bluesci issue 08 - lent 2007
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Cambridge University science magazine FOCUS: The Future of NeuropsychiatryTRANSCRIPT
Issue 8 Lent 2007 www.bluesci.org
• Poincaré Conjecture • Science Documentaries • Pharmaceuticals •• Human Uniqueness • The Whipple Museum • RNAi •
• Stock Markets • Parliamentary Office of Science and Technology •
The Future of NeuropsychiatryUnravelling the biological basis of mental health
in association withCambridge’s Science Magazine produced by
Darwinian ChemistrySelection of the fittest molecules
Biological WarfareDoes biodefence research make us safer?
cover_LN 9/1/07 21:21 Page 1
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02 ad 10/1/07 22:11 Page 1
Editorial ..............................................................................................................................Focus ...................................................................................................................................In Brief ................................................................................................................................A Day in the Life of ...........................................................................................................Away from the Bench .....................................................................................................Initiatives ............................................................................................................................History ...............................................................................................................................Arts and Reviews .............................................................................................................Dr Hypothesis ..................................................................................................................
Chemistry Steals Tricks From DarwinJonathan Gledhill explains why DarwinÕs dogma may revolutionize chemistry...........................
Are Humans Special?Mico Tatalovic questions the behavioural basis of human uniqueness...........................................
Black-Scholes: The Black Hole of Maths and Money Tristan Farrow tells the story of the formula that crashed the stock market.............................
Biodefence: Is Prevention Always Better Than Cure?Three authors debate the benefits and risks of furthering biowarfare research.......................
RNAi:Taking Control of the GeneCatherine Jopling describes a novel method of silencing gene expression...................................
The Dilemma of the Third DimensionMichaela Freeland discusses one of mathematicsÕ most alluring problems....................................
Features
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Cover image by Jeff Huang"The image was generated at the Wellcome Trust/Cancer Research Gurdon Institute, and depicts a bird’s eye view of the head of aXenopus laevis tadpole which was genetically tagged with a neuronal-specific alkaline phosphatase reporter. Because tadpole larvaedevelop externally, and are generally transparent once hatched, the brain of an intact tadpole is highly visible under a dissecting micro-scope. Here, the cranial nerve network was detected after an alkaline phosphatase reaction—a simple enzymatic reaction that caus-es the genetically labelled axons to turn blue."
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Visit www.bluesci.orgWeekly science news storiesAdditional Bluesci articles Complementary material to the printed issuePodcasts of speakers, lectures, interviews, and more!Schedule of CUSP software workshopsArchives of all past issues of BluesciInformation on getting involved with Bluesci
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From The Editor
From The CUSP Chairman
Welcome to the first BlueSci of 2007!This latest issue comes out as we finish
implementing a great many changes to theorganization of CUSP and BlueSci. At thestart of Michaelmas Term, we began run-ning weekly training workshops, address-ing all aspects of producing the magazine.These have been very popular and wethink the results, in terms of the standard ofthe magazine, speak for themselves. Theworkshops will be continuing throughoutLent Term, with a particular focus ongraphic design and web development.Anyone interested in coming along shouldvisit our website for details.
On the web front, the BlueSci websitehas been redesigned with a sleeker look.The website hosts our weekly news serv-ice, which runs throughout each term tokeep you up-to-date on the latest scientif-ic developments, in Cambridge andbeyond. Over the last year the news serv-
ice has been heavily expanded and now hasa large team of writers, many of whom arealso involved with the print magazine.Thenews is also published, in an abbreviatedform, in Varsity.
Alongside the news, at the BlueSci web-site you can find our podcasts and videos,produced by our film team led by TristanFarrow.We were particularly pleased to beable to offer a podcast of Richard Dawkins’speech at the Cambridge Union Societylast term.Visit the website now for inter-views with the TV psychiatrist Raj Persaud,Amnesty International’s Kate Allen and theenvironmentalist George Monbiot.
As ever we would like to thank theVarsity Business Manager,Adam Edelshain,for finding the time in his busy schedule tohelp us out, in more ways than we havespace to list.
Michael MarshallCUSP Chairman
Issue 8: Lent 2007
Produced by CUSP &Published by
Varsity Publications Ltd
Editor: Lorina NaciManaging Editor: Louise WoodleyProduction Manager: Ryan Roark
Pictures Editor: Jon HerasSubmissions Editor: Maya Tzur
Business Manager: Adam Edelshain
Focus Editors:Hannah Critchlow, Peter Davenport, Michael
MarshallFeatures Editors:
Sheena Gordon, Michelle Percharde, Sharon TateA Day in the Life of... Editor:
Si-houy Lao-SirieixAway from the Bench Editor:
Serena ScollenInitiatives Editor:Serena ScollenHistory Editor:
Emily TweedArts and Reviews Editor:
Mico TatalovicDr Hypothesis:
Rob YoungSecond Editors:
Lynne Aitkenhead, Beth Ashbridge, ChloeHardman,Thomas Kluyver, Jonathan Zwart
Copy Editors:Lynne Aitkenhead, Brendan DÕArcy, Michael
Marshall, Lorina Naci, Bojana Popovic, JonathanZwart
Production Team:Terry Evans, Jon Heras, Lara Moss, Kelly Neaves
Distribution Manager:Terry Evans
Web News/In Brief Editor:Michael Marshall
Web News Photographer:Abinand RangeshWeb News Team:
Chris Adriaanse, Lynne Aitkenhead, BethAshbridge, Hannah Critchlow, Subhajyoti De,
Michaela Freeland, Gurman Kaur,Thomas Kluyver,Lorina Naci, Michelle Percharde, Abinand Rangesh,
James Shepherd, Mico Tatalovic, Emily TweedCUSP Chairman:Michael Marshall
ISSN 1748—6920
Varsity Publications Ltd11/12 Trumpington Street
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03www.bluesci.org
Happy New Year! Welcome back toCambridge and to a fresh issue of BlueSci.
