Wellcome News 66

Issue 66, spring 2011

Wellcome NEWS INVESTING IN POLLINATOR RESEARCH Protecting insect pollinators’ health – and our food supply.

Technology Transfer

The McGRATHÂŽ Series 5 video laryngoscope, developed with Trust funding.

Designed and manufactured by Aircraft Medical

Technology Transfer: Pushing the boundaries of medical innovation We are a committed funder of translational R&D, bridging the gap between fundamental research and the development of new health products.

We work with world-class investigators in academic institutions and companies alike, in pursuit of solutions for unmet medical needs.

14 Beautiful creatures: Lainson and his parasites CONTENTS

INSIDE THIS ISSUE In brief Message from the Director Funding news Research news

4 6 8

In depth How I Got Into‌ cancer genetics: Prof. Mike Stratton Beautiful creatures: Prof. Ralph Lainson The dirty truth: Dirt at Wellcome Collection YouTube and blog update Q&A: Dr Beau Lotto Protecting the pollinators

10 14 20 24 25 28

Opinion Museums need more compelling games Appliance of Science: bringing real life into art

13 34

Picture features Wellcome Image Awards 2011 Nuts and Bolts: primary cilia From the Archive: Nuremberg Chronicle

22 26 32

www.wellcome.ac.uk/technologytransfer 2 | WELLCOME NEWS

SPRING 2011 | 3

Wellcome NEWS Telling the stories of the Wellcome Trust’s work

MESSAGE FROM THE DIRECTOR

UKCMRI plans approved

SIR MARK WALPORT

Plans to build a world-leading medical research institute at St Pancras in London have been approved by Camden councillors. The UK Centre for Medical Research and Innovation (UKCMRI), designed by the architects HOK with PLP Architecture, will have around 1500 staff, including 1250 scientists. The Development Control Committee voted in favour of the £500 million project on 16 December 2010.

Sir David Cooksey, Chairman of UKCMRI, says: “UKCMRI will harness the talent and potential of doctors, nurses, biologists, mathematicians, physicists, chemists, computer scientists and engineers to understand the underlying causes of disease. This will accelerate our ability to treat disease – bringing benefits to patients through the NHS and to the economy by developing a sector in which the UK already excels.” We are co-founders of UKCMRI, in partnership with the Medical Research Council, Cancer Research UK and University College London.

Construction is expected to begin this year, and to be completed by 2015.

Editor Chrissie Giles Assistant Editor Tom Freeman Writers Craig Brierley, Chrissie Giles, Mun-Keat Looi, Jen Middleton Design Malcolm Chivers, Marianne Dear Photography David Sayer Publisher Hugh Blackbourn Contributors: Mike Stratton illustration Bret Syfert Primary cilium illustration Lucy Farfort Ideas, comments, suggestions? Get in touch: Wellcome News Wellcome Trust Gibbs Building 215 Euston Road London NW1 2BE E wellcome.news@wellcome.ac.uk www.wellcome.ac.uk/wellcomenews To subscribe: T +44 (0)20 7611 8651 E publishing@wellcome.ac.uk www.wellcome.ac.uk/subscribe

www.ukcmri.ac.uk Impression of the UKCRMI entrance atrium. Wadsworth3d

All images, unless otherwise stated, are from the Wellcome Library. You can get copies through Wellcome Images (images.wellcome.ac.uk).

Wellcome Trust We are a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. www.wellcome.ac.uk This is an open access publication and, with the exception of images and illustrations, the content may, unless otherwise stated, be reproduced free of charge in any format or medium, subject to the following constraints: content must be reproduced accurately; content must not be used in a misleading context; the Wellcome Trust must be attributed as the original author and the title of the document specified in the attribution. The views and opinions expressed by writers within Wellcome News do not necessarily reflect those of the Wellcome Trust or Editor. No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. ISSN 13569112. First published by the Wellcome Trust, 2011. Wellcome News is © the Wellcome Trust and is licensed under Creative Commons Attribution 2.0 UK. The Wellcome Trust is a charity registered in England and Wales, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England and Wales, no. ce is at 215 Euston Road, London NW1 2BE, UK).

PU-5047/12.8K/03-2011/MD,MC 50%

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

Cover: 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

The Wellcome Trust supports and forms partnerships with a diverse range of people working on an equally diverse range of topics.

However, there is a common denominator that unites everyone with whom we work – a passion for their work. In this, the first issue of the new-look Wellcome News, we are proud to be able to bring you some stories of these people and what drives them to succeed.

As Mike Stratton, Director of the Wellcome Trust Sanger Institute and co-leader of the Cancer Genome Project, tells us, his fascination with cancer began early in his career, when as a pathologist he would look down a microscope to diagnose cancer. This fascination has driven his career, and the Institute that he now heads is working to understand the genetic changes behind the cancers he used to examine.

It was a similar passion for the microscopic world that took Ralph Lainson from his native England to Brazil. The Wellcome Trust’s longest-serving grantholder – 47 years so far – he has forged a formidable reputation as a parasitologist, specialising in the disfiguring disease leishmaniasis. He has discovered nearly 100 new parasite species, as well as the sand-fly vectors that carry the disease.

An interest in insects also unites the researchers working as part of the £10 million Insect Pollinators Initiative. Through this, nine diverse groups are examining the pressing issue of how populations of bees and other pollinators are collapsing and what can be done to reverse this trend. From neurobiologists to beekeepers, mathematical modellers to nutritionists, this is a great example of people with different interests coming together for a common, important cause.

Experiments with bees also feature heavily in the work of Beau Lotto, a neuroscientist and enthusiastic advocate for involving the public in the process of discovery. He recently worked with primaryschool children to help them become the first in the world to plan, perform and publish their own scientific study in a peer-reviewed journal. Now, with Wellcome Trust support, he has taken his laboratory to the Science Museum, where people can take part in experiments.

These stories illustrate just a small proportion of the motivated and passionate people with whom we work, and we look forward to bringing you the stories of many more in future issues.

Dirty work at Wellcome Collection The doors have now closed on Wellcome Collection’s High Society exhibition – its most successful to date – but there’s a wealth of events coming up in the spring.

Replacing High Society is Dirt: The filthy reality of everyday life (see page 20). There will be a series of events around Dirt, including – for the strong of stomach perhaps – a dirt-themed Supper Salon on 13 April.

Other happenings include ‘Tell it to Your Doctor’, two events that explore the conversations between doctors and patients, which will run on 16 and 21 April. The ‘Born Today’ series, which looks at the moment of childbirth,

includes events on 28 April and 5 May. On 8 April, the whole building will be taken over by ‘Elements’. This event, curated by chemist Andrea Sella and author Hugh Aldersey-Williams, will allow visitors to explore the Janus-like qualities of some elements, including arsenic, mercury, oxygen and iodine. www.wellcomecollection.org

In January the Wellcome Library welcomed Dr Vicki Porter as Head of Discovery and Engagement. Dr Porter will be responsible for transforming audience strategy, including finding new ways for people to get involved with the work and the resources of the Library. She joins from the J Paul Getty Trust in Los Angeles, where she managed digital policy and audience strategy.

She has also worked at the National Gallery, Tate, the Royal Collection and the National Gallery of Art in Washington, DC.

New-look SPIN We have relaunched our SPIN (Science Policy in the News) service with a new look. A weekly email produced by our Strategic Planning and Policy Unit, SPIN provides concise digests of news stories relating to science policy. The new format includes direct web links to the original stories, where available.

There’s a new dedicated website for the service at spin.wellcome. ac.uk. Here, you can browse the complete archive of SPIN, which dates back to 1992, or sign up to receive the weekly emails.

You can also subscribe by emailing spin@wellcome.ac.uk.

Big Picture: The Cell out now From the ethics of stem cell research to sculptures made of frozen blood, Big Picture: The Cell, the latest issue of the free Wellcome Trust educational resource for 16+ students, explores all aspects of animal cells. Go to www.wellcome.ac.uk/bigpicture/cell to download a PDF of the magazine, order a cell-themed poster, subscribe to receive all future issues, and browse articles, films, image galleries and more.

Library welcomes Head of Discovery

Illustration bby Glen McBeth

New ethics chairman

Rare disease drug development

Professor Roger Brownsword has been appointed Chairman of the UK Biobank Ethics and Governance Council (EGC), replacing Professor Graeme Laurie. The independent EGC, which we fund in partnership with the Medical Research Council, advises UK Biobank on rigorous standards of ethical, legal and social consideration.

UK Biobank, a long-term project to build a resource for health research, has already recruited over 530 000 volunteers. www.ukbiobank.ac.uk

Oxford prize success Three University of Oxford researchers are celebrating awards. Dr Roi Cohen Kadosh, a Wellcome Trust Research Career Development Fellow who studies how the brain represents numbers, has won the Career Development category at the Society of Neuroscience Achievement Awards. This recognises earlycareer promise and achievement.

Also a Research Career Development Fellow, Dr Rob Klose, who works in the field of epigenetics, has been named as one of this year’s European Molecular Biology Organization Young Investigators. These prestigious awards are given to the most promising European young researchers at a critical stage of their scientific careers.

Dr Emily Holmes has been awarded the 2010 Spearman Medal by the British Psychological Society. Dr Holmes, a Trust Intermediate Clinical Fellow, is a research clinical psychologist whose experimental work is based on cognitive behavioural therapy.

BAFTA win We’re thrilled to report that that Timelines.tv’s smallpox resource Smallpox Through Time, which was funded by a Wellcome Trust Medical History and Humanities public engagement grant, won the Secondary Learning category at the 2010 Children’s BAFTAs. The free resource was launched to celebrate the 30th anniversary of the global eradication of smallpox, and is aimed at teachers and students studying history of medicine at GCSE level. timelines.tv 6 | WELLCOME NEWS

The X-ray crystal structure of transthyretin and the small molecule mds84. Dr Simon Kolstoe

Pentraxin Therapeutics Ltd, a spin-out company from University College London (UCL), has licensed a drug development programme to GlaxoSmithKline (GSK). This builds on Wellcome Trust-funded research.

Pentraxin was established by UCL’s Professor Mark Pepys to hold the intellectual property arising from his research. Now, the company is collaborating with GSK to develop Professor Pepys’s invention of novel small molecules, including one called mds84, that stabilise transthyretin.

Transthyretin is a blood protein that can in certain circumstances cause amyloidosis, a rare but fatal disease.

A £2.5 million award made to Professor Pepys and colleagues through our Seeding Drug Discovery initiative in 2007 supported some of the research that led to this recent deal. “The creation of mds84 involved cutting-edge science and some serendipity,” says Professor Pepys.

“The subsequent generous support of the Wellcome Trust for this early-phase drug design programme created the opportunity for further progression and evaluation. Now, GSK will bring its drug discovery and development expertise to work with the team on developing the potential of these small molecules.”

Catalyst CEO appointed Dr Martino Picardo has become the first Chief Executive Officer of Stevenage Bioscience Catalyst, a ‘hub’ for earlystage biotechnology companies.

Previously Managing Director of the University of Manchester Incubator Company (UMIC), Dr Picardo says of his appointment: “I am absolutely delighted to be taking up this new role.

Although I am sad to be leaving friends and colleagues in UMIC, I am also looking forward to working with new colleagues in what will be a very exciting and unique opportunity for UK plc in

drug discovery and development.”

Construction has begun on the £38 million development in Stevenage, Hertfordshire, which will neighbour the GSK research and development campus. It is hoped that the facility will eventually create up to 1500 new jobs. The five funding partners for the facility are the Wellcome Trust, the UK Department of Business, Innovation and Skills, GlaxoSmithKline, the East of England Development Agency and the Technology Strategy Board. www.stevenagecatalyst.com

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Testing the tsetse fly Among the grants made recently through our Populations and Public Health stream are two exploring aspects of the tsetse fly, the carrier of the parasites that cause African trypanosomiasis in humans (sleeping sickness) and in animals. Dr Alvaro AcostaSerrano from the University of Glasgow has been funded to investigate how, on a molecular level, the parasites (trypanosomes) cross the protective lining of the tsetse fly gut, where they live and develop before being transmitted to people and livestock.

Also at Glasgow, Professor Mike Turner will work with

Wellcome Library

Medical humanities update Historical aspects of the British Navy, hospital politics and twin beds are just some of the topics under investigation thanks to our Medical History and Humanities awards.

Professor Mark Harrison, University of Oxford, has been awarded a programme grant of over £700 000 for his project ‘From Sail to Steam: Health, medicine and the Victorian navy’, which will explore the role of the Royal Navy in bringing health information to Britain in the 19th century.

Funded by a Research Leave Award, Professor Barry Doyle from the University of Huddersfield is investigating the politics of hospital provision in Britain in the early 20th century. He’ll use case studies of Leeds, Middlesbrough and Sheffield to explore how the pre-NHS health system worked, questioning the idea that a national organisation is the only way to ensure effective provision of hospitals.

At the University of Lancaster, Dr Hilary Hinds will use her Research Leave Award to explore how changing ideas about health and hygiene between 1870 and 1970 affected the rise and fall of twin beds for married couples.

Pavement projections To mark the International Day of Persons with Disabilities on 3 December 2010, we hosted a special one-day video installation outside Wellcome Trust HQ of Motion Disabled, a digital exploration of the bodies of people who are physically different. The work, part-

Wellcome Trust Genome Campus

Dr Daniel Masiga from the International Centre of Insect Physiology and Ecology in Nairobi, Kenya, to sample tsetse flies and trypanosomes from different parts of Kenya.

They will test the idea that local host and parasite populations are adapted to each other, comparing how well different tsetse populations transmit different trypanosomes.

Advanced Courses and Scientific Conferences

Oliver Burston, Wellcome Images

FUNDING NEWS

At the cutting edge of biomedical training, discussion and debate.

Wellcome Trust Advanced Courses and Scientific Conferences are hosted in dedicated facilities at the Wellcome Trust Genome Campus in Hinxton – a short distance from the historic city of Cambridge.

Funding is now available for new Advanced Courses and to seed the developemnt of new Scientific Conferences. Please contact Dr Rebecca Twells, Programme Manager, for more information (rt@hinxton.wellcome.ac.uk).

For details of all upcoming Advanced Courses and Scientific Conferences, please visit: www.wellcome.ac.uk/hinxton

funded by us, was created by artist Simon Mckeown from Teesside University. Thanks to VSA, the International Organization on Arts and Disability, Motion Disabled is now being exhibited worldwide. For more details, see wellcometrust. wordpress.com.

SPRING 2011 | 7

RESEARCH NEWS

Pilot study The brains of fighter pilots are wired differently from those of the rest of us, say scientists at UCL. They used cognitive tests to show that RAF Tornado fighter pilots had superior cognitive control to members of the public – but were more sensitive to irrelevant, distracting information.

The findings suggest that, in humans, expert control of cognitive processes, as demonstrated by the pilots, may be linked to a heightened response to both relevant and irrelevant stimuli, accompanied by ‘re-wiring’ in the white matter of the brain.

Roberts RE et al. J Neurosci 2010;30(50):17063–7.

Lay counselling Professor Vikram Patel and colleagues at the Sangath Centre, Goa, India, and the London School of Hygiene and Tropical Medicine have shown that trained lay counsellors can be effective at helping to treat depression and anxiety in public primary care facilities. The intervention they tested was a collaborative approach between a lay counsellor, a primary care doctor and a psychiatrist.

Patel V et al. Lancet 2010;376(9758):2086–95.

Faster sequencing Scientists from Imperial College London have taken an important step towards developing a technology that could sequence a genome in mere minutes, and at a fraction of the cost of current commercial techniques.

The technology – nanopore sequencing – involves propelling a DNA strand through tiny holes, or nanopores, cut into a silicon chip, then reading the sequence. The researchers are confident that their finding could lead to an ultrafast commercial DNA-sequencing tool in just ten years.

Ivanov AP et al. Nano Lett 2011;11(1):279–85.

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Studying how we see

Larynx transplant restores woman’s voice

Two studies that received Wellcome Trust support have added to our knowledge of how we see the world.

Professor Rob Lucas and Dr Tim Brown from the University of Manchester have been studying the neurons that carry signals from the eye’s rods and cones to the brain, and have found that 2 per cent of these neurons produce a lightsensitive protein known as melanopsin.

Previously, these cells were thought to be responsible for detecting light for subconscious responses such as changing pupil size. However, the researchers showed that melanopsin also helped brain regions involved in conscious perception to measure brightness – in both normally sighted mice and those previously considered to be blind.

“Now we are asking to what extent melanopsin could help the normally sighted to see, and what it might contribute to the blind and partially sighted,” says Prof. Lucas. These findings could also change how we design computer displays and TV screens, currently made with only rods and cones in mind.

In other research, scientists have shown that how we see our environment

A pioneering transplant technique, developed with Wellcome Trust funding, has restored the voice of a woman who had lost the ability to breathe on her own and had not spoken for 11 years.

Brenda Charett Jensen, a 52-year-old woman from California, had lost the use of her larynx during surgery in 1999. In October 2010, an international team of surgeons performed an operation to replace her larynx, thyroid gland and trachea. The 18-hour procedure, which took place at the UC Davis Medical Center in Sacramento, was followed by two months of rehabilitation, during which the nerves were regenerating, and she has learned to speak again.

“Every day is a new beginning for me,” says Ms Jensen. “I’ll probably never sing in a choir or anything, but it’s exciting to talk normally, and I can’t wait to eat and drink and swim again.”

This is the second ever documented larynx transplant, and the first in which the larynx, trachea and thyroid were transplanted together. The techniques used were developed by Professor Martin Birchall, a visiting professor of otolaryngology at UC Davis and then at the University of Bristol. His work

Kirlian photograph of the eye. N Seery/Wellcome Images

depends on the size of the visual parts of the brain. Researchers at the Wellcome Trust Centre for Neuroimaging at UCL used functional magnetic resonance imaging and optical illusions to show that the smaller a person’s primary visual cortex, the more pronounced visual illusions seemed.

Brown TM et al. Melanopsin contributions to irradiance coding in the thalamo-cortical visual system. PLoS Biol 2010;8(12):e1000558.

Schwarzkopf DS et al. The surface area of human V1 predicts the subjective experience of object size.

Nat Neurosci 2011;14(1):28–30.

Neural neighbours activate stem cells Stem cells, responsible for the maintenance and repair of many tissues, spend much of their time dormant, being activated when new cells are needed. The signals to grow and proliferate are often relayed to the stem cells by their neighbours, which form a microenvironment known as the ‘stem cell niche’.

Professor Andrea Brand and Dr James Chell of the Gurdon Institute, Cambridge, have studied some of the neighbours of neural stem cells – glial cells – to investigate their role in activating stem cells. In the larval stages of a developing fruit fly, neural stem cells are activated in response to a nutritional stimulus, the protein in fly food. The researchers found that neighbouring glial cells pass on this stimulus by producing insulin-like molecules. By genetically programming glial cells to produce these molecules even without a nutritional stimulus, they were able to activate the neural stem cells.

As well as highlighting the importance of insulin-like molecules in signalling stem cells to activate, this work hints at the potential of being able to develop stem cell therapies that target stem cells’ ‘neighbourhoods’ rather than the cells themselves.

Chell JM, Brand AH. Nutrition-responsive glia control exit of neural stem cells from quiescence.

Cell 2010;143:1161–73.

Drosophila neural stem cells (green), showing their large nucleoli (blue) and the nuclei of the surrounding neurons (red). James Chell and Andrea Brand

was funded principally by us – the first time that a surgeon had received Trust funding.

Watch a video on this from UCL at www.youtube.com/ucltv

Brenda Charett Jensen and her medical team.

UC Davis Health System

Artesunate is preferred treatment for malaria The largest ever clinical trial among people hospitalised with severe malaria has concluded that the drug artesunate should now be the preferred treatment for the disease in both children and adults worldwide.

An international consortium of researchers, led by Professor Nick White of the Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme in Bangkok, compared artesunate treatment (used in Asia for severe malaria) with quinine treatment, which has been in use worldwide for over 300 years.

The African Quinine versus Artesunate Malaria Trial (AQUAMAT) was carried out over five years in hospitals across nine African countries,

Chromolithograph recommending quinine to prevent malaria,

by Benjamin Armand Rabier (1869–1939). Wellcome Library

studying 5425 children with severe malaria. With artesunate treatment 8.5 per cent of the patients died, compared with 10.9 per cent of those who had quinine. Children treated with artesunate were also less likely to suffer other effects, such as falling into a coma,

having seizures or developing dangerously low blood sugar.

Dondorp AM et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial.

Lancet 2010;376(9753):1647–57.

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 interested in biology.

For example, I was fascinated by the then novel notion that mitochondria were ancient infectious microorganisms with which we were all now living in cooperative and peaceful harmony, and wooed my future wife with tales of such extraordinary phenomena. I was excited by the notion of doing biological experiments to reveal such marvels. Indeed, I entered medicine thinking that medical practice would naturally and inevitably entail asking intriguing questions about human biology and disease. And in some senses it is like that. However, during much of the period I spent as a junior doctor I felt frustrated at the distance there existed from thinking about the mysteries of normality and disease.

I became a histopathologist because I wished to get closer to those core questions. As a pathologist one mostly spends time looking down the microscope at diseased tissues. Peering into this hidden world provides you with profound and powerful insights into the ways disease is generated. You see order and disorder. Indeed, although there is considerable ugliness there is sometimes

10 | WELLCOME NEWS

awful beauty in the way cells conspire to orchestrate life-threatening conditions.

Pathology was certainly inspiring and thought-provoking. Nevertheless, it was still at arm’s length from the real action.

As a pathologist, about half the samples I was asked to look at were from tumours of various types. At the time we already knew that all cancers arose from a single cell that was behaving badly, with loss of normal growth control, because of abnormalities in its DNA. As a young doctor straining to do research, encountering the diverse patterns of abnormal cell proliferation in cancer down the microscope almost inevitably drove me to speculate on the invisible abnormalities in the DNA within those blue cancer cell nuclei that were responsible for all this. I could not imagine a more direct search for fundamental biological insight than this endeavour. At this time, in 1984, the revolution in recombinant DNA technology was having major impact and I moved to the Institute of Cancer Research to do a PhD using this technology to explore the genetics of cancer.

I was hooked on cancer genetics from that point. After my PhD I went back to medicine for two years to qualify

as a consultant histopathologist, but subsequently returned to the ICR to begin work on the genetics of breast cancer susceptibility.

It has become of almost mystical fascination to me that you can look down a microscope and see the misbehaving cells of a tumour, and then delve into their nuclei to pick out, from the thousands of millions of bases of DNA, the few that are mutated and cause the abnormal proliferation.

I still occasionally look down a microscope and make a stab at diagnosing the type of cancer present, but obviously would not seriously trust my judgement on this anymore. I no longer practise as a pathologist but I have a huge amount of respect for those who do. When one has looked down a microscope every day for years those images of a private, subterranean world become second nature, and they remain with me.

Professor Stratton is Director of the Wellcome Trust Sanger Institute (www.sanger.ac.uk), and co-leader of the Cancer Genome Project.

SPRING 2011 | 11

OPINION “Museums need more compelling games” Take your next group meeting to a cultural hub of activity

Contact us on 020 7611 2200 or email conferencecentre@wellcome.ac.uk 183 Euston Road, London www.wellcomecollectionconference.org Wellcome Collection is part of the Wellcome Trust. The Wellcome Trust is a charity registered in England and Wales, no. 210183.

WELLCOME TRUST CONFERENCE CENTRE

Bring together your brightest minds in a location to inspire

MARTHA HENSON AND DANNY BIRCHALL

Contact us on 01223 495000 or email info@wtconference.org.uk Hinxton, Cambridgeshire

o you play games? We might dismiss them as childish, but in his 1938 work Homo Ludens, Johan Huizinga argued that play is an essential component of all human culture. The chances are that you enjoy playing something – whether it’s Angry Birds or a round of charades at Christmas.

Globally, gaming is big business, with a market worth an estimated $50 billion (£30bn) in 2011 and a demographically diverse audience with an even gender split. But it’s not just about numbers: the dedication of gamers to the pleasure of play means time spent at the console can exceed that spent with a feature film or novel.

The educational potential seems obvious. So why have museums and educationalists, with all the information and resources at their disposal, failed to make more than a handful of really compelling educational games? The work of game designers and researchers such as Jane McGonigal (author of Reality is Broken) and Channel 4 Education (including the Wellcome Trust-funded Routes) has amply demonstrated the power of games to bring both children and adults cultural and scientific ideas in new forms.

But many have assumed that any game-like feature is enough to engage people, and tacking minimal interactivity onto a barely disguised

didactic lesson plan has unfortunately been the dismal standard in this field. However, others, such as the Science Museum, have begun to harness the potential of games for learning. The physics-based Launchball game was hugely popular and they have just released Rizk (about climate change).

We’ve had our own success recently with High Tea, a strategy game centred on the dubious actions of the British Empire in the run-up to the Opium Wars of 1839. From over 1.5m plays in its first fortnight after release, plus comments, reviews and survey responses, we can see that we have achieved both a wide reach and our educational aims.

Why are these particular games successful?

Because they put gameplay at the centre of the experience and use experienced digital agencies to deliver this. These examples are a great start, but surely more could be done in this area.

Games might seem a trivial way of approaching the public with new ideas, but the playful and exploratory impulses that draw gamers to great games are still largely untapped as a means of engagement. By pushing boundaries ourselves, we hope to show others what can be achieved. www.wellcomecollection.org.uk/hightea • Martha Henson is Multimedia Editor at the Wellcome Trust.

• Danny Birchall is the Editor of the Wellcome Collection website.

www.wtconference.org.uk The Wellcome Trust is a charity registered in England and Wales, no. 210183.

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Played any great educational games lately?

Email us at wellcomenews@wellcome.ac.uk or tweet @wellcometrust 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 threeyear Wellcome Trust grant. He never came back. What was it about tropical Brazil that appealed to the young man?

The parasites, of course.

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SPRING 2011 | 15

1959–62

DIRECTOR OF DERMAL LEISHMANIASIS UNIT IN CAYO DISTRICT, BELIZE

alph Lainson, like many, loves Brazil, but not for the reasons you might expect.

“The Amazon region is a veritable mine of parasitological information, yet very, very few people work in this field here,” says the 84-year-old scientist, enthusiastically. “I’ve always said to young Brazilian students what a wonderful place they’re in. If you turn over a stone you are likely to find four new species underneath it.”

It was this passion for the microscopic world that drew him away from his native England to the tropics some 50 years ago. It has also resulted in Professor Ralph Lainson now holding the titles of Fellow of the Royal Society and Officer of the Order of the British Empire, and being the Wellcome Trust’s longest-serving grantholder – a record 47 years and counting. Such a background might not seem to fit with his strange-but-true stories of 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 protozoan (single-celled) parasites.

The clues to this are his sand-flypatterned tie and the smile on his face when I ask about his specialism, the neotropical Leishmania.

Ralph’s long relationship with the parasite began in 1959 in Belize (then British Honduras). At the time, no one in the country was sure of the origin of ‘Chiclero ulcer’ (cutaneous leishmaniasis). Ralph says: “We had the parasite isolated from human beings and we knew that most of the people who acquired the disease worked in the forest, often for long periods. It was reasonable to assume, therefore, that there were some reservoir hosts of the parasite among the forest animals.”

For two years they tracked all manner of creatures, with little success until a natural disaster lent a helping hand.

“Hurricane Hattie I’ll always remember,” says Ralph. “It was a terrible experience, levelled flat a lot of the forest, but the result was the wild animals found it difficult to find food.

We had no problem capturing a large 16 | WELLCOME NEWS

1968

1965

1958

DIRECTOR OF NEWLY ESTABLISHED WELLCOME PARASITOLOGY UNIT IN BELÉM, BRAZIL

KEY WORK ON TRANSMISSION OF TOXOPLASMA

WITH JEFFREY SHAW, DESCRIBES AND NAMES L. AMAZONENSIS, THE PARASITE THAT CAUSES ANERGIC CUTANEOUS LEISHMANIASIS

1964

1955–59

LECTURESHIP AT LSHTM

AWARDED DSC FROM UNIVERSITY OF LONDON

1964

FIRST WELLCOME TRUST GRANT

1955

GAINS PHD IN PARASITOLOGY FROM LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE

1962

1951

1927

GRADUATES WITH BSC IN SPECIAL ENTOMOLOGY WITH SUBSIDIARY BOTANY FROM BRIGHTON TECHNICAL COLLEGE

BORN IN UPPER BEEDING, SUSSEX, UK

1920s

1930s

1940s

WITH JOHN STRANGWAYS-DIXON, IDENTIFIES FOREST RODENTS AS HOSTS OF THE SPECIES CAUSING HUMAN CUTANEOUS LEISHMANIASIS. OBTAINS THE FIRST EXPERIMENTAL TRANSMISSION OF A NEW WORLD LEISHMANIA SPECIES (L. MEXICANA) TO HUMANS VIA THE PHLEBOTOMINE SAND FLY

1950s

1960s

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 Hygiene (1971, 1984), SPL (page 18 top left), Swiss Tropical Institute, courtesy of R Knechtli (1977), The Royal Society (1982), Wellcome Images (others).

number of rodents, opossums and other animals in our baited traps.”

Among them was a rodent with lesions on its tail, lesions that turned out to be full of the parasite. Ralph identified three different species of rodent frequently carrying the parasite.

He and his team also captured hundreds of phlebotomine sand flies (using themselves as bait!) and offered them hamsters experimentally infected with Leishmania from patients.

Dissection of the sand flies several days after their hamster blood meal revealed the parasite inside. This left Ralph and his entomologist, John Strangways-Dixon, in no doubt that the same species of insect that transmitted Leishmania in the Old World did it in the New World.

It only remained to prove the sand fly’s role in the transmission of the causative parasite to humans.

“Now was the time to obtain a volunteer and feed these infected insects on him,” says Ralph. “Strangways-Dixon was keen to be this person. He said that as the entomologist he was the correct person to do this. He said, they’re my sand flies so if they’re going to feed on anything or anyone it’s going to be me.

I’m their boss!”

“We fed the flies on StrangwaysDixon’s belly, and a few weeks later a tiny lesion appeared, containing the parasites. It was most exciting: the first experimental proof of transmission to man of a neotropical Leishmania species by the bite of a phlebotomine sand fly!

The moment we worked that out was, I suppose, when I realised that I was a real scientist.”

New World order Ralph soon returned to the UK, but pined for the tropics and the

opportunity to continue his research in the New World. So, in 1963, he toured Latin America collecting strains of Leishmania and sizing up different research institutes. He went through Central America, down to Colombia, Venezuela and elsewhere, until his final stop, the Instituto Evandro Chagas in Belém, part of the Amazon delta of north Brazil.

There, he showed the researchers his photographs of rodent lesions in Belize. One of them, Dr Otis Causey, said he had seen very similar lesions on the Oryzomys capito rodents common to the region, but thought they were simply bacterial or fungal infections growing on damaged tails. Two weeks later in Rio de Janeiro, he approached Ralph with a slide made from a rodent in Belém. It was teeming with Leishmania parasites. They had for the first time found the reservoir host of at

least one Leishmania species infecting humans in Brazil.

Although cutaneous leishmaniasis manifested itself in different forms in Central and South America, many clinicians thought the disease was due to the same parasite, Leishmania braziliensis, and that this was the same as L. tropica, the strain that caused leishmaniasis in the Old World. Ralph was among those certain that different leishmanial parasites were involved in the disease in different parts of the continent. Arriving in Brazil with a three-year Wellcome Trust grant, his team collected parasite samples from all sorts of animals: armadillos, opossums, foxes, porcupines, monkeys and more, as well as human patients with different forms of leishmaniasis.

Their findings were striking: the parasites found in Oryzomys were clearly much larger than those of L. braziliensis

– the human parasite was tiny, only about 2–3 micrometres in diameter, whereas those that Otis Causey found were nearly twice the size.

Furthermore, when they inoculated the Oryzomys-derived parasite into hamsters it produced huge tumour-like lesions in the skin very quickly, whereas L. braziliensis took six months or more for one tiny lesion to appear.

Ralph’s team found a small number of the parasites that were the same as those from Oryzomys (which they named L. mexicana amazonensis). In the following years they identified a (still-increasing) number of different Leishmania species, often with specific or closely related sand fly vectors and different wild animal reservoirs. By 1979, so many different Leishmania species had been discovered – at the time, 13 from the Americas, eight of which infected humans – that SPRING 2011 | 17

1984

AWARDED MANSON MEDAL BY ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE

1977

FIRST EXPERIMENTAL PROOF THAT THE SAND FLY IS A VECTOR OF VISCERAL LEISHMANIASIS PUBLISHED IN NATURE

1982

2005

ELECTED FELLOW OF THE ROYAL SOCIETY

WELLCOME TRUST RESEARCH GRANT

1982

1971

AWARDED CHALMERS MEDAL BY ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE

1970s

AWARDED HONORARY MEMBERSHIP OF THE LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE. PRESENTED AT THE SCHOOL BY PRINCE PHILIP

1980s 1980s

“It’s not work, more of a very interesting hobby. Because these parasites are rather beautiful little creatures.” the researchers proposed a new classification of them. Ralph has speculated that, “considering the remarkable number of Leishmania species that have now been recorded in the neotropics, and particularly in the Amazon region, this area might well be the birthplace of this genus”.

These findings have helped to define outbreaks of the disease in the region, with considerable public health implications. People infected with L. amazonensis may develop diff use, 18 | WELLCOME NEWS

1992

RETIRES FROM DIRECTORSHIP OF THE WELLCOME PARASITOLOGY UNIT

1990s

anergic cutaneous leishmaniasis (affecting patients whose immune systems are incomplete, a condition incurable at the time), and those infected with L. braziliensis stand the risk of developing mucocutaneous leishmaniasis, which can be very disfiguring. Such patients require prompt and particularly intensive treatment. Moreover, people immune to one species of the parasite are usually vulnerable to others, complicating vaccine production. And Brazil’s increasing urbanisation and population movement has meant that groups are often exposed to different species – and the different sand flies that transmit them – as their environment changes.

“One by one, we’ve shown that there is not a single parasite causing neotropical human cutaneous leishmaniasis, but six or seven,” says Ralph. “These are now known, identified

2002

WELLCOME TRUST RESEARCH GRANT

2000s

and recognisable such that people can tell which one a man is infected with. Every bit of knowledge gained regarding the ecology, epidemiology and distribution of the different species is of help in control of the diseases they cause.”

Ralph’s three years in Brazil turned into 30 and firmly established the research group that became the Wellcome Parasitology Unit. Under his directorship, the Unit made a string of important discoveries, in leishmaniasis and other parasitic diseases. In 1969, they published the first record of Chagas’ disease in the Amazon region of Brazil, demonstrating that the disease could spread easily through food contaminated with faeces from species of blood-sucking triatomine bugs. In 1977 they published in Nature, describing the first experimental evidence that the bite of sand fly Lutzomyia longipalpis transmits Leishmaniasis chagai (the cause

of American visceral leishmaniasis) to vertebrates. And in 1981, the Unit discovered a new sand fly transmitting L. braziliensis in Amazonian Brazil, which they named Lutzomyia (Psychodopygus) wellcomei (says Ralph: “We have an expression in Portuguese: pucha saco, which means that by giving it this name, we might persuade the Trust to continue our grant!”).

Although the Unit closed in 1992, its legacy continues at the Instituto Evandro Chagas, now a hub for visiting scientists researching all aspects of Leishmania and other parasites, from ecology to epidemiology, immunology and the genetics of host responses to infection. It also boasts a significant resource in its collection of cryopreserved parasite material and records, amassed during the Wellcome Unit’s life.

Ralph has helped to discover nearly 100 new parasite species and even had

one named after him: L. (Viannia) lainsoni, discovered in 1987. His efforts have earned him a string of awards.

He tells me of his pride on becoming a Fellow of the Royal Society (“the finest 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 underpaid and usually not very much appreciated by the majority of the population”). And though he ‘retired’ in 1996, Ralph never got out of the lab.

Fourteen years later he spends his spare time staring down a microscope, addicted to filling in a jigsaw puzzle that will never be complete: an everfuller picture of the parasites.

“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 very interesting hobby. Because these parasites are rather beautiful little creatures.”

Lainson R. The neotropical Leishmania species: a brief historical review of their discovery, ecology and taxonomy. Rev Pan-Amaz Saude 2010;1(2):13–32.

Lainson R et al. Experimental transmission of Leishmania chagasi, causative agent of neotropical visceral leishmaniasis, by the sandfly Lutzomyia longipalpis. Nature 1977;266(5603):628–30.

Lainson R et al. Leishmaniasis in Brazil: XVI. Isolation and identification of Leishmania species from sandflies, wild mammals and man in north Para State, with particular reference to L. braziliensis guyanensis causative agent of ‘pianbois’. Trans R Soc Trop Med Hyg 1981;75(4):530–6.

Lainson R, Strangways-Dixon J. Dermal leishmaniasis in British Honduras: some host-reservoirs of L. brasiliensis mexicana. BMJ 1962;1(5292):1596–8.

Lainson R et al. Chagas’ disease in the Amazon Basin: speculations on transmission per os. Rev Inst Med Trop Sao Paulo 1980;22(6):294–7.

Lainson R. Observations on the development and nature of pseudocysts and cysts of Toxoplasma gondii. Trans R Soc Trop Med Hyg 1958;52(5):396–407.

Lainson R et al. On a new family of non-pigmented parasites in the blood of reptiles: Garniidae fam.nov., (Coccidiida: Haemosporidiidea). Some species of the new genus Garnia. Int J Parasitol 1971;1(3–4):241–50.

SPRING 2011 | 19

WELLCOME COLLECTION

International Senior Research Fellowships in Basic Biomedical Science

THE DIRTY TRUTH

Long, low, looming. There are five mottled brown rectangles laid out imposingly in Wellcome Collection, as part of its latest exhibition, Dirt: The filthy 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 landfill in 2030, Dirt encompasses locations in six different cities, at six different points in history.

‘The Community: New Delhi and Kolkata’ is the section housing the faecal sculptures. To create the work, artist Santiago Sierra worked with waste collected by manual scavengers, working in India. These scavengers, or safai karamchari, spend their lives cleaning dry latrines, often no more than areas of dusty ground with a couple of bricks between which people defecate. There are no rubber gloves, bleach or loo brushes. Using their bare hands or crude tools, the scavengers must collect other people’s excrement in baskets and carry it to the dump, often miles away.

Most manual scavengers are ‘untouchables’, or Dalits. They exist outside and below India’s caste system, and are shunned by many other Indians who consider them unclean. Born into this social group, Dalits face lifelong discrimination, disadvantage and have to do some of the dirtiest jobs imaginable. The Constitution of India – a copy of which is on display in the exhibition – came into effect in 1950 and formally outlawed untouchability.

Derren Ready, Eastman Dental Institute/Wellcome Images

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 filthy things. We found out more.

International Senior Research Fellowships A Durga goddess sculpture being carried in procession, 19th century. Wellcome Library

However, many hundreds of thousands of Dalits still depend on the practice for their and their family’s livelihoods.

A number of organisations and charities are working to improve the lives of manual scavengers, and improve the availability of public toilets in India. Details of one of these, Sulabh International, can be found in the neighbouring room to where the sculptures are displayed, as can information on a public compost toilet it has developed. The largest non-profit organisation in India, Sulabh International employs the manual scavengers who collected the waste for Sierra’s sculptures.

Dirt is not always seen as an object of revulsion – sometimes it can be considered sacred. Alongside the sculptures is a Durga goddess, built to

celebrate the Hindu festival of Durga Puja. These striking structures are coated in clay, cow dung and mud from the banks of the Ganges before being painted. After the celebration, the idols are returned to the river there to be dissolved back into the water.

So does dirt have to be disgusting?

With exhibits including human excrement as sculpture, and dung as deities, Dirt might just make you think again.

To provide support for outstanding researchers, either medically or scientifically qualified, who wish to establish an independent career in a Croatian, Czech, Estonian, Hungarian, Polish, Slovakian or Slovenian academic institution.

William Henry

Deadline for preliminary applications: 6 June 2011.

Dirt: The filthy reality of everyday life runs at Wellcome Collection from 24 March to 31 August 2011. www.wellcomecollection.org/dirt

www.wellcome.ac.uk/isrf/wn 20 | WELLCOME NEWS

CLOSE-UP

WELLCOME IMAGE AWARDS

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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 fluorescent 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 Wellcome Collection until mid-July 2011, or browse them online: www.wellcomeimageawards.org

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3D reconstruction of a mouse embryo,

by Agnieszka Jedrusik and Magdalena Zernicka-Goetz, Gurdon Institute, Cambridge.

Scales on the wing of a moth, by Kevin Mackenzie, University of Aberdeen.

Periodontal bacteria, by Derren Ready, Eastman Dental Institute.

Zebrafish retina, by Kara Cerveny, Steve Wilson’s lab, UCL. Embryonic mouse kidney, by Bob Kao and Kieran Short, Monash University.

Base of a silkworm caterpillar’s proleg,

by Spike Walker.

SPRING 2011 | 23

BLOG AND FILM

Q&A Wellcome Trust open access

Wellcome Trust blog

To contribute to the blog, contact the Editor: m.looi@wellcome.ac.uk

Wellcome Trust YouTube channel Recent additions to our YouTube channel consider cells, 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 as part of her research into understanding how blood vessels grow to feed tumours (below).

Cell culture on a different scale is examined in ‘True Blood: The reality of making red blood cells’. With 2.5 million bags of blood being used in the UK each year, the prospect of being able to manufacture a potentially limitless supply of tailored, infection-free red blood cells is compelling. In this film, two researchers – Marc Turner and Joanne Mountford – talk us through their project to produce red blood cells from stem cells.

Could combating climate change be good for our health?

‘Tackling Climate Change: The good news’ presents findings from studies published in the Lancet that explored the potential health benefits of strategies to mitigate the effects of climate change.

Lastly, two films outline large-scale projects on genetics supported by the Trust. ‘People of the British Isles: The genetic landscape of Islay’ tells the story of a project that is cataloguing the genetic basis of the UK. In ‘1000 Genomes: A new foundation for genetic research’, Dr Richard Durbin and Dr Chris Tyler-Smith describe the key findings of the pilot phase of the project aiming to create the most comprehensive map of common human genetic variation.

DR BEAU LOTTO Making anyone part of scientific discovery

We’re opening up knowledge to everyone – the freedom to find out starts with freedom of access.

A repository of 2 million fulltext articles, 20 million PubMed abstract records, clinical guidelines and theses – UK PubMed Central provides a single, free-to-access gateway to high-quality research in the life sciences.

For more information and to discover how to comply with our open access policy, visit our website. www.wellcome.ac.uk/ukpmc

Annie Cavanagh, Wellcome ellcome Images

As the Wellcome Trust celebrates its 75th birthday, our blog (wellcometrust.wordpress.com) celebrates its first. And a busy year it has been: over 60 000 unique page views and nearly 300 posts. We have covered everything from fish to football, synthetic biology to surgery, and the blog is still growing. The last few months have seen the blog break news about the first scientific 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 of folic acid and even fly guts. We are looking forward to the blog’s next 74 years…

IN THE HOT SEAT

Dr Beau Lotto is a neuroscientist on a mission: to get us to understand 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 become the first in the world to plan, perform and publish their own scientific experiment in a peer-reviewed journal. Their study resulted in some novel findings about how bees perceive colour.

How did this project come about?

I’d been doing public experiments in public space for several years – largely on bumblebees. Indeed, I’d been engaging with the public with the idea that we are makers of our own perceptions, which for me is a fundamental point, not only for understanding how the brain works, but also for getting people to question their common-sense notions of self. I run both a lab and a studio: the lab aims to understand perception, and the studio creates opportunities for people to become observers of themselves making sense.

When the headteacher at Blackawton Primary School in Devon – Dave Stradwick – asked me to come in for Science Week and talk to the school about science, I was more than happy to – largely because my children go there. We then started thinking about bringing the bees down to the school. But rather than me design the experiment, we wanted to get the kids to think about creating one, getting them to think about science as a way of being, not just a thing to do.

What were you trying to do?

We wanted to do real science, but science as game (i.e. playing with rules), and for the kids to know, from the start, that they were asking a question no one had ever asked before. If you know you’re doing something new, there’s a level of excitement you just can’t explain, and the kids sensed this.

Did you find the children open-minded?

View, comment on and share our films at: www.youtube.com/wellcometrust

24 | WELLCOME NEWS

Yes – it’s adults that have the problems! I find it when I show my optical illusions of colour to adults, they usually say, “Oh, my goodness!” (or more),

whereas children often say, “Ah, and…?” I think kids are far more able to deal with uncertainty.

How did it go?

It went wonderfully well, which isn’t to say that we knew it would, as we didn’t even know what the next day would bring. In the end, the kids devised an experiment to see if bees could learn to use the spatial relationships between colours to work out which flowers contained sugar water, and which salt water. For writing up the paper, we worked with four kids in particular. I had my laptop and asked them what to write, which is why the paper is in the kidspeak. They would then give me the words (though I made sure that they knew that as far as I was concerned nothing was out-of-bounds) and I’d put them into the form of a narrative.

We submitted the paper to Biology Letters, it underwent peer review and was then published.

Would this type of project work with adults?

Absolutely. With the support of the Wellcome Trust, we’ve moved my lab from University College London to the Science Museum. We have a grey lab, where people can interact with the objects that we create, such as installations; a black lab, where people can become subjects of experiments; and a white lab, where people can come and design experiments, by invitation. You’re making the public part of the process of discovery – not consumers of it.

• Blackawton PS et al. Blackawton bees. Biol Lett 2010 Dec 22 [Epub ahead of print].

• Maloney LT, Hempel de Ibarra N. Commentary on PS Blackawton et al., Blackawton Bees. Biol Lett 2010 Dec 22 [Epub ahead of print].

SPRING 2011 | 25

NUTS AND BOLTS 3

PRIMARY CILIA

Primary cilium

Cilia are fine, hair-like protrusions found on the surface of many kinds of cells. Defects in cilia – whether motile or primary – can lead to diseases, collectively termed ciliopathies. This quick guide gives you the lowdown on these intriguing organelles.

Almost all types of vertebrate cell have a primary cilium on their surface. Primary cilia don’t move, unlike motile cilia, and have a slightly different structure (see left).

First seen in the 17th century by Dutch scientist Antonie van Leeuwenhoek, hair-like motile cilia cover the surface of many cells. They make things move: everything from whole cells (such as the protozoa seen by Leeuwenhoek) to fluid in the trachea to an egg along the fallopian tube.

Motile cilia are not the only protrusions on cells. Curiously, cells lacking motile cilia often have a single cilium on their surface. Named primary or non-motile cilia, these were once written off as evolutionary leftovers with unknown function – the cellular

equivalent of the appendix. Now, however, primary cilia are gaining attention too.

In the last decade, research into diseases caused by defects in cilia – ciliopathies – has emerged as a field in its own right. Researchers have identified over 40 genes mutated in ciliopathies, thought to affect cilia components and functioning (see diagrams).

Researchers are studying ciliopathies to understand what cilia do in normal development and functioning. Evidence is mounting for the role of primary cilia in how our bodies develop, how cells

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communicate and how we sense our surroundings. Their involvement in limb development, for example, is hinted at by the fact that many non-motile ciliopathies cause additional fingers and toes. Other common features include diabetes, obesity, kidney disease, problems with seeing and smelling, bone defects and cognitive impairment.

To date, around 20 ciliopathies are known, and with some researchers suggesting that motile and nonmotile forms may total over 100, interest in these curious organelles looks set to continue.

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Axoneme The basic structure of the cilium, which is around 0.25 micrometres in diameter and up to 20 micrometres long. At the lower part of the cilium, the microtubules are in triplets, not pairs.

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Retrograde transport

Cilia and flagella don’t contain protein-making machinery, so their proteins have to be made in the main body of the cell and transported into the cilia to build and maintain them. Proteins called kinesins – molecular motors – carry proteins from the cell to the tip of the cilium where the axoneme is made.

Proteins called dyneins – molecular motors – move cargo down from the tip of the cilium back to the cell. This cargo includes kinesins that have delivered their components to the tip of the cilium.

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Dyneins See 8 above.

Kinesins See 4 above.

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Want to know more?

• Badano JL et al. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 2006;7:125–48.

• Tobin JL, Beales PL. The nonmotile ciliopathies. Genet Med 2009;11(6):386–402.

• Baker K, Beales PL. Making sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet 2009;151C(4):281–95.

• www.ciliopathyalliance.org.uk

Wellcome Trust-funded researchers working in this field include: • Prof. Philip Beales, Institute of Child Health, UCL. • Prof. Micheal Cheetham, Institute of Opthalmology, UCL. • Dr Martin Knight, Queen Mary, University of London.

26 | WELLCOME NEWS

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Cell membrane

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The structure from which the cilium grows. This sits in the cell membrane, and is made up of nine triplets of microtubules arranged in a ring.

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Cilium cross-section The structure of cilia, and of the closely related flagella (the ‘tails’ of sperm), is conserved across organisms. While motile cilia have nine pairs of microtubules in a ring surrounding a central pair (the ‘9 + 2’ arrangement), primary cilia lack the central pair, showing a 9 + 0 arrangement.

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SPRING 2011 | 27

FUNDING INITIATIVES

BY CHRISSIE GILES

PROTECTING THE POLLINATORS Insect pollinators, including honeybees, bumblebees and hoverflies, are in decline. The £10 million Insect Pollinators Initiative – partfunded by the Wellcome Trust – has been launched to find 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 make honey, but they do much more for the food we eat. Bees and other insects, including butterflies and hoverflies, pollinate plants. By transferring pollen from the male parts of flowers to the female parts, they are a vital part of the process that eventually leads to fruit, nut and seed production.

For some crops, such as melons, no pollinators means no fruit. For others, it means a lesser harvest.

This widespread role of insects in food production is reflected in insect pollinators’ economic value – estimated at €153 billion (£130bn) globally in 2005.1 Pollinators are under threat, though.

Research published in 2006 indicates that the diversity of wild bees – a key pollinator group – has declined severely since the 1980s.2 Another major 28 | WELLCOME NEWS

pollinator, honeybees, are prone to a number of diseases. The mite Varroa destructor, for example, carries viruses that can quickly destroy entire colonies, and has spread almost completely around the world in the last 30 years.

While disease is a serious risk, it is not the only one pollinators face.

“There’s likely a smorgasbord of problems,” says Professor Jane Memmott from the University of Bristol, a lead investigator on one of the projects funded by the Initiative.

“And they probably interact in different ways too – if bees are not properly fed, then they’re more likely to catch diseases, and so on.”

The nine projects funded through the Insect Pollinators Initiative are setting out to understand these threats better. We have looked at three below, and details of all nine can be found at www.wellcome.ac.uk/pollinators.

How do diseases affect the honeybee, and could they spread to other bee species?

“We’ve picked what we think are the most important disease organisms for the honeybee,” says Dr Robert Paxton, from Queen’s University Belfast and the University of Halle, Germany. His team is studying deformed wing virus, carried by the Varroa destructor mite, and a fungus-like microorganism called Nosema ceranae.

“Before the Varroa mite came to the UK, deformed wing virus was found in maybe 1 in 10 000 colonies,” says Robert.

This changed after its discovery in the UK in 1992, when the amount of virus carried by bees increased dramatically.

Varroa is a rusty-coloured mite, which feeds on the haemolymph (circulatory fluid) of adult and pupal bees. This increases the amount of deformed wing virus carried by bees and

can lead to symptoms including – as the name suggests – misshapen wings that prevent bees from flying. The grounded bees are taken by predators and the colonies suffer as their numbers drop.

Robert says at least half of the colonies in the UK contain clinical symptoms of deformed wing virus – severe infection with which can lead to the collapse of colonies.

Nosema, meanwhile, has spread from East Asia in the last 10–15 years to the western honeybee. Robert suspects that the interaction between this and deformed wing virus may act as a “double whammy”, greatly increasing the ill-effects on honeybees. Not only honeybees are at risk: these diseases also affect bumblebees, and there are fears that they will be transmitted to other pollinators too.

Dr Mark Brown and his team at Royal Holloway, University of London,

will be investigating how bumblebees come to be infected with deformed wing virus and N. ceranae, and the impact that these emergent diseases have on individuals and colonies of the important native bumblebee species.

In their project, researchers are studying how the diseases affect the bees physically, and whether they have any impact on insects’ flight behaviour, orientation and learning – so-called sub-lethal effects, which don’t kill the bees but affect how they function.

“We’re working with Juliet Osborne’s team at Rothamsted Research that has very refined methods for tracking how individual bees fly,” says Robert. “It will be really nice to understand the impact of these disease organisms on individuals.”

Professor Vincent Jansen, also at Royal Holloway, will use the data collected to model the spread of the SPRING 2011 | 29

study the effects on the insects’ abilities to learn at the neuronal level,” he says.

To assess the impact of pesticides, research in the lab of Dr Geraldine Wright at Newcastle University (see below) will investigate how such chemicals affect learning and memory in both honeybees and bumblebees.

“After the bees have been exposed to chemicals, we can ask: are they slower at learning? Do they forget what they’ve learned?” says Chris.

This part of the project will involve the radiotagging of 6000 bees, overseen

by Dr Nigel Raine at Royal Holloway. A scanner will monitor bees as they enter and leave the hive. And the bees will be weighed, allowing researchers to work out not only each individual bee’s contribution to the hive throughout its life but also the performance of the whole colony throughout a season.

Are British bees getting the right diet?

Bumblebee (Bombus pascuorum) foraging on red clover. © Claire Carvell, Centre for Ecology and Hydrology

“The mite Varroa destructor carries viruses that can quickly destroy entire colonies” disease organisms in the pollinator community, to try to understand the threat to both honeybees and bumblebees.

On top of all these efforts, the team will also attempt to find ways to treat these infections. Robert and his colleagues will be testing the use of RNAi (RNA interference) methods in controlling deformed wing virus, an RNA virus. The technique involves blocking the multiplication of the virus and has been effective in other RNA viruses in honeybees, though it is not 30 | WELLCOME NEWS

completely understood how.

They are also looking in some detail at the bacterial species associated with the honeybee gut. Researchers have only recently discovered that insect guts hold a huge variety of lactic acid bacteria and related species, the kind you find in probiotic yoghurts. They will investigate whether the two diseases have an impact on these bacteria, and whether these bacteria can help overcome the disease symptoms, particularly those caused

by Nosema, which bees contract by swallowing spores.

How do pesticides and other chemicals affect bees’ behaviour?

Pesticides and other agricultural chemicals used to maximise crop yields may also be affecting the health of bees.

The treatment of honeybees with pesticides – miticides – to try to prevent infestation with the Varroa mite could be detrimental to their wellbeing.

Dr Chris Connolly is a neurobiologist at the University of Dundee. Though usually found investigating the human brain, he is now applying his expertise to bees.

“I was thinking about pesticides and realised that, although people have looked at the concentrations that kill pest and non-pest species, so-called sub-lethal doses may affect how bees behave. Moreover, there have been no studies to investigate whether the sub-lethal effects of multiple pesticides might create the ‘perfect storm’ through

synergistic interactions,” Chris says.

“I decided that this is more or less the kind of thing we’ve been doing on mammalian brain cells, so if we could apply this to the bee brain, we could find out if these chemicals have sub-lethal effects at the level of individual cells, neural networks, whole animals or entire colonies.” There are fears that these exposures may affect the bees’ abilities to move, communicate and find food.

The Varroa-killing miticides are a reformulation of the pesticides used in the field and one of the prime targets for synergistic toxicity. “If the bees encounter this and then another pesticide, then the double hit might be the problem,” Chris says.

His team is designing assays to study the effects of different combinations of pesticide on brain cells. “Our next step will be to look at neural networks and to

Like doing the grocery shopping for your family, foraging worker bees have to pick food that’s right not only for them but also for those back home.

The bee’s shopping list is simpler though: pollen is the main source of protein and nectar the main source of carbohydrate.

“How worker bees choose food is not well understood,” says Dr Geraldine Wright from Newcastle University. She is investigating bee nutrition, and how a bee’s nutritional state affects how it forages.

Geraldine is working with Dr Annie Borland, a plant physiologist at Newcastle, and Dr Phil Stevenson, from the Royal Botanic Gardens at Kew, to measure the nutritional content of nectar and pollen from different agricultural, horticultural and native UK species.

“We’re looking to find out if bees need to forage from one or several different species to achieve their optimal carbohydrate-to-protein ratio,” says Geraldine. “One thing that’s emerging from the work of our collaborator, Professor Sue Nicolson at the University of Pretoria in South Africa, is that workers don’t survive well on a high-protein diet, but this is in fact what the brood [the immature bees] need. It will be really interesting to find out how much the honeybee has to disregard its own nutritional state while it’s foraging.”

While bee nutrition is the focus of

the project, research by Geraldine’s laboratory is mainly around understanding the mechanisms of learning and memory. She and her colleagues have been using the honeybee as a model for some time, and are bringing that knowledge to their new project.

“We don’t know a lot about nutrition and how it influences learning and memory. This project will allow us to understand exactly what honeybees and bumblebees need, in terms of pollen and nectar, but also how their foraging can feed back on to what they do when they’re learning.” For example, she says, if a bee is low on protein in its diet, is it more likely to learn to associate a floral scent with an amino acid (which proteins are made of) than with a sugar?

With Professor Sharoni Shafir at the Hebrew University, Israel, Geraldine will be investigating how bees weigh rewards – or, as she describes it: “We’re going to look at how nutrition affects the cognitive behavioural decisions that forager bees have to make when they’re out doing the shopping.”

• Dr Robert Paxton is working with Dr Mark Brown (Royal Holloway, University of London) and Dr Juliet Osborne (Rothamsted Research).

• Dr Chris Connolly is working with Dr Jenni Harvey (University of Dundee), Dr Nigel Raine (Royal Holloway), Dr Geraldine Wright (Newcastle University) and Professor Neil Millar (UCL).

• Dr Geraldine Wright is working with Dr Phil Stevenson (Royal Botanic Gardens, Kew), Dr Annie Borland (Newcastle University), Prof. Sue Nicolson (University of Pretoria), Prof. Sharoni Shafir (Hebrew University of Jerusalem) and Prof.

Steve Simpson (University of Sydney).

1. Gallai N et al. Economic valuation of the vulnerability of world agriculture confronted with pollinator decline. Ecological Economics 2009;68(3):810–21.

2. Biesmeijer JC et al. Parallel declines in pollinators and insect-pollinated plants in Britain and the Netherlands. Science 2006;313(5785):351–4.

The Insect Pollinators Iniatitive is supported by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government and the Wellcome Trust, under the auspices of the Living With Environmental Change partnership.

SPRING 2011 | 31

FROM THE ARCHIVE

BY ROSS MACFARLANE

NUREMBERG CHRONICLE

What is it?

Published in 1493, the book is a history chronicle that follows Biblical lines, beginning with the Creation and ending with the Last Judgement. The largest section, however, consists of scenes of contemporary life and contains many illustrations of European places. The book was produced in Nuremberg – then the centre of the German book trade. The city is afforded a double-page 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 Henry Wellcome 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

Mary McCartney

DIARY

Courses, conferences and workshops Wellcome Trust Genome Campus, Hinxton, unless otherwise specified. For more, see www.wellcome.ac.uk/ advancedcourses and www.wellcome.ac.uk/conferences

Senior Research Fellowships in Basic Biomedical Science

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

APPLIANCE OF SCIENCE “It’s all about bringing real life into art – literally” MARC QUINN

From Beads on a String to the Pearls of Regulation: The structure and dynamics of chromatin Conference, 3–4 August Wellcome Trust School on Biology of Social Cognition Conference, 14–21 August The Leena Peltonen School of Human Genomics Conference, 21–25 August The Genomics of Common Diseases Conference, 30 August–2 September

or me, science is important, but this isn’t true for all artists.

Some have no interest in science at all – and they make a different kind of art.

I’m interested in bringing real life into art in some way – literally. With the blood head, ‘Self’, I was trying to think of an organ that could be harvested without killing the host. You can take blood out and the body will rebuild it. You have a sense of the wonder of the way that the body can re-create itself. It’s a metaphor for life and death.

For the work I’ve done using DNA, it just so happened that, at that moment, the same philosophical questions interested me and interested science. For example, the idea of DNA as the instructions for building someone, and the question of how complexity evolved out of a binary code.

I worked with Professor Sir John Sulston to create a portrait of him that contained his DNA. That was very interesting – I went to meet him with no preconceptions about what to make. He showed me around the Wellcome Trust Sanger Institute, and it was through his eyes seeing how everything worked that I came up with the ideas for the portrait. It was a literal collaboration too, because I got some of his DNA.

A lot of artwork to do with DNA was so boringly illustrative, it doesn’t really tell you anything to draw a double helix. It was very interesting to actually get to the nitty-gritty and work with the actual stuff – that gave it a reality.

I am continuing to work with the body as inspiration. I’ve just done a series of paintings of people’s irises, which are close-ups, 2 to 4 metres wide. You get an image that is at once incredibly colourful and abstract in a way, but also a complete signifier of identity in the way that DNA is, because an iris doesn’t change. In the middle you have this black hole, which, to me, signifies the void and mystery of life.

Science and art are two very different things.

Science wishes to discover facts about the world, art is about creating objects of philosophical meditation and emotional communication, again, about what it is to be a person living in the world.

But they coincide in that they’re both interested in the mysteries of life: where do we come from? What are we made of? Who are we? Where do we go when we die? These questions are common questions – but art doesn’t find answers, it just poses a question in a new way.

Find out more at www.marcquinn.com

Molecular Approaches to Clinical Microbiology in Africa Course, Malawi–Liverpool–Wellcome Trust Clinical Research Programme, Blantyre, Malawi, 10–16 September Epigenomics of Common Diseases Conference, 13–16 September Next Generation Sequencing Workshop, 2–10 October

William Henry

Senior Research Fellowships in Basic Biomedical Science

Euston Road, London. www.wellcomecollection.org

Candidates are expected to have an excellent track record in their scientific field and be able to demonstrate their ability to carry out independent research.

Dirt: The filthy reality of everyday life Exhibition, 24 March–31 August

Deadline for preliminary applications: 6 June 2011.

Elements Event, 8 April

www.wellcome.ac.uk/uksrf/wn

Functional Genomics and Systems Biology Conference, 29 November–1 December

Wellcome Collection events and exhibitions

Derren Ready, Eastman Dental Institute/Wellcome Images

Human Genome Analysis: Genetic analysis of multifactorial diseases Course, 23–29 July

Supper Salon Event, 13 April Tell it to Your Doctor Events, 16 & 21 April Born Today Events, 28 April & 5 May

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, Tenofivir, 3TC (HIV)’ at Wellcome Collection.

34 | WELLCOME NEWS

SPRING 2011 | 35

A FREE DESTINATION FOR THE INCURABLY CURIOUS

TUESDAY–SUNDAY (UNTIL 18.00) LATE-NIGHT THURSDAY (UNTIL 22.00) 183 EUSTON ROAD, NW1 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