wellcome news 67

8/6/2019 Wellcome News 67

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Wellcome NEWSIssue 67, summer 2011

MEMORIES ARE MADEOF THISEleanor Mag ire talks taxis,amnesia and getting lost.


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We have expanded o r Investigator Awards to cover the medicalh manities, bioethics and aspects o the social sciences. We are invitingapplications rom world-class scholarsasking the most important q estionsat the inter ace o science, medicineand the wider h manities.

The scheme will cover two categories Medical History and H manities, andEthics and Society enabling scholarsto p rs e bold individ al visions withgreater exibility.

Applications now open.

www.wellcome.ac.uk/mhinvestigators/wn

Wellcome Trust Investigator Awards

Marcus Aurelius

Nothing hass ch power to

broaden the mindas the abilityto investigate

systematicallyand tr ly

P a s i e k a / S P L


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In brie Message rom the Director

F nding newsResearch news

In depthHow I Got Into the biology o bee brains: Dr Chris Connolly

Eleanor Mag ire: mapping memories

Any q estions? Taking part in Im A ScientistBlog and lm pdate

Q&A: Dr Gareth OwenSmooth Operator: Making the i-Snake

OpinionDogma on mental illness is a threat to progress

Appliance o Science: m sic estivals and science

Pi ture eaturesHijacking nat ral systems

N ts and Bolts: MRIFrom the Archive: Ann Fanshawes recipe book

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CONTENTS

INSIDE THIS ISSuE

14Eleanor Maguire:mapping memories

D e e j p i l o t / i S t o c k p h o t o


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Cover: Pro essor EleanorMaguire, who workson the neuroscience o memory. See page 14.Wellcome Images

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This document was printed on materialmade rom 25 per cent post-consumerwaste & 25 per cent pre-consumer waste.

50%

MESSAgE FROM THE DIREcTOR SIR MARK WALPORT

M ch o the scienti c process is inherently repetitive. There are days,perhaps even years, o developing and re ning techniq es, checkingcontrols and ens ring that res lts are replicable. B t this repetition isp nct ated with moments o inspiration when a new idea strikes, o delight when an experiment nally works, and o serendipity whensomething nexpected sparks a completely new line o enq iry. It is s chmoments that make science come alive.

The rst 75 years o the Wellcome Tr st the anniversary we celebratethis year are ll o examples o this. Take Graham Mont Liggins, whosework we nded rom the 1960s. His moment o revelation came rom the

nexpected breathing o a newborn lamb. As part o his research into whattriggers labo r, he in sed a pregnant ewe with cortisol. This led to as ccess l birth 37 days be ore ll term, when the lambs immat re l ngssho ld have been incapable o in ating. This led to the development o corticosteroid treatment or women showing signs o giving birthpremat rely, estimated to have helped save h ndreds o tho sands o newborn in ants by accelerating mat ration o the l ngs.

Nick Whites key moment came in 1979 when he chanced pon adog-eared paper in a Chinese scienti c jo rnal detailing the antimalarialproperties o a herb called qinghao, derived rom sweet wormwood. Bytracking down the a thors and b ilding on their work, he and his teamproved that derivatives o qinghao (artemisinin) are indeed power l

antimalarial dr gs. These are now rontline treatments or the disease.I am immensely pro d o the progress made possible by the WellcomeTr st over its rst three-q arters o a cent ry. This anniversary a ords agreat opport nity not only to re ect on the considerable achievementsmade in science, medicine and the medical h manities in this time, b talso to recognise the great personal e ort and dedication behind each one.

This anniversary is also an opport nity to look to the t re, andconsider how contemporary research may prod ce great stories in comingyears. I have invited researchers rom nine o o r biggest nded initiativesacross the uK (holders o Wellcome Tr st Strategic Awards) to r n events

or the general p blic d ring the second hal o 2011. These will showcasethe best o their elds o science, showing how these have developedd ring the last 75 years and what rther progress may be possible.

Telling the stories o the Wellcome Trusts work

Editor Chrissie GilesAssistant Editor Tom FreemanWriters Craig Brierley, Chrissie Giles,Mun-Keat Looi, Jen MiddletonDesign Anja FouadPhotography David SayerPublisher Hugh Blackbourn

Contributors:Chris Connolly illustration Bret Sy ertMRI illustration Malcolm Chivers

Ideas, comments, suggestions? Get in touch:Wellcome NewsWellcome TrustGibbs Building215 Euston RoadLondon NW1 2BEE [email protected]/wellcomenews

To subscribe:T +44 (0)20 7611 8651E [email protected]/subscribe

All images, unless otherwise stated, are rom theWellcome Library. You can get copies throughWellcome Images ( images.wellcome.ac.uk ).

Wellcome TrustWe are a global charitable oundation dedicated toachieving extraordinary improvements in humanand animal health. We support the brightest mindsin biomedical research and the medical humanities.Our breadth o support includes public engagement,education and the application o research to improvehealth. We are independent o both political andcommercial interests. www.wellcome.ac.uk

This is an open access publication and, with theexception o images and illustrations, the contentmay, unless otherwise stated, be reproduced reeo charge in any ormat or medium, subject to the

ollowing constraints: content must be reproducedaccurately; content must not be used in a misleadingcontext; the Wellcome Trust must be attributed asthe original author and the title o the documentspeci ed in the attribution. The views and opinionsexpressed by writers within Wellcome News do notnecessarily re ect those o the Wellcome Trust orEditor. No responsibility is assumed by the publisher

or any injury and/or damage to persons or property asa matter o products liability, negligence or otherwise,or rom any use or operation o any methods, products,instructions or ideas contained in the material herein.ISSN 1356-9112. First published by the Wellcome Trust,2011.Wellcome News is the Wellcome Trust and islicensed under Creative Commons Attribution 2.0 UK.The Wellcome Trust is a charity registered in Englandand Wales, no. 210183. Its sole trustee is The Wellcome

Trust Limited, a company registered in England andWales, no. 2711000 (whose registered o ce is at 215Euston Road, London NW1 2BE, UK).PU-5122/15K/06-2011/AF

Wellcome NEWS


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S mmer at Wellcome Collection As eat red in Wellcome News66, Wellcome Collections Dirt Season iswell nderway. Yo can catch the Dirt exhibition ntil 31 A g st, as well as ahost o events. These incl de theEvol tion o Disg st debate on 14 J ly,the exploration o unclean Beings on1516 J ly and Archaeological Dirt on 21J ly. There are also two amily days, on23 J ly and 20 A g st.

I yo are not near London, thenkeep an eye o t or some dirt-related nat a n mber o estivals over thes mmer, and the closing o the DirtSeason in Glasgow. Yo can also testyo r own lthiness by playing Filth Fair ,o r hidden word game, available onlineand as an app or Phone and iPad.

Find o t more at www.wellcomecollection.org/dirt

New writing prizeComedian Dara O Briain,Editor-in-Chie o GuardianNews & Media Alan Rusbridgerand Director o the WellcomeTrust Sir Mark Walport areamong the judges o the rstWellcome Trust Science WritingPrize. The competition invitesnon-pro essional sciencewriters based in the UK orRepublic o Ireland to submitarticles o up to 800 words onan area o science. Entries arenow closed or this yearscompetition. The winners, whowill be announced at anceremony in October 2011, willhave their work printed in theGuardian or Observer , receive a1000 cash prize and a sciencewriting workshop at theGuardian .

Test your re exesI you happen to pass by ourheadquarters on Euston Road,London, keep an eye out orthe new interactive windowdisplay, Re ex by rAndomInternational. This lightinstallation contains LEDs thatrespond to the movementso people walking past thewindows, emulating thecollective decision-making

processes o swarming animalssuch as bees.

The s mmer the new Wellcome Tr st Director o ScienceF nding, Dr Kevin Moses, arrives, ollowing thedepart re o Dr Alan Scha er last year. Kevin takes p hispost in J ly.

The key nction o the Director o Science F ndingis to contin e to nd, s pport and rigoro sly assess thebest scientists. The best scientists make the best science,he says. I nd the breadth o opport nity at the Wellcome Tr st to be very exciting.

Kevin joins s rom Janelia Farm/Howard H ghesMedical Instit te, where his most recent role was Chie Administrative Ofcer. His responsibilities incl ded

ac lty recr iting, mentoring and review, and trainingprogrammes.

His backgro nd is in academic research. A ter st dying at the university o Cambridgeor his degree, MA and PhD in nat ral sciences, he spent over 20 years st dying the

developmental biology and molec lar genetics o Drosophila.I am very pleased that we have made s ch a strong appointment to this post, and look

orward to welcoming Kevin, says Sir Mark Walport, Director o the Wellcome Tr st.

We have awarded the rst Wellcome Tr st Investigator Awards in biomedical science. Intotal, 20 Senior Investigators and seven New Investigators were named, and 26 awardswere made (one being a joint Senior and New Investigator Award). The Investigators come

rom 12 instit tions across the uK and one in Brazil.

The New Investigators incl de Dr Pedro Hallal rom the Federal university o Pelotasin Brazil, who will be st dying the e ects o exercise in pregnancy on the t re health o the child. Dr Christopher Thompson rom the university o Manchester will se his NewInvestigator Award to nderstand the actors behind cell ate d ring development.

At the Liverpool School o Tropical Medicine, Pro essor Alister Craig has been made aSenior Investigator, and will be exploring the role o cytoadherence when red blood cellsstick to capillaries in cerebral malaria. Senior Investigator Pro essor Sara Rankin romImperial College London is b ilding on previo s Tr st nding, incl ding a ResearchCareer Development Fellowship and a university Award, to research the pharmacology o the mobilisation o stem cells rom bone marrow and their se in tiss e regeneration.

We are accepting applications or Investigator Awards on a rolling basis. For morein ormation see www.wellcome.ac.uk/investigators

Investigator Awards inbiomedical science anno nced

Director o Science F nding named

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FUNDINg NEWS

Investigators expandWe have expanded the newWellcome Trust InvestigatorAwards scheme to cover themedical humanities and bioethics,inviting applications rom world-

class scholars asking the mostimportant questions at theinter ace o science, medicineand the humanities.

The latest set o InvestigatorAwards covers two categories Medical History and Humanities,and Ethics and Society enablingscholars to pursue bold individualvisions more exibly. Our currentbioethics programme hasexpanded to include the socialaspects o biomedical researchand health interventions morebroadly, as well as researchevaluating public engagementand health communicationinterventions.

Applications or InvestigatorAwards are now open and thedeadline or the rst ullapplications will be 2 September2011. For more, seewww.wellcome.ac.uk/ unding

Parasite prizesPro essor Hector Hugo Garciahas celebrated receiving theprestigious 2011 Prix ChristopheMerieux rom the Institut deFrance. Pro essor Garcia is our

rst Senior Fellow in PublicHealth and Tropical Medicine.He works on neurocysticercosis,a widespread, serious in ection o the brain caused by the larvae o the pork tapeworm, Taenia solium.The 500 000 prize is awardedto a researcher or team studying

in ectious diseases in low-income countries.Congratulations to Dr Simon

Brooker, a Wellcome TrustResearch Career DevelopmentFellow based at the KEMRIWellcome Trust ResearchProgramme in Kenya, on beingawarded the CA Wright medalby the British Society o Parasitology. The award is madeto a mid-career scientist who, itis considered, will con rm theiralready outstanding achievementsto become a truly distinguished

uture leader o their eld.Previous recipients include ourown Director o TechnologyTrans er, Ted Bianco.

F nding or in ection response

Primitive Streak grows

The theme or the latest ro nd o nding rom the Health Innovation

Challenge F nd has been anno nced. Applications are now welcome ordeveloping in ection response systems scalable sol tions that will betterprepare the uK or the next p blichealth emergency.

The Health Innovation ChallengeF nd (HICF) is a nding partnershipbetween the Wellcome Tr st and theDepartment o Health. It is making pto 15 million available or healthcare

In 1997, we awarded Sciart nding toartist and ormer ashion designer HelenStorey and her developmental biologistsister, Kate Storey, or their projectPrimitive Streak. Together they createda series o textile and ashion designsthat spanned the rst 1000 ho rs o h man gestation. Now, some 14 years

on, they have received rther nding toadd new dresses to their collection. Thenew pieces explore the development o the l ngs and incorporate bespoketextiles that evoke the eel and nction

innovators who can o er sol tionsor improved detection, prediction,

prevention and management o in ectio s diseases. Applicationsare d e by 2 September 2011.

This is the th call or proposalsrom the HICF, which stim lates

the creation o innovative healthcareprod cts, technologies andinterventions, to bene t patients inthe NHS and beyond.

www.wellcome.ac.uk/hic

o respiratory s r aces.Over the spring, ten o the original

27 dresses and the new item, the L ngDress, have been exhibited in Shefeld,Newcastle and London. Helen and KateStorey will be speaking abo t PrimitiveStreak at Wellcome Collection on 28J ly, where the L ng Dress will be on

display or a short period. Find o t moreabo t the designs and the science thatinspired them at www.primitive-streak.org

FuNDING OPPORTuNITIESwww.wellcome.ac.uk/ unding

Heart Tube Hat. Photo: Justine; model: Korinna at Models 1


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New medicalhistory ellows

The Children o the 90s st dy is celebrating 20 years o research into the health o tho sands o people in and aro ndBristol, and is now covering the children o the original

children st died. The project ormally the Avon Longit dinalSt dy o Parents and Children (ALSPAC) recr ited over14 000 pregnant women in 1991 and 1992 and has charted thehealth o the women and their children ever since.

Now, with 6 million rom the Wellcome Tr st, theMedical Research Co ncil and the university o Bristol, theproject is planning to contin e st dying the originalparticipants as well as involving all other interested amilymembers, incl ding grandchildren and other children o thest dy mothers.

This additional nding means that we can investigatehow the health o s bseq ent generations depends in part onwhat happens in the early li e o t re parents, says Pro essorGeorge Davey Smith, Scienti c Director o Children o the90s. Contrib ting to improved health o c rrent and t regenerations is o r ltimate goal.

The ndings o the project to date incl de that athers cans er rom postnatal depression and that taking paracetamolin pregnancy can lead to childhood asthma.

Watch a short flm on ALSPAC: www.wellcome.ac.uk/ News/2011/News/WTVM050756.htm

Children o the 90scome o age

We have awarded ve new Medical Historyand H manities Fellowships. The recipientsincl de Dr Mingji C om , a trained Tibetanmedical practitioner working at theuniversity o Ox ord. She will explore,eval ate and doc ment c rrent ed cationalmethods sed or Tibetan medicine, toens re that traditional techniq es do not

die o t.Dr Sarah Walters rom the LondonSchool o Hygiene and Tropical Medicinewill apply methods sed to st dy historicalpop lations in E rope to ve co ntries in A rica. She will separish registers to explore how pop lations have changed ins b-Saharan A rica over the 20th cent ry, to boost o r

nderstanding o the impact o colonial r le on mortalityand ertility.

At the university o Cambridge Dr Hannah Newton wil lbe looking at recovery rom illness in England between 1580and 1720, a time when contrary to pop lar nderstanding most ailments ended in recovery rather than death. She willinvestigate how doctors, patients and their amilies

nderstood, experienced and responded to recovery, singso rces incl ding personal and legal doc ments, religio sliterat re and medical texts. T i

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Wellcome Trust Genome Campus

Advanced

Co rsesand Scientifc

Con erences

At the cutting edge o biomedicaltraining, discussion and debate.

Wellcome Tr st Advanced Co rsesand Scienti c Con erences are hostedin dedicated acilities at the WellcomeTr st Genome Camp s in Hinxton a short distance rom the historic cityo Cambridge.

F nding is now available or new Advanced Co rses and to seedthe developemnt o new Scienti cCon erences. Please contactDr Rebecca Twells, Programme

Manager, or more in ormation([email protected]) .

For details o all pcoming AdvancedCo rses and Scienti c Con erences,please visit:

www.wellcome.ac.uk/hinxton


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RESEARcH NEWS

Cancers linkedThe rst genome scan or wombcancer, part- unded by us, hasidenti ed a genetic region linkedto susceptibility to the disease.The region, which overlapswith the gene HNF1Bonchromosome 17, has previouslybeen linked to prostate cancerrisk in men. This is the rstregion common to both cancersto be discovered, somethingthat could indicate sharedmechanisms o disease.

Spurdle AB et al.Nat Genet 2011;43:45154.

Weight-loss surgerySupported by a 1 millionWellcome Trust StrategicTranslation Award, Irishcompany Crospon has launcheda new tool, an imaging cathetercalled the EF-620, the latestaddition to the companysexisting EndoFLIP imagingsystem. The catheter will givesurgeons a consistent andreliable way o measuring thesize o a sleeve they create

during weight-loss surgery. Itis hoped this will help surgeonscreate sleeves in real time,sa ely and consistently, andbetter understand why someweight-loss procedures ail.www.crospon.com

Tracking a killerAn international team includingSitali Simwami and Dr MatthewFisher rom Imperial CollegeLondon has studied theevolution o the ungus thatcauses cryptococcal meningitis,responsible or a third o allAIDS-related deaths. Theresearchers showed that theCryptococcus neoformans variety grubii ound in Thailand exhibitssigni cantly less geneticdiversity than that elsewhere,especially in A rica consistentwith the idea that that thepathogen was introduced romA rica to Asia at some point

within the past 7000 years.Simwami SP et al. PLoS Pathog2011;7(4):e1001343.

Researchers rom the Wellcome Tr stMajor Overseas Programme at theOx ord university Clinical Researchunit in Vietnam and the Ox orduniversity Clinical Research unitPatan Academy o Health Sciences in Nepalhave cond cted the largest randomisedcontrolled trial or typhoid to date, andare now calling or the se o the dr ggati oxacin to treat yo ng people withthe disease.

They compared the standardtreatment or typhoid, chloramphenicol,to gati oxacin one o a new generationo antibiotics called oroq inolones.

Gati oxacin was released in North America in 1999 b t was withdrawna ter a 2006 st dy claimed that it can

ca se serio s side-e ects, incl ding veryhigh and low blood s gar.

The researchers o nd both dr gs tobe eq ally e ective, b t showed that theside-e ects were signi cantly worsewith chloramphenicol, a co rse o whichtakes longer to complete and costs morethan gati oxacin. They have nows bmitted evidence to the World HealthOrganization arg ing that gati oxacinsho ld be retained in yo ng people notat risk o diabetes. The dr g is also inphase III tria ls or the treatment o t berc losis.

Arjyal A et al. Gati oxacin versus chloramphenicolor uncomplicated enteric ever: an open-label,

randomised, controlled trial. Lancet In ect Dis 2011[epub ahead o print].

Call to se new antibiotic in typhoid

Scientists have solved the 3D str ct re o an enzyme involved in tooth decay,in ormation that sho ld prove se l inthe design o new inhibitors that co ldbe added to toothpaste and mo thwashto help protect teeth.

Tooth decay can occ r when dentalplaq e a bio lm containing bacteriaand ood debris is ormed by a largegl cose polymer called gl can on thetooth s r ace. Acid secreted by thebacteria breaks down the tooths enamel.

Scientists sing Diamond LightSo rce, the uKs national synchrotronscience acility, worked with researchers

rom the Photon Factory in Ts k bacity, Japan, to st dy how the enzymeGTF-SI orms gl can.

Several inhibitors that prevent thistype o enzyme orming gl can havebeen identi ed b t to date there has beenlittle str ct ral in ormation available,says the projects lead researcher, SoheiIto rom the university o Shiz oka inJapan. We now have a better

nderstanding o how the enzymenctions and how it can be stopped.

Ito K et al. Crystal structure o glucansucrase romthe dental c aries pathogen Streptococcus mutans. J Mol Biol 2011;408(2):17786.

Solving str ct res or nicer gnashers

Computer-generated graphical view o glucansucrase orming theglucan rom sucrose. Fructose is the residual product o the reaction. Sohei Ito, University of Shizuoka, Japan


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Every day, 4700 people die rom t berc losis. The onlyavailable vaccine, BCG, protects against severe diseasein children b t is not e ective in ad lts. Now, scientistshave discovered a protein prod ced by Mycobacteriumtuberculosis the bacteri m that ca ses t berc losis that co ld be the key to a new vaccine.

In the new st dy that we have nded, scientists haveidenti ed a protein called EspC that triggers a strongerimm ne response in people in ected with M. tuberculosis than any other known molec le does. This protein is notpresent in the BCG vaccine, which means that a vaccinebased on EspC wo ld provide imm nity over and abovethat provided by BCG.

Weve shown that EspC, which is secreted by thebacteri m, provokes a very strong imm ne response, andis also highly speci c to MTB [ M. tuberculosis], says seniora thor Pro essor Ajit Lalvani, rom the National Heart andL ng Instit te at Imperial College London. S rprisingly,o r res lts also show that this molec le co ld nderpinnext-generation diagnostic blood tests that can rapidlydetect latent TB in ection.

In other work, researchers have claimed that thestandard approach to re-treating TB in low- and middle-income settings is ailing. They cal l or improvements inthe way the disease is managed, incl ding greater accessto rapid diagnostics or dr g-resistant TB, second-linetreatment and antiretroviral HIV therapy.

Millington K et al. EspC is a highly immunodominant E1-dependentsecreted antigen speci c or Mycobacterium tuberculosis in ection.Proc Natl Acad Sci USA 2011;108(14):57305.

Jones-Lpez EC et al. Efectiveness o the standard WHOrecommended retreatment regimen (category II) or tuberculosisin Kampala, Uganda: a prospective cohort study.PLoS Med 2011;8(3):e1000427.

The loss o blood s pply to parts o the bodycan ca se serio s tiss e damage, incl dingstroke and heart attack. Now, researchershave identi ed a speci c pathway o theinnate imm ne system that ca ses anin ammatory response to oxygen-deprived

cells and tiss es, and have managed to block this response in mice with a single injection.

This in ammatory response contrib testo major loss o tiss e and organ nction.Now, with long-term Wellcome Tr st andMedical Research Co ncil s pport, aninternational team led by Pro essor WilhelmSchwaeble rom the university o Leicesterhas identi ed a new therape tic target tolimit this type o tiss e loss.

The target is mannan-binding lectin-associated serine protease-2 (MASP-2), a keycomponent o the lectin pathway o

complement activation. The researcherso nd that when this enzyme was absent or

blocked, the tiss e in ammation and loss thats ally occ rs when tiss es are reper sedollowing a temporary loss o blood s pply

was signi cantly red ced. They also red ced

tiss e damage in mice sing a single injectiono a ne tralising antibody against MASP-2.

Therapies based on these ndings havethe potential to improve the o tcomes o heart attacks, strokes and t ransplant s rgery,and may be applicable to any s rgicalproced re where a temporary disr ption o blood ow co ld p t tiss e at risk.

Schwaeble WJ et al. Targeting o mannan-binding lectin-associated serine protease-2 con ers protection rommyocardial and gastrointestinal ischemia/reper usion injur y.Proc Natl Acad Sci USA 2011;108(18):75238.

Limiting the e ects o a loss o blood s pply

New target or TB vaccine

Illustration showing the circulatory system.Medical Art Service, Munich/Wellcome Images

Anti-TB poster eaturing Albert Calmette,co-discoverer o the BCG vaccine, 1934. Wellcome Library


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cAREERS

n Christmas Day 2008 , mymother-in-law gave me AWorld Without Bees by

Alison Benjamin andBrian McCall m, a book that describes the decline o

the honeybee. As a ne robiologistreading, it str ck me that many o thesymptoms o colony collapse disorderwere consistent with some kind o braindisorder.

I was thinking abo t pesticides andrealised that so-called s b-lethal doses[which dont kill pests] may a ect howbees behave. I decided that this is moreor less the kind o thing weve beendoing on mammalian brain cells, so i we co ld apply this to the bee brain, weco ld nd o t i these chemicals haves b-lethal e ects at the level o individ al cells, ne ral networks[circ its o nerve cells], whole animalsor entire colonies.

So, I had the idea, b t tho ght that itmight be hard to get nding beca se Ididnt work in the eld. I applied as anindivid al to the Co-operatives PlanBee, which nds research into the

decline o the honeybee, b t wasns ccess l. B t something wasnt

letting me drop the idea, as then I heardabo t the Insect Pollinators Initiative,and the 10 million o nding it was

making available. This got methinking abo t orming a larger,m ltidisciplinary team.

I researched the science in moredetail on P bMed, the online library o scienti c papers, and tho ght abo thow Id assemble a team. Altho gh Iknew many ne robiologists who co ldhelp me with the cell lar and molec laraspects o the project, I had noexperience working with bees. I called

p Pro essor Pat Wilmer, a pollinationbiologist at St Andrews, or some help.She p t me in to ch with expertne roscientists who are sing bees asmodels to investigate mechanisms o learning and memory. This was a

antastic advance in assembling aworld-class team. We applied, and heardo r proposal was one o nine chosen tobe nded.

Serendipito sly, the proposed work on bee receptors overlapped with mywork on h man receptors. In beeresearch, there is lack o stable cell lines(di erent types o bee cells to grow and

se in the lab), as, nlike h man celllines, these are very hard to make.

Partic larly tricky are insect cellsst dded with nicotinic acetylcholinereceptors, o nd in the nervo s systemso vertebrates and invertebrates alike.

Fort ito sly, in a separate project,

Ive been working with Pro essor NeilMillar, a ne ropharmacologist atuniversity College London, on a

chaperone protein that helps cellsprod ce these receptors. Hes a partneron o r pollinator project, and we willattempt to create the rst ever honeybeecell line or pesticide screening.

Since getting the nding, Ive giventalks to many organisations andcon erences, incl ding CropWorld, the Association o Independent CropCons ltants and both the Scottish andBritish Beekeepers Associations q itea di erent circ it to what Im sed to.

In what private time I have, Iminterested in wildl i e, nat re and theenvironment; as a pro essional, Iminterested in the medical implicationso dys nctional ne ronalcomm nication. Reading the book onbees, bells started ringing in my head asI realised that I co ld join p myinterests in one project. My mother-in-law is very excited too, especially as thisis all thanks to her. O co rse, now I

nd it impossible to get that workli ebalance j st as I like it.

On this project, Chris is working with Dr JenniHarvey (University of Dundee), Dr Nigel Raine(Royal Holloway, University of London), Dr GeraldineWright (Newcastle University) and Professor NeilMillar (UCL). For more on the Insect PollinatorsInitiative, see www.wellcome.ac.uk/pollinators .

DR CHRIS CONNOLLY

HOW I GOT INTO...THE BIOLOGY OFBEE BRAINSIn the jokes o a certain kind o comedian, the mother-in-lawcomes across as part menace, part millstone. B t orne roscientist Dr Chris Connolly rom the university o D ndee,his mother-in-law was the so rce o the impet s to open p awhole new area o research. By Chrissie Giles.


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Can youcontribute to ourworld-classimage resource?

The Wellcome Images collection incorporates a broadspectrum o images, rom the history o medicine to cutting-edge biomedical science.

We are currently looking or new images rom research scientists,clinical photographers and illustrators to expand our biomedicalcollection. We are particularly keen to receive high-quality images

rom research on stem cells, parasites, in ectious diseases,neuroscience and genetics.

Find out more about our collection at images.wellcome.ac.uk

Or contact Dr Laura Pastorelli:

E [email protected] +44 (0)20 7611 8347

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t is commonplace or people to holdvery rm views abo t the nat re andca ses o mental illness, based onh nch, ideological perspective and

anecdote. For example, some believe allmental illness is explained by adverse social

circ mstances; others think that it simply re ectsa lack o ability to cope with li es stresses. Whilemany people are very s pportive o the need orbetter nderstanding o mental health, evenhighly intelligent and otherwise open-mindedindivid als not in req ently hold dogmatic b till-in ormed views abo t mental illness.

This thinking extends to biological scientists,Nobel Prize winners and even members o grantspanels. Many naive views seem to be based onextrapolation o knowledge o sit ations o

relatively mild mental distress. However, thisextrapolation does not work. Consider thecommon ass mption that all depression is theres lt o inability to deal with li e, a characterweakness. While this view might be o val e ormild depression, it is woe lly inadeq ate orsevere depression accompanied by st por ordel sions sit ations that can be li e-threatening.In contrast, ew people wo ld be com ortablemaking similar generalising ass mptions abo tthe ca ses and management o severecardiovasc lar disease ( or example myocardialin arction) based only on their observations o people who get breathless on exercise.

Within the scienti c and lay press, psychiatricillnesses are disc ssed in a more heated,opinionated and less help l way than non-psychiatric illnesses. An example was the media

rore s rro nding the report that rare str ct ralgenomic variants are more common in cases o attention de cit hyperactivity disorder (ADHD)than controls. Despite voicing o all the caveatsabo t the complexity o ca sation and importanceo environmental actors, there was great disq ietvoiced rom some commentators that ADHD wasre erred to as a genetic disorder. Had similarwording been sed abo t heart disease or diabetes,there wo ld not have been s ch in ammatorydebate. And yet the evidence or genetic in enceon ADHD is as strong as or these physicalillnesses. All involve a complex mixt re o genes

and environment. An increasing nderstanding o basicne roscience, together with h man investigativetools s ch as molec lar genetics and m ltimodalbrain imaging, provide the opport nity or arevol tion in diagnosis and management o mentalillness over the coming two to three decades.However, realising this opport nity will req ire sall to be open-minded and g ided by evidencerather than prej dice. This incl des politicians,the p blic, pro essionals, nders and grantspanels, as well as researchers.

For the sake o the many people whose lives area ected by severe mental illness we need to walk the walk and not j st talk the talk.

PROFESSOR NICK CRADDOCK, CARDIFF uNIVERSITY

Dogma on mental illness is a threat to progress OPINION


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BRAIN RESEARcH

PROFESSOR ELEANOR MAGuIRE

MAPPINGMEMORIES From taxi drivers to people with amnesia,Eleanor Mag ire has st died the brains o h ndredso people in her q est to nderstand how we makememories o both o r personal experiences and theworld aro nd s. Roger High eld navigated to the Wellcome Tr st Centre or Ne roimaging atuCL to nd o t more.


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he way that ourrecollections shape whowe are and the way wethink has long been

explored in literat re andpop lar c lt re, rom the

writings o Marcel Pro st and Philip KDick to lms s ch as Strange Days, Memento and Eternal Sunshine o theSpotless Mind. B t when EleanorMag ire rst became interested in thes bject, her motivation to p t memoryon a scienti c basis was more personal.I am absol tely appalling at nding myway aro nd, she con esses. Iwondered: How are some people so

good and I am so terrible?She started o t her q est to

nderstand memory while workingwith patients or a doctorate atuniversity College D blin. TodayEleanor is still dedicated to the q est, asa Wellcome Tr st Senior ResearchFellow and Pro essor o CognitiveNe roscience at the Wellcome Tr stCentre or Ne roimaging at universityCollege London, where she heads theMemory and Space research laboratory.

She wanted to explore how o rexperiences, both big and h mdr m,orge and s nder the vast network o

connections between cells in a h manbrain. So, she and her colleag es arest dying memory sing brain scanners,notably magnetic resonance imaging(MRI) techniq es. Some are t ned toreveal the extraordinary str ct ra lcomplexity o the brain (str ct ralMRI), others to the tiny changes inblood ow that accompany tho ght( nctional MRI, or MRI).

B t central to her work is the eld o ne ropsychology, working with patientswho s er some kind o memoryimpairment s ch as amnesia. MRI cantell yo which brain areas are involvedin memory b t yo are never s re whichones are really necessary. That is wherethe st dy o patients comes in.

She is most ascinated by one regionlocated deep in the brain, called thehippocamp s. This is known to be amemory centre and is damaged in

people with amnesia b t Eleanorsinvestigations s ggest that its role ismore s btle and interesting. Shebelieves that it provides a kind o spatialsca old or memories, one that is

essential i we are to make sense o o rexperiences. In the long r n, herresearch will help s nderstand howo r memories can be a ected by ageand shredded by dementia anddevelopmental disorders. With that

nderstanding may, o co rse, comenew tests and treatments. We are all

abo t helping patients, ltimately. B twe cant come p with new kinds o rehabilitation ntil we nderstandprecisely how memory works.

Her rst big advance came in 2000,

in a st dy that wo ld generate headlinesworldwide, capt re the p blicimagination and even win her a share o the highly coveted Ig Nobel Prize, aparody o the Nobel Prizes that ishanded o t each year or achievementsthat rst make people la gh, and thenmake them think . She scanned the

brains o 16 London black-cab driverswho had spent an average o three or

o r years learning the Knowledge the entire layo t o the 25 000 streetsin London. What was remarkable was

Cabbies o ten tell me about my work, not realising whoI am. What is extraordinary is that they usually talk about the hippocampus.


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that she o nd the taxi drivers had alarger hippocamp s than controls bjects, partic larly on the r ight side.The longer they had been on the job, thelarger their hippocamp s. These

ndings seem to indicate that thehippocamp s plays an important role instoring spatial memories. F rthermore,when Eleanor and colleag es ollowedthe progress o trainee taxi drivers, they

o nd that the drivers who s ccess llypassed the Knowledge were those whoshowed the greatest alteration o thehippocamp s. Experience can changethe brain, she says.

Do similar changes accompanyother eats o memory? Not necessarily,according to Eleanors st dies o

participants in the World MemoryChampionships and o b s dr ivers: inneither gro p co ld she nd str ct ralchanges o the kind seen in the taxidrivers. Memory champions o ten se

navigation strategies to boost theirper ormance, b t the amo nt o large-scale space memorised is small. And b s drivers se m ch morerestricted ro tes than taxi drivers. So itappears that their memory eats do notplace the same demands on thehippocamp s.

In recent years, Eleanor has oc sedmore on the second critical role o thehippocamp s, in laying downa tobiographical memories o o r pastexperiences. Here, people withanterograde amnesia have played acentral role in her st dies.

These people live permanently inthe present. Their speech and intellecttends to remain intact, beca se

remembering acts and generalknowledge is not dependent on thehippocamp s. However, theirexperience o the world is rozen intime: they cannot remember anything

that occ rs a ter their brain damagetook place. Eleanor says: I they do aco ple o ho rs o tests with me, orexample, and I leave the room or tenmin tes and come back, they cantremember anything abo t me or whatthey had been doing.

In the healthy brain, many regionsare involved in s pporting personal,a tobiographical memories, beca sethese are colo red with emotions anddepend on the spatial, temporal andsocial context. To nderstand how thebrain stores and recalls this orm o memory, it is important to evoke thewhole memory d ring st dies. Oneway o doing this is to project a photo o a party or wedding rom a amily alb m

onto the screen, prompting theparticipant to recall and re-create thispartic lar event in their past while theirbrain is being scanned.

In this way, Eleanor and her team

BIM/iStockphoto


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have investigated the episodic memorieso everyday events, s ch as seeingsomeone posting a letter or preparing toride a bike. To explore how s chmemories are recorded, her teamshowed ten vol nteers three short lmsand asked them to memorise what theysaw. The lms were basic, sharing an mber o similar eat res allincl ded a woman carry ing o t aneveryday task in a typical rban street,and each lm was the same length,seven seconds long.

The vol nteers were then asked torecall each o the lms in t rn whileinside an MRI scanner. A comp terprogram then st died the patterns andhad to identi y which lm the vol nteer

was recalling p rely by looking at thepattern o their brain activity.Remarkably, it was possible to tell which

lm they were thinking o .Altho gh a network o brain areas

s pport memory, the comp ter programper ormed best when analysing activityin the hippocamp s itsel , s ggestingthat this is the most important region

or representing episodic memories. Inpartic lar, three areas o thehippocamp s the rear r ight, ront le tand ront right areas seemed to beinvolved consistently across allparticipants.

This work s ggests that o rmemories are encoded within the brainin a predictable way. While earlier MRIwork has shown the typical brain areasinvolved, this st dy, a ter averaging theactivity in many heads, showed theprecise circ its sed to recall onepartic lar memory trace in an

individ als brain, down to a resol tiono j st over one c bic millimetre revealing m ch more detailedin ormation abo t the hippocamp sat work.

Now it is possible to investigateprecisely which brain areas hold a givenmemory, how their se varies with timeand what happens to these areas as ares lt o disease or inj ry. B t, o co rse, there are even more spec lativeimplications. Does this mean that wewill one day be able to se a scanner toread a mind?

Eleanor emphasises that herparticipants were tasked with recallingone o three short lms that they hadprevio sly viewed, so the researcherswere already aware o the nat re o what it was they were thinking abo t, j st not the identity. There are ethicaliss es b t we did do the st dy with thecooperation o the patients and,

altho gh arg ably a orm o mindreading, it does take place nder verycontrolled circ mstances.

While con rming the key role o thehippocamp s in recalling the past,

From knots to notes, people use many tricks toremember things. Eleanor Maguire says that thebest way is to make a list.

Stop pressSince this interview, Eleanor Mag ire has been electeda Fellow o the Academy o Medical Sciences. This hono r

recognises her important work in the eld o cognitivene roscience.


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Eleanor and colleag es went on to makea ascinating discovery when she askedamnesic patients to describe imaginaryexperiences. She and her team asked thepatients to imagine and then describe indetail sit ations in commonplacesettings, s ch as a beach, p b and orest,as well as potentially pla sible t reevents s ch as a Christmas party. Thepatients ability to constr ct t re and

ctitio s events was also severelyimpaired. The role played by thehippocamp s in processing memorywas ar broader than merely relivingpast experiences, she says. It alsoseems to s pport the ability to imagineany kind o experience incl dingpossible t re events. That is why, in

this sense, people with damage to thehippocamp s are orced to live in thepresent.

F rthermore, the patients reportedthat they were nable to vis alise the

whole experience in their minds eye,seeing instead j st a collection o separate images. We believe thiss ggests a common mechanism thatmight nderpin both recalling realmemories and how we vis aliseimaginary and t re experiences,with the hippocamp s providing thespatial backdrop or context into whichthe details o o r experiences arebo nd, she explains. The work closesthe loop with her st dies on spatial

navigation, showing that space may bethe key to nderstanding the nctiono the hippocamp s and its role inmemory.

Despite these advances, h gechallenges remain i she is to convinceher peers that the hippocamp s plays acentral role in providing the spatialcontext or o r experiences and helping

s to think abo t the t re. I believethat it is there to s pport coherentscenes. It is providing a spatialbackdrop, or canvas, on which we playo t the recall o memories, plan a ro teor sim late what will happen to s inthe t re. B t that is still q itecontroversial and we need to link a lack o spatial representation directly toamnesia.

She is also keen to apply her work innovel treatments or memory disorders.The good news is that the st dy o taxidrivers s ggests that it is possible totrain a hippocamp s. For people whohave hippocampal damage and

associated difc lties with memory,the q estion o whether the brain canmend itsel , and memory be recovered,is a pressing one.

Today, Eleanor is grati ed to nd

that her work has gone beyond thecon nes o the internationalcon erence circ it and academic jo rnals. More than a decade a ter shestarted her pioneering research, shesometimes nds hersel in the back o aLondon taxi. Cabbies o ten tell meabo t my work, not realising who I am. What is extraordinary is that they

s ally ta lk abo t the hippocamp s.

Read an extended version of this

( rom early J ly) and o r othereat res to celebrate the WellcomeTr sts 75th anniversary at www.wellcome.ac.uk/75

Roger High eld is the Editor of New Scientist . For two decades hewas the science editor o the Daily Telegraph and he still contrib tes acol mn to the science page o thenewspaper. He has written orcoa thored several books. The latest,written with Martin Nowak o Harvard university, isSuperCooperators: The mathematics o evolution, altruism and humanbehaviour (Or, why we need each other to succeed). www.rogerhighfeld.com

Want to fnd out more?

Woollett K et al. Talent in the taxi: a model system orexploring expertise. Philos Trans R Soc Lond B Biol Sci2009;364:140716.

Chadwick MJ et al. Decoding individual episodicmemory traces in the human hippocampus.Curr Biol 2010;20:5447.

Hassabis D et al. Patients with hippocampal amnesiacannot imagine new experiences.Proc Natl Acad Sci USA 2007;104:172631.

This study, a ter averaging theactivity in many heads, showedthe precise circuits used to recallone particular memory trace inan individuals brain


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On Mar h , ma aria resear herDr Ju ian Ra ner sat down at his desk inthe We ome Trust San er Instituteand exed his fn ers. The questions

started to appear on the s reen. Whats our avourite made up movie

hemi a ? How mu h paperwork doesbein a s ientist invo ve? Do a t peso mosquitoes arr ma aria?

Over two weeks, J lian answeredthese and 250 other q estions, as one o the 30 contestants in the latest Im aScientist, Get Me o t o Here event. Ima Scientist was piloted in 2008,s pported by a Wellcome Tr st People Award. Prod ced by Gallomanor, its an

o shoot o Im a Co ncillor, Get Me o to Here, la nched to engage teenagerswith local politics by allowing them totalk directly to co ncillors. The pilot o the science version was a hit, and theteam has r n events every March andJ ne since 2009.

The events are not j st abo tattracting st dents to st dy and la nchcareers in science, b t also to eq ip al linvolved with ways to think scienti cally and help them becomeresponsible citizens. Theyl l all havevotes to cast, goods to b y, decisions tomake, says project director SophiaCollins, writing on the Wellcome Tr stblog. I want them to be doing that withsome ability to think abo t the iss ess rro nding science.

J lian heard abo t the competitionthro gh a colleag e in the SangerInstit tes P blic Engagement team,applied, and was assigned to the Argonzone with a cell biologist, a soilscientist, a PhD st dent working on

vitamins and a rocket engineer. Everyday or two weeks they tackled st dentsq estions online and participated in atleast one live 30-min te chat session.

never considered. Scientists get lots o practice talking abo t their work andexplaining science.

The st dents vote o t scientistsrom each zone one by one. The last

scientist standing in the Argon zonewas J lian. He plans to se the 500prize money to cover the travel expenseso schools visiting the Sanger Instit te,which already welcomes some 2000st dents a year. What was the secret tovictory? Winning or losing was arandom process as ar as I co ld tell,J lian la ghs. B t Id certainlyrecommend taking part to anyone!

Check out Julians answers here:

argonm11.imascientist.org.uk/pro le/julianrayner The June event was just beginning as we went

to press, but its not too late for students orscientists to apply to take part in the 2012 events see more at imascientist.org.uk/about

It was q ite a j mp rom takingq estions rom a small a dience o st dents at the end o a presentation,says J lian. T he chat sessions weregreat tho gh: yo cant prepare orthem, and when theyre done, theyredone, J lian says. Theres a need toexplore instant messaging more as atool to engage b sy scientists.

Were there any rec rring themes?The st dents wanted to know what itslike to be a scientist what I do on aday-to-day basis, what exams I took. Itseems that they know that scientist is acareer, b t they never get to talk to acareer scientist.

Its not j st the st dents that learn alot: St dents ask great q estions thatcan help scientists see their work di erently, or think abo t things theyd

To nd o t what working in science is like, nothing beats talking to someone whodoes it day in, day o t. A Wellcome Tr st-s pported event has given this approach areality-TV-style twist by giving st dents live and direct access to scientists, whomthey then vote o t one by one. We meet one scientist who took part to nd o t more.

PUBlIc ENgAgEMENT

DR JuLIAN RAYNER

ANY QuESTIONS?


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Summer 2011 | 21 www.we ome.a .uk/ta

Wellcome Trust Translation Awards

We are a committed ndero translational R&D. Wework with world-classinvestigators in academicinstit tions and companiesalike, in p rs it o sol tions

or nmet medical needs.

We nd medical innovationsin the ollowing areas:

therapeutics diagnostics enabling technologies regenerative medicines vaccines medical devices.

Next deadline orTranslation Awardpreliminary applications:22 July 2011

Bridgingthe gap between

ndamentalresearch andinnovative

healthprod cts


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22 | We ome NEWS

1


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clOSE-UP

For one da a week over a six month period, artistJo Berr stepped up to the aborator ben h to ethands on with a ran e o e ima in te hniques. Working alongside scientists Dr NicholasHolliday and Tim Sel rom the School o Biomedical Sciences, university o Nottingham,she cond cted experiments involving the appetite

hormone ghrelin. These incl ded investigatinghow di erent dr gs a ect the localisation o ghrelin receptors in cells. She gained experience

sing a variety o imaging techniq es, incl dinglive cell con ocal, high content and total internalre ection microscopy.

Berry, based in Carsington, Derbyshire, sedthe images generated d ring the work to create aseries o short lms, vinyl drawing and m lti-layered lightboxes. Her research prod ced morethan ascinating imagery, tho gh she was leada thor on a poster and abstract presented at the

British Pharmacological Society Winter Meeting2010 ( www.pa2online.org ).Her project, Hijacking Nat ral Systems, goes

on show in Derby rom J ly 2011, be ore moving toNottingham. The project was nded in part by a Wellcome Tr st Arts Award.

Find o t more at www.joberry.co.uk and joberry-artist.blogspot.com

1 Vinyl artwork created or the exhibition at theDerby Art Museum and Gallery.

2 Movement o HL60 cell projections calledlapodia.

36 Based on uorescence images o the cellulartra cking o ghrelin and its receptor.

6

2

3

4

5

ARTS AWARDS

HIJACKINGNATuRAL SYSTEMS


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Contact us on 020 7611 2200 or email con erencecentre@wellcome.ac.ukwww.wellcomecollectionconference.orgWellcome Collection Con erence Centre is operated through two companies: The Wellcome Trust Limited, a company registered in England and Wales (no. 2711000), as sole trustee o theWellcome Trust (a charity registered in England and Wales, no. 210183); and Wellcome Trust Trading Limited, a non-charitable company registered in England and Wales (no. 3227027),controlled by the Wellcome Trust. The registered o fces o b oth companies are at 215 Euston Road, London NW1 2BE, UK. PU5122.9/05-2011/AF

STEM CELLS, ELEMENTS AND MORE

BLOG & FILM

ONlINE HIgHlIgHTS

Wellcome Trust blogOne o the aims or o r blog is to provide a place where themany researchers we s pport can tell stories abo t their work.Over the last ew months we have been delighted as more andmore o o r researchers whether PhD st dents or research

ellows have written or s, covering everything rom thene roscience o lang age ( wp.me/pJJaZ-1dZ ) and masc linityand madness in the Victorian age ( wp.me/pJJaZ-1bn ) to stemcells (wp.me/pJJaZ-18Y ) and centrioles, via a Lord o the Rings p n ( wp.me/pJJaZ-19B). We have been hono red to host

established bloggers s ch as Dorothy Bishop ( wp.me/ pJJaZ-1gz) and Daniel Macarth r ( wp.me/pJJaZ-1hU ), b teq ally pro d to give a voice to so many rst-time bloggers.I yo have a story to tell, email [email protected]. k.

Wellcome Trust and Wellcome Collection flmsThe new lms added to o r Yo T be channels deal withtopics as varied as bipolar disorder, the secrets o chemicalelements and li e as a medical photographer.

Ever wondered what colo r oxygen is? What solid iodinelooks like? Why merc ry is so important to chemists? Inthree short lms, Dr Andrea Sella gives the lowdown on

these three elements, demonstrating how to t rn oxygen

into a liq id and iodine into a p rple gas, and taking a look at the bea ti l b t deadly merc ry. www.wellcomecollection.org/elements

In the early 1990s, more than 14 000 mothers wererecr ited to the Children o the 90s project, which aimed tost dy parents and children at a level o biological, behavio raland psychological detail never seen be ore. Project directorPro essor George Davey Smith shows s aro nd the st dysbase in Bristol. www.youtube.com/watch?v=xjO 0GTTliE

The Bipolar Bl es eat res Twink, ormer photographeror The Jam, who has experienced the extremes o bipolar

disorder or more than two decades, and Pro essor NicholasCraddock (see page 13), the principal investigator or bipolardisorder in the Wellcome Tr st Case Control Consorti m.This lm garnered over 1000 views in its rst week onYo T be and was eat red in several science blogs and theGuardian website. www.youtube.com/watch?v=pAIJGX3RICA

Finally, look behind the scenes o a 2011 Wellcome Image Awards winner in a lm that ollows medical photographerDavid Bishop, to give yo a taste o what its like to be anobserver d ring s rgery.

www.youtube.com/watch?v=b0s3-XSKhB0


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What area do you work in?Im an academic psychiatrist at theInstit te o Psychiatry, Kings CollegeLondon working to nderstand howpeople with mental health disordersmake decisions, and the problems theycan have with decision making. This isnow operating within a new legal

ramework the Mental Capacity Act2005 (MCA) which speci es the r les

nder which people sho ld be assessinganothers ability to make a speci c

decision (their capacity). The new Actchallenges the idea that people withmental health problems are j st nso nd o mind,and tries to oc s more closely on which decisionscan and cant be made by people with conditionslike schizophrenia or brain inj ry.

What does the law say about this? Weve got two pieces o mental health law now.The Mental Health Act is based on the idea o protecting individ als and society; the newer MCA is based on peoples right to decide or themselves.

When the MCA was a Bill, many o the debateswere abo t whether it wo ld permit e thanasia bythe back door. Post-legislatively, thats not thedebate at all. Now, were trying to nderstand howthis Act ts with the Mental Health Act and dealwith the con sion that this ca ses on the gro nd.

The MCA also introd ced the idea o devolveddecision making via a legal instr ment calledlasting power o attorney or health and wel are,which is completely new or England. Ad lts canappoint a tr sted riend or relative to become theirhealth decision maker or when they lose capacity.People are starting to think abo t the

conseq ences o that now.

What were your priorities or the POSTnote?For the last ve years or so, Ive been interviewingpeople to b ild p a better pict re o what capacitylooks like on the gro nd. The POST ellowship wasa chance to look at this at the policy level. I haveinterviewed parliamentarians, phi losophers,lawyers and those working across medicine, whichprod ced a massive amo nt o material.Compressing that into a o r-page POSTnote was a job! I tried to tell the story o the MCA and p t itinto the context o mental health law in general.

What do the changes mean or us?The MCA makes decisions aro nd capacity aresponsibility o all o s as citizens, beca se itacknowledges that m ch o the care or people thatmight not have capacity is given in the comm nity.In practice tho gh, most assessments o decision-making capacity are carried o t by healthcare orsocial workers, beca se these iss es come o t inclinical settings.

Another part o the Act is to try and changepeoples mindsets and get them to plan or any

t re loss o capacity, partic larly in the elderly.Its exciting that society is now m ch more

ace-to- ace with these iss es. Theyve beenslightly repressed in the past, consistent with thehistory the Mental Health Act came o t o theasyl m tradition and its o t o sight, o t o mindmentality. Capacity is an evolving area, itsde nitely not game over!

Read Gareths POSTnote atwww.parliament.uk/post

DECIDING WHOS FIT TO MAKE DECISIONS

DR GARETH OWENDr Gareth Owen completed a degree in philosophy and physics be ore becominga psychiatrist. He has recently completed a Wellcome Tr st- nded ellowship atthe Parliamentary Ofce o Science and Technology (POST) looking at the ethical,practical and legal iss es s rro nding decision making by people with mentaldisorders. He has prod ced a POSTnote to get s all to think abo t who sho ldmake decisions or s when were deemed n t to do so.

IN THE HOT SEAT


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26 | We ome NEWS26 | We ome NEWS

Patient plat ormThis is where the patientlies, with the body part to bescanned in the exact centreo the magnetic eld. Theamount o water and at in ourbodies means that were ull o hydrogen atoms, and its thesethat MRI targets.

MRI (magnetic resonance imaging) iscommonly sed in hospitals to look atwhat is happening inside the body orexample, to monitor blood ow and todiagnose or stage t mo rs. Thetechniq e (and variations o it s ch as

nctional MRI) has also been sedextensively in biomedical research, oreverything rom exploring how thebrain interprets speech and m sic toseeing how taxi drivers brains di er

rom other peoples (see pages 1419).Compared with other imaging

methods, MRI has plenty o advantages:

it is non-invasive, and does not sepotentially harm l radiation, as X-raysand many other imaging techniq es do.It also does better or looking at so ttiss es and, with one scan, a llows yo toview the body rom m ltiple angles. B thow does it work?

MRI is all abo t magnets and radiowaves. It relies on the act that atoms(in this case, hydrogen atoms) areconstantly spinning; most o them will

all into synch when yo p t them inthe scanners magnetic eld. Then, yosend in radio waves to make them spin

in a new direction, and when theya terwards ret rn to their previo salignment, they emit energy (i.e. wavesare bo nced back the resonance inMRI). This energy is what the scanner

ses to create an image.The lower the water content o a

body area, the ewer hydrogen atomsthere will be emitting signals. Theweaker the signal, the darker the areaappears on the scan. The res lt isvario s shades o grey: at is q itelight, b t bone is dark.

On 3 J ly 1977, the rst magnetic resonance imaging scan on ah man was per ormed. Today, MRI is sed widely in both medicineand research. This q ick g ide explores the science behind the

biq ito s technology that can get right nder o r skin.By M n-Keat Looi.

NUTS AND BOlTS

Mini MRIThe Wellcome Trust recentlyawarded a Strategic TranslationAward worth almost 2.5 million toGE Healthcare to investigate the useo MRI or newborns at high risk o brain injury.

In the UK, approximately ve inevery 1000 babies born sufer braininjury, and o those, approximatelyone in ve dies. Getting aster andmore accurate diagnosis o brainproblems in babies is essential ormaking treatment more efective.While MRI is widely acceptedas a better diagnostic tool thanultrasound, it is o ten not practical totake babies out o neonatal intensivecare to the MRI scanner, which iso ten in another part o the hospitalor a diferent centre altogether.

This unding will initially be usedto investigate how MRI could be

placed within the neonatal unit itsel ,removing the need to take babies outo intensive care.

Want to know more?Florida State university Magnet Lab: www.magnet. su.edu/education/ tutorials/magnetacademy/mri

MRI or newbies:psychology.uwo.ca/ mri4newbies/

IMAGING TECHNIQuES

MRI SCANNER


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Summer 2011 | 27

Gradient coilsThese are other magnets withinthe main magnet. Lower instrength than the main magnet(typically 0.0180.027 T),they are arranged to alter the

magnetic eld. This helps toocus in on the area you wantto look at, literally slicing theimage any way you want.

Radio req encycoilThis directs a radio wave at thearea you want to examineand detects the waves bouncedback. The room is shielded so

that other radio waves (e.g.those carrying The Archers)dont inter ere. With MRI, youcan use diferent dyes to alterthe magnetic eld and producea wider range o contrasts,which can make it easier todistinguish between normaland abnormal tissue.

MagnetMagnets commonly used in MRIscanners today are 0.53.0 teslastrong, but some research usesmagnets as power ul as 60 T (a

ridge magnet is about 0.005 T).

No metal is allowed anywherenear the scanner. Coins, jewelleryand other objects accidentallyle t in scanning rooms becomepotentially dangerous projectileswhen close to the magnet. Andany bankcards will be erased

Most magnets used today aresuperconducting, so containliquid helium as a coolant(at 269C). In the case o aquench, when the helium boils,helium gas is directed out o the room via a quench pipe.

Comp ter system(not shown)

This takes the signals romeach point and maps the tissue,creating 2D and 3D models usinga mathematical ormula. StandardMRI orms a static image o abody part. Functional MRI looks

at brain activity. By measuringthe amount o oxygenatedblood owing around the head(the blood oxygenation leveldependent or BOLD response),it ollows brain unctioning. Thisallows researchers to track whichareas are active when peopleper orm a speci c task.


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MEDICAL DEVICES

SMOOTHOPERATOR

eoples dedication totheir work comes outin all kinds o ways.

Today, there are six o sand a camera crammed

into the mechatronics lab atthe Hamlyn Centre, Imperial CollegeLondon. As we chat abo t how some o the machines are sed in the jewellerytrade, engineer and Co-Director o theCentre Pro essor G ang-Zhong Yangslips o his wedding ring and passes itaro nd. It seems his passion orengineering extends even to thesymbolism o love, as he explains thatthe ornate ring has been made with onepiece in three dimensions sing atechniq e called electric discharge

machining. I note this down on agrowing list o things Im learning thisa ternoon.

O r visit here to a department thatdevelops technology to minimise the

physical and psychological impact o s rgery began in m ch the same vein,with my colleag e and me str ck d mbby the labs rapid prototyper. Rapid isright: in ront o o r gaping eyes, itprod ced a lly ormed mechanicalcomponent, three-dimensionally printedin layers j st 16 microns deep. Yo co ldeven scan yo r head and get a model o that printed, one o the projectsengineers tells s.

In the next ofce, a s rgeon talks tos as he assembles an endoscope rom a

large case. In an engineering lab acrosscamp s sits a large plastic box with smallholes in the lid, sed to train s rgeons inkeyhole s rgery. Inside, garish latexorgans wobble omino sly. Its becoming

clear that this is no ordinary engineeringproject.

The project nded by a StrategicTranslation Award made by the Wellcome Tr sts Technology Trans er

division aims to trans orm keyholes rgery. S ch minimally invasivetechniq es have already improved thecare o many patients. Instead o havingto c t open the body to expose theorgans, s rgeons can slide cameras ands rgical instr ments into the body,thro gh tiny incisions, on the end o

exible rods.Led by G ang-Zhong and his

colleag e s rgeon (and ormer healthminister) Pro essor Lord Ara Darzi, theteam o engineers and s rgeons aredeveloping a robotic snake-like devicecalled i-Snake. It will be sel -propelled,able to move thro gh the body to itstarget, where the s rgeon can operate itby remote control. This project is abo t

advancing the c rrent generation o keyhole s rgery into something thatsmore accessible and more exible in thelong term, says G ang-Zhong.

Robots in the operating theatre may so nd like the st o science ction, b t robotic devices are being sed more andmore, promising sa er, more acc rate and even scar- ree s rgery.Chrissie Giles meets a team rom Imperial College Londonworking on i-Snake, a robotically controlled snake that co ldtrans orm s rgery.

TEcHNOlOgy TRANSFER


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Robots in surgeryusing robots in the operating theatre isnot new. At St Marys Hospital we werethe rst gro p in the uK to se robots tohelp s do some s rgical proced res,says Ara. The robotically assistedplat orm was itsel q ite a big step inallowing s to do s rgery m ch moreprecisely, even more than thro gh akeyhole or open approach.

St Marys Hospital, part o ImperialCollege, acq ired in 2001 a da Vincis rgical robot, made by Int itiveS rgical. used originally in cardiacs rgery, the robot was adopted bys rgeons removing the prostate gland a proced re that carries the risk o leaving the patient incontinent and

impotent, with h ge implications ortheir t re q ality o li e.

There are many proposed bene tso the da Vinci, b t there are costs too,explains Mr James Clark, a s rgeon and

PhD st dent on the i-Snake team. Inthe uK, the robot is predominantly sed

or removing the prostate or prostatecancer, altho gh some gro ps areexploring its potential in other eldsincl ding bowel and thyroid s rgery. Itenhances the s rgeons precision, andred ces the chance that vital nerves closeto the operation site will be damaged.For many operations, only speci c partso the proced re req ire s ch precision.

With i-Snake were trying to exploitthis and see i we can develop a devicethat is not only compact b t that can be

sed on an on-demand basis. We arealways looking or new s rgicalapplications that co ld be derived romthis sort o technology.

Keyhole s rgery is not the onlypotential se o i-Snake it may also be

se l in an emerging eld o s rgerycalled nat ral ori ce transl minalendoscopic s rgery (NOTES), in which

s rgeons operate thro gh body ori cess ch as the mo th or vagina. This meansthat no incision is req ired so therewill be no scar (see panel, page 31).

The robotic snake is not j st abo timproved access to distant tiss es, b talso abo t a gmenting the s rgeonsown senses acting as an extension o their eyes and hands. i-Snake stands

or imaging-sensing navigated andkinematically enhanced, says G ang-Zhong. We se imaging and sensing sothat it can view the tiss e its to chingand can see where it is going.

Imaging will be a major bene t o therobot. When removing a t mo r, orexample, clinicians co ld scan the tiss ebe ore s rgery to di erentiate between

cancero s and healthy tiss e. Then,d ring the operation, the tiss e co ld beoverlaid with the scans, to help ens rethat all the cancer is removed and thathealthy tiss e is spared.

Pro essor Guang-Zhong Yang ( ar right) andother members o the i -Snake team.


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30 | We ome NEWS

S rgeons will also be able to sereal-time imaging d ring the operationto see beyond the tiss e theyre workingon. This will help to stop them damagingtiss es, s ch as blood vessels, that theycant see, and will obviate the need orother imaging, s ch as histopathology,to be per ormed be ore the operation.

Taking control Visions o slithering reptiles are p t torest as we are shown a prototype along, thin metal device made o narrow jointed segments connected in a line.The robot is j st over 1 cm wide, andhollow, so that instr ments can be p tinside, emerging rom the tip whenreq ired. The length o the robot will

vary rom 20 cm to two or three timesthis, depending on the type o operationand how the organ is accessed.

Altho gh the word robot impliesa tomation, with this device, the

s rgeon is always in control. It is,essentially, a telemanip lator something that yo control man allyb t that works remotely. Balancing whatthe s rgeon can and cant do with therobot, the so-called h manrobotinter ace, is a major activity or some o the engineers working on the project.

i-Snake consists o manyartic lated parts. Its not efcient tocontrol the joints one by one, so mywork is to design a control scheme orthe operator to manip late those jointssim ltaneo sly, says medical roboticsengineer and PhD st dent Ka-Wai Kwok.His colleag e and ellow PhD st dent Valentina Vitiello adds: We consider thehead o the robot to be controlled by the

s rgeon we dont want to make thewhole thing a tomatic. However, whilethe s rgeon is carrying o t theproced re we need to make s re that therest o the artic lated body is not

ca sing tiss e damage.To do this, the engineers can set a

limited workspace, which means thatcertain body areas are made physicallyo t o bo nds to the snake. Sa ety isalways o r concern, says Ka-Wai.Thanks to advanced medical imagingwe can req ently pdate the allowableworkspace o the s rgical robot insidethe body to provide appropriateg idance to the robot. Were doing morethan making the robot avoid obstacles,were preventing tiss e damage andcontrolling the orce the robot applies tothe tiss e.

A testing environment While some engineering projects can

r n or years be ore the prod ct is testedin a real-li e environment, i-Snakeco ldnt be more di erent. In the threeyears o the project so ar, six di erentiterations o the snake robot have

Be ore coming to this group, I would see a virtual robotmoving on the screen, but to control a real robot using myalgorithms is a whole diferent story. Its very exciting, butchallenging too.

Valentina Vitiello (above le t)

getting into trials earlyin the design process

The collaboration works so well because were able to telleach other where the limitations are. Its easy or an engineerto build a device thats wonder ul, but that when its put intoa real surgical environment has no clinical relevance.

Mr James Clark (le t)

a s rgeons view onworking with engineers

Its really opened my eyes. While all your attention might bedirected to some technical problems, a clinician might cometo you and tell you that some situations will never exist in aclinical scenario.

Ka-Wai Kwok (above right)

an engineers view on workingwith s rgeons


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Summer 2011 | 31

existed, each tested in s rgical trialssing pigs. Each trial sees the team test

the previo s and the new model o robot. The reality is that wereconstantly re ning and improving,says engineer and research assistantDavid Noonan. Well improve theact al robot, the artic lated sections,b t also the so tware, the driverelectronics to control it, the serinter ace. Its almost a completeoverha l o the system each time.

Its also the time that the s rgeonsget to be hands-on with the device, whichcan be nerve-wracking or the engineers.We had one trial where the system wasdamaged by the s rgeon testing it. Itsnot their a lt altho gh we do joke

abo t it with them within the team.The team hopes to complete the

design and engineering in the next 18months, and the next stage is to seek reg latory approval to test the device in

h mans. ultimately, it co ld havem ltiple applications: gastrointestinal,gynaecological and, event ally,cardiothoracic s rgery. B t will s rgeonsadapt to the new technology?

Clinicians are a airly conservativeb nch they dont like change, says Ara.When laparoscopic s rgery rstemerged, people tho ght I was mad. Hetells o several other occasions in hiscareer when new technologies received a

rosty welcome rom some, incl dingthe introd ction o s rgical robots. Hesees i-Snake as the next advance in line,b t is adamant abo t the need toinnovate: I Henry Ford had taken theadvice to invest in a cart, not in a car,wed be in a very di erent place now.

For more on the Hamlyn Centres research, see: www3.imperial.ac.uk/roboticsurgery/research

For a lm on this project, see: www.wellcome.ac.uk/isnake

Taking NOTES

What is it? NOTES (natural ori cetransluminal endoscopic surgery)is an emerging surgical techniquein which surgeons go through anatural ori ce (such as the mouth,rectum or vagina) instead o making an incision on the outsideo the body.

What bene ts does it ofer?No incision means no incision-related complications and novisible scars.

What about the risks? It can be di cult to navigateprecisely to the target organ withcurrent instruments. There is stillan access hole (albeit inside thebody) that needs to be closedsa ely.

Whats happening at St Marys ?There is a clinical trial o NOTESunderway. To date, twogallbladder removals have beencompleted, with access via thevagina.

The best thing that you can actually dois to try and make things that can helppeople. Its obviously very interestingto build a robot that will drive around acorridor, but i its a practicalapplication using the same technologyinside a human, it has potentially muchmore bene t.

David Noonan (above right)

on translationalresearch

The word multidisciplinary is rhetoric some departments use the term toattract money but they dont knowwhat theyre talking about. This projectis very, very diferent.

Pro . Ara Darzi (above)

on m ltidisciplinaryworking

Vitiello V et al. DOF minimization or optimizedshape con ormance under active constraints or ahyper-redundant exible robot. In: P Jannin et al.(eds). In ormation Processing in Computer-AssistedInterventions 2011 (Lecture Notes in Computer Science).Springer: Berlin/Heidelberg; 2011.

Kwok KW et al. Control o articulated snake robotunder dynamic active constraints. Med Image ComputComput Assist Interv 2010;13(pt 3):22936.

Noonan DP et al. Gaze contingent control oran articulated mechatronic laparoscope. IEEEInternational Con erence on Biomedical Robotics andBiomechatronics, Tokyo, Japan. IEEE; 2010.

Shang J. et al. An articulated universal joint basedexible access robot or minimally invasive surgery.

IEEE International Con erence on Robotics andAutomation (accepted).


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32 | We ome NEWS

DIGITISED MANuSCRIPT

ANN FANSHAWESRECIPE BOOK

FROM THE ARcHIVE


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Summer 2011 | 33

Helen Wakely shows s one o the Wellcome Librarys mostmo th-watering treas res.

What is it?Lady Ann Fanshawe compiled this

recipe collection rom 1651, and passed iton to her da ghter Katherine shortlybe ore she died in 1680. The vol me is avast acc m lation o c linary andmedicinal knowledge, and re ectsFanshawes intense interest in testingo t a broad range o recipes, rom icecream to per mes to c res ormelancholy.

Wh is it so spe ia ?Fanshawes vol me is j st one o nearly300 recipe man scripts held in the Wellcome Library, b t hers stands o t asit re ects her time in Spain and Port galas the wi e o Charles IIs ambassador.D ring her travels Fanshawe noteddown several n s al recipes (incl dinginstr ctions on how to dresschocolatte, or make drinkingchocolate). B t her everyday recipes areeq ally interesting, as they shed light on17th-cent ry medical knowledge andthe role o women as ho seholdphysicians.

can ou see it?The man script is kept in a climate-controlled strongroom, b t yo canview it in the Library by ordering itthro gh the Library catalog e. Yo canalso access it digitally (along with 75other recipe man scripts in thecollection) rom the Librarys website.

Want to know more?Then come along to WellcomeCollections Recipes and Remediesevents this a t mn. A series o disc ssions, talks and tasting eventswill explore the c lt ral, economic andscienti c aspects o ood and health overtime, and ncover the s rprisingresonances o 17th-cent ry recipes oro r 21st-cent ry lives.

Find out more at

library.wellcome.ac.uk/recipebooks


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34 | We ome NEWS

usic estivals are places o wonder. They provide a riot o live art,per ormance and play l mayhem

that stim lates the mind, body and

so l. The c rio s and the q irky cometogether to explore this transient world whereeveryone desires to escape the con nes o theireveryday existence and experience something new,captivating and exciting.

It seems nat ral to me that sciencecomm nication wo ld there ore thrive in thiskind o eye-opening space. A ter all, sciencereveals the nimaginable realities o o r niversethat many o s can only wonder at. Since 2007,G erilla Science has bro ght bespoke activities,per ormances and events to nconventionalhabitats or science. Theres always a demand ornovelty and s rprise at m sic estivals, and scienceprovides h ge inspiration or this.

By blending science with art, m sic and play weattract a target a dience o yo ng artsy ad lts withlittle backgro nd in science. Independenteval ation shows aro nd 80 per cent werentexpecting to enco nter science at a estival. Manyremarked that theyd come across o r activities bychance and stayed beca se they looked n. Alls rveyed said they wo ld like to see more. Thein ormal, open-minded and slightly bizarre nat reo o r activities helps them remain meaning l.

JEN WONG, GuERILLA SCIENCE

Music estivals are an ideal place to share science APPLIANCE OF SCIENCE

Aiming to embed science into c lt re, we takeresearchers o t o the lab and into the estivals places that inspire. The niq e opport nities wecreate provide scientists with the chance to engage

with people they might never otherwise comeacross. Eighty- o r per cent o s rveyedparticipants involved in 2010 said they wo ldde nitely take part again. Scientists avo riteaspects incl ded the q estions people asked. This

orced me to think on my eet and p t across a viewo my s bject which challenged some o myass mptions as well, said one scientist. Ana dience member said: I loved the way people gotenth siastic abo t st that they might notnormally think abo t or care abo t.

The interdisciplinary space we work withinalso shows how m ch science needs the arts to beinspired and remain inspiring, and vice versa. O rExperimental Ward within Secret Cinemas OneFlew Over the Cuckoos Nest prod ction introd cedpractising psychiatrists into an abandonedn rsing-home-c m-Oregon State Hospital. Actorsportraying mental health conditions were trainedby psychiatrists, while o r psychos rgical classeswere in ormed by both patient and psychiatricperspectives. Participating psychiatrists and actorsall remarked how val able they had o nd theenco nter. The 1500-strong a dience raved abo tthe event. The o tcome was a richer experience or

all. guerillascience.co.uk

Plus Catch G erilla Science at Glastonb ry in J ne, the Secret Garden Party in J ly and Bestivalin September, commissioned as part o the Wellcome Tr sts Dirt Season.


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Summer 2011 | 35

DIARy

courses, on eren es and workshops Wellcome Tr st Genome Camp s, Hinxton, nlessotherwise speci ed. For more, see www.wellcome.ac.uk/ advancedcourses and www.wellcome.ac.uk/con erences

Epigenomics o Common DiseasesCon erence, 1316 September

Practical Aspects o Biopharmaceutical Drug DiscoveryCo rse, 1924 September

Design and Analysis o Genetic-based Association Studies Workshop, 2630 September

UK Pharmacogenetics and Stratifed Medicine Network Con erence, 28 September

Pharmacogenomics and Personalised Medicine 2011Con erence, 29 September2 October

Next Generation Sequencing Workshop, 210 October 2011

Working with Parasite Database Resources Workshop, 37 October

Working with the Human Genome SequenceCo rse, KEMRIWellcome Tr st Research Programme, Kili ,Kenya, 31 October2 November

Working with Pathogen Genomes Workshop, 2026 November

Genomic Epidemiology o MalariaCo rse, Mahidol university, Bangkok, Thailand,27 November2 December

Functional Genomics and Systems BiologyCon erence, 29 November1 December

Protein Interactions and Networks Workshop, 1117 December

Mathematical Models or In ectious Disease DynamicsCo rse, 1224 Febr ary 2012

We ome co e tion events and exhibitionsE ston Road, London. www.wellcomecollection.org

Wellcome Image Awards 2011Exhibition, ntil 10 J ly

Dirt: The flthy reality o everyday li eExhibition, ntil 31 A g st

Medicine Man and Medicine NowPermanent exhibitions

Event listingsSee website or details

IN YOuR NEXT ISSuEExploring a career in medical engineering, pl s

pdates on o r nding and research activities.

Science Policy in the News (Spin)

Keep p to date with worldwidebiomedical science policythro gh o r ree weeklynewsletter Science Policy inthe News (Spin) .

Sign p to receive Spin straightto yo r inbox and access o r

ree, searchable archive dating

back to 1992. www.wellcome.ac.uk/spin/wn

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h manity, andis the torch

which ill minatesthe world

H u m a n e m

b r y o

. Y o r g o s N i k a s / W e l l c o m e I m a g e s

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TUESDAYSUNDAY (UNTIL 18.00)LATE-NIGHT THURSDAY (UNTIL 22.00)

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