Issue 8 presents an exiting set of articles.Our FOCUS section opens a window intothe future of mental health care, while ourfeature and regular articles discuss topicsranging from biodefence to science muse-ums and science documentaries.
CHEMISTRY STEALS TRICKS FROMDARWIN explains how Darwin’s dogmamay successfully quench the modernworld’s voracious appetite for new mole-cules. BIODEFENCE: IS PREVENTION ALWAYSBETTER THAN CURE? discusses the benefitsand perils of learning to engineer deadlybioagents. THE DILEMMA OF THE THIRDDIMENSION unravels the drama that ensuedfrom Grigori Perelman’s cracking thePoincaré conjecture—one of theMillennium Prize Problems in mathemat-
ics. On the artistic end of the spectrum,ARTS AND REVIEWS illustrates how moderntechnology is enabling inspired individualsto bridge the gap between art and science.
Complementary material to the printededition of BlueSci, as well as weekly newsupdates, podcasts and videos of high-impact science events in Cambridge can befound online at www.bluesci.org.
BlueSci is the product of dedicated workfrom Cambridge undergraduates, gradu-ates, and postdocs who love science, com-munication and giving back to society. Ifyou’d like to contribute to the magazine,be it in writing, editing, production, graph-ic design or online material, please don’thesitate to get in touch. I hope you enjoyreading the eighth issue of BlueSci.
Lorina [email protected]
BlueSci is published by Varsity Publications Ltd and printed byWarners (Midlands) plc. All copyright is the exclusive property ofVarsity Publications Ltd. No part of this publication may be repro-duced, stored in a retrieval system or transmitted in any form or
by any means, without the prior permission of the publisher.
Next Issue: 27 April 2007Submissions Deadline: 29 January 2007
05 editorials_LN 11/1/07 02:45 Page 3
To be diagnosed with a psychiatric disorder such as schiz-ophrenia, a patient must display certain behavioural symp-toms for most of a one-month period, if the symptoms aresevere, or continuous signs, for at least six months, for lessextreme symptoms.
Schizophrenia exhibits a diverse set of symptoms—rangingfrom delusions and hallucinations to disorganized speech andbehaviours—and its underlying nature is hotly debated.
One theory, advanced by Professor Tim Crow, posits thatschizophrenia is unique to humans, and, specifically, that schiz-ophrenia is associated with an anomaly of the genetic mecha-nism that controls hemispheric lateralization. Lateralization is aproperty unique to human brains, in which language is con-trolled mainly by one hemisphere, usually the left. When lan-guage lateralization fails, the processes generating speech andthose generating thought can be confounded in the brain.As aresult, a person may fail to distinguish between oneself, otherpeople and the environment.
Among the 327 mental illnesses currently recognized, manyshare the psychotic symptoms seen in schizophrenia.Accordingto Dr Sabine Bahn, psychotic features can be present not only
in mental disorders like schizophrenia, but also in drug-inducedpsychosis, neurological disorders such as epilepsy, Parkinson’sand Alzheimer’s, as well as in immunological disorders affectingthe brain, such as systemic lupus erythematosus.
In Professor Bullmore’s opinion, “the problem with the cur-rent categorization system is that it’s the end product of a histor-ical process of consensus building.” However, he points out thatthis internationally standardized diagnosis method has drasticallyimproved reliability and comparability in psychiatric diagnosis.
In spite of these improvements, the current diagnostic criteriaare often criticised by mental health professionals for poor sci-entific validity. For example, according to an article published inthe American Journal of Psychiatry by McGorry and colleagues,the rate of agreement between any two psychiatrists when diag-nosing schizophrenia is about 65%, at best. Dr Bahn argues thatthis is because the “current diagnosis is based on findings thatare really 100 years old.”
Biologically-based diagnostic tests that can uniquely identi-fy each psychiatric disorder don’t exit. Instead, the diagnosis isbased on the patient’s self-reported experiences, in combina-tion with secondary signs observed by a psychiatrist or clini-
04 Lent 2007
FOCUS
Problems With Current Diagnosis and Treatment
Mental illness is estimated to affect 450 million people worldwide.The effects for patients and their families can be dev-astating.The economic cost of treatment, rehabilitation and lost income is £18 billion per year in the UK alone.
Even the most ardent supporter of the current mental health services would struggle to argue that the system providessatisfactory patient care. Many patients are misdiagnosed or remain undiagnosed for a long period, psychological therapy isnot always readