drug development Testing the tsetse fl y Wellcome Trust Genome Campus New ethics chairman Among the grants made Dr Daniel Masiga from the Professor Roger Brownsword recently through our International Centre of Insect has been appointed Chairman Populations and Public Physiology and Ecology in of the UK Biobank Ethics and Health stream are two Nairobi, Kenya, to sample Governance Council (EGC), exploring aspects of the tsetse fl ies and trypanosomes replacing Professor Graeme tsetse fl y, the carrier of the from diff erent parts of Kenya. Laurie. The independent EGC, parasites that cause African They will test the idea that which we fund in partnership trypanosomiasis in humans local host and parasite with the Medical Research (sleeping sickness) and in populations are adapted to Council, advises UK Biobank animals. Dr Alvaro Acosta- each other, comparing how on rigorous standards of ethical, legal and social consideration. Serrano from the University well diff erent tsetse UK Biobank, a long-term project to of Glasgow has been funded populations transmit build a resource for health research, to investigate how, on a diff erent trypanosomes. has already recruited over 530 000 molecular level, the parasites Wellcome Library volunteers. www.ukbiobank.ac.uk (trypanosomes) cross the protective lining of the tsetse fl y gut, where they Oxford prize success The X-ray crystal structure of transthyretin and the small molecule mds84. Dr Simon Kolstoe live and develop before being Three University of Oxford Pentraxin Therapeutics Ltd, a A £2.5 million award made to transmitted to people and Advanced researchers are celebrating spin-out company from University Professor Pepys and colleagues livestock. awards. Dr Roi Cohen Kadosh, a College London (UCL), has licensed through our Seeding Drug Discovery Also at Glasgow, Professor Courses Wellcome Trust Research Career Development who studies a drug development programme to initiative in 2007 supported some of Mike Turner will work with how the brain represents numbers, GlaxoSmithKline (GSK). This builds the research that led to this recent and Scientific has won the Career Development on Wellcome Trust-funded research. deal. “The creation of mds84 involved category at the Society of Pentraxin was established by cutting-edge science and some Conferences Neuroscience Achievement UCL’s Professor Mark Pepys to hold serendipity,” says Professor Pepys.

Awards. This recognises early- the intellectual property arising from “The subsequent generous support Medical humanities update Images Wellcome Burston, Oliver career promise and achievement. his research. Now, the company is of the Wellcome Trust for this Historical aspects of the British Navy, hospital politics and Also a Research Career collaborating with GSK to develop early-phase drug design programme twin beds are just some of the topics under investigation At the cutting edge of biomedical Development Fellow, Dr Rob Professor Pepys’s invention of novel created the opportunity for further thanks to our Medical History and Humanities awards. training, discussion and debate. Klose, who works in the fi eld small molecules, including one called progression and evaluation. Now, Professor Mark Harrison, University of Oxford, has been of epigenetics, has been named Wellcome Trust Advanced Courses mds84, that stabilise transthyretin. GSK will bring its drug discovery and awarded a programme grant of over £700 000 for his project as one of this year’s European and Scientific Conferences are hosted Transthyretin is a blood protein that development expertise to work with ‘From Sail to Steam: Health, and the Victorian Molecular Biology Organization in dedicated facilities at the Wellcome can in certain circumstances cause the team on developing the potential navy’, which will explore the role of the Royal Navy in Young Investigators. These Trust Genome Campus in Hinxton – amyloidosis, a rare but fatal disease. of these small molecules.” bringing health information to Britain in the 19th century. prestigious awards are given to a short distance from the historic city the most promising European Funded by a Research Leave Award, Professor Barry young researchers at a critical Doyle from the University of Huddersfi eld is investigating of Cambridge. stage of their scientifi c careers. the politics of hospital provision in Britain in the early 20th Funding is now available for new Dr Emily Holmes has been century. He’ll use case studies of Leeds, Middlesbrough and Advanced Courses and to seed awarded the 2010 Spearman Catalyst CEO appointed Sheffi eld to explore how the pre-NHS health system worked, the developemnt of new Scientific Medal by the British Psychological Dr Martino Picardo has become the fi rst drug discovery and development.” questioning the idea that a national organisation is the only Society. Dr Holmes, a Trust Conferences. Please contact Chief Executive Offi cer of Stevenage Construction has begun on the way to ensure eff ective provision of hospitals. Intermediate Clinical Fellow, is Dr Rebecca Twells, Programme Bioscience Catalyst, a ‘hub’ for early- £38 million development in Stevenage, At the University of Lancaster, Dr Hilary Hinds will use a research clinical psychologist Manager, for more information stage biotechnology companies. Hertfordshire, which will neighbour her Research Leave Award to explore how changing ideas whose experimental work is based ([email protected]). on cognitive behavioural therapy. Previously Managing Director of the the GSK research and development about health and hygiene between 1870 and 1970 aff ected University of Manchester Incubator campus. It is hoped that the facility the rise and fall of twin beds for married couples. For details of all upcoming Advanced BAFTA win Company (UMIC), Dr Picardo says will eventually create up to 1500 new Courses and Scientific Conferences, of his appointment: “I am absolutely jobs. The fi ve funding partners for the please visit: We’re thrilled to report that that delighted to be taking up this new role. facility are the Wellcome Trust, the UK Timelines.tv’s smallpox resource Although I am sad to be leaving friends Department of Business, Innovation www.wellcome.ac.uk/hinxton Smallpox Through Time, which Pavement projections and colleagues in UMIC, I am also and Skills, GlaxoSmithKline, the East was funded by a Wellcome Trust To mark the International funded by us, was created by looking forward to working with new of England Development Agency and the Medical History and Humanities Day of Persons with artist Simon Mckeown from colleagues in what will be a very exciting Technology Strategy Board. public engagement grant, won the Disabilities on 3 December Teesside University. Thanks and unique opportunity for UK plc in www.stevenagecatalyst.com Secondary Learning category at the 2010, we hosted a special to VSA, the International 2010 Children’s BAFTAs. The free one-day video installation Organization on Arts and resource was launched to celebrate outside Wellcome Trust HQ Disability, Motion Disabled the 30th anniversary of the global eradication of smallpox, and is NEWS & FEATURES BLOG of Motion Disabled, a digital is now being exhibited aimed at teachers and students exploration of the bodies of worldwide. For more studying history of medicine at www.wellcome.ac.uk/news wellcometrust.wordpress.com people who are physically details, see wellcometrust. GCSE level. timelines.tv diff erent. The work, part- wordpress.com.

6 | WELLCOME NEWS SPRING 2011 | 7 RESEARCH NEWS Studying how we see Larynx transplant restores woman’s voice

Two studies that received Wellcome A pioneering transplant technique, Pilot study Trust support have added to our developed with Wellcome Trust funding, The brains of fi ghter pilots are knowledge of how we see the world. has restored the voice of a woman who wired diff erently from those of Professor Rob Lucas and Dr Tim Brown had lost the ability to breathe on her own the rest of us, say scientists at from the University of Manchester have and had not spoken for 11 years. UCL. They used cognitive tests been studying the neurons that carry Brenda Charett Jensen, a 52-year-old to show that RAF Tornado signals from the eye’s rods and cones woman from California, had lost the use fi ghter pilots had superior to the brain, and have found that 2 per of her larynx during surgery in 1999. In cognitive control to members cent of these neurons produce a light- October 2010, an international team of of the public – but were sensitive protein known as melanopsin. surgeons performed an operation to more sensitive to irrelevant, Previously, these cells were thought replace her larynx, thyroid gland and distracting information. The fi ndings suggest that, to be responsible for detecting light for trachea. The 18-hour procedure, which in humans, expert control subconscious responses such as changing took place at the UC Davis Medical of cognitive processes, as pupil size. However, the researchers Center in Sacramento, was followed demonstrated by the pilots, showed that melanopsin also helped by two months of rehabilitation, during may be linked to a heightened brain regions involved in conscious Kirlian photograph of the eye. N Seery/Wellcome Images which the nerves were regenerating, response to both relevant and perception to measure brightness – and she has learned to speak again. irrelevant stimuli, accompanied in both normally sighted mice and depends on the size of the visual parts of “Every day is a new beginning for by ‘re-wiring’ in the white those previously considered to be blind. the brain. Researchers at the Wellcome me,” says Ms Jensen. “I’ll probably matter of the brain. “Now we are asking to what extent Trust Centre for Neuroimaging at UCL never sing in a choir or anything, but Roberts RE et al. J Neurosci melanopsin could help the normally used functional magnetic resonance it’s exciting to talk normally, and I can’t 2010;30(50):17063–7. sighted to see, and what it might imaging and optical illusions to show wait to eat and drink and swim again.” contribute to the blind and partially that the smaller a person’s primary This is the second ever documented Lay counselling sighted,” says Prof. Lucas. These visual cortex, the more pronounced larynx transplant, and the fi rst in which Professor Vikram Patel and fi ndings could also change how we visual illusions seemed. the larynx, trachea and thyroid were colleagues at the Sangath design computer displays and TV Brown TM et al. Melanopsin contributions to irradiance transplanted together. The techniques was funded principally by us – the Brenda Charett Jensen and her medical team. Centre, Goa, India, and the screens, currently made with only coding in the thalamo-cortical visual system. PLoS Biol used were developed by Professor Martin fi rst time that a surgeon had received UC Davis Health System London School of Hygiene and rods and cones in mind. 2010;8(12):e1000558. Birchall, a visiting professor of Trust funding. Tropical Medicine have shown Schwarzkopf DS et al. The surface area of human In other research, scientists have V1 predicts the subjective experience of object size. otolaryngology at UC Davis and then Watch a video on this from UCL that trained lay counsellors can shown that how we see our environment Nat Neurosci 2011;14(1):28–30. at the University of Bristol. His work at www.youtube.com/ucltv be eff ective at helping to treat depression and anxiety in public primary care facilities. The intervention they tested was a collaborative approach between Neural neighbours activate stem cells Artesunate a lay counsellor, a primary care doctor and a psychiatrist. Stem cells, responsible for the As well as highlighting the is preferred Patel V et al. Lancet maintenance and repair of many importance of insulin-like molecules 2010;376(9758):2086–95. tissues, spend much of their time in signalling stem cells to activate, this treatment for dormant, being activated when new work hints at the potential of being able Faster sequencing cells are needed. The signals to grow to develop stem cell therapies that target malaria and proliferate are often relayed to the stem cells’ ‘neighbourhoods’ rather than Scientists from Imperial stem cells by their neighbours, which the cells themselves. The largest ever clinical trial among College London have taken form a microenvironment known as people hospitalised with severe malaria an important step towards the ‘stem cell niche’. Chell JM, Brand AH. Nutrition-responsive glia has concluded that the drug artesunate developing a technology control exit of neural stem cells from quiescence. that could sequence a genome Professor Andrea Brand and Dr Cell 2010;143:1161–73. should now be the preferred treatment in mere minutes, and at a James Chell of the , for the disease in both children and fraction of the cost of current Cambridge, have studied some of adults worldwide. commercial techniques. the neighbours of neural stem cells – An international consortium of The technology – nanopore glial cells – to investigate their role in researchers, led by Professor Nick sequencing – involves propelling activating stem cells. In the larval stages White of the Wellcome Trust–Mahidol a DNA strand through tiny of a developing fruit fl y, neural stem cells University–Oxford Tropical Medicine Chromolithograph recommending quinine to prevent malaria, holes, or nanopores, cut into are activated in response to a nutritional Research Programme in Bangkok, by Benjamin Armand Rabier (1869–1939). Wellcome Library a silicon chip, then reading the stimulus, the protein in fl y food. The compared artesunate treatment (used sequence. The researchers are researchers found that neighbouring in Asia for severe malaria) with quinine studying 5425 children with severe having seizures or developing confi dent that their fi nding glial cells pass on this stimulus by treatment, which has been in use malaria. With artesunate treatment dangerously low blood sugar. could lead to an ultrafast producing insulin-like molecules. By worldwide for over 300 years. 8.5 per cent of the patients died, commercial DNA-sequencing Dondorp AM et al. Artesunate versus quinine in tool in just ten years. genetically programming glial cells to The African Quinine versus compared with 10.9 per cent of those the treatment of severe falciparum malaria in African Ivanov AP et al. Nano Lett produce these molecules even without Artesunate Malaria Trial (AQUAMAT) who had quinine. Children treated with children (AQUAMAT): an open-label, randomised trial. Drosophila neural stem cells (green), showing their large Lancet 2010;376(9753):1647–57. 2011;11(1):279–85. a nutritional stimulus, they were able nucleoli (blue) and the nuclei of the surrounding neurons was carried out over fi ve years in artesunate were also less likely to suff er to activate the neural stem cells. (red). James Chell and Andrea Brand hospitals across nine African countries, other eff ects, such as falling into a coma,

8 | WELLCOME NEWS SPRING 2011 | 9 CAREERS

PROFESSOR MIKE STRATTON HOW I GOT INTO... CANCER GENETICS

A pathologist drawn into molecular biology in the mid-1980s, Professor Mike Stratton tells Chrissie Giles how he’ll never stop being fascinated by cells.

s a teenager I was keenly awful beauty in the way cells conspire to as a consultant histopathologist, but interested in biology. orchestrate life-threatening conditions. subsequently returned to the ICR to For example, I was Pathology was certainly inspiring and begin work on the genetics of breast fascinated by the thought-provoking. Nevertheless, it was cancer susceptibility. then novel notion that still at arm’s length from the real action. It has become of almost mystical mitochondria were ancient As a pathologist, about half the fascination to me that you can look infectious microorganisms with which samples I was asked to look at were down a microscope and see the we were all now living in cooperative and from tumours of various types. At the misbehaving cells of a tumour, and peaceful harmony, and wooed my future time we already knew that all cancers then delve into their nuclei to pick wife with tales of such extraordinary arose from a single cell that was out, from the thousands of millions of phenomena. I was excited by the notion behaving badly, with loss of normal bases of DNA, the few that are mutated of doing biological experiments to reveal growth control, because of abnormalities and cause the abnormal proliferation. such marvels. Indeed, I entered medicine in its DNA. As a young doctor straining I still occasionally look down a thinking that medical practice would to do research, encountering the diverse microscope and make a stab at naturally and inevitably entail asking patterns of abnormal cell proliferation diagnosing the type of cancer present, intriguing questions about human in cancer down the microscope almost but obviously would not seriously trust biology and disease. And in some senses inevitably drove me to speculate on the my judgement on this anymore. I no it is like that. However, during much of invisible abnormalities in the DNA longer practise as a pathologist but the period I spent as a junior doctor I felt within those blue cancer cell nuclei I have a huge amount of respect for frustrated at the distance there existed that were responsible for all this. I those who do. When one has looked from thinking about the mysteries of could not imagine a more direct search down a microscope every day for years normality and disease. for fundamental biological insight than those images of a private, subterranean I became a histopathologist because this endeavour. At this time, in 1984, world become second nature, and they I wished to get closer to those core the revolution in recombinant DNA remain with me. questions. As a pathologist one technology was having major impact mostly spends time looking down the and I moved to the Institute of Professor Stratton is Director of the Wellcome Trust Sanger Institute (www.sanger.ac.uk), and co-leader microscope at diseased tissues. Peering Cancer Research to do a PhD using of the Cancer Genome Project. into this hidden world provides you with this technology to explore the genetics profound and powerful insights into the of cancer. ways disease is generated. You see order I was hooked on cancer genetics and disorder. Indeed, although there is from that point. After my PhD I went considerable ugliness there is sometimes back to medicine for two years to qualify

10 | WELLCOME NEWS SPRING 2011 | 11 OPINION “Museums need more compelling games” Contact us on 020 7611 2200 Take your next group meeting or email [email protected] MARTHA HENSON AND DANNY BIRCHALL to a cultural hub of activity 183 Euston Road, London www.wellcomecollectionconference.org Wellcome Collection is part of the Wellcome Trust. The Wellcome Trust is o you play games? We might dismiss didactic lesson plan has unfortunately been the a charity registered in England and Wales, no. 210183. them as childish, but in his 1938 work dismal standard in this fi eld. However, others, such Homo Ludens, Johan Huizinga argued as the Science Museum, have begun to harness the that play is an essential component of potential of games for learning. The physics-based all human culture. The chances are that Launchball game was hugely popular and they have you enjoy playing something – whether just released Rizk (about climate change). it’s Angry Birds or a round of charades at Christmas. We’ve had our own success recently with Globally, gaming is big business, with a market High Tea, a strategy game centred on the dubious worth an estimated $50 billion (£30bn) in 2011 and actions of the British Empire in the run-up to the a demographically diverse audience with an even Opium Wars of 1839. From over 1.5m plays in its fi rst gender split. But it’s not just about numbers: the fortnight after release, plus comments, reviews and dedication of gamers to the pleasure of play means survey responses, we can see that we have achieved time spent at the console can exceed that spent with both a wide reach and our educational aims. a feature fi lm or novel. Why are these particular games successful? The educational potential seems obvious. So Because they put gameplay at the centre of the why have museums and educationalists, with all the experience and use experienced digital agencies WELLCOME TRUST information and resources at their disposal, failed to deliver this. These examples are a great start, CONFERENCE CENTRE to make more than a handful of really compelling but surely more could be done in this area. educational games? The work of game designers Games might seem a trivial way of approaching and researchers such as Jane McGonigal (author the public with new ideas, but the playful and of Reality is Broken) and Channel 4 Education exploratory impulses that draw gamers to great (including the Wellcome Trust-funded Routes) has games are still largely untapped as a means of amply demonstrated the power of games to bring engagement. By pushing boundaries ourselves, both children and adults cultural and scientifi c we hope to show others what can be achieved. ideas in new forms. www.wellcomecollection.org.uk/hightea But many have assumed that any game-like feature is enough to engage people, and tacking • Martha Henson is Multimedia Editor at the Wellcome Trust. minimal interactivity onto a barely disguised • Danny Birchall is the Editor of the Wellcome Collection website. Contact us on 01223 495000 Bring together your brightest or email [email protected] minds in a location to inspire Hinxton, Cambridgeshire www.wtconference.org.uk The Wellcome Trust is a charity registered in England and Wales, no. 210183. Played any great educational games lately? Email us at [email protected] or tweet @wellcometrust

12 | WELLCOME NEWS SPRING 2011 | 13 TROPICAL MEDICINE

BY MUN-KEAT LOOI BEAUTIFUL CREATURES LAINSON AND HIS PARASITES

In 1965, Ralph Lainson left London for Brazil with a three- year Wellcome Trust grant. He never came back. What was it about tropical Brazil that appealed to the young man? The parasites, of course.

14 | WELLCOME NEWS SPRING 2011 | 15 1959–62 DIRECTOR OF DERMAL LEISHMANIASIS UNIT IN CAYO DISTRICT, BELIZE

alph Lainson, like 1968 many, loves Brazil, WITH JEFFREY SHAW, DESCRIBES AND NAMES but not for the reasons L. AMAZONENSIS, THE you might expect. PARASITE THAT CAUSES “The Amazon region 1965 ANERGIC CUTANEOUS LEISHMANIASIS is a veritable mine of DIRECTOR OF NEWLY 1958 ESTABLISHED WELLCOME parasitological information, yet very, KEY WORK ON TRANSMISSION PARASITOLOGY UNIT very few people work in this fi eld here,” OF TOXOPLASMA IN BELÉM, BRAZIL says the 84-year-old scientist, enthusiastically. “I’ve always said to young Brazilian students what a 1964 wonderful place they’re in. If you turn AWARDED DSC FROM UNIVERSITY OF LONDON over a stone you are likely to fi nd four 1955–59 new species underneath it.” LECTURESHIP AT LSHTM 1964 It was this passion for the FIRST WELLCOME TRUST GRANT microscopic world that drew him away from his native England to the tropics some 50 years ago. It has also resulted 1955 in Professor Ralph Lainson now holding GAINS PHD IN PARASITOLOGY FROM LONDON SCHOOL OF the titles of Fellow of the Royal Society HYGIENE AND TROPICAL MEDICINE and Offi cer of the Order of the British Empire, and being the Wellcome Trust’s 1962 longest-serving grantholder – a record WITH JOHN STRANGWAYS-DIXON, IDENTIFIES FOREST 47 years and counting. Such a 1951 RODENTS AS HOSTS OF THE SPECIES CAUSING HUMAN 1927 GRADUATES WITH BSC IN SPECIAL ENTOMOLOGY CUTANEOUS LEISHMANIASIS. OBTAINS THE FIRST EXPERIMENTAL background might not seem to fi t BORN IN UPPER WITH SUBSIDIARY BOTANY FROM BRIGHTON TRANSMISSION OF A NEW WORLD LEISHMANIA SPECIES with his strange-but-true stories of BEEDING, SUSSEX, UK TECHNICAL COLLEGE (L. MEXICANA) TO HUMANS VIA THE PHLEBOTOMINE SAND FLY the anaconda that swallowed a visiting dentist, and the angler attacked by piranhas while clearing his boat’s propeller. Yet Ralph is a leading authority on parasites, particularly 1920s 1930s 1940s 1950s 1960s protozoan (single-celled) parasites.

The clues to this are his sand-fl y- Image credits: London School of Hygiene and Tropical Medicine/SPL (above left), R Lainson (1962, 2005), Odilson Sá/Flickr (1965), Royal Society of Tropical Medicine and patterned tie and the smile on his face Hygiene (1971, 1984), SPL (page 18 top left), Swiss Tropical Institute, courtesy of R Knechtli (1977), The Royal Society (1982), Wellcome Images (others). when I ask about his specialism, the neotropical Leishmania. number of rodents, opossums and “Now was the time to obtain a opportunity to continue his research least one Leishmania species infecting – the human parasite was tiny, only Ralph’s long relationship with the other animals in our baited traps.” volunteer and feed these infected insects in the New World. So, in 1963, he humans in Brazil. about 2–3 micrometres in diameter, parasite began in 1959 in Belize (then Among them was a rodent with lesions on him,” says Ralph. “Strangways-Dixon toured Latin America collecting strains Although cutaneous leishmaniasis whereas those that Otis Causey British Honduras). At the time, no on its tail, lesions that turned out to was keen to be this person. He said that of Leishmania and sizing up diff erent manifested itself in diff erent forms found were nearly twice the size. one in the country was sure of the be full of the parasite. Ralph identifi ed as the entomologist he was the correct research institutes. He went through in Central and South America, many Furthermore, when they inoculated origin of ‘Chiclero ulcer’ (cutaneous three diff erent species of rodent person to do this. He said, they’re my Central America, down to Colombia, clinicians thought the disease was the Oryzomys-derived parasite into leishmaniasis). Ralph says: “We had the frequently carrying the parasite. sand fl ies so if they’re going to feed on Venezuela and elsewhere, until his due to the same parasite, Leishmania hamsters it produced huge tumour-like parasite isolated from human beings He and his team also captured anything or anyone it’s going to be me. fi nal stop, the Instituto Evandro Chagas braziliensis, and that this was the same lesions in the skin very quickly, whereas and we knew that most of the people hundreds of phlebotomine sand fl ies I’m their boss!” in Belém, part of the Amazon delta as L. tropica, the strain that caused L. braziliensis took six months or more who acquired the disease worked in (using themselves as bait!) and off ered “We fed the fl ies on Strangways- of north Brazil. leishmaniasis in the Old World. Ralph for one tiny lesion to appear. the forest, often for long periods. It was them hamsters experimentally infected Dixon’s belly, and a few weeks later a There, he showed the researchers was among those certain that diff erent Ralph’s team found a small number reasonable to assume, therefore, that with Leishmania from patients. tiny lesion appeared, containing the his photographs of rodent lesions in leishmanial parasites were involved of the parasites that were the same as there were some reservoir hosts of the Dissection of the sand fl ies several parasites. It was most exciting: the fi rst Belize. One of them, Dr Otis Causey, in the disease in diff erent parts of the those from Oryzomys (which they parasite among the forest animals.” days after their hamster blood meal experimental proof of transmission to said he had seen very similar lesions on continent. Arriving in Brazil with a named L. mexicana amazonensis). In For two years they tracked all manner revealed the parasite inside. This left man of a neotropical Leishmania species the Oryzomys capito rodents common three-year Wellcome Trust grant, his the following years they identifi ed a of creatures, with little success until a Ralph and his entomologist, John by the bite of a phlebotomine sand fl y! to the region, but thought they were team collected parasite samples from (still-increasing) number of diff erent natural disaster lent a helping hand. Strangways-Dixon, in no doubt that The moment we worked that out was, simply bacterial or fungal infections all sorts of animals: armadillos, Leishmania species, often with specifi c “Hurricane Hattie I’ll always the same species of insect that I suppose, when I realised that I was a growing on damaged tails. Two weeks opossums, foxes, porcupines, monkeys or closely related sand fl y vectors and remember,” says Ralph. “It was a terrible transmitted Leishmania in the Old real scientist.” later in Rio de Janeiro, he approached and more, as well as human patients diff erent wild animal reservoirs. By experience, levelled fl at a lot of the World did it in the New World. Ralph with a slide made from a rodent with diff erent forms of leishmaniasis. 1979, so many diff erent Leishmania forest, but the result was the wild It only remained to prove the New World order in Belém. It was teeming with Their fi ndings were striking: the species had been discovered – at the animals found it diffi cult to fi nd food. sand fl y’s role in the transmission Ralph soon returned to the UK, Leishmania parasites. They had for the parasites found in Oryzomys were clearly time, 13 from the Americas, eight We had no problem capturing a large of the causative parasite to humans. but pined for the tropics and the fi rst time found the reservoir host of at much larger than those of L. braziliensis of which infected humans – that

16 | WELLCOME NEWS SPRING 2011 | 17 1984 AWARDED MANSON MEDAL BY ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE

1977 FIRST EXPERIMENTAL one named after him: L. (Viannia) PROOF THAT THE SAND lainsoni, discovered in 1987. His eff orts FLY IS A VECTOR OF have earned him a string of awards. VISCERAL LEISHMANIASIS PUBLISHED IN NATURE 1982 He tells me of his pride on becoming a ELECTED FELLOW 2005 Fellow of the Royal Society (“the fi nest OF THE ROYAL SOCIETY WELLCOME TRUST RESEARCH GRANT appreciation that anybody can give a scientist”) and receiving the OBE from the Queen in the name of science (“you get footballers who are knighted, probably because they’re very useful economically – a scientist is usually 1982 underpaid and usually not very much AWARDED HONORARY MEMBERSHIP appreciated by the majority of the 1971 OF THE LONDON SCHOOL OF population”). And though he ‘retired’ AWARDED CHALMERS MEDAL BY HYGIENE AND TROPICAL MEDICINE. 1992 2002 ROYAL SOCIETY OF TROPICAL PRESENTED AT THE SCHOOL BY RETIRES FROM DIRECTORSHIP OF THE WELLCOME TRUST in 1996, Ralph never got out of the lab. MEDICINE AND HYGIENE PRINCE PHILIP WELLCOME PARASITOLOGY UNIT RESEARCH GRANT Fourteen years later he spends his spare time staring down a microscope, addicted to fi lling in a jigsaw puzzle that will never be complete: an ever- fuller picture of the parasites. 1970s 1980s1980s 1990s 2000s “What I love about my work is the opportunity to discover and enjoy the extraordinary beauty of structure and complicated life cycles of these little organisms. It’s not work, more of a anergic cutaneous leishmaniasis and recognisable such that people can tell of American visceral leishmaniasis) very interesting hobby. Because these “It’s not work, more of a very (aff ecting patients whose immune which one a man is infected with. Every to vertebrates. And in 1981, the Unit parasites are rather beautiful little systems are incomplete, a condition bit of knowledge gained regarding the discovered a new sand fl y transmitting creatures.” interesting hobby. Because these incurable at the time), and those ecology, epidemiology and distribution L. braziliensis in Amazonian Brazil, infected with L. braziliensis stand the of the diff erent species is of help in which they named Lutzomyia Lainson R. The neotropical Leishmania species: a brief historical review of their discovery, ecology and parasites are rather beautiful risk of developing mucocutaneous control of the diseases they cause.” (Psychodopygus) wellcomei (says Ralph: taxonomy. Rev Pan-Amaz Saude 2010;1(2):13–32. leishmaniasis, which can be very Ralph’s three years in Brazil “We have an expression in Portuguese: Lainson R et al. Experimental transmission of disfi guring. Such patients require turned into 30 and fi rmly established pucha saco, which means that by giving Leishmania chagasi, causative agent of neotropical visceral leishmaniasis, by the sandfl y Lutzomyia little creatures.” prompt and particularly intensive the research group that became the it this name, we might persuade the longipalpis. Nature 1977;266(5603):628–30. treatment. Moreover, people immune Wellcome Parasitology Unit. Under his Trust to continue our grant!”). Lainson R et al. Leishmaniasis in Brazil: XVI. Isolation and the researchers proposed a new to one species of the parasite are usually directorship, the Unit made a string of Although the Unit closed in 1992, identifi cation of Leishmania species from sandfl ies, wild mammals and man in north Para State, with particular classifi cation of them. Ralph has vulnerable to others, complicating important discoveries, in leishmaniasis its legacy continues at the Instituto reference to L. braziliensis guyanensis causative agent of speculated that, “considering the vaccine production. And Brazil’s and other parasitic diseases. In 1969, Evandro Chagas, now a hub for visiting ‘pianbois’. Trans R Soc Trop Med Hyg 1981;75(4):530–6. remarkable number of Leishmania increasing urbanisation and population they published the fi rst record of Chagas’ scientists researching all aspects of Lainson R, Strangways-Dixon J. Dermal leishmaniasis in British Honduras: some host-reservoirs of L. brasiliensis species that have now been recorded movement has meant that groups are disease in the Amazon region of Brazil, Leishmania and other parasites, from mexicana. BMJ 1962;1(5292):1596–8. in the neotropics, and particularly in often exposed to diff erent species – and demonstrating that the disease could ecology to epidemiology, Lainson R et al. Chagas’ disease in the Amazon Basin: the Amazon region, this area might the diff erent sand fl ies that transmit spread easily through food and the genetics of host responses to speculations on transmission per os. Rev Inst Med Trop Sao Paulo 1980;22(6):294–7. well be the birthplace of this genus”. them – as their environment changes. contaminated with faeces from species infection. It also boasts a signifi cant Lainson R. Observations on the development and nature These fi ndings have helped to “One by one, we’ve shown that of blood-sucking triatomine bugs. In resource in its collection of cryo- of pseudocysts and cysts of Toxoplasma gondii. Trans R defi ne outbreaks of the disease in the there is not a single parasite causing 1977 they published in Nature, describing preserved parasite material and records, Soc Trop Med Hyg 1958;52(5):396–407. region, with considerable public health neotropical human cutaneous the fi rst experimental evidence that the amassed during the Wellcome Unit’s life. Lainson R et al. On a new family of non-pigmented parasites in the blood of reptiles: Garniidae fam.nov., implications. People infected with leishmaniasis, but six or seven,” says bite of sand fl y Lutzomyia longipalpis Ralph has helped to discover nearly (Coccidiida: Haemosporidiidea). Some species of the L. amazonensis may develop diff use, Ralph. “These are now known, identifi ed transmits Leishmaniasis chagai (the cause 100 new parasite species and even had new genus Garnia. Int J Parasitol 1971;1(3–4):241–50.

18 | WELLCOME NEWS SPRING 2011 | 19 WELLCOME COLLECTION International Senior Research Fellowships in Basic Biomedical Science

THE DIRTY TRUTH

To anthropologist Mary Douglas, dirt is “matter out of place”. To explore this idea, Wellcome Collection’s latest exhibition – Dirt – is inviting all of us to get up close and personal with all kinds of fi lthy things. We found out more.

Long, low, looming. There are fi ve mottled brown rectangles laid out imposingly in Wellcome Collection, as part of its latest exhibition, Dirt: The fi lthy reality of everyday life. But, despite their loamy appearance, these rectangular blocks are not made of soil or clay but human excrement. Collected in New Delhi and Jaipur, India, the excrement was dried, compressed and mixed with plastic resin, and moulded into these shapes. Dirt is about more than excrement, though. Visitors experience dirt in many guises, including soil, dust, bacteria and rubbish. From 1670s Netherlands to a New York landfi ll in 2030, Dirt encompasses locations in six diff erent cities, at six diff erent points in history. ‘The Community: New Delhi and Kolkata’ is the section housing the Images Eastman Dental Institute/Wellcome Derren Ready, International Senior faecal sculptures. To create the work, Research Fellowships artist Santiago Sierra worked with waste A Durga goddess sculpture being carried in procession, 19th century. Wellcome Library collected by manual scavengers, working To provide support for in India. These scavengers, or safai outstanding researchers, karamchari, spend their lives cleaning However, many hundreds of thousands celebrate the Hindu festival of Durga either medically or dry latrines, often no more than areas of Dalits still depend on the practice Puja. These striking structures are scientifically qualified, of dusty ground with a couple of bricks for their and their family’s livelihoods. coated in clay, cow dung and mud from who wish to establish an between which people defecate. There A number of organisations and the banks of the Ganges before being independent career in a are no rubber gloves, bleach or loo charities are working to improve the painted. After the celebration, the idols Croatian, Czech, Estonian, brushes. Using their bare hands or crude lives of manual scavengers, and improve are returned to the river there to be Hungarian, Polish, William Henry tools, the scavengers must collect other the availability of public toilets in dissolved back into the water. Slovakian or Slovenian people’s excrement in baskets and carry India. Details of one of these, Sulabh So does dirt have to be disgusting? academic institution. it to the dump, often miles away. International, can be found in the With exhibits including human Most manual scavengers are neighbouring room to where the excrement as sculpture, and dung Deadline for preliminary ‘untouchables’, or Dalits. They exist sculptures are displayed, as can as deities, Dirt might just make you applications: 6 June 2011. outside and below India’s caste system, information on a public compost think again. and are shunned by many other Indians toilet it has developed. The largest who consider them unclean. Born into non-profi t organisation in India, Dirt: The fi lthy reality of everyday life runs at Wellcome Collection from 24 March to 31 this social group, Dalits face lifelong Sulabh International employs the August 2011. www.wellcomecollection.org/dirt discrimination, disadvantage and manual scavengers who collected have to do some of the dirtiest jobs the waste for Sierra’s sculptures. imaginable. The Constitution of India Dirt is not always seen as an object – a copy of which is on display in the of revulsion – sometimes it can be exhibition – came into eff ect in 1950 considered sacred. Alongside the and formally outlawed untouchability. sculptures is a Durga goddess, built to www.wellcome.ac.uk/isrf/wn 20 | WELLCOME NEWS CLOSE-UP

WELLCOME 3 IMAGE AWARDS

From the foreleg of a diving beetle to blood clotting on a plaster, the subjects captured by the winners of the Wellcome Image Awards 2011 are certainly varied. The Awards celebrate the most informative, striking and technically excellent images acquired by Wellcome Images – the Wellcome Library’s image repository – in the past 18 months. The 2011 winners were announced at a ceremony in London on 23 February hosted by writer and presenter Dr Adam Rutherford. He and his fellow judges, including science broadcaster Alice Roberts, BBC Medical Correspondent Fergus Walsh and Guardian Picture Editor Eric Hilaire, selected 20 winning images and one winning animation. Special Awards were given to David Bishop’s photograph of a live donor kidney transplant and a fl uorescent micrograph by Fernan Federici and Lionel Dupuy, showing cell division and gene expression in plant cells. You can see the winning images in person at 4 Wellcome Collection until mid-July 2011, or browse them online: www.wellcomeimageawards.org

2

5

1. 3D reconstruction of a mouse embryo, by Agnieszka Jedrusik and Magdalena Zernicka-Goetz, Gurdon Institute, Cambridge. 2. Scales on the wing of a moth, by Kevin Mackenzie, University of Aberdeen. 3. Periodontal bacteria, by Derren Ready, Eastman Dental Institute. 4. Zebrafi sh retina, by Kara Cerveny, Steve Wilson’s lab, UCL. 5. Embryonic mouse kidney, by Bob Kao and Kieran Short, Monash University. 6. Base of a silkworm caterpillar’s proleg, 1 6 by Spike Walker.

22 | WELLCOME NEWS SPRING 2011 | 23 Q&A BLOG AND FILM Wellcome Trust open access

Wellcome Trust blog IN THE HOT SEAT As the Wellcome Trust celebrates its 75th birthday, our blog (wellcometrust.wordpress.com) celebrates its fi rst. And a busy year it has been: over 60 000 unique page views and nearly 300 posts. We have covered everything from fi sh to football, DR BEAU LOTTO synthetic biology to surgery, and the blog is still growing. The Making anyone part of scientifi c discovery last few months have seen the blog break news about the fi rst scientifi c paper written by primary-school students (for more on this, see Q&A opposite) and further contributions from our grantholders, describing everything from olfactory cells that could cure paralysis to how we sense time based on the movement of clouds. We’ve also seen some beautiful images We’re

of folic acid and even fl y guts. We are looking forward to the s blog’s next 74 years… opening come Image

ell Dr Beau Lotto is a neuroscientist on a mission: to get us to understand To contribute to the blog, contact the up knowledge Editor: [email protected] that we are each makers of how we see and understand the world. In a recent project he worked with primary school children to help them to everyone – become the fi rst in the world to plan, perform and publish their own Wellcome Trust YouTube channel Images Wellcome Annie Cavanagh, scientifi c experiment in a peer-reviewed journal. Their study resulted Recent additions to our YouTube channel consider cells, the freedom to in some novel fi ndings about how bees perceive colour. climate change and genetics. Produced to support our educational magazine Big Picture: The Cell, ‘Working with Cells’ follows Marianne Baker, a PhD student who uses cells find out starts How did this project come about? whereas children often say, “Ah, and…?” I think as part of her research into understanding how blood vessels I’d been doing public experiments in public space kids are far more able to deal with uncertainty. grow to feed tumours (below). with freedom for several years – largely on bumblebees. Indeed, Cell culture on a diff erent scale is examined in ‘True Blood: I’d been engaging with the public with the idea How did it go? The reality of making red blood cells’. With 2.5 million bags of of access. that we are makers of our own perceptions, It went wonderfully well, which isn’t to say that blood being used in the UK each year, the prospect of being able which for me is a fundamental point, not only for we knew it would, as we didn’t even know what the to manufacture a potentially limitless supply of tailored, understanding how the brain works, but also for next day would bring. In the end, the kids devised infection-free red blood cells is compelling. In this fi lm, two getting people to question their common-sense an experiment to see if bees could learn to use the researchers – Marc Turner and Joanne Mountford – talk us notions of self. I run both a lab and a studio: the spatial relationships between colours to work out through their project to produce red blood cells from stem cells. A repository of 2 million full- lab aims to understand perception, and the studio which fl owers contained sugar water, and which Could combating climate change be good for our health? text articles, 20 million PubMed creates opportunities for people to become salt water. For writing up the paper, we worked ‘Tackling Climate Change: The good news’ presents fi ndings abstract records, clinical guidelines observers of themselves making sense. with four kids in particular. I had my laptop and from studies published in that explored the and theses – UK PubMed Central When the headteacher at Blackawton Primary asked them what to write, which is why the paper potential health benefi ts of strategies to mitigate the eff ects provides a single, free-to-access School in Devon – Dave Stradwick – asked me to is in the kidspeak. They would then give me the of climate change. gateway to high-quality research come in for Science Week and talk to the school words (though I made sure that they knew that as Lastly, two fi lms outline large-scale projects on genetics in the life sciences. about science, I was more than happy to – largely far as I was concerned nothing was out-of-bounds) supported by the Trust. ‘People of the British Isles: The because my children go there. We then started and I’d put them into the form of a narrative. genetic landscape of Islay’ tells the story of a project that is For more information and to thinking about bringing the bees down to the We submitted the paper to Biology Letters, it cataloguing the genetic basis of the UK. In ‘1000 Genomes: discover how to comply with school. But rather than me design the experiment, underwent peer review and was then published. A new foundation for genetic research’, Dr Richard Durbin our open access policy, visit we wanted to get the kids to think about creating and Dr Chris Tyler-Smith describe the key fi ndings of the pilot our website. one, getting them to think about science as a way Would this type of project work with adults? phase of the project aiming to create the most comprehensive of being, not just a thing to do. Absolutely. With the support of the Wellcome map of common human genetic variation. www.wellcome.ac.uk/ukpmc Trust, we’ve moved my lab from University College What were you trying to do? London to the Science Museum. We have a grey We wanted to do real science, but science as game lab, where people can interact with the objects that (i.e. playing with rules), and for the kids to know, we create, such as installations; a black lab, where from the start, that they were asking a question no people can become subjects of experiments; and one had ever asked before. If you know you’re doing a white lab, where people can come and design something new, there’s a level of excitement you experiments, by invitation. You’re making the just can’t explain, and the kids sensed this. public part of the process of discovery – not consumers of it. Did you fi nd the children open-minded? • Blackawton PS et al. Blackawton bees. Biol Lett 2010 Dec 22 View, comment on and share our fi lms Yes – it’s adults that have the problems! I fi nd it [Epub ahead of print]. at: www.youtube.com/wellcometrust when I show my optical illusions of colour to adults, • Maloney LT, Hempel de Ibarra N. Commentary on PS Blackawton they usually say, “Oh, my goodness!” (or more), et al., Blackawton Bees. Biol Lett 2010 Dec 22 [Epub ahead of print].

24 | WELLCOME NEWS SPRING 2011 | 25 NUTS AND BOLTS 3

3 7 PRIMARY CILIA Primary cilium 8 Axoneme Cilia are fi ne, hair-like protrusions found on the surface of many Almost all types of vertebrate The basic structure of the cilium, kinds of cells. Defects in cilia – whether motile or primary – can cell have a primary cilium on their which is around 0.25 micrometres in surface. Primary cilia don’t move, diameter and up to 20 micrometres lead to diseases, collectively termed ciliopathies. This quick guide unlike motile cilia, and have a long. At the lower part of the cilium, gives you the lowdown on these intriguing organelles. slightly diff erent structure (see left). the microtubules are in triplets, not pairs.

4 First seen in the 17th century by Dutch equivalent of the appendix. Now, communicate and how we sense our 4 scientist Antonie van Leeuwenhoek, however, primary cilia are gaining surroundings. Their involvement in Anterograde 8 hair-like motile cilia cover the surface attention too. limb development, for example, is hinted Retrograde of many cells. They make things move: In the last decade, research into at by the fact that many non-motile transport everything from whole cells (such as the diseases caused by defects in cilia – ciliopathies cause additional fi ngers Cilia and fl agella don’t contain transport protozoa seen by Leeuwenhoek) to fl uid ciliopathies – has emerged as a fi eld in its and toes. Other common features include protein-making machinery, so Proteins called dyneins – in the trachea to an egg along the own right. Researchers have identifi ed diabetes, obesity, kidney disease, their proteins have to be made molecular motors – move cargo fallopian tube. over 40 genes mutated in ciliopathies, problems with seeing and smelling, in the main body of the cell and down from the tip of the cilium Motile cilia are not the only thought to aff ect cilia components and bone defects and cognitive impairment. transported into the cilia to build 8 back to the cell. This cargo protrusions on cells. Curiously, cells functioning (see diagrams). To date, around 20 ciliopathies are and maintain them. Proteins 7 includes kinesins that have lacking motile cilia often have a single Researchers are studying ciliopathies known, and with some researchers called kinesins – molecular motors delivered their components cilium on their surface. Named primary to understand what cilia do in normal suggesting that motile and nonmotile – carry proteins from the cell to to the tip of the cilium. or non-motile cilia, these were once development and functioning. Evidence forms may total over 100, interest in these the tip of the cilium where the written off as evolutionary leftovers is mounting for the role of primary cilia curious organelles looks set to continue. axoneme is made. with unknown function – the cellular in how our bodies develop, how cells 9 5 Dyneins Kinesins See 8 above. See 4 above. 4 10 1 Want to know more? 6 Cell membrane • Badano JL et al. The ciliopathies: 9 an emerging class of human Basal body genetic disorders. Annu Rev The structure from which the Genomics Hum Genet cilium grows. This sits in the 2006;7:125–48. cell membrane, and is made up 5 • Tobin JL, Beales PL. The 2 of nine triplets of microtubules nonmotile ciliopathies. Genet Med 1 arranged in a ring. 2009;11(6):386–402. • Baker K, Beales PL. Making Dynein arms sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet 2009;151C(4):281–95. 2 10 • www.ciliopathyalliance.org.uk Cilium cross-section The structure of cilia, and of the closely related Wellcome Trust-funded fl agella (the ‘tails’ of sperm), is conserved across researchers working organisms. While motile cilia have nine pairs of in this fi eld include: microtubules in a ring surrounding a central pair (the ‘9 + 2’ arrangement), primary cilia lack the • Prof. Philip Beales, Institute of central pair, showing a 9 + 0 arrangement. Child Health, UCL. • Prof. Micheal Cheetham, Institute of Opthalmology, UCL. • Dr Martin Knight, Queen Mary, 6 University of London.

26 | WELLCOME NEWS SPRING 2011 | 27 FUNDING INITIATIVES

BY CHRISSIE GILES PROTECTING THE POLLINATORS

Insect pollinators, including honeybees, bumblebees and hoverfl ies, are in decline. The £10 million Insect Pollinators Initiative – part- funded by the Wellcome Trust – has been launched to fi nd out why. We met researchers from three of the nine projects funded to hear about their plans.

