Issue 19 University of Cambridge Research Horizons

University of Cambridge research magazine www.cam.ac.uk/research

Issue 19

HoRIzoNSRESEARCH

In this issue

RISk AND UNCERTAINTYplus expanding the heart and lungs of medicine, alchemical imaginings and the science of art

2 | Guest editorial

Research news 3–5

Spotlight: Risk and 6–19uncertainty

How risky is your breakfast? 6–7

Crash, crisis, calamity: system 8–9shock in a globalised world

Ounce of prevention, 10–11pound of cure

Privacy by design 12

Cybercrime economics 13

The future of flying 14–15

Apocalyptic thinking and 16urban resilience

Original sin and the risk of 17epidemics

Modelling impacts of a 18–19warming world

Preview 20–21

Memory remains 20–21

Features 22–31

Expanding the heart and 22–23lungs of medicine

Body, soul and gold: quests 24–25for perfection in English alchemy

Opening new windows on 26–27the Universe

How the brain is made 28–29

Science illuminating art 30

Research online 31

The back page 32

None of us know what is going to happen in the future, either to ourselves or to society. Yetwe still have to make decisions, whether it’s a personal dilemma (should I cut down mydrinking?) or a political choice (should there be a minimum alcohol price?). Making importantdecisions in the face of uncertainty is unsettling and difficult, and so is a vital area ofacademic research.

The articles in this issue represent just a fraction of the relevant activity going on inCambridge, and an appropriately wide range of disciplines and approaches. From cybercrimeto earthquakes, influenza to air travel, the topics reflect issues that are of crucial importance.It is an extraordinarily diverse area, although many informal interactions are increasinglyfocused on the Centre for Risk Studies, in the Cambridge Judge Business School, and theCentre for Risk in the Built Environment, in the Department of Architecture. The inclusion inthis issue of discussion of the National Risk Register by John Tesh, the Cabinet Office officialresponsible for the Register and Policy Fellow at the Cambridge Centre for Science and Policy(CSaP), also reflects the growing role of CSaP in promoting engagement between policyprofessionals, business leaders and experts in the sciences and engineering.

But what do we mean by risk and uncertainty? A common distinction is as follows. If wefeel we understand what is going on, and have some confidence in our assessment of thechances of different futures, then we can say we are dealing with risks, and can hope toproduce a numerically balanced judgement. When we have the humility to acknowledge thatwe cannot put numbers on everything, then we are dealing with deeper uncertainty, and mayinstead aim for resilience to surprises. Much of the research described here is attempting toextend the domain that can be adequately quantified.

Finally, there has been a traditional division between risk assessment (what are the risks?)and risk management (what should we do about them?). This issue of Research Horizons,however, shows that this is not so straightforward – how we analyse threats is closelyconnected to what we might be able to do about them. Academics need to be grounded inthe real world in order to know both what is important and what is feasible, and the followingexamples display just such engaged research.

Professor David SpiegelhalterWinton Professor for the Public Understanding of Riskunderstandinguncertainty.org

Editor: Dr Louise WalshDesign: Cambridge Design StudioPrinters: Falcon PrintingContributors: Sarah Collins, Jacqueline Garget,Tom Kirk, Fred Lewsey, Louise Walsh; and others as identified©2012 University of Cambridge andContributors as identified. All rights reserved

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Photography:Rob Hultkrantz(www.flickr.com/photos/esko/3233223222)

Contents Issue 19, October 2012

Research news | 3

Wellcome Trust and MedicalResearch Council invest inworld-class Stem Cell Institute

The Wellcome Trust/Medical ResearchCouncil (MRC) Cambridge Stem Cell Institutewill advance our understanding of stem cellsand their potential to treat a range of life-threatening conditions that currently have noeffective cures.

Building on existing investment by theMRC and the Wellcome Trust, the Institutewill unite 30 leading research teams withexpertise across the three main types of stemcells: embryonic, adult and inducedpluripotent cells (body cells that have beentreated to behave like embryonic stem cells).

Research scientists will work alongsidetechnology specialists and doctors todevelop new therapeutic approachesunderpinned by a strong base offundamental stem cell biology. Located inCambridge, the Institute is near the largestcluster of biotechnology companies inEurope, allowing unrivalled opportunities forindustry collaboration.

Stem cells can renew themselves almostindefinitely and can develop into any of thecell types in the body. They are an invaluabletool for scientists studying the mechanismsof human disease and could be used as analternative to animal models bypharmaceutical companies developing newdrugs. They also show great promise aspotential treatments for devastatingconditions such as liver disease, diabetes,blindness, spinal cord injury and

neurodegenerative disorders like Parkinson’sdisease.

“The Wellcome Trust/MRC CambridgeStem Cell Institute will be an invigoratingenvironment for cross-fertilisation betweenfundamental and translational researchers,”explained Professor Austin Smith, Director ofthe new Institute. “Our aim is to close theknowledge gap and drive stem cell researchforward towards clinical applications. Theworld-class facilities will attract the bestinternational talent from the fields of stemcell biology and regenerative medicine topursue this goal.”

“This joint funding initiative from theWellcome Trust and MRC gives us theopportunity to link Cambridge’s greatstrengths in stem cell biology with ourstrengths in translational clinical research,and thus to give new insights into diseasemechanisms – and ultimately to develop newtherapies,” added Professor Sir Patrick Sissons,Regius Professor of Physic. “In associationwith the initiative, we all look forward to thefuture co-location of stem cell biology andmedicine in the new building planned for theCambridge Biomedical Campus.”

It is intended that the Institute willeventually be housed in a purpose-built8,000 m2 facility to be constructed on theCambridge Biomedical Research Campus.

For more information, please visitwww.stemcells.cam.ac.uk

Two of the Uk’s largest funders of medical research are to invest£8 million in a new world-leading centre for stem cell biology andmedicine.

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Oligodendrocytes (red) derived from human embryonic stem cells

Increasing amounts of researchmaterial are now being produced,collected and stored in digital form,and scholars across all disciplines havebecome not only the creators but alsothe consumers, curators and archivistsof their own digital assets. For the pastnine months, PrePARe, a projectmanaged by the University Library’sdigital repository team and funded byJISC, has been exploring how researchstaff and students at the University ofCambridge are dealing with thesechanging roles.

Having interviewed researchersacross the University to identify theirattitudes, experiences and needsrelating to digital management andpreservation issues, the team foundthat although scholars wanted toprotect their digital legacy, a lack ofeither guidance or time often meantthat digital preservation was treatedas a low priority.

Now, aiming to advise on goodpractice and to raise awareness ofdigital preservation generally, theteam has responded by deliveringsimple guidance centred around four key signposts: ‘Store it safely’,‘Explain it’, ‘Share it’ and ‘Start early’. New online resources have beencreated, training modules are beingintegrated into the University’sgraduate training provision, and across-disciplinary seminar series hasbeen organised.

“Managing data well ensuresresearch integrity and replication,provides opportunities for researchersto discover and share information, and increases the longevity ofresearch,” said Grant Young, theLibrary’s Digital Preservation Manager.“The PrePARe project aims to provideresearchers with the guidance theyneed to ensure that their digitalresearch material can have a lastingimpact.”

For more information, please contactBarbara Bültmann, PrePARe ProjectManager ([email protected]) or visitwww.lib.cam.ac.uk/dataman

UniversityLibrary projecthelps preservedigital legaciesNew resources have beenlaunched to help academicssuccessfully manage andpreserve their digital materialfor the future.

When institutionalised care for the mentallydisabled was phased out under MargaretThatcher in 1983, and the responsibility forcare shifted principally to family members,the policy was considered to be one of thebiggest political changes in the history ofmental healthcare. But the approach to carewas really coming full circle.

Mental illness and disability were familyproblems for English people living between1660 and 1800. While mental illness was asubject of morbid fascination to the English

public, and queues formed to see incarceratedwomen, the reality was more mundane. Mostwomen and men who were afflicted by mentalillness were not institutionalised in asylumsand instead were cared for by other familymembers.

Now a new study by Cambridge historianDr Elizabeth Foyster will reveal the impact onfamilies of caring for mentally ill and disabledrelatives.

Much has been written about the insanethemselves but few studies have considered

mental illness from the perspective of thecarers. The lifetime burden of caring for thoseindividuals whose mental development didnot progress beyond childhood has been littleexplored. Foyster’s research, which has beenfunded by the Leverhulme Trust, will unpickthe emotional and economic consequencesfor families at a time when the Poor Lawbound them to look after their mentally ill anddisabled family members.

By asking key questions about the impactof ‘care in the community’ in the 18th century,Foyster hopes that her research will bridgesocial and medical history. Specifically, sheaims to provide an historical perspective tocontemporary debates such as how resourcescan be stretched to provide for children withlearning difficulties and an ageing population.

“The stresses and strains of family life wereexacerbated by high infant mortality and lowlife expectancy, and many individuals werepushed towards mental breakdown,” sheexplained. “Moreover, inherited conditions,senility and what today would be described as‘special needs’ could put great emotionaldemands on family members who hadprimary responsibility for their sick or disabledrelatives.”

“The family must have seemed aninescapable feature of daily life between 1660and 1800. Although there were those whowere abandoned and rejected, for themajority, insanity and mental disability wasaccommodated within the family unit. I aim toget to the heart of what this really meant forpeople’s lives.”

For more information, please contact Dr Elizabeth Foyster ([email protected]).

4 | Research news

Risk test for breast cancer

Breast cancer affects one in nine women inthe UK, and one in eight in the UnitedStates. It’s by far the most common cancerdiagnosed in women, with approximatelyone million new diagnoses made eachyear.

A woman’s risk of developing breastcancer is determined by both her genes andher lifestyle. Mutations in some genes, suchas BRCA1 and BRCA2, greatly increase awoman’s risk of developing breast cancer;however, women with mutations in eitheror both of these two genes represent fewerthan 10% of breast cancer cases. Mostwomen who develop breast cancer havelittle or no family history of the disease.

BREVAGen is a simple two-part test thatcan help determine a woman’s five-year andlifetime risk of developing non-familialbreast cancer, and was developed based onresearch carried out by the University of

Cambridge, Cancer Research UK andcollaborators worldwide.

In the largest study of breast cancergenetics ever conducted, researcherscollected and analysed the DNA of morethan 50,000 women in order to completethe first full-genome scan of the disease in2007. The study, led by Professor Sir BrucePonder and Professor Doug Easton,identified breast cancer susceptibilitymarkers that are present in approximately20% of cases in the UK.

Cambridge Enterprise and CancerResearch Technology licensed the markersin 2009 with the aim of using them todevelop and commercialise a diagnostictest, and the BREVAGen test was launchedby the Australian company GeneticTechnologies Limited in 2011.

The BREVAGen test helps to identifywomen at increased risk so that their

A test based on research conducted in Cambridge effectively measures a woman’s risk for developingcertain forms of breast cancer.

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health can be more positively managed(such as through increased surveillance,risk reduction or chemoprevention).Approximately 30% of women are reclassified into a different risk group afterBREVAGen testing.

The BREVAGen test is commerciallyavailable in regions throughout the UnitedStates and Australasia, and plans are inplace to launch it in Europe in the nearfuture.

Meanwhile, further research mainlyled by Cambridge has identified morethan 25 susceptibility markers for breastcancer. Use of these markers, togetherwith other risk factors, should improvepredictive tests even further.

For more information, please contact Dr Iain Thomas([email protected]) at Cambridge Enterprise.

Care in the community A new study will investigate the emotional and economicconsequences of what care in the community meant to 18th-centuryfamilies.

‘Madness’, James McArdell,after Robert Edge Pine 1760

Whether it’s setting the agenda on renewableenergy, cutting cybercrime or determiningalcohol pricing policy, governments facechallenges that require measured approachesbased on rigorous analysis of the evidence.Now, a new Master’s in Public Policy (MPP)being launched by Cambridge’s Department ofPolitics and International Studies aims toencourage long-term thinking and betterstrategic planning among policy professionals.

The course, which will take its first studentsin October 2013, draws on teaching fromacross the University, as well as fromprofessionals in the policy world, to provide athorough grounding in practical andtheoretical aspects of policy making.

Director of the MPP, David Howarth, aReader in the Department of Land Economyand a former Member of Parliament, explainedhow the course aims to help policy making:“It’s important to make sure that enoughpeople in the political system respect evidenceand rational argument. Policy makers can’t beexperts in all areas but we aim to equip themwith the broad range of skills needed tounderstand the types of evidence there is andthe questions to ask.”

During the one year course, students learnabout the nature of evidence through a seriesof substantive case studies. They will alsoparticipate in simulations and experience firsthand how complex messages are negotiatedand communicated under intense pressure.Such skills are essential to equip policy makerswith the tools to promote urgently needednew thinking on national, European and globalchallenges.

A further aspect of the course, explainedHowarth, is to encourage policy-relatedresearch across the University: “The Master’s isthe first major output of the Cambridge PublicPolicy (CPP) initiative, which has been set up topromote and support public policy researchand teaching at the University. The courseprovides a focus to build capacity at theUniversity to respond to opportunities inpolicy research and analysis.”

The CPP initiative and development of theMaster’s were made possible by generoussupport from The Constitution Society.Sponsorship opportunities are available tosupport dedicated scholarships, as Dr MirandaGomperts, one of the key organisers of theProgramme, explained: “We hope to attractstudents from a broad range of areas and it’sessential that we can attract the very bestirrespective of their financial circumstances.”

For more information, please visitwww.cpp.csap.cam.ac.uk/mpp

Mastering publicpolicyA new Master’s Programme inPublic Policy will equip policymakers with the tools to makeeffective and informed decisions.

A recently launched database will help researchers seek out andaccess high-value equipment across five universities.

Share and share alike

In today’s climate of cutbacks and austeritymeasures, opportunities to increaseefficiency and reduce costs are sought after.With this in mind, a new resource launchedby the University of Cambridge aims toimprove research management by makinggreater use of existing equipment andfacilities, and by sharing these betweenuniversities wherever possible.

The online Research Facilities andEquipment Database will help academicsaccess information about facilities,equipment and research services across theUniversity. As the database expands,researchers will be able to look for, and use,equipment across five partner universities inthe project – Cambridge, Imperial College,University College London, and theUniversities of Oxford and Southampton.

The initiative is part of a drive by theResearch Councils UK to increase theeffectiveness of equipment use. Universitiesare now required to check with other peerinstitutions to see if there is an opportunityto share equipment before submitting grantapplications. The database will facilitate thisprocess and help researchers make a strongercase for new research facilities andequipment in grant applications.

Led by Cambridge’s Research Office andfunded by the Engineering and PhysicalSciences Research Council, the project hasalready amassed information on over 300high-value research facilities. Importantly, thedatabase neither monitors nor controlsaccess to these facilities and equipment, asaccess remains at the equipment owner’sdiscretion, but it does provide an indicationof their current usage levels, ranging from‘very low’ to ‘fully utilised’.

Professor Lynn Gladden, the Pro-Vice-Chancellor for Research said: ‘The EquipmentProject has been an excellent example ofresearch-intensive southern universitiesworking together to pool resources at a timeof significant funding constraints. Sharingresearch equipment is not a simple matter,nor is it always feasible and it certainlyrequires trust between the differentresearchers involved. Yet, allowing othersaccess to equipment has, in the past, helpedto strengthen burgeoning researchcollaborations and, occasionally, even led toserendipitous collaborative research findings.With budgetary constraints likely to continue,tools such as these are invaluable if we are tosupport our world-class researchers and helpthem to accomplish their intellectualendeavours with the best resources available.”

For more information, please visitwww.equipment.admin.cam.ac.uk

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Confocal laser scanning microscopy of a locustbrain

6 | Risk and uncertainty

Understanding how the numbersadd up in relation to risk can helpus deal with our own uncertainty,as David Spiegelhalter, WintonProfessor for the PublicUnderstanding of Risk, explains.

How risky is your breakfast?

Like it or not, risks get communicated tous every day. Whether it’s the climate,the euro crisis or the booze, someone

is warning us to change our ways or we maybe in trouble. We may get irritated by all thisfinger-wagging, but there is a seriousscience that can be applied to all thesemessages.

Let’s assume we want to communicatesome risk. Are we trying to inform people orpersuade them to do something? Thetraditional view is that these were much thesame thing: the public are ‘irrational’ becausethey are ill-informed, and so if we justeducate people then they will not holdmisguided beliefs and do silly things.

Fortunately this ‘deficit model’ has beensuperseded by a slightly more sophisticatedview, which recognises that people varyconsiderably, and that their reactions andbehaviour are not going to be primarilyinfluenced by the information they receive.Their ‘affect’ – that is the overall positive ornegative feeling of individuals towards apotential hazard – is vital, and this isinfluenced by context, culture and habit.These feelings can be tricky to change, andthe simple provision of information can haveminimal influence. In contrast, the advice of a trusted source can be crucial.

This may appear rather discouraging,but we have an ethical duty to providetransparent information so that people can,if they wish, weigh up the pros and cons, settheir own risk threshold and decide what todo. This is the mind-set underlying theWinton Programme for the PublicUnderstanding of Risk; our team tries toexplain risk and debunk myths by engagingthe public through stories, creatingattractive graphics and entertaininganimations, and explaining the ideas behindthe numbers.

So what are ethical and transparentrepresentations? First, we need to recognisethat there will always be an emotionalaspect to the communication, whether it’sthe images used or even the colours.Advertisers exploit this all the time. Second,more philosophically, I would argue thatthere is no ‘true risk’ in the sense that thesechances and values actually exist as part ofthe outside world – they are constructed onthe basis of our judgement and knowledge.This means we have to use metaphor andnarrative to communicate.

Let’s assume that we are willing to putnumbers on the chances. For example, arecent newspaper story reported a 20%increased risk of developing pancreaticcancer per 50 g of processed meat eaten perday. Such relative risk formats have beenshown in controlled trials to exaggerate themagnitude of effects, and so instead it isrecommended (and even mandated by

the Association of the BritishPharmaceuticalIndustry) thatabsolute risksare used. Thelifetime risk ofdevelopingpancreaticcancer is 1 in80; however, ifwe look at thisrisk in terms ofhow manypeople out of400 might beexpected to

develop pancreaticcancer after a daily

healthy breakfast (five)compared with a bacon

sandwich (six), thedifference doesn’t look very

impressive (see far right).

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Risk and uncertainty | 7

Professor David Spiegelhalter For more information, please contact Professor Spiegelhalter([email protected]), or visitthe Winton Programme for the Public Understanding of Risk(understandinguncertainty.org).

The making of a National Risk Register Why does Britain need a National Risk Register (NRR)? To understand what the risksare and how to improve resilience, explains John Tesh, the Cabinet Office officialresponsible for the NRR and Fellow of Cambridge’s Centre for Science and Policy.

This is not a particularly disaster-prone country when compared with other countries.After the Cold War, the British approach to what seemed like a rather modest risklandscape emphasised improvisation. Until, that is, the 2000 and 2001 emergencies –foot and mouth disease, fuel strike, flooding – and the aftermath of the 9/11 attacks,which suggested that ‘muddling through’ would no longer do. The government had toshow that it understood what the risks were and how best to organise to improveresilience.

Which is why, since 2004, British governments have based planning for domesticemergencies on a national risk assessment that ranks the risks according to likelihoodand impact. First published in 2008, the NRR was updated in 2010 and 2012. Riskmanagement approaches are increasingly being used to plan for events – for theolympic Games as an example – and for national security in general.

A risk management strategy provides the best approach to making informeddecisions on the necessary investments in resilience. It enables us to avoid attemptingto predict future shocks in an inherently unpredictable risk landscape. Risks can beprioritised, and the highest risks identified – currently, pandemics, coastal flooding,mass killings by terrorists and gas-rich volcanic eruptions – to enable specialprogrammes of mitigation to reduce vulnerabilities to such risks by preventing,preparing for, responding to and recovering from them.

In a time of unprecedented resource constraint, it is essential to be able to prioritiseplanning to make sure that help goes where it can do the most good. Identifying andplanning for the common consequences of risks, irrespective of source, also helpsprevent wasteful duplication and can aid business continuity and recovery.

If having clear objectives has been the secret to effective risk managementstrategy in the past few years, the key for the future will be a balanced collaborationbetween science and policy. This was the main finding of the House of CommonsSelect Committee for Science and Technology in its work on the use of science foremergency planning and crisis management. We are taking this seriously: the nationalrisk assessment process includes reinforced mechanisms for independent cross-disciplinary scientific advice.

University of Cambridge scientists are already working on some of the risks thatpose the greatest challenge for risk assessment, where particular uncertainties attachto calculations of probability or impact or both… and where significant investment inresilience of national infrastructure and public safety hangs in part on getting theanswer right, or at least good enough for government work.

For a longer version of this article, please visit www.cam.ac.uk/research

I have been collaborating with Dr Mike Aitkenin the Department of ExperimentalPsychology on the Big Risk Test run by BBCLab UK, in which over 60,000 participantshave taken part in an online randomised trialof different formats and images. The insightsgained are being used to help design revisedpatient information leaflets and websites fora cancer screening programme in the UK.

But in many situations there is deeperuncertainty, and we are rightly not so happyto give concrete numbers to risks. TheNational Risk Register (see panel) gives wideintervals for the chances of various disastersoccurring, while the Intergovernmental Panelon Climate Change and other organisationshave developed measures of ‘confidence’

or star ratings for their risk analyses. The UK government officially encourages theacknowledgement of such scientificuncertainty, but can we retain trust if we are so open?

Fortunately there are signs that these issues are being taken seriously, with the House of Commons SelectCommittee for Science and Technologyrecently recommending a RiskCommunication Strategy Group acrossgovernment. But a problem is that this area cuts across many academic boundaries,and there is little focused infrastructure in the UK. Risk communication is a topic thatdeserves investment in research and training.

“I would argue that there is no ‘true risk’ in the sense that thesechances and values actually exist as part of the outside world –they are constructed on the basis of our judgement andknowledge.”

Approximate number of people developingpancreatic cancer in their lifetime out of 400people whose daily breakfast is either healthy(top) or a bacon sandwich (bottom)


Threats that cause supply chains and other networks to break down cancascade through today’s interconnected world of social, economic andfinancial interaction. New research is redefining this global risk to helpbusinesses and governments build resilience.

Crash, crisis, calamity: systemshock in a globalised world

Many of us will never have heard ofPA-12. But when an explosion in afactory in Germany on 31 March

2012 halved its global source, this little-known component of car fuel lines gainednotoriety by threatening production in theautomotive industry. It’s a scenario that hadalready been played out twice in thepreceding year when specialised automotiveparts became scarce following the Tohokuearthquake and tsunami in Japan, andfollowing a factory fire in the USA.

The tale of PA-12 demonstrates thefragility of global supply chains but is notaltogether a surprise. Businesses understandthe risks inherent in globalised supply chainsthat might be affected by naturalcatastrophes, geopolitical conflicts, diseaseoutbreaks, trade disputes and so on. Butwhat might be less obvious is howinterconnected are the networks ofrelationships of trade, business and macro-economics, and how quickly the effects of acatastrophe can cascade.

“It used to be the case that catastropheson the other side of the world had littleeconomic impact on the UK,” explained

Dr Andrew Coburn, researcher in the Centrefor Risk Studies at Cambridge JudgeBusiness School, “but in today’sinterconnected world, few countries areisolated from the knock-on effects ofcatastrophes, whether it’s a freeze in Europe,piracy around the Horn of Africa or apandemic in Asia.”

Coburn is also Senior Vice President atRisk Management Solutions (RMS), theleading provider of catastrophe risk modelsto the insurance industry. By modelling riskto extreme events, he has provided researchinputs into government policy on disastermitigation and terrorism risk managementpolicy. Now, a research programme that heleads at the University of Cambridge aims toprovide new understanding of howsocioeconomic risks (or ‘system shock’) cannot only damage supply chains but alsodisrupt the networks that keep our livesgoing.

The programme, which is funded byDeloitte, the Institute of Catastrophe RiskManagement at Singapore’s NanyangTechnological University and RMS, has takenthe ambitious step of combining

catastrophe science with systems analysis.It’s a challenging but high-gain move, asCoburn explained: “This is a very new area.Catastrophe science is a multi-billion dollarindustry that’s been around for a fewdecades, but putting it together withnetwork analysis has not been done before.We are having to start with the nuts andbolts and develop a new methodology.”

Part of this methodology, developed incollaboration with Nanyang TechnologicalUniversity, has been to derive a list ofthreats. Working with colleagues atCambridge’s Centre for Financial History, theresearchers have taken a remarkably longhistorical perspective, as Research AssociateDr Gary Bowman explained: “Analysingevents from only the recent past can paintquite a misleading picture. We’re taking a1,000-year perspective that allows us to bemuch more rigorous in terms of assessingthe frequency of events and the resultingeffect. In fact some of the best examples ofthreats such as asset crashes can be found inthe 17th and 18th centuries – in theAmsterdam Tulip bubble and the South Seabubble for instance.”

Global supply chains like thosethat underpin car manufacturingcan be affected by threats suchas natural catastrophes,conflicts, disease outbreaks andtrade disputes

The result is a systematic taxonomy ofsocioeconomic threats that could conceivablythreaten human and financial capital,damage assets and disrupt the systems thatsupport our society, at either a national or aninternational level.

With the help of a peer review processinvolving risk professionals, academics andcorporate advisory groups, the researchershave captured 12 broad types (broken downinto 47 subclasses) of the most significantthreats that could interrupt a major region’snormal life patterns, wipe more than 1% of acountry’s GDP, or, where applicable, kill morethan 1,000 people or cause a loss of assets orinfrastructure amounting to $10 billion.

Over time, the Centre for Risk Studiesplans to expand their research website(systemshock.org.uk) to provide state-of-knowledge illustrative scenarios for each ofthe 47 subclasses of threat; already five are inpreparation. The scenarios are objective,transparent, evidence-based, useful inbusiness decisions and available to the riskmanagement community.

“For piracy, for instance, we are reviewingall of the instances of piracy in the Horn ofAfrica and factoring in the cost to shipping,”explained Bowman. “We’ll then ask at whatpoint does the threat become so significantthat the system starts to adapt – shippinglanes change or a military presence protectscommerce in the region.”

In parallel, for each scenario, ProfessorDanny Ralph is coordinating research onwhat system shock means for the automotive,pharmaceutical and electronic industries,each of which has a highly interconnectedglobal network: “Where we think we can addvalue is to take what businesses understandwell – their markets, components andcontractors – and set alongside it a higherlevel framework of system shock.”

The System Shock project is part of theCambridge Risk Framework research projectat the Centre for Risk Studies, a multi-disciplinary centre for the study of societaland economic risks. “We believe the Centrehas a unique opportunity for studying globalrisk strategies and their impacts to businesses

and governments,” added Michelle Tuveson,the Centre’s Founder and Executive Director.“Although often perceived narrowly, we view‘risk’ as a broad topic. It has far-reachingimplications particularly to culture,governance and decision making.”

Ralph, like his colleagues, admits thatmuch work on System Shock lies ahead: “It’slike looking at an Encyclopaedia Britannicathat’s been written but hasn’t beenassembled. At the least, this task will helpthese industries visualise, categorise anddiscuss their broader risks. But the greatestchallenge of all will be to reach the stagewhen businesses and governments can plugin real-world data to help them quantify andmake decisions about future investments orcurrent configurations of supply chains.”

The researchers are also interested in howthe management of risk relates to nationalsystems: how the nation’s food or fuel supplynetworks function and how they can be moreresilient to threat. “None of us has a crystalball and all of us are going to be subject tocontinued pressures. There is no magic wand.But if you think about the risks andopportunities an organisation or a countryfaces, you have to take a holistic viewbecause your network is integrated inobvious and less obvious ways with othernetworks,” said Ralph.

Simon Ruffle, Director of TechnologyResearch in the Centre, has begun the task ofbuilding the computer infrastructure that willstore the taxonomy, illustrative scenarios anddata. “Part of this will involve electroniccollaboration with databases around theworld that can provide historical and up-to-date information on global air routes, sealanes, communications, environmentalchanges and so on,” he explained.

“Can this project redefine how we thinkabout risk globally?” asked Coburn. “We hopeso – we think that considering risk as anetwork problem is the way forward. To thinkabout it as a threat issue is misleading. Youhave to understand all of the complexconnections to be able to really understandrisk.”


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Left to right, Simon Ruffle, Dr Andrew Coburn, Dr GaryBowman, Professor DannyRalph, Michelle TuvesonFor more information, please contact Professor Ralph([email protected]) at the Centrefor Risk Studies at Judge BusinessSchool or visit systemshock.org.uk

Recent shocks to the system Although the taxonomy of threats developed by the research project has taken a1,000-year look back through history, an example of many of the types of threatshas happened in recent years:

• Political violence: Arab Spring 2011• Natural catastrophe: earthquake and tsunami, Tohoku, Japan 2011• Technological catastrophe: nuclear meltdown, Fukushima Daiichi, Japan 2011• Geopolitical conflict: civil war, Libya 2011• Humanitarian crisis: Horn of Africa drought 2011• Climatic crisis: heatwave, USA 2011• Financial shock: Greek sovereign debt crisis 2010• Environmental catastrophe: BP oil Spill Deepwater Horizon 2010• Trade dispute: US tax on Chinese tyres 2009 reciprocated by Chinese tax on US

chicken imports• Disease outbreak: swine flu pandemic 2009

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“This is a very new area.Catastrophe science is a multi-billion dollar industry that’s beenaround for a few decades, butputting it together with networkanalysis has not been donebefore.”


Benjamin Franklin famously advisedfire-threatened Philadelphians in1736 that “An ounce of prevention is

worth a pound of cure.” Clearly, preventingfires is better than fighting them, but towhat extent can we protect ourselves fromnatural disasters? Hazards such asearthquakes, tsunamis, floods, hurricanesand volcanic eruptions are not in themselvespreventable, but some of their devastatingeffects could be reduced through forwardplanning.

“It’s important to be able to recoverresiliently from disasters and, as part of this,it’s vital to identify the vulnerabilities ofcommunities living in hazard-prone regions,” explained Michael Ramage fromthe Centre for Risk in the Built Environment(CURBE). By putting resources into resilience and building back better,communities can reduce the risk ofdisastrous consequences should a similar event reoccur.”

Now, thanks to an information system that Cambridge researchers developedoriginally for tracking how regions recoverfrom disasters, communities could soonhave the means to understand how best toprotect themselves from futurecatastrophes.

The story begins in Haiti, where CURBEresearcher Daniel Brown has been workingover the past year with the British Red Crossand the United Nations following the

devastating earthquake in 2010, which killed316,000, displaced 1.3 million and destroyedalmost 100,000 houses. In a country that wasdeeply impoverished before the earthquake, people continue to live under tarpaulinsexposed to safety and security risks, withlimited access to water, livelihoods and keyservices.

Brown travelled to the country to field-test a system that he and colleagues atCambridge Architectural Research (CAR) andImageCat had developed during theprevious four years as a mapping techniquefor tracking post-disaster recovery.

With funding from the Engineering andPhysical Sciences Research Council (EPSRC),Brown had identified a suite of 12‘performance indicators’ spanning corerecovery sectors extracted from high-resolution satellite imagery. He used these tomap the recovery process in Ban Nam Khem,Thailand, after the 2004 Indian Oceantsunami, and Muzaffarabad, Pakistan, afterthe 2005 Kashmir earthquake, by looking ataspects such as the movement ofpopulations, the construction of dwellings,the accessibility of roads, and the loss andrebuilding of livelihoods.

In Thailand and Pakistan, the system had already proved to be extremely useful.Brown’s work provided data and results that assisted decision making and had thepotential to ensure the recovery process was both transparent and accountable.

In Haiti, the EPSRC-funded follow-onproject aimed to fine-tune the performanceindicators within operational situations tosuit the workflow of aid agencies.

What Brown found, however, was that inthe complex and dynamic situation thatfollows a disaster, agencies desperatelyneeded a real-time system to help themdecide where to put resources. “Many of thehundreds of maps produced within the firstweek of the Haiti earthquake were soon outof date because of the changeability of thesituation,” he explained. “There was also amassive duplication of effort, with agenciesoften lacking trained staff to ensure the rightinformation about buildings and people wasacquired at the right time.”

Dr Stephen Platt, Chairman of CAR, whohas also been working on the project,described how these findings confirmed theresults of a survey the team had previouslycarried out: “Agencies told us that they lackcoordinated mapping information on wheredisplaced populations have gone and wherethey have begun to return to, as well asdamage to livelihoods, and rehabilitation ofhomes and infrastructure. It’s very hard forthem to decide where to put funds to thebest effect for positive and resilient change.”

Brown’s first task was a remote analysisof the affected area from his office inCambridge, using pre-disaster satelliteimagery together with a new techniquebased on high-resolution oblique aerial

Working with humanitarianorganisations in Haiti,Cambridge researchers havefound that an informationsystem they designed to trackhow regions recovered fromdisasters can also be used tosupport preparedness, planningand project management.

Ounce ofprevention,pound of cure


photographs that capture views of thefaçade of buildings, and Lidar, whichmeasures building height. On his arrival inHaiti, he identified which of the performanceindicators was relevant for planning andused these to gather field information on the state of buildings, the socioeconomicimpact on people, the safest places torebuild and the community’s views. All datawere integrated into a single database to aid the design of a rebuilding programme.

“We were delighted to find that theinformation system can be used for allphases of the disaster cycle, frompreparedness through to damageassessment, then planning and finallyrecovery monitoring. You could think of eachphase comprising a single module in thedatabase. All these phases are effectivelyinterrelated with each other – data producedduring one phase can be used in anotherphase. So when we collected damage data,these could be used as a baseline to informplanning, and so on,” explained Brown.

Ramage, Principal Investigator for thefollow-on project, added: “You can see how a system that can be used to predictwhere future vulnerabilities might be in acommunity is so important. And, throughSteve’s work in New Zealand, Chile and Italy, we have learnt more about howgovernments and agencies in developedcountries are currently responding todisasters, which has allowed us to learn

more about how our system and ideas might be adapted for different contexts.”

Echoing this, Dr Emily So, Director ofCURBE, explained how the project fitted into what’s been called the disastermanagement cycle: “Governments andagencies think in terms of mitigation,preparedness, response and recovery. What we are trying to do in our research –which builds on 25 years of work in this area in the Department of Architectureunder the leadership of Professor RobinSpence – is to make sure that we not only do reactive groundwork after the disasterbut also proactive work, to mitigate andprepare ahead of the event and reduce the risk of disaster.”

The team has recently been awardedfunding for a two-year project involvingeight global institutions with the remit ofusing satellite remote sensing to understand risk and vulnerabilities incommunities around the world, under theEuropean Commission’s Seventh Framework Programme.

“The hazard itself is not what creates the disaster,” added So. “It’s thequality of the housing and the social fabric.This is where CURBE can help in terms ofassessing exposure and proposing methods of evaluating it. Better informationmeans better ideas, means betterprotection.”

“Better information means betterideas, means better protection.”

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Top: Dr Emily So, Dr StephenPlatt; bottom: MichaelRamage, Daniel Brown For more information, please contactDr So ([email protected]), Director ofthe Centre for Risk in the BuiltEnvironment, which is aninterdisciplinary research centreinvolving the Departments ofArchitecture, Engineering,Geography, and Public Health andPrimary Care.

Earthquakes without frontiers Just as better rebuilding is important for mitigating repeat natural disasters, sotoo is understanding the threat posed by unanticipated earthquakes – now thefocus of a new study led by the University of Cambridge.

A new five-year study is to target a neglected area of earthquake research – the 10 million km2 of the Alpine–Himalayan belt stretching from Italy, Greece and Turkey,across the Middle East, Iran and central Asia, to China. Earthquakes in continentalinteriors such as these lead to significantly more deaths than those on the better-studied plate boundaries because they often take place on unknown faults.

The £3.5 million ‘Earthquakes without frontiers’ project will not only pinpointfaults in the Earth’s crust but will also understand the vulnerabilities of communitiesat risk and communicate this knowledge to policy makers. Led by Professor JamesJackson from Cambridge’s Department of Earth Sciences, the study involves physicaland social scientists from six Uk universities and four institutes and organisations,together with collaborators in some of the most earthquake-prone regions of theworld.

An important feature of the work, which is funded by the Natural EnvironmentResearch Council and the Economic and Social Research Council, is to buildmultinational collaborations that span entire regions and connect scientists workingin affected areas with a larger international community of scientists.

For a longer version of this article, please visitwww.cam.ac.uk/research/news/earthquakes-without-frontiers

Aftermath of the 7.0-magnitude earthquake thatstruck Haiti in January 2010

online services that store our personalinformation have proliferated, yet thetechnology to underpin how our

privacy is safeguarded has lagged behind.This was the conclusion of a 2008 report bythe UK’s Information Commissioner’s Office, abody set up to uphold privacy for individuals,which pressed for “the evolution of a newapproach to the management of personalinformation that ingrains privacy principlesinto every part of every system in everyorganisation.”

This ethos underpins research led byProfessor Jon Crowcroft, the MarconiProfessor of Communications Systems in theComputer Laboratory. Two projects he leadsaim to minimise privacy risks, and at the heartof both is the concept of ‘privacy by design’.

“Privacy by design means that it’s in-builtas part of the technology, rather than boltedon in order to comply with data protectionlaws,” he explained. “With privacy by design, itwould simply not be possible for incidentssuch as the leaking of LinkedIn passwords tohappen.”

One project is tackling the challenge ofhow to maintain privacy when all your dataare stored by a central service – the so-calledcloud. Anyone who stores images on flickr, oraccesses emails from a central server, is cloudcomputing, and today many businesses areturning to centralised data centres as aneconomic means of storing their information.However, concerns have also been raisedabout the scale of control that cloud serviceproviders wield over the data they store andcan potentially monitor.

Crowcroft and colleague Dr AnilMadhavapeddy are building technologies tosupport the control of networked personaldata as part of a five-year £12 million researchhub (‘Horizon’), which is led by the Universityof Nottingham and funded by theEngineering and Physical Sciences ResearchCouncil (EPSRC). The research is driven by theoverarching concept of a lifelong contextualfootprint – the idea that each of usthroughout our lifetime will lay down a digitaltrail that captures our patterns of interactionwith digital services – and how best toprotect this.

A second project, FRESNEL (for ‘FederatedSecure Sensor Network Laboratory’), isfocusing on privacy in networks that peopleuse to modify their heating, lighting andhome entertainment when they are not athome, as well as networks that monitor trafficflow and air quality, and enable a doctor inhospital to check a patient’s health at home.

“Current technologies have usually beendevised for single-owner sensor networks

that are deployed and managed by a centralcontrolling entity, usually a company that hasset themselves up to offer this capability,” hesaid. “They don’t have the right scalability andsecurity required to deal with a secure multi-purpose federated sensor network, runningdifferent applications in parallel. Our aim is tobuild a network framework with multipleapplications sharing the same resources.”

With funding from EPSRC, Crowcroft andDr Cecilia Mascolo and colleagues, workingwith Dr Ian Brown at the University of Oxfordand industrial project partners, now have ademonstrator program in operation that iscurrently being evaluated through a large-scale federation of sensor networks across the University of Cambridge.

The aim of these projects, explainedCrowcroft, is not to lock up personal data,removing the ability to socialise it, but ratherto support systems that process data withoutsacrificing privacy: “We are buildingtechnologies to support lifelong control ofnetworked personal data. For instance, asignificant driver behind social networkinghas been the ecosystem of data processorsthat aggregate and provide services such asrecommendations, location searches ormessaging. But the big drawback is that usershave to divulge more of their personal data toa third party than is necessary, because of thedifficulty of distinguishing what is needed.Our research starts from a single premise –that individuals require control over access to, and use of, their personal data for ever.”


New research aims to ensure that we can exploit the full benefits ofthe digital world and still protect our online privacy.

Privacy by design

Left to right, Professor JonCrowcroft, Dr Cecilia Mascolo,Dr Anil Madhavapeddy For more information, please contact Professor Crowcroft([email protected]) at theComputer Laboratory(www.cl.cam.ac.uk).

Crowcroft and colleagues have launched a not-for-profit foundation, Digital Life Foundation(http://dlfn.org), which will build an open-sourcecommunity around these technologies.


In the ‘good old days’ of cybercrime, onlinemisdemeanours were mostly the work ofteenage hackers or small-scale crooks

with a card-coding machine. Now, however,PIN numbers are harvested in industrialquantities, and criminal networks of‘phishermen’, ‘botnet herders’ and writers ofmalicious software are costing societybillions of dollars every year.

Online crime is a sophisticated andefficient business, involving tax and creditcard fraud, fake antivirus, unlicensed Viagraand ‘stranded traveller’ scams. ‘Phishing’emails may appear to be from your bank butare designed to steal your identity. ‘Botnetherders’ take over your computer as one ofmany ‘bots’ and use it to send out email spam.

The police and courts are struggling to catch up, as Professor Ross Andersonexplained: “Thus far, the world has not coped well with the rapid growth andindustrialisation of online wickedness. Banksoften hide fraud losses, or even blame theircustomers for fraud, and they hesitate toshare information with other banks. Policeagencies have little idea how to deal withindustrial-scale globalised petty crime.”

His team of researchers work on high-tech computer security mechanisms and alsostudy how and why internet security fails. In2008, they reported to the EuropeanCommission on how governments can pushback on cybercrime, identifying an increasein consumer protection as key to the process.

However, most governments still don’tunderstand the true costs of cybercrime:“Hard statistics on losses from online crimeare hard to come by in most countries. Butwithout them, other figures – vulnerabilitiesin computer systems, number of botnets orsize of spam flows – lack a groundedconnection to the real economy,” saidAnderson, who is Professor of SecurityEngineering in the Computer Laboratory.

A recent study by Anderson, Dr RichardClayton and colleagues completed the firstsystematic measure of the cost of cybercrimefor the UK and the world. It found that fraudwithin the welfare and tax systems –increasingly performed in the ‘cyber’ world –cost each citizen a few hundred pounds ayear on average, and fraud associated withpayment cards and online banking cost just a few tens of pounds a year. However, thefear of fraud by businesses and consumers is leading some to avoid online transactions,giving an indirect cost to the economy that is several times higher. By contrast, purecybercrimes – the new scams thatcompletely depend on the internet –

are costing citizens an average of only a fewtens of pence per year.

Another interesting and unexpectedfinding concerned the ratio of direct costs(the money stolen) to indirect costs (themoney spent on preventing crime, and oncompensating victims or prosecutingperpetrators afterwards). In traditional fraudslike tax and welfare fiddles, the direct costsare much larger than the indirect ones; withpure cybercrimes, the indirect costs are muchlarger; and with card fraud, they’re aboutequal. These differences, explained Anderson,reflect the maturity of our technicalcountermeasures, the incentives for fraudprevention and the social norms that alsopush back on crime.

Overall, the team of researchers fromGermany, the Netherlands, USA and UK foundthat although cybercriminals are pulling in afew tens of pounds from every citizen peryear, the indirect costs to those citizens, eitherin protective measures such as antivirus or incleaning up infected PCs, are at least tentimes as much.

They conclude that we should spend lesson defence and more on policing, asAnderson explained: “The number ofphishing websites, distinct attackers anddifferent types of malware is consistently overreported, leading some police forces tobelieve that the problem is too large to tackle.In fact, a small number of gangs lie behindmany incidents and a police response againstthem would be far more effective than tellingthe public to fit an anti-phishing toolbar orpurchase antivirus software. Cybercrooksimpose disproportionate costs on society andyet we are extremely inefficient at fightingcybercrime.”

As the internet becomes biggerand more complex, so do theopportunities for cybercrime.Where should resources bedirected to combat the risk?

Cybercrimeeconomics

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Dr Richard Clayton (left) andProfessor Ross Anderson For more information, please contact Professor Anderson([email protected]) at theComputer Laboratory(www.cl.cam.ac.uk).


Air traffic across Europe is likely todouble by 2020 according to currentforecasts. This estimated increase

represents a remarkable number of flightswhen you consider that last year in the UKalone almost 2.2 million flights carrying 200million passengers were handled by theNational Air Traffic Services.

It also represents a massive challenge forUK aviation policy, which is faced withairports operating at near full capacity suchas Heathrow – the busiest in the UK and oneof the busiest in the world. Increased airtraffic, rising fuel prices and tight security allcombine to increase the vulnerability tosystem-wide breakdowns, delayed flights,long queues and rising costs.

Efforts to reduce pressure onoverstretched airport facilities are beingaided by research projects involvingUniversity of Cambridge engineers workingwith industrial and academic partners. Eachproject is aimed at tackling some of theuncertainties associated with air traffic, andthe risks these pose to heavily loadedairports, wherein even a short delay findinga wheelchair for a passenger with reducedmobility can affect the tight workings of theairport.

Database in the skyOne limiting factor in dealing with a vastlyincreased air traffic density is the workloadfalling on air traffic management (ATM).“Some of the technologies assisting ATMdate from the 1950s,” explained Professor JanMaciejowski, who led the University ofCambridge component of a recentlycompleted pan-European study, iFly. “We’vebeen looking at how we can modernise andautomate ATM to improve safety at the sametime as reducing workload, costs andenvironmental impact.”

The project, funded by the EuropeanCommission and coordinated by the NationalAerospace Laboratory in the Netherlands,brought together 17 partners from academiaand aerospace industries across Europe. Theirmission was to develop an advancedairborne flight information system so thatprocesses normally carried out on theground by air traffic controllers can becarried out mid-flight by multiple aircraftrequiring the same airspace.

“Essentially the idea is for the aircraft touse onboard computers to predict futurepositions of other aircraft and to dynamicallyshare information,” explained Maciejowski,who worked on the project with PhD student

Ellie Siva and colleagues at the Swiss FederalInstitute of Technology Zürich and theNational Technical University of Athens. “Thecomputers communicate with each other,negotiating how best to use the airspacewith least cost in terms of fuel and time,while respecting the priorities of otheraircraft and the comfort of passengers, and ofcourse maintaining safe separation fromeach other.”

The automated system enables differentaircraft to solve complex mathematicaloptimisation problems between them – eachone solving the problem for itself and thenpassing on its current solution and intentionsto the next aircraft, which then responds, andso on. In a simulation of about 1,000 flights,the researchers found that this cooperativeactivity results in only a very small extradistance being flown (less than 1%) peraircraft.

Ultimately, the hope is that if such asystem came into operation, it wouldaccommodate a three-to-six fold increase incurrent en-route traffic levels and be part of aSystem Wide Information Management‘database in the sky’ proposed across Europe.

At the heart of the project is thediscipline of control engineering. A recent

Aircraft that work together tosolve complicated mathematicalproblems and airports with moreflexibly used runways could bethe future of flying, according tostudies by University ofCambridge engineers and theirindustrial and academic partners.

The futureof flying

programme grant awarded to the Universityof Cambridge and Imperial College London bythe Engineering and Physical SciencesResearch Council has assembled a team topush the boundaries of control engineering inrelation to power systems and transportation.As part of the programme, Maciejowski islooking at another aspect of air traffic control– the terminal manoeuvring area between theairport and 10,000 feet up.

Here, a very different scenario is inoperation: many aircraft in a small spacerequire coordination to land using the leastamount of fuel, a situation too complicated tosolve by aircraft communicating with eachother. Maciejowski and colleague Dr AlisonEele are creating a new mathematical systemto optimise the landing trajectories of eachplane. Their formulae use thousands ofprocessors, now economically available asgraphical processor units, to combine locationmeasurements by radar, work out the flightplan for landing, give instructions and thenrecalculate every few seconds.

Although both projects are a long wayfrom implementation – they would first needto go through rigorous safety checks incollaboration with airlines and authorities –Maciejowski explained that each has now

reached a proof-of-concept stage and initialtalks have begun: “I’ve been delighted by howpositively airport operators have reactedalready. It’s a sign of the times – airports arerunning at capacity and it’s becoming a matterof urgency to look at how systems can beimproved.”

Flexible workingMeanwhile, the focus of Professor DuncanMcFarlane’s research is what happens on theground. Working with Alan Thorne and othercolleagues at the University’s Institute forManufacturing (IfM), the team is involved intrials conducted by BAA at Heathrow Airporton measures to increase punctuality, reducedelays and strengthen resilience at the UK’shub airport. The trials are centred on makingthe best use of the airport’s two runways,which are in heavy demand.

In the first phase of the OperationalFreedoms trial, which was completed inFebruary 2012, Heathrow explored how itsrunways and airspace can be better used torecover quickly following airport disruption,such as that caused by bad weather. Onestrategy was to use both runways for eitherarrivals or for departures, instead of one foreach. Initial results indicated improvements inpunctuality, reduced emissions and fewerplanes having to taxi across runways. A secondphase is now ongoing until March 2013 tocarry out a more-detailed analysis.

“The Civil Aviation Authority is overseeingthe tests. Our role has been to independentlyaudit the trial and ensure its objectives aremet,” explained McFarlane. “We measureeverything to do with the impact of changeson the performance of the airport, from howlong the aircraft are in overhead ‘circulationstacks’, to take-off delays, to emissions andnoise, and then we generate what we think areappropriate recommendations.”

A further study has also just started, thistime examining the order of aircraft landing onrunways. “A big aircraft creates a huge airturbulence behind it and small aircraft have towait proportionally longer before landing,” saidMcFarlane. “Flexible use of runways couldmean landing larger aircraft on one andsmaller on another, or ordering planes inoverhead circulation stacks into optimallanding sequences. Using runways effectivelycould go a long way towards helping airportoperations recover quickly and efficiently fromunwanted variability.”

The current studies build on a majoraerospace programme at the IfM driven by theend users of the research – the aircraftmanufacturers, airlines and airports. Forinstance, the researchers have previouslyexamined how radio-frequency identification(RFID) technology and better data sharing in

airports can reduce costs and achieve greaterbusiness efficiencies.

Many of the delays in airports occur as aresult of bottlenecks in the sequence ofactivities that take place when an aircraft is at agate between flights. Referred to as theturnaround process, the operation involves thecoordination of activities such as baggagehandling, refuelling, maintenance tasks andpassenger transfer. Because the companiescarrying out these tasks don’t always shareinformation, a breakdown somewhere alongthe line can cause a system-wide snarl-up.

Tiny electronic RFID tags can be used toprovide visibility for different assets used inairport operations, such as bags, baggagecontainers and catering trolleys, which canthen be fed back to computers used by thedifferent service teams on the ground,allowing them to recognise and shareproblems quickly.

Working with airlines such as Easyjet andFlyBe, and Manchester, Luton and HeathrowAirports, the researchers looked at whatcauses delays and whether better informationusage can improve aircraft turnaround time.“For example, one cause of aircraft delay canbe the unavailability of a wheelchair to take apassenger to a flight. Something as simple asa strategy for locating and ensuringwheelchairs are in the right place at the righttime can make a considerable difference toguarding against delays,” explainedMcFarlane. “What our aerospace programmeis trying to do is quantify the risk anduncertainty associated with differentdisruptions, and then redesign and pilotrobust practices that will eliminateunexpected delays or increased costs.”


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Professor Duncan McFarlane(left) and Professor JanMaciejowskiFor more information, please contact Professor Maciejowski([email protected]) at theDepartment of Engineering(www.eng.cam.ac.uk) and ProfessorMcFarlane ([email protected]) atthe IfM (www.ifm.eng.cam.ac.uk).

“I’ve been delighted by how positively airport operators have reactedalready. It’s a sign of the times – airports are running at capacity andit’s becoming a matter of urgency to look at how systems can beimproved.”

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Apocalyptic thinking andurban resilienceThrough analysis of human resilience, particularly in cities,Professor Ash Amin believes that state guarantees of welfare andinfrastructure will prove vital for our future – a view that is counterto much of the West’s current policy emphasis on the responsibilityof the ‘individual’ in a turbulent age.

Professor Ash Amin For more information, please contact Professor Amin([email protected]) at theDepartment of Geography(www.geog.cam.ac.uk).

As global boundaries continue tocrumble in the face of technologicaladvance, the proliferation of possible

threats has become overwhelming. Theeffects of climate change, rogue behaviour,financial swings and pandemics will amplifyand take unexpected courses in this century’scomplex and interdependent world.

Ash Amin, the 1931 Professor ofGeography, believes that this uncertainty hasfostered a new rhetoric of risk management,describing a future where we must become‘resilient’ individuals. We are told that we canno longer expect to rely on our governments;we need to be vigilant and ‘prepared’ourselves.

“This kind of shift is accompanied by areturn to fatalist or apocalyptic thinking –public narratives of an out-of-control future,”said Amin, author of the recently publishedbook Land of Strangers (2012), whichexamines the challenges of living withdifference in Western multicultural societiesthat perceive the future as uncertain andturbulent. “In the late 20th century, there wasa conviction that science and calculationcombined with central planning allowed forfuture preparations.”

“Now, in the West, you have a public thatis more informed but more sceptical, isolatedand paranoid, and fed by a hyperactive media.The result is a potentially destructive mixtureof mistrust, resignation and expectancy.”

Every step taken by states to developnew vaccines, secure borders and so on isaccompanied by public campaigns thatdeliberately dampen expectations of theireffectiveness. We are constantly made awarethat comprehensive security no longerapplies.

“Innate in a new culture of riskmanagement by resilience is a cataloguingof risk-bearing subjects, so thatmanagement of our unknown future can begiven tangible shape – vigilance againstnamed subjects,” he explained.

“Catastrophism in a post-9/11 world hasquickly turned towards vilification ofparticular humans – such as asylum seekers,the Occupy movement, Muslims, angryyouth. It’s part of an active pathology of riskmanagement, often hiding bureaucraticbewilderment in the face of escalatingglobal risks.”

Such a shift in the calculus of control –from institutions to individuals, fromprotectionism to preparedness – hasimportant urban implications. The Planet’svast metropolises continue to swell aspopulation increases, with millionsmigrating to the cities to find work in aneconomically precarious world. By 2030, atleast 70% of the global population will beliving in urban environments, with up to 2 billion dwelling in slums.

“I am an urbanist – I study cities – andurban resilience is central to our collectivefutures,” said Amin. “To speak of citizensubjectivity – the ‘resilient’ individual – in thecontext of those living in abject poverty isabsurd. We need a return to language ofprotection, so that the poor are given someof the basic infrastructure to deal with risk.”

“In the West especially, we still live in asociety where people expect protection tobe provided by someone else – but thatrequires resources.”

Amin uses Sweden as an example of astate that invests heavily in riskmanagement, so that in the event of a

catastrophe there is sufficient slack in thesystem of emergency services and welfareprovision, allowing rapid recovery. But thisrequires a different form of social contract, inwhich acceptance of higher taxes meansthat the public have a right to expectprotection by the state.

For Amin, scaling back the state whenpreparing for a turbulent future seemsdangerous. While individuals need to bevigilant, he warns against scapegoatingparticular subjects for the risks we face. “Inthe end, the capabilities of everyone willneed to be harnessed in a responsible anddemocratic way to meet the myriad risks ofthe future. We can’t leap into the dark withboth guns loaded – shooting wildly ateverything and anything – and hope tocome out on top.”

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Original sinand the riskof epidemicsMathematicians are helping tobuild a better picture of howpopulations develop immunityto flu and which groups are most at risk of getting – andtransmitting – infection each year.

Adam Kucharski andDr Julia Gog For more information, please contactDr Gog ([email protected]) at theDepartment of Applied Mathematicsand Theoretical Physics(www.damtp.cam.ac.uk).

The adage ‘what doesn’t kill you makesyou stronger’ may ring true for certaininfectious diseases – those where

repeated exposure to the pathogenprogressively builds population immunity –but not for influenza. When scientistsinvestigated age-specific immunity toinfluenza strains after the 2009 swine flupandemic, a curious pattern emerged.Antibodies against seasonal flu appear topeak in school-age children, drop in middleage and rise again in the over 65s.

Now mathematicians in Cambridge havedeveloped a model that explains this little-understood pattern, and in so-doing arehelping to build a better picture of how flumight be controlled. At the heart of theirmodel is the concept of ‘original antigenicsin’, a phenomenon first identified in the1960s by American epidemiologist ThomasFrancis that describes how the body’simmune system, in effect, takes short cuts.

Rather than generating a specificantibody response every time a newpathogen is encountered, the immunesystem may instead reproduce a previousresponse to something similar (the ‘originalantigenic sin’) it has seen before. What this

means for immunity is that it’s not just theinfections we’ve had in the past but theorder in which we’ve had them that could beimportant for how protected we are againsta disease.

Dr Julia Gog and PhD student AdamKucharski at the Department of AppliedMathematics and Theoretical Physics believethat the strikingly characteristic profile ofimmunity to influenza can be explained inthese terms, and they’ve built amathematical model to test it.

Understanding how immunity developsin a population is crucial for developing arobust public health defence, especially for a pathogen like pandemic influenza, whichthe UK government’s latest National RiskRegister has listed as the most likely risk tohave the highest impact in the next fiveyears.

Yet, modelling the dynamics of influenza on population immunity is nostraightforward exercise, as Gog explained:“The evolving nature of the virus –necessitating an annual race to identify anappropriate vaccine – means that individualscan be exposed to many different strainsover a lifetime. And for every new strain thatappears, the number of possible infectionhistories a person could have had doubles.To build a model, mathematicians need tokeep track of millions, if not billions, ofpossible combinations of infections.”

According to Gog and Kucharski’s model,the trick is to reconstruct the combinationsof past exposures from the probabilities ofhaving seen each particular strain. There is acatch, however. Individuals who have beenexposed to one particular strain are morelikely to have been exposed to other strains;this is because individuals who havepreviously been exposed are more likely tobe old than young. The model thereforehandles each age group separately:individuals who are the same age will havelived through the same series of epidemics,which means that past exposures will beindependent.

Their model has enabled them to explainthe distinctive pattern of age-specific immunityfor flu. Immunity increases initially, peaking inschool-age children, then decreases as previousexposures prevent new antibodies being made.Only when the strain evolves ‘out of reach’ of theoriginal antigenic sin are new antibodiesgenerated in later middle age. In the elderly,complete freedom from original antigenic sin,along with vaccination programmes, leads toanother increase in immunity.

But what does this mean for disease controland identifying risk? “There could be gaps inimmunity because less-effective immuneresponses are being generated as a result oforiginal antigenic sin,” explained Kucharski.“Over time, certain age groups may develop‘blind spots’ in their antibody profile. We arebuilding ‘gap maps’ to understand how oftenthis happens. Moreover, the view that severeepidemics only arise when the virus has evolvedsignificantly may be oversimplified. They couldalso arise if there are individuals whose immuneresponse is ineffective because of originalantigenic sin, which would explain whyunassuming flu strains occasionally cause largeoutbreaks.”


How different will the world be if it’s2°C, 3°C or 4°C warmer? Ask thisquestion of the multitude of

different climate change impact models –each built by researchers interested indifferent aspects of global warming – andthe likelihood is that you will get a multitudeof answers. Modelling the global impact ofclimate change is an extremely complexprocess, and yet it’s absolutely essential ifpolicy makers are to understand theconsequences tomorrow of emissionspolicies adopted today.

Earlier this year, an international groupof researchers initiated a joint project toattempt the first systematic quantification ofsome of the uncertainties surroundingclimate change impacts to agriculture,health, biomes and water. Uncertainties suchas: to what extent will the world’s vegetationchange? Which regions will succumb todrought or flood? What will be the impact onglobal food crops? And how will the spreadof human diseases be affected?

The Inter-Sectoral Impact ModelIntercomparison Project (ISI-MIP),coordinated by the Potsdam Institute forClimate Impact Research in Germany andthe International Institute for Applied

Systems Analysis in Austria, involves two-dozen research groups from eight countries. Dr Andrew Friend from Cambridge’sDepartment of Geography is coordinatingthe analysis of results concerning changes tothe world’s biomes – the communities ofplants, animals and soil organisms that arecharacterised by a similar structure andclimatic requirement.

It’s a fast-track programme. All of theteams are working to a tight deadline and,by January 2013, they hope to be ready topublish their findings on the likely impactsof climate change predictions. The collectiveresults will contribute towards the nextreport of the Intergovernmental Panel onClimate Change (IPCC), the leadinginternational body that provides a clearscientific view on the current state ofknowledge in climate change and itspotential environmental and socioeconomicimpacts.

Each group is using their own model,together with the very latest climatepredictions produced by leading climatemodelling groups around the world, to runcomparable simulations for four differentwarming scenarios – conservative, drasticand two in between – from 1950 to 2099.

For Friend, this means Hybrid, the modelhe first developed 15 years ago. At its heartis a set of equations that dynamically modelglobal vegetation: “It works by simulatingthe dynamics of individual trees and anunderlying herbaceous layer. You assumethe plants compete within patches, and thenscale these up to 50-km grid boxes. We usedata to work out the mathematics of howthe plant grows – how it photosynthesises,takes-up carbon and nitrogen, competeswith other plants, and is affected by soilnutrients and water – and we do this fordifferent vegetation types. Effectively, thewhole of the land surface is understood in2,500 km2 portions. We then input realclimate data up to the present and look atwhat might happen every 30 minutes to2099.”

For the most extreme scenario of climatechange being modelled, Friend expects tosee significant impact: “this scenario couldshow the whole of the Amazon rainforestdisappearing this century, depending on theclimate model. The circumpolar Borealforest, which began to emerge at the end ofthe last ice age, could migrate into thetundra and perish at its southern limit. Bycontrast, Russia may benefit from an

A community-driven modellingeffort aims to quantify one of thegravest of global uncertainties:the impact of global warming onthe world’s food, health,vegetation and water.

An initial ISI-MIP simulation, showing the effect onvegetation productivity at the highest emissionsscenario; strong reductions in productivity arepredicted in the Amazon region, as well as in manysemi-arid regions, whereas production increasesglobally by about 30%, mainly as a result of CO2boosting photosynthesis

Modelling impacts of awarming world

Change in Net Primary Productivity (gC m-2 yr-1)

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increased ability to grow crops in regions thatwere previously too cold, and this greaterproductivity would help absorb atmosphericcarbon.”

Modelling impacts is complex, as Friendexplained: “the increase in CO2 in theatmosphere from the burning of fossil fuelscreates global warming. CO2 can act onvegetation, increasing their rate ofphotosynthesis and therefore productivity.However, in heatwaves, ecosystems can emitmore CO2 than they absorb from theatmosphere. We saw this in the 2003European heatwave when temperatures rose6°C above mean temperatures and theamount of CO2 produced was sufficient toreverse the effect of four years of netecosystem carbon sequestration.”

One of the greatest uncertainties inclimate change is the feedback from changesin terrestrial carbon cycling. “Many scientiststhink that if soil warms it will release carbonbecause of the increased breakdown of deadorganic matter by bacteria and fungi,” addedFriend. “But there’s a lot of debate overwhether this stimulation will be sustainedover a long time – if it is, then you end upreleasing enormous amounts of CO2 into the

atmosphere, causing further global warming.”

Working with PhD student RozennKeribin, Friend is using Darwin, theUniversity’s High Performance ComputingService’s supercomputer, to run thesimulations; what takes a month to performon a PC can be easily accomplished overnighton Darwin.

As the results of each group’s simulationsbecome available over the coming months,the data will be assembled and compared.Friend fully expects that this process willreveal differences: “each equivalent modelhas its own strengths and weaknesses. That’swhy the comparison process is so valuable –no single model is sufficient but together wecan reduce the uncertainty.”

Why is this so important? “To make policyyou need to understand the impact ofdecisions,” said Friend. “There hasn’t been acoordinated impacts project for IPCC acrosssectors before, and now this is covering fourkey sectors across four climate changescenarios from multiple climate models. Theidea is to understand at what point theincrease in global temperature starts to haveserious effects across all the sectors, so that

policy makers can weigh up the probableimpacts of allowing emissions to go above acertain level, and what mitigation strategiesare necessary to avoid significant risk ofdangerous climate change.”

Dr Andrew Friend For more information, please contact Dr Friend([email protected]) at the Department of Geography(www.geog.cam.ac.uk).

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Climate chemistry and the tropicsJust as global vegetation can be affected by a warming climate, the other side ofthe coin is true: changes in land use in the tropics could have unplanned side-effects on the Earth’s atmosphere.

A team of atmospheric chemists at the Department of Chemistry are developing newmodels to predict how changes in land use in the tropics could affect future climate,air quality and crop production through their impact on ozone levels.

High in the stratosphere, ozone filters sunlight and protects us from thedamaging effects of ultraviolet light. At ground level, however, it causes respiratoryproblems and damages crops. This ground-level ozone is formed by the reaction ofsunlight on greenhouse gases emitted by cars, power stations and industrialprocesses. But it’s also formed when volatile organic solvents (VoCs) emitted fromplants react with nitrogen oxides (Nox).

“It’s a complicated mechanism,” explained Professor John Pyle, who leads theresearch. “In pristine conditions, such as in the tropical rainforests, VoCs can reduceozone levels. However, in the presence of Nox, VoCs can increase ozone levels.”

Research carried out in collaboration with Lancaster University demonstratedthat the conversion of rainforest to oil palm plantations in Borneo substantiallyincreased the local concentrations of VoCs and Nox. Modelling the effect on ozone,the researchers predicted that if Nox levels rise in the region as a result ofindustrialisation to the levels typical of North America and Europe, then ozone levelswould exceed levels known to be harmful to human health and crop production.


“Each model has its ownstrengths and weaknesses. That’swhy the comparison process is sovaluable – no single model issufficient but together we canreduce the uncertainty.”

The research leading to these results has receivedfunding from the European Community’s SeventhFramework Programme (FP7 2007-2013) undergrant agreement No. 238366.

20 | Preview

As the generation that witnessed thetwin horrors of the Holocaust andWorld War II slips away, some have

begun to fear that the devastating lessons ofour recent history may grow faint with itspassing. In the case of the Holocaust inparticular, however, the level ofremembrance seems remarkably high, as aprofusion of memorials, museums, annualcommemoration events and the mandatorystudy of the ‘Shoah’ on national curriculaaround the world attest.

It is difficult to believe that this was notalways the case. At the end of World War II,what we now call the Holocaust was far from amatter of general discussion. Attention wasfocused on Allied victory and the building of apost-war world. What had happened in thecamps was subsumed into that generalnarrative. The Italian Auschwitz survivor PrimoLevi, later wrote: “At that time, people hadother things to get on with: building houses,looking for jobs… People didn’t want to hear[about the camps], they wanted other things.”

Levi is a recurring figure in RobertGordon’s new book, The Holocaust in ItalianCulture, 1944–2010, which explores howItalians have handled the memory of theHolocaust, but also the war, which intersectswith it in unpredictable ways. Both are

intertwined aspects of a global humantragedy, but in Italy this takes on particularlycomplex and troubling dimensions, becauseit was a former Fascist state and Nazicollaborator.

Researchers like Gordon have come tounderstand that the Holocaust was not thesubject of sudden public concern at the war’send. Instead, most countries handled thecataclysm with an initial stance that almostresembles disregard. This was followed by aperiod of rediscovery in the 1950s and 1960s,and then growing awareness that peaked inthe 1990s. Now, the Shoah is a general aspectof world history, perhaps the defining eventof the 20th century, to some extentdecoupled from the local contexts in which itwas acted out.

Each country, however, also has its ownstory to tell and its own paths to memory.Surprisingly, how post-war Italy confronted,or at times failed to confront, its participationin the genocide has never been addressed bya major study. Gordon, a specialist in Italianculture, argues that by mapping culturaloutput about the Holocaust we can see howthe nation’s response to the catastropheshifted over time. Through it, we see not justItaly’s take on its Fascist past, but itsengagement with the anti-Fascist Resistance,

As the birthplace of Fascism –and both ally and victim ofNazi Germany – Italy presentsa particularly complex casestudy of how countries cameto terms with the catastrophicevents of the Holocaust afterthe war. Robert Gordon’s newbook charts the cultural faultlines that emerged as it slowlylearned to acknowledge itspart in the tragedy.

Memoryremains

A square in Rome’s Jewish ghetto area, nowrenamed as a memorial to the deportation ofRome’s Jews in 1943

Cold War politics, the Church, Europe,immigration and multiculturalism.

“Encounters with the Holocaust canchange the way we perceive ourselves,”Gordon said. “In the 1960s, an Italianschoolchild might have read Anne Frank orPrimo Levi. From the 1990s, class trips toconcentration camps became common. Manychildren never forget this first contact, andeven if they don’t study it further, it comes todefine their understanding of history, of theircountry and their identity.”

Italy has made a significant culturalcontribution to making the Holocaust aubiquitous presence in our culture. Bestknown are the works of Levi, and the Oscar-winning 1997 film by Roberto Benigni, Life isBeautiful. Beyond these, however, lies a richseam of less familiar first-hand accounts, worksof fiction, poetry and drama, films anddocumentaries, television programmes, art,music, and architecture, museums, galleriesand cultural events.

However, as in other nations, social andcultural recognition of what had happenedstarted slowly in Italy. At the end of World WarII, floods of people returned and the Jews weretreated as part of a more general category of‘The Fallen’ or the survivors, rather than as aspecial case.

The dominant local narrative stressed thatthe deportation of Jews had happened underthe Germans, after the Italian governmentcapitulated in 1943, and was a policy resistedby Italians themselves. “In 1945, the countrywanted to be seen as a victim,” Gordon said. “Itwanted to get into the UN. The myth waspropagated that the average Italian on thestreet had not wanted Fascism, had deepdown been a decent person and was notreally racist.” Jews themselves, returning fromthe camps, saw little social value in exposingthe crimes of their neighbours. They, too,wanted to rebuild.

The step-change came at the end of the1950s, with the emergence of new first-handaccounts, such as those of Edith Bruck andEmilio Jani, historical reassessments by thelikes of Renzo de Felice, and films such asCarlo Lizzani’s The Gold of Rome (1961). Amidglobal reawakening about the Holocaust,triggered by the trial and execution of Adolf Eichmann, a new sense of responsibilityto consider what had happened, and –eventually, Italy’s part in the process –began to gain momentum.

As the space between the terrible eventsof the Holocaust and the present expanded,more people felt able to cope with personalaccounts from the camps. Levi’s If This is a Manhad sold few copies when first published in1947, but in 1958 a new edition boosted hisreputation, which was then cemented by TheTruce (1963). Such personal accounts,however, proved that the Holocaust could notbe seen purely as a Nazi crime. The notion ofItalian involvement was slowly gainingacceptance.

In the 1980s, a new generation ofhistorians who believed that Italy was nottelling enough of the truth about its wartimeexperience changed the picture again.Researchers began to reveal a network ofFascist concentration camps that had existedin southern Italy but had been largelyforgotten. What followed was an outpouringof engagement with the Holocaust, boostedfurther by the fall of the Soviet Union, whichenabled visits to sites such as Auschwitz.

Filmmakers, artists, architects andintellectuals had contributed to each of thesewaves of attention. They included authorssuch as Giorgio Bassani and Natalia Ginzburg,and directors such as Vittorio De Sica, LinaWertmuller and Francesco Rosi. Many weredetermined to show specifically Italianaspects of the Holocaust, often in advance ofwider acceptance of Italian involvement. In1997, Benigni released Life is Beautiful andRosi a film version of The Truce. “Theconjunction of these films, both in their wayfocused on the specifics of an Italian inflexionto the history and experience of theHolocaust, is of cardinal importance inreading the cultural sensitivities of themoment,” Gordon writes.

The crescendo built towards the firstofficial Holocaust Memorial Day in Italy, its‘Day of Memory’ in 2001, which Gordon calls“the high-water mark of the entry of the

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Professor Robert Gordon For more information, pleasecontact Professor Gordon([email protected]) at theDepartment of Italian(www.mml.cam.ac.uk/italian).

The Holocaust in Italian Culture, 1944–2010, byProfessor Robert Gordon, is published by

Stanford University Press

Holocaust into national public life in Italy.”The event certainly showed how far thecountry had come in its acknowledgement ofthe Shoah, explicitly recognising thepersecution of its own Jewish citizens andtheir deportation, as well as participating inan international commemoration.

Yet ambiguities still remained. The label‘Day of Memory’ was deliberately neutral,and the date chosen, January 27th, wasdeliberately that of the anniversary of theliberation of Auschwitz – a date ofinternational importance, certainly, but not specific to Italy.

In the 21st century, for the generationafter Life is Beautiful and Schindler’s List, theHolocaust is part of a shared, global history.At the same time, its local history stillpresents problems. Italy’s part inperpetrating the tragedy is now a matter ofwidespread recognition and culturalreflection. But even now, the same nationoccasionally struggles to place this awkwardand terrible chapter within its sharednational story.

“Encounters with the Holocaustcan change the way we perceiveourselves.”

Diseases of the heart and lung aresome of the biggest killers worldwide.According to the latest figures from

the World Health Organization, cardiovasculardisease causes an estimated 17 million deathsper year, with respiratory disease ranking justbehind with 4.2 million deaths. Despite agrowing awareness of risk factors, such assmoking and poor diet, the prevalence ofsuch diseases is increasing.

Cardiorespiratory research has seensignificant growth in Cambridge over the past15 years. The University now has five BritishHeart Foundation (BHF) professorships andthree Chairs in respiratory medicine.Fundraising is under way to expand yetfurther, with the creation of a new Heart andLung Research Institute (HLRI) by theUniversity and Papworth Hospital, to sitalongside the new Papworth Hospital whichis anticipated to relocate to the CambridgeBiomedical Campus.

“The growth trajectory incardiorespiratory research here has beenpretty phenomenal,” explained ProfessorMartin Bennett, who holds the BHF Chair ofCardiovascular Sciences. “The ambition forthe HLRI is to put two excellent partnerstogether synergistically, achieve a criticalmass of clinical and basic scientists who havea single focus on cardiorespiratory disease,and create something truly world leading.”

“The HLRI will provide a virtuous cycle ofdiscovery,” added Professor of RespiratoryMedicine, Edwin Chilvers. “By bringingtogether researchers of different disciplines –basic, clinical, population science – and

adding a specialist R&D unit, you can coverevery step in the chain from fundamentalresearch through to drugs and devices beingused in patients.”

The Institute will allow for significantexpansion of basic and clinical researchcapacity, with 40% new recruitment over andabove existing staff levels, as well as enablethe co-location of research groups that arecurrently dispersed across Cambridge.

Crucially, it will take researchcollaboration between the University andPapworth Hospital to a new level, as Chilversexplained: “There is already strongconnectivity. Each institution has its ownstrengths: the University has huge basicscience and translational research capacity,and Papworth is an international centre ofexcellence for the treatment of patients, someof whom have the rarest and most difficult todiagnose and treat forms of disease. The twohave joint research and treatmentprogrammes, and the new Institute will allowthe scientists and clinicians to workgeographically together for the very first time.”

The research portfolio of the HLRI will bedrawn both from the University, where thecardiorespiratory research portfolioamounted to £164 million last year inresearch grants from sources that include theBHF, Medical Research Council and WellcomeTrust, and Papworth Hospital, where nearly140 active research projects are pioneeringnew treatments and surgical approaches.

However, the HLRI offers the opportunityfor a major new strategic realignment ofcardiorespiratory science. Chilvers and

Bennett, together with Dr Ian Smith,Consultant Physician at Papworth Hospital, areresponsible for developing the Institute’sscientific vision, which has been organisedunder six themes: arterial disease, heart andlung failure, population studies, infection andimmunity, lung cancer, and evaluation andimplementation.

A growing area of research within thetheme of heart and lung failure is thepotential for stem cells to be used to repairdamaged tissues, an area that is being led inCambridge by Professor Karl Ludwig Laugwitz,who was recently awarded a BHFProfessorship of Regenerative Medicine. Thehope is that patient-specific stem cells derivedfrom blood might be used to developpersonalised treatments and generate optionsaside from transplantation for the repair ofdamaged organs.

Biomedical devices are central to thepractice of cardiorespiratory medicine.Devices are used to open blood vessels andairways, replace heart valves, pace the heartand diaphragm, and assist the heart to pumpblood and the lungs to ventilate effectively.“Papworth clinicians have led on thedevelopment of ground-breakingtechnologies, and there will be huge newopportunities when the HLRI is established atthe heart of the Biomedical Campus,”explained Smith, who will lead the evaluationand implementation theme, which will buildon existing collaborations with Universityresearchers and industry.

As well as focusing on achieving a better understanding of the basis of

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Expanding the heart and lungsof medicine

Fundraising is under way for a joint Cambridge University and Papworth Hospital Heart and LungResearch Institute – to sit alongside the anticipated new Papworth Hospital on the CambridgeBiomedical Campus – enabling a major expansion of cardiorespiratory research in Cambridge.

cardiorespiratory disease and its treatment,research at the Institute will be increasinglydirected towards prevention and the interplaybetween genetics and lifestyle. A proposedBiomarkers Laboratory for population studieswill translate the findings of several uniquepopulation studies on the causes ofcardiovascular disease into strategies forpredicting, preventing and treating diseases.Such studies include EPIC-Heart, an analysis ofgenes and lifestyle in 520,000 people acrossEurope that is being led at the Department ofPublic Health and Primary Care by ProfessorJohn Danesh, who will lead the populationstudies theme of the HLRI.

Clinical trials are also a critical part of theresearch process, and the Institute willincorporate a new and dedicated ClinicalResearch Facility. Already, for conditions such aspulmonary hypertension, Papworth Hospital isthe largest referral centre in the UK, and newtreatment strategies are benefiting from closeties with the Department of Medicine underthe leadership of Professor Nick Morrell (seepanel).

Not least, the HLRI will enableenhancement of education and training, asBennett explained: “We want to be a majorcentre for training the next generation ofclinical scientists in this area, as well as provideunrivalled opportunities to attract newinvestigators to the UK. The setup will allowunrivalled access to patients, and optimalsupport and facilities for translational andclinical studies. Our vision, once funding is inplace, is to create a world-class researchenvironment leading to improved patient care.”

“We have a unique opportunity tocreate a world-class environmentto drive forward progress intranslating cardiovascular andrespiratory medicine research intoimproved patient care. A newInstitute will enable us to drawtogether our existing strengths,develop collaborations and attractnew expertise to ensure that wecontinue as a world-leading centreof innovation and care.”

Professor Sir Leszek BorysiewiczVice-Chancellor, University of Cambridge

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Dr Ian Smith (left) andProfessor Edwin Chilvers For more information, please contact Professor Chilvers([email protected]) and ProfessorBennett ([email protected])at the Department of Medicine(www.med.cam.ac.uk).

Breathtaking researchA translational research programme that links basic science in the University’sDepartment of Medicine through to patient care at Papworth Hospital is pioneeringnew treatments for a fatal lung disease.

Professor Nick Morrell has his feet firmly in two camps. His team in the Department ofMedicine carries out fundamental research on the molecular basis of pulmonary arterialhypertension (PAH), a rare lung disease that is characterised by narrowing of the lungarteries. Without a lung transplant, PAH can lead to heart failure just three years after thefirst symptoms of breathlessness appear. Meanwhile, as Research Director of Papworth’sNational Pulmonary Hypertension Service, he oversees the trialling of new treatments inpatients who have severe PAH.

Recently, a Phase III trial demonstrated the success of a new treatment strategy, usingthe drug imatinib, based on targets identified by Morrell and colleagues. As Morrellexplained, it represents a paradigm shift in treating PAH: “Unlike current treatments, thedrug is inhibiting a growth factor pathway rather than dilating blood vessels. It’s acompletely different approach to treating the disease and possibly many others in thepulmonary hypertension family.”

Morrell’s team is also involved in a new drive to understand the genetic architectureof PAH. A large-scale genetic sequencing programme is now under way at theBioResource facility at the National Institute for Health Research Cambridge BiomedicalResearch Centre. By providing the first comprehensive genetic analysis of the PAH defect,the programme will help to identify new targets for drug discovery.

Both studies have benefited immeasurably from the strong linkage between theUniversity’s basic science laboratories and Papworth’s National Pulmonary HypertensionService. “We do translational research in a very joined-up way,” explained Morrell, whoholds the BHF Chair in Cardiopulmonary Medicine in Cambridge. “But there’s a lot ofgoodwill that goes into making that happen. Proximity means so much, and being ableto talk to people immediately about ideas and problems to overcome is more of achallenge if you are located in different places. To bring the basic research geographicallycloser to the clinical studies will achieve even more.”


Image (subject to final design selection) ofthe Heart and Lung Research Institute (left)and the new Papworth Hospital (right), whichare to be located on the CambridgeBiomedical Campus

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We are often told that ‘balance’ is thekey to life – work/family balance, abalanced diet, and so on. But in

early modern England, the quest for theperfect balance was thought to lead toprolonged life, more gold than could bedreamed of, and even the possibility ofsurviving the apocalypse.

Alchemy was the science that made thesegoals seem possible. We think of alchemistsas fixated on precious metals, but alchemyoverlapped with a field with which we are allfamiliar – medicine, and the fight to stay alive.

For Dr Jennifer Rampling, from theDepartment of History and Philosophy ofScience, the origins of English alchemy arebound up with beliefs about medicine anddisease. Rampling’s research, funded by theWellcome Trust, takes a long-term view,spanning centuries – from 1300 to 1700 – and tracing the thread of English alchemy through hundreds of texts andmanuscripts, taking in medicine, religion and culture.

At the start of this period, medicine wasstill guided by Ancient Greek and Romannotions about the need to balance the body’sfour humours – black bile, yellow bile, bloodand phlegm. If a person was sick, an‘imbalance’ of the humours was assumed, andit was the physician’s job to rectify thesituation by restoring equality.

“According to conventional academicmedicine, illness wasn’t something thatinvaded your body from outside. Everyonehad their own individual ‘complexion’ ofhumours, and to rebalance this required amore-tailored, systemic healing method,”explained Rampling.

“A common approach was to try andforcibly ‘purge’ excess humours, oftenconsidered the cause of illness, in order torebalance. Bleeding and vomiting wereroutine forms of treatment.”

But some diseases did not fit this ancientframework, and when the Black Deathravaged 14th-century Europe, killing tens of thousands regardless of individualcomplexions, physicians needed a new kind of medicine. Alchemy offered hope for a last-ditch cure.

A new alchemical medicine came intovogue – known as ‘quintessence’ – whichwent beyond conventional remedies, aspiringinstead to the celestial. Made by repeatedly

distilling alcohol, quintessence was used toextract essences from plants and metals,particularly gold.

In the medieval world view, the Earth wascomposed of the four Aristotelian elements:earth, air, fire and water. However, the heavenswere made of a perfect, fifth element, immuneto change and corruption. For alchemists,their distilled quintessences echoed thisheavenly element, offering a potential cure byejecting imperfection from the body.

“Plague was supposed to kill bypoisoning the heart. But these elixirs were soperfect that they couldn’t coexist with poison.The corruption would be literally forced out ofthe body – restoring the balance of health.”

Chemical medicine began to catch on.Today, we aim for medication without violentside-effects. But in early modern England, thefact that powerful bodily reactions could beproduced by ingesting tiny amounts of achemical substance was seen as hugelyimpressive.

“Patients often welcomed strong, physicalreactions to remedies – such as antimonycompounds, which make you projectile vomit– because they saw them as indicators ofeffectiveness; perhaps that some blockagewas being cleared,” said Rampling. “If youthink of your body as a sack of fluid humours,you will probably want to see, and feel,movement.”

But if such concoctions could transformthe flesh, why not metals as well? Ramplingtalks of ‘slippage’ between medical andmetallurgical alchemy, and the most sought-after elixirs – such as the ‘vegetable stone’, afocus of her research – were believed to bothheal sickness and transmute metals, purgingimpurity to leave only perfection.

Rampling has been in the lab with Dr Peter Wothers, from the Department ofChemistry, attempting to decipher anencrypted recipe for the vegetable stone by15th-century alchemist George Ripley,perhaps the most influential of all Englishalchemists.

“If you distil vinegar several times, youcan use it to dissolve lead. That results in agum that Ripley called the ‘Green Lion’, butthat modern chemists would think of as leadacetate,” explained Rampling. “Distil this, anda white smoke is produced which – if youcollect and condense it – forms a clear fluid.Ripley thought this ‘menstruum’ was the basis

From the elixirs of legend to transmutation of base metals into gold,medieval medical practice and social mobility were steeped in alchemy.

Body, soul and gold: quests for perfection in English alchemy

for the vegetable stone.” But the recipe fadesinto opacity as the alchemist’s languagebecomes increasingly enigmatic.

Alchemical practices and ingredients were often concealed using symbolic, riddlinglanguage, enticing with their hint ofotherworldly secrets, but ultimately difficult to decipher. This language is magnificentlydisplayed in the ‘Ripley Scrolls’ – emblematicscrolls full of dazzling imagery, depictingdragons, angels, turrets in the clouds and giant droplets of blood.

These scrolls baffle at every level. Thedesign is probably not by Ripley at all – it wasattributed to him after his death, when hisfame had spread. Their meaning was alsosubject to distortion over time. For 300 years,copyists emphasised different aspects of thescrolls’ imagery, struggling to make sense oftheir source.

Such eye-catching manuscripts offeredalchemical practitioners one way of marketingtheir expertise. Knowledge is power, and thenatural and medical knowledge promised byalchemical treatises could be used as abartering chip for social mobility by those who claimed to be its gatekeepers.

“A lot of the alchemists’ rhetoric is aboutprotecting the secret: knowledge that is toodangerous to fall into the hands of theignorant or rapacious,” said Rampling. “Inreality, they had to be discreet with thisknowledge, since it was their livelihood.”

“Practitioners could use this knowledge towin the patronage of princes and nobles, bydangling the possibility of long life, riches andsecret wisdom. The imagery of the RipleyScrolls refers to medicine as well astransmutation – all in a very glamorouspackage.”

Besides prolonged life and wealth,alchemy also offered insight into the secrets ofnature, and even divine power. In Aristoteliancosmology, the Earth itself was flawed as itlacked the unchanging perfection of theheavens. As Rampling points out, this model“mapped very nicely” onto a Christian theologythat viewed the natural world as damaged byoriginal sin: “If nature was poisoned by the Fall,then alchemy promised to redeem it. It’s nocoincidence that the Ripley Scroll (pictured)shows the Garden of Eden.”

By generating perfection on Earth,alchemists could claim they were doing God’swork. The quest for the perfect elixir, able to

purge both man and metal, had a powerfulapocalyptic resonance.

For hundreds of years, Christian prophetsclaimed that the end of the world was close.On Judgement Day, God was expected to‘purify’ the Earth with divine fire – only theperfect could survive. Some alchemists arguedthat the possessor of the elixir would play animportant role. This idea resurfaced inElizabethan England, and was presented toQueen Elizabeth I a number of times.

But corruption and redemption were alsoallegories for material processes. Tellingly, theScroll’s Adam and Eve are not eating thebiblical apple, but bunches of grapes.Rampling has an answer: “Wine made fromgrapes produces both vinegar and thequintessence – key ingredients of thevegetable stone.”

For all its striving for perfection, alchemyremained grounded in the physical, requiringits practitioners to get their hands dirty. ForRampling, there is a romance in the alchemists’relationship with the world, one we haveperhaps lost.

“These people knew materials in anintimate way – they would taste them, smellthem, listen to them. There are lots ofdescriptions in manuscripts of substancesmaking cracking sounds, or producing aheavenly odour or bitter taste. Alchemists wereearly explorers of the material world. With onlytheir senses and imagination to guide them,they had to be attuned to the slightestvariation.”

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“A lot of the alchemists’ rhetoric is about protecting the secret:knowledge that is too dangerous to fall into the hands of the ignorantor rapacious.”

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Image from a George Ripley Scroll, MS.276

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How do planetary systems form? Whatdo the surfaces of stars look like? Doeslife exist elsewhere in the Universe?

Astronomers have developed manytheoretical models, but until now the ability tovalidate these with observations has beenseverely constrained by the telescopecapabilities available.

Taking the lead in three major newinternational projects, Cambridgeastronomers are tackling the enormoustechnical challenges involved in developingbigger and better telescopes to open newwindows onto the Universe. Building onCambridge’s strong legacy of achievement inastronomical instrumentation, the newtelescopes all utilise one important underlyingtechnique –interferometry by aperturesynthesis – to probe the Universe at a level ofdetail far beyond the capabilities of anytelescope currently in existence. Eachtelescope will detect light at a differentwavelength and help to build a fuller pictureof exactly what is out there.

Filling in the detail“When we look at regions of star formationwith the best existing high-frequency radiotelescope, we see blobs. We can learn a lot bylooking at the radio waves that come out ofthese, but inside there will be all sorts of

complicated structures that the telescopecan’t resolve,” said Dr John Richer,astrophysicist at the Cavendish Laboratoryand the Kavli Institute for Cosmology.

Richer is UK Project Scientist for theAtacama Large Millimetre Array (ALMA), apartnership project involving Europe, NorthAmerica, East Asia and the Republic of Chile.Currently under construction in Chile, thisrevolutionary sub-millimetre radio telescopewill consist of 66 high-precision antennasworking in perfect synchrony when fullyoperational in 2013.

Interferometry will be used to combinethe information they collect, ‘synthesising’ anaperture with an effective diameter of 16 kmto create an ultra-high-resolution telescope.Professor Richard Hills, who is currently onsecondment in Chile, designed the set of radioreceivers that calibrate the telescope and arecentral to ALMA achieving its scientific goals,and Richer’s team is developing the softwareto correct the images from ALMA.

“ALMA is an incredible piece ofengineering that will enable us to zoom in totake pictures with a thousand times betterresolution than we can now, so we’ll actuallysee all the detailed structure instead of blobs,”said Richer. “We’re hoping to unlock the secretof how planetary systems form, and to lookback in time at the very early Universe.”

A new picture of the dust ring around the bright star Fomalhaut from ALMA; the underlying blue pictureshows an earlier picture obtained by the NASA/ESA Hubble Space Telescope

Advances in telescopetechnology being developedat Cambridge will drive arevolutionary period ofdiscovery in astronomy.

Opening new windows on the Universe

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(Left to right) Dr David Buscher,Dr John Richer, Professor ChrisHaniff and Professor PaulAlexander For more information, please contact Professor Alexander([email protected]) at theCavendish Laboratory(www.phy.cam.ac.uk).

With 33 of the antennas currentlyoperational, the telescope is already returningstunning images. “The whole astronomicalcommunity wants to use ALMA because it’sunique, and a huge breakthrough incapabilities,” said Richer. “There’s anunprecedented level of oversubscription,because nearly everything in the Universe hassome emission at these radio wavelengthsthat is interesting and not well understood.”

Building a fuller pictureDr David Buscher and Professor Chris Haniff,astrophysicists at the Cavendish Laboratory,are system architects for the MagdalenaRidge Observatory Interferometer (MROI), acollaborative project with New Mexico Tech,USA, that also uses interferometry, but thistime at visible wavelengths.

“Optical interferometry providesinformation not available from conventionaloptical telescopes or from radiointerferometers,” said Buscher. “Both radioand optical interferometers can see finedetail: putting together this detail allows usto answer new questions.”

The pair started with a set of high-levelscientific questions, drawn up by aconsortium of UK astrophysicists, and usedthese to specify a new high-precision opticalarray. “The great thing about this project isthat we’ve been able to design and build,from scratch, an instrument to answerfundamental scientific questions that cannotbe answered in any other way,” said Buscher.Haniff added: “We are involved in all themajor design questions, from what sizetelescopes are the best, to how many, towhich configuration would produce the bestimages, and we’re developing the softwarethat will make images from the data.”

When constructed on its mountain-topsite in New Mexico, the MROI will be the leadinstrument in its field, consisting of 10telescopes that will produce images with 100times the resolution of those from theHubble Space Telescope. By looking atexternal galaxies, it is expected torevolutionise understanding of astrophysicalphenomena ranging from active galacticnuclei to black holes. Closer to Earth, it willhelp answer questions about the formationof stars and planets.

“There are models for what’s going on,”said Haniff, “but these could be completelywrong – at the moment the detail is far toofine to see. By using interferometry tosimulate the resolving power of a singleoptical telescope of up to 340 m in diameter,the MROI will enable us to see structures that

are so small they couldn’t otherwise bedetected at visible wavelengths.” Theadvanced technology of the MROI could alsohave important commercial applications,such as in taking images of brokentelecommunications satellites ingeostationary orbit to help diagnose whathas gone wrong.

Signs of life?The third telescope in the trio, the SquareKilometer Array (SKA), will be the largest andmost sensitive radio telescope ever, and itsdesign involves astronomers, engineers andindustry partners from 20 countries. ProfessorPaul Alexander, Head of Astrophysics at theCavendish Laboratory, is playing a leadingrole in its development. Involving a ‘sea’ ofantennas – over half a million in the firstphase – acting as one enormousinterferometer covering 1 km2, the conceptcalls for a very simple design with low unitcost. “At the moment we’re working veryclosely with our industrial partner,Cambridge Consultants, on the detaileddesign,” he said. “It’s also going to be a majorcomputing challenge – the data transportfrom the dishes will produce 10 times thecurrent global internet traffic.”

With one of its design goals being “tomaximise the ability to explore the unknown”,SKA will enable astronomers to see incrediblyfaint signals. “With SKA we will be able to lookback to the time when the first objectsformed in the Universe, and try tounderstand how we got from there to whatwe have now,” explained Alexander. “A secondexperiment will use pulsars, originallydiscovered by Antony Hewish and JocelynBell-Burnell in Cambridge, as extremelyaccurate natural clocks. Finding a pulsar inorbit around a black hole will enable us toproperly test Einstein’s gravitational theory.”

This extremely powerful telescope alsoprovides an exciting new approach to thesearch for extra-terrestrial intelligence (SETI).“The trouble with most SETI searches is thatthey rely on someone communicating withyou just at the time when you’re listening,”said Alexander. “SKA is so much moresensitive than anything we’ve had before.We’ll be able to look for evidence ofunintentional radio emissions, the equivalentof airport radar, from our nearby stars andplanetary systems that may indicateintelligent life.”

Although work on SKA has alreadybegun, construction will not start until 2016and the telescope will not be fullyoperational until 2024. Development work

“We’ll be able to look forevidence of unintentional radioemissions, the equivalent ofairport radar, from our nearbystars and planetary systems thatmay indicate intelligent life.”

for all three telescopes extends backdecades, as Alexander explained: “We’rebuilding on our legacy”. The idea forinterferometry was originally conceived inthe 1880s, but it wasn’t until the 1950s that itwas developed and used at radiowavelengths – a technique for whichCambridge astronomers Martin Ryle andAntony Hewish won a Nobel Prize in 1974. Itwas also in Cambridge in the 1980s thatreliable interferometric imaging was firstshown to be feasible at optical wavelengths,and this paved the way for building theMROI.

A challenge of many disciplines“To build these big telescopes you needteams of people with expertise acrossastronomy, technology and computing,”explained Alexander. “You’ve got to pulleveryone together to do good, competitivescience”. Recognising this, the Universityplans to build a new Centre for ExperimentalAstrophysics to enable greater integration ofits strengths. Construction of the Centre willbegin this October on a site adjacent to theUniversity’s Kavli Institute, thanks togenerous philanthropic support fromCavendish Alumnus Mr Humphrey Battcockand The Wolfson Foundation. “The newbuilding will enable us to create the teamsneeded to take on these big scientificchallenges, which will lead to majoradvances in our knowledge andunderstanding of the Universe,” saidAlexander.

28 | Features

With an incredible diversity of celltypes, the central nervous system(CNS), comprising the brain, spinal

cord and retina, can be considered to be themost complex organ in the body. ProfessorBill Harris, an experimental biologist andHead of the Department of Physiology,Development and Neuroscience, is fascinatedby how this complex and sophisticatedsystem is built out of a collection ofundifferentiated cells. By putting an advancedtechnology to novel use, he has been able toobserve for the first time the entire process ofretinal development at the cellular level inzebrafish embryos. This has achieved a long-sought goal in developmental neurobiology:a complete analysis of the building of avertebrate CNS structure in vivo.

Terra incognito“What surprises me most is the inscrutablelogic of it all,” said Harris. “Every experimentdesigned to differentiate between differenthypotheses leads down one or other branchof an untravelled winding way, through acomplex and cleverly evolved network thateventually leads to the functioning CNS.”

“We use the retina as a model for the restof the brain, and zebrafish are a usefulresearch model species because theirtransparent embryos are easy to see into,and develop rapidly,” he added. The zebrafishprocess of retinal development is completeby about three and a half days afterfertilisation; in humans, it takes up to a year.Focusing on the developing visual system inthis lower vertebrate, Harris has broken theprocess down into discrete events to unravelsome of the mysteries that lead to theformation of a perfectly built nervoussystem.

“At 24 hours after fertilisation, to aninexperienced eye, all the cells of theembryo look the same,” explained Harris.“But already the decisions as to what theywill become have been made. The littlebulge that is destined to become the eye isnow committed, but all the cells within thatbulge still have the potential to give rise tovarious types of retinal neurons. We callthose retinal progenitor cells (RPCs)”.

Harris’ research focuses onunderstanding how the cellular diversity inthe retina arises: how the RPCs produce

different cell types, and how, what and whendecisions are made. He and his colleagueshave found that each RPC seems to behaveindividually, producing clones of variablesize and composition. One of the big puzzlesis how, from beginnings that show suchvariability, a retina of just the right size andcellular composition forms. “The fully formedretina has a hundred different types ofneurons. I want to know how it all comesabout so perfectly,” he said, “it’s a terrificpuzzle, and a fundamental issue indevelopmental neuroscience.”

Pushing boundariesCombining imaging with powerful geneticlabelling techniques helps to elucidate thefine detail. “We discovered a zebrafish genethat was necessary for the formation ofretinal ganglion cells, the first cells to exit thecell cycle and start to differentiate,” saidHarris. “We used the promoter of that geneto drive a fluorescent protein, then when thegene was turned on just before the finaldivision of the RPC, it made the cellfluorescent,” said Harris. These fluorescentcells can then be followed under themicroscope throughout retinaldevelopment.

Harris uses a sophisticated confocalmicroscope to take a set of images oflabelled cells in the developing zebrafishembryo in a single plane, and then stacksthem to build up a 3D view of the cells. Byrepeating this at regular intervals, a 4D, ortime-lapse image, is created over severaldays that shows the set of undifferentiatedcells proliferating and differentiating intoparticular types of neurons. A pioneer of thisapproach, he has transformed the wayscientists can look at the developing brain.An article due to be published in Neuron thisyear describes his ground-breaking work.

“Forty years ago you would look at theembryo and label some cells, then later lookagain to see what cells were now labelled orwhere they were. You’d get snapshots underthe microscope and surmise what happenedin between. Now we are actually seeing howthe cells divide, which gives us a lot moreinformation to help distinguish certainhypotheses from others,” said Harris.

“We’ve made some spectacular movieswhere we can actually see the RPCs going

By combining advanced imagingwith powerful genetic labellingtechniques, Professor Bill Harrishas imaged the entire process ofretinal development in fourdimensions, providing newinsights into the enormouscomplexity of the nervoussystem.How the brain is made

Features | 29

through cell division to produce twodaughter cells in vivo in the retina. We also seetransient processes that people didn’t noticebefore,” Harris added. “We see that all theRPCs remain attached to one side of theepithelium by a tiny little thread throughoutcell division. Since the 1930s, we’ve knownthat the RPCs let go of one side but we’dnever seen this thread before. Now we wantto know what its purpose is – is it importantfor keeping a cell arranged in the right way?Does it serve a purpose later on indevelopment?”

Using 4D analysis for hundreds of cells atdifferent stages throughout retinal formation,Dr Jie He, a Postdoctoral Fellow in the Harrislab, found there was a stochastic, or chance,element involved in the types of daughtercells formed each time a cell divides. Incollaboration with Ben Simons, Professor ofTheoretical Physics at the CavendishLaboratory, they developed a model toexplain this variability in the proliferation ofRPCs, and how, in spite of this variability, RPCsmanaged to produce a perfect retina everytime.

Cambridge Advanced ImagingCentreHarris is driving the development of a newpurpose-built imaging centre – theCambridge Advanced Imaging Centre (CAIC)– which opens in October 2012 and has beenmade possible through generous fundingfrom The Wolfson Foundation, the WellcomeTrust and support from the University. Byaugmenting the best commercial andUniversity-developed instruments, this facilitywill offer to the broader scientific communitythe latest developments in light and electronmicroscopy, adapted to specific scientificquestions, with the aim of acceleratingprogress in research across a broad range ofareas.

“CAIC will enable us to look inside a livingtissue at any resolution from single moleculesto thousands of cells, and see the machinerythat’s operating there in real time,” said Harris.“It took us three years to track the hundredsof cells in our study. Once the newmicroscopes are built, they will perform at amuch higher resolution, and much faster,” saidHarris. “Our hope is to be able to see all theRPCs dividing and giving rise to all the cells in

the retina, and to do this over severalembryos and see the variations so that wecan properly describe the statisticalproperties. We also need a lot more data tounderstand the nature of the stochasticmachine that generates the right proportionsof different cell types, and CAIC will help usdo that.”

Human aspectThe process Harris has observed in thezebrafish also occurs in humans, and achallenge for the field will be to understandhow the stochastic machine changes so thathuman-sized retinas come out of a collectionof human RPCs. Beyond the field of neuraldevelopmental biology, Harris’ findings mayhave far-reaching implications.

“The repair of neural tissue is a verychallenging field. In order to make progress,it is often helpful to understand more abouthow the brain is originally made, then try torecreate that in an injured brain. Scientists atCambridge’s Brain Repair Centre are usingideas from neural development in thiscontext,” said Harris. “A better understandingof the control and regulation of cellproliferation is also highly relevant toresearch into neural-origin cancers. Themore we understand retinal development,the more information we can feed into thedevelopment of novel therapies.”

“What surprises me most is theinscrutable logic of it all.”

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Professor Bill Harris For more information, please contact Professor Harris([email protected]) at theDepartment of Physiology,Development and Neuroscience(www.pdn.cam.ac.uk).

To view one of Bill Harris’ movies of thedeveloping retina, please visitwww.cam.ac.uk/research

A confocal image from a retina of amulti-transgenic zebrafish in which the

different neuronal cell types of theretina are labelled with different

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30 | Features

Illuminated manuscripts are revealing their secrethistories thanks to the application of techniquesmore commonly found in scientific laboratories.

Science illuminating art

Fairy-tale pinnacles stretch to thehorizon in an azure sky, scarlet flagsflutter, an angel plays a golden horn,

and the Madonna, shrouded in folds oftumbling ivory, serenely cradles hernewborn baby. This painting (pictured) isone of the many that illuminate The Hours ofIsabella Stuart, a sumptuous prayer bookillustrated by a group of French painters inthe 15th century.

All that is known and speculated aboutthe manuscript, which is part of the richcollection of illustrated manuscripts inCambridge’s Fitzwilliam Museum, has beenpieced together from painstaking arthistorical analysis and circumstantialevidence. But much remains shrouded inmystery. Who designed the exceptionallyrich and complex images? How were they tobe used? Were they the creation of aworkshop, with the Madonna painted by theworkshop master? Or did several mastersmake guest appearances? Did the artistsshare materials and techniques? Where didthe pigments come from?

Now, thanks to an innovative project atthe University of Cambridge, some of thehidden histories of the Book of Hours, andmany other illuminated manuscripts, will beuncovered. Led by Dr Stella Panayotova,Keeper of Manuscripts and Printed Books atthe Fitzwilliam Museum, and ProfessorStephen Elliott, from the Department ofChemistry, the MINIARE project is usingscientific techniques to identify thecomposition of illuminations. The researchwill help conservators repair priceless worksof art and provide new insights into thecultural, social and economic circumstancesof their production. And, crucially for objectsof such rarity and fragility, none of thetechniques involves touching themanuscripts or removing samples.

Illuminated manuscripts often have longand complex construction histories: amanuscript copied in Italy in the 1300s, forinstance, might receive its illumination inFrance decades later and be bound inGermany. “This is a reflection of the traderoutes operating at the time and theinternational mobility of artists, scholars,patrons, manuscripts and ideas,” saidPanayotova, “but it’s also a consequence ofwar and of political and religious upheaval.”

Scientific analysis of the pigments canprovide valuable contextual information, asresearch scientist Dr Paola Ricciardi isdiscovering. Using analytical techniquessuch as fibre optic reflectance spectroscopyand X-ray fluorescence, as well as visual

imaging techniquessuch as microscopicobservation andinfraredreflectography, she is identifying thecomposition ofpigments as well asreveallingunderdrawings andpreparatory sketches.

“The challenge forthe chemists and thephysicists in the team isto use well-knownscientific techniques ina new situation, wherevery low concentrationsof complex mixturesneed to be identified asa function of depth,”explained Elliott. “One ofour interests is to pushthe technology to itslimit by building newhardware that can analyse thefingerprint of paint at the sub-micron scale.”

Member of the project team, Dr SpikeBucklow from the Hamilton Kerr Institute – adepartment of the Fitzwilliam Museum thatspecialises in the conservation andrestoration of paintings – explained why theproject will bridge the gap between scienceand art: “Artists had a fantastic knowledge ofhow to get the effect they wanted from thepigments they used. How much they knewabout why the materials worked is of greatinterest. This research will help to unpick theart of manuscript illumination.”

The goal is to expand the currentproject, which has been funded by theNewton Trust and a private sponsor, toencompass not only the 2,000 manuscriptsheld by the Fitzwilliam Museum, but alsothose held by the University Library andCambridge Colleges, and the team is activelyseeking new funding to do this.

“Art historical and linguistic research cantake you a long way towards answeringquestions but scientific analysis can clincharguments and dispel myths,” saidPanayotova. “There are very few institutionsin the world that combine such richcollections with multidisciplinary expertise.This unique synergy will have a verysignificant impact, informing a larger study of the changing artistic, cultural,ideological, social, political and economicenvironments in which the manuscriptswere created.”

Professor Stephen Elliott andDr Stella Panayotova For more information, please [email protected] or visitwww.miniare.org

Painting from The Hours of Isabella Stuart, France(c.1431); MS 62, fol. 141v

MINIARE (Manuscript Illumination: Non-InvasiveAnalysis, Research and Expertise) is a collaborationbetween the Fitzwilliam Museum, the HamiltonKerr Institute, the Departments of Chemistry,Physics, History of Art, History and Philosophy ofScience, and the Victoria & Albert Museum.

To view a video about the MINIAREproject, please visitwww.cam.ac.uk/research

www.cam.ac.uk/research | 31

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Video: The Future of Energy

The most recent film in the flagship Cambridge Ideas series examinesthe world’s skyrocketing consumption of energy, and asks whattechnology and behavioural change can do to help. Dr RichardMcMahon, Professor Andy Woods and Dr Julian Allwood look at windpower, carbon capture and storage, and material efficiency asexamples of how we can cut emissions. They suggest that we mustact now in order to avoid the serious risks of man-made globalwarming, one of the greatest challenges of the 21st century.

Visit: www.cam.ac.uk/research/video-and-audio/the-future-of-energy

Research onlineIf you’re interested in finding out more about research at the University of Cambridge, take a look at ourdedicated website (www.cam.ac.uk/research). Here you’ll find news, features, discussion, themed areas,videos and audio that cover research across the disciplines, all in a fully searchable and easy-to-use format.The latest themed area focuses on Risk and Uncertainty, launched to coincide with this issue of ResearchHorizons. And, if you’d like to keep up to date by email with what’s new on the website, you can subscribe toour weekly e-bulletin at www.cam.ac.uk/research/bulletin

A selection of the latest video and audio:

Photo film: Welcome to Bastion – war zoneethnography with the combat surgeons

Dr Mark de Rond from the Cambridge Judge Business School wasgiven unprecedented access to the military hospital at Camp Bastion inAfghanistan to study the teamwork of the combat surgeons. Theunique photographs he took – now the subject of this photo film –reveal the realities of life and death in the operating theatre of modernwar. For six weeks beginning in June 2011, de Rond embedded himselfwith the surgeons at the field hospital to study how these high-performing teams work together under extreme pressure, forced tomake life and death decisions in the blink of an eye and deal withharrowing injuries.

Visit: www.cam.ac.uk/research/news/welcome-to-bastion-warzone-ethnography-with-the-combat-surgeonsVideo: Alan Turing – celebrating the life

of a genius

We celebrate the centenary this year of the birth of Alan Turing with ashort film on his life and work. Perhaps best known for his part inbreaking the German Enigma code during World War II, Turing had,aged 22 years old at King’s College, Cambridge, already conceived ofthe ‘Turing Machine’ – a universal machine that could imitate allpossible calculating devices. This mathematical model went on tobecome one of the cornerstones of computer science and is arguablythe most influential mathematical abstraction of the 20th century.

Visit: www.cam.ac.uk/research/news/alan-turing-celebrating-the-life-of-a-genius

Video: ‘Everything, everywhere, ever’ – anew door opens on the history of humanity

Take a short video tour through the newly reopened Museum ofArchaeology and Anthropology after its £1.8 million redevelopment.Home to one of the finest and most important collections of its kind inthe country, the Museum charts the history of humanity, from ourearliest ancestors to today’s indigenous people spread across the globe.

Visit: www.cam.ac.uk/research/news/everything-everywhere-ever-a-new-door-opens-on-the-history-of-humanity

32 | The back pageAll materials in Research Horizons, including but notlimited to text, data, designs, logos, illustrations,still images, are protected by copyright, designrights, database rights, trademarks and otherintellectual property and proprietary rights. The materials in Research Horizons are eitherowned by the University of Cambridge or havebeen licensed by the owners to the University ofCambridge for inclusion in the publication. Contributors to this publication have assertedtheir moral right under the Copyright, Designs andPatents Act 1988 to be identified as authors of theirrespective works. Except for the purposes ofprivate study and noncommercial research or ‘fairdealing for the purposes of criticism or review’ aspermitted under the Copyright, Designs andPatents Act 1988, this publication or any partthereof may not be reproduced, stored ortransmitted in any form or by any means withoutthe prior permission in writing of the University ofCambridge and the authors of contributions asidentified. Requests for further reproduction or repostingor reproduction for commercial purposes shouldbe addressed to the Editor, Research Horizons,Office of External Affairs and Communications, ThePitt Building, Trumpington Street, Cambridge, CB21RP, UK; email [email protected] Research Horizons has made all reasonableefforts to ensure that the reproduction of allcontent in this publication is done with the fullconsent of copyright owners. Research Horizonswould be grateful to hear from intellectualproperty rights owners who are not properlyidentified in the publication so that ResearchHorizons may make the necessary corrections.

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Issue 19 University of Cambridge Research Horizons

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