False-coloured scanning electron micrograph of a honeybee (winner of a 2011 Wellcome Image Award – see page 22). David McCarthy and Annie Cavanagh/Wellcome Images

e all know that bees pollinator, honeybees, are prone to a How do diseases aff ect the honeybee, can lead to symptoms including – as the will be investigating how bumblebees make honey, but they number of diseases. The mite Varroa and could they spread to other bee name suggests – misshapen wings that come to be infected with deformed wing do much more for the destructor, for example, carries viruses species? prevent bees from fl ying. The grounded virus and N. ceranae, and the impact that food we eat. Bees and that can quickly destroy entire colonies, “We’ve picked what we think are the bees are taken by predators and the these emergent diseases have on other insects, including and has spread almost completely most important disease organisms for colonies suff er as their numbers drop. individuals and colonies of the butterfl ies and hoverfl ies, around the world in the last 30 years. the honeybee,” says Dr Robert Paxton, Robert says at least half of the important native bumblebee species. pollinate plants. By transferring pollen While disease is a serious risk, it from Queen’s University Belfast and the colonies in the UK contain clinical In their project, researchers are from the male parts of fl owers to the is not the only one pollinators face. University of Halle, Germany. His team symptoms of deformed wing virus – studying how the diseases aff ect the bees female parts, they are a vital part of the “There’s likely a smorgasbord of is studying deformed wing virus, carried severe infection with which can lead physically, and whether they have any process that eventually leads to fruit, problems,” says Professor Jane by the Varroa destructor mite, and a to the collapse of colonies. impact on insects’ fl ight behaviour, nut and seed production. Memmott from the University of fungus-like microorganism called Nosema, meanwhile, has spread orientation and learning – so-called For some crops, such as melons, Bristol, a lead investigator on one of Nosema ceranae. from East Asia in the last 10–15 years to sub-lethal eff ects, which don’t kill the no pollinators means no fruit. For the projects funded by the Initiative. “Before the Varroa mite came to the the western honeybee. Robert suspects bees but aff ect how they function. others, it means a lesser harvest. “And they probably interact UK, deformed wing virus was found in that the interaction between this and “We’re working with Juliet Osborne’s This widespread role of insects in in diff erent ways too – if bees are not maybe 1 in 10 000 colonies,” says Robert. deformed wing virus may act as a team at Rothamsted Research that has food production is refl ected in insect properly fed, then they’re more likely This changed after its discovery in the “double whammy”, greatly increasing very refi ned methods for tracking how pollinators’ economic value – estimated to catch diseases, and so on.” UK in 1992, when the amount of virus the ill-eff ects on honeybees. Not only individual bees fl y,” says Robert. “It will at €153 billion (£130bn) globally in 2005.1 The nine projects funded through carried by bees increased dramatically. honeybees are at risk: these diseases be really nice to understand the impact Pollinators are under threat, though. the Insect Pollinators Initiative are Varroa is a rusty-coloured mite, also aff ect bumblebees, and there are of these disease organisms on Research published in 2006 indicates setting out to understand these threats which feeds on the haemolymph fears that they will be transmitted to individuals.” that the diversity of wild bees – a key better. We have looked at three below, (circulatory fl uid) of adult and pupal other pollinators too. Professor Vincent Jansen, also at pollinator group – has declined severely and details of all nine can be found at bees. This increases the amount of Dr Mark Brown and his team at Royal Holloway, will use the data since the 1980s.2 Another major www.wellcome.ac.uk/pollinators. deformed wing virus carried by bees and Royal Holloway, University of London, collected to model the spread of the

28 | WELLCOME NEWS SPRING 2011 | 29 study the eff ects on the insects’ abilities the project, research by Geraldine’s to learn at the neuronal level,” he says. laboratory is mainly around To assess the impact of pesticides, understanding the mechanisms research in the lab of Dr Geraldine of learning and memory. She and Wright at Newcastle University (see her colleagues have been using the below) will investigate how such honeybee as a model for some time, chemicals aff ect learning and memory and are bringing that knowledge to in both honeybees and bumblebees. their new project. “After the bees have been exposed to “We don’t know a lot about nutrition chemicals, we can ask: are they slower and how it infl uences learning and at learning? Do they forget what they’ve memory. This project will allow us to learned?” says Chris. understand exactly what honeybees This part of the project will involve and bumblebees need, in terms of pollen the radiotagging of 6000 bees, overseen and nectar, but also how their foraging by Dr Nigel Raine at Royal Holloway. A can feed back on to what they do when scanner will monitor bees as they enter they’re learning.” For example, she says, and leave the hive. And the bees will be if a bee is low on protein in its diet, is it weighed, allowing researchers to work more likely to learn to associate a fl oral out not only each individual bee’s scent with an amino acid (which proteins contribution to the hive throughout its are made of) than with a sugar? life but also the performance of the With Professor Sharoni Shafi r at the whole colony throughout a season. Hebrew University, Israel, Geraldine will be investigating how bees weigh rewards Are British bees getting the – or, as she describes it: “We’re going to right diet? look at how nutrition aff ects the Like doing the grocery shopping for cognitive behavioural decisions that your family, foraging worker bees have forager bees have to make when they’re to pick food that’s right not only for out doing the shopping.” them but also for those back home. The bee’s shopping list is simpler • Dr Robert Paxton is working with Dr Mark Brown though: pollen is the main source (Royal Holloway, University of London) and of protein and nectar the main source Dr Juliet Osborne (Rothamsted Research). of carbohydrate. • Dr Chris Connolly is working with Dr Jenni Harvey (University of Dundee), Dr Nigel Raine “How worker bees choose food is (Royal Holloway), Dr Geraldine Wright (Newcastle not well understood,” says Dr Geraldine University) and Professor Neil Millar (UCL). Wright from Newcastle University. She • Dr Geraldine Wright is working with Dr Phil Bumblebee (Bombus pascuorum) foraging is investigating bee nutrition, and how Stevenson (Royal Botanic Gardens, Kew), Dr Annie on red clover. © Claire Carvell, Centre for Borland (Newcastle University), Prof. Sue Nicolson Ecology and Hydrology a bee’s nutritional state aff ects how (University of Pretoria), Prof. Sharoni Shafi r it forages. (Hebrew University of Jerusalem) and Prof. Geraldine is working with Dr Steve Simpson (University of Sydney). 1. Gallai N et al. Economic valuation of the How do pesticides and other synergistic interactions,” Chris says. Annie Borland, a plant physiologist at vulnerability of world agriculture confronted “ The mite Varroa destructor chemicals aff ect bees’ behaviour? “I decided that this is more or less Newcastle, and Dr Phil Stevenson, from with pollinator decline. Ecological Economics Pesticides and other agricultural the kind of thing we’ve been doing on the Royal Botanic Gardens at Kew, to 2009;68(3):810–21. 2. Biesmeijer JC et al. Parallel declines in pollinators carries viruses that can quickly chemicals used to maximise crop yields mammalian brain cells, so if we could measure the nutritional content of and insect-pollinated plants in Britain and the may also be aff ecting the health of bees. apply this to the bee brain, we could fi nd nectar and pollen from diff erent Netherlands. Science 2006;313(5785):351–4. The treatment of honeybees with out if these chemicals have sub-lethal agricultural, horticultural and native

destroy entire colonies” pesticides – miticides – to try to prevent eff ects at the level of individual cells, UK species. infestation with the Varroa mite could neural networks, whole animals or “We’re looking to fi nd out if bees be detrimental to their wellbeing. entire colonies.” There are fears that need to forage from one or several disease organisms in the pollinator completely understood how. Dr Chris Connolly is a neurobiologist these exposures may aff ect the bees’ diff erent species to achieve their The Insect Pollinators Iniatitive is community, to try to understand the They are also looking in some detail at the University of Dundee. Though abilities to move, communicate and optimal carbohydrate-to-protein supported by the Biotechnology threat to both honeybees and at the bacterial species associated with usually found investigating the human fi nd food. ratio,” says Geraldine. “One thing and Biological Sciences Research bumblebees. the honeybee gut. Researchers have only brain, he is now applying his expertise The Varroa-killing miticides are a that’s emerging from the work of our Council, the Department for On top of all these eff orts, the team recently discovered that insect guts hold to bees. reformulation of the pesticides used collaborator, Professor Sue Nicolson Environment, Food and Rural will also attempt to fi nd ways to treat a huge variety of lactic acid bacteria and “I was thinking about pesticides in the fi eld and one of the prime targets at the University of Pretoria in South Aff airs, the Natural Environment these infections. Robert and his related species, the kind you fi nd in and realised that, although people have for synergistic toxicity. “If the bees Africa, is that workers don’t survive Research Council, the Scottish colleagues will be testing the use of probiotic yoghurts. They will investigate looked at the concentrations that kill encounter this and then another well on a high-protein diet, but this is in Government and the Wellcome RNAi (RNA interference) methods in whether the two diseases have an impact pest and non-pest species, so-called pesticide, then the double hit might fact what the brood [the immature bees] Trust, under the auspices of the controlling deformed wing virus, an on these bacteria, and whether these sub-lethal doses may aff ect how bees be the problem,” Chris says. need. It will be really interesting to fi nd Living With Environmental RNA virus. The technique involves bacteria can help overcome the disease behave. Moreover, there have been no His team is designing assays to study out how much the honeybee has to Change partnership. blocking the multiplication of the virus symptoms, particularly those caused studies to investigate whether the the eff ects of diff erent combinations of disregard its own nutritional state while and has been eff ective in other RNA by Nosema, which bees contract by sub-lethal eff ects of multiple pesticides pesticide on brain cells. “Our next step it’s foraging.” viruses in honeybees, though it is not swallowing spores. might create the ‘perfect storm’ through will be to look at neural networks and to While bee nutrition is the focus of

30 | WELLCOME NEWS SPRING 2011 | 31 FROM THE ARCHIVE What is it? Published in 1493, the book is a history chronicle that follows Biblical lines, beginning with the Creation and ending BY ROSS MACFARLANE with the Last Judgement. The largest section, however, consists of scenes of contemporary life and contains many illustrations of European places. The NUREMBERG book was produced in Nuremberg – then the centre of the German book trade. The city is aff orded a double-page CHRONICLE spread (shown) and the book is known in English as the Nuremberg Chronicle.

Why is it so special? Due to the variety of the integration of its text and images, the Nuremberg Chronicle has been hailed as the most sophisticated printed book published before 1500. It’s recognised as one of the treasures of the Wellcome Library’s Rare Books Collection.

What’s the Wellcome link? Written in Latin by Hartmann Schedel, a physician, the book was purchased by in 1898 at Sotheby’s for £20.10s., at an auction of the library of the artist and designer William Morris. This was a major early purchase for Wellcome, made at a time when he was as interested in books that could inspire designs for advertisements for his pharmaceutical business, as in artefacts relating to the history of medicine.

Can you see it? The Chronicle is held in closed access in the Wellcome Library, but it can be ordered through the Library catalogue. A modern facsimile is also available on the Library’s open shelves.

Find out more online at library.wellcome.ac.uk

32 | WELLCOME NEWS SPRING 2011 | 33 DIARY Courses, conferences and workshops Senior Research Fellowships in Wellcome Trust Genome Campus, Hinxton, unless Basic Biomedical Science Mary McCartney Mary otherwise specifi ed. For more, see www.wellcome.ac.uk/ advancedcourses and www.wellcome.ac.uk/conferences

Applied Bioinformatics and Public Health Microbiology Conference, 1–3 June Molecular Biology of Hearing and Deafness Conference, 6–9 July Proteomics Bioinformatics Workshop, 15–19 July Human Genome Analysis: Genetic analysis of multifactorial diseases Course, 23–29 July From Beads on a String to the Pearls of Regulation: The structure and dynamics of chromatin APPLIANCE OF SCIENCE Conference, 3–4 August Wellcome Trust School on Biology of Social Cognition “It’s all about bringing real life into art – literally” Conference, 14–21 August The Leena Peltonen School of Human Genomics MARC QUINN Conference, 21–25 August The Genomics of Common Diseases Conference, 30 August–2 September or me, science is important, A lot of artwork to do with DNA was so boringly Molecular Approaches to Clinical Microbiology in Africa but this isn’t true for all artists. illustrative, it doesn’t really tell you anything to Course, Malawi–Liverpool–Wellcome Trust Clinical Research William Henry Some have no interest in science draw a double helix. It was very interesting to Programme, Blantyre, Malawi, 10–16 September at all – and they make a diff erent actually get to the nitty-gritty and work with the Images Eastman Dental Institute/Wellcome Derren Ready, Epigenomics of Common Diseases kind of art. actual stuff – that gave it a reality. Conference, 13–16 September I’m interested in bringing real life into I am continuing to work with the body as Senior Research Fellowships art in some way – literally. With the blood head, inspiration. I’ve just done a series of paintings of Next Generation Sequencing in Basic Biomedical Science ‘Self’, I was trying to think of an organ that could people’s irises, which are close-ups, 2 to 4 metres Workshop, 2–10 October Candidates are expected to be harvested without killing the host. You can take wide. You get an image that is at once incredibly Functional Genomics and Systems Biology have an excellent track record blood out and the body will rebuild it. You have a colourful and abstract in a way, but also a complete Conference, 29 November–1 December in their scientific field and be sense of the wonder of the way that the body can signifi er of identity in the way that DNA is, because able to demonstrate their ability re-create itself. It’s a metaphor for life and death. an iris doesn’t change. In the middle you have this Wellcome Collection events and exhibitions For the work I’ve done using DNA, it just so black hole, which, to me, signifi es the void and to carry out independent Euston Road, London. www.wellcomecollection.org happened that, at that moment, the same mystery of life. research. philosophical questions interested me and Science and art are two very diff erent things. Dirt: The fi lthy reality of everyday life Deadline for preliminary interested science. For example, the idea of DNA Science wishes to discover facts about the world, Exhibition, 24 March–31 August applications: 6 June 2011. as the instructions for building someone, and art is about creating objects of philosophical the question of how complexity evolved out of a meditation and emotional communication, again, Elements www.wellcome.ac.uk/uksrf/wn binary code. about what it is to be a person living in the world. Event, 8 April I worked with Professor Sir to But they coincide in that they’re both interested in Supper Salon create a portrait of him that contained his DNA. the mysteries of life: where do we come from? What Event, 13 April That was very interesting – I went to meet him are we made of? Who are we? Where do we go when with no preconceptions about what to make. He we die? These questions are common questions – Tell it to Your Doctor showed me around the Wellcome Trust Sanger but art doesn’t fi nd answers, it just poses a question Events, 16 & 21 April Institute, and it was through his eyes seeing how in a new way. Born Today everything worked that I came up with the ideas Events, 28 April & 5 May for the portrait. It was a literal collaboration too, Find out more at www.marcquinn.com because I got some of his DNA.

IN YOUR NEXT ISSUE MRI scanner in ‘Nuts and Bolts’ and updates on our funding and research activities. Plus You can see Marc’s work ‘Silvia Petretti – Sustiva, Tenofi vir, 3TC (HIV)’ at Wellcome Collection.

34 | WELLCOME NEWS SPRING 2011 | 35 TUESDAY–SUNDAY (UNTIL 18.00) A FREE DESTINATION FOR LATE-NIGHT THURSDAY (UNTIL 22.00) 183 EUSTON ROAD, NW1 THE INCURABLY CURIOUS EUSTON, EUSTON SQUARE

The Filthy Reality of Everyday Life

Free exhibition Until 31 August

This exhibition and accompanying events are part of a Wellcome Trust season of activity at special dirty locations across the UK, including the Eden Project, Glasgow, Glastonbury and other summer festivals. Wellcome Collection is part of the Wellcome Trust. www.wellcomecollection.org/dirt

The Wellcome Trust is a charity registered in England and Wales, no. 210183. PU-5047.36/03-2011/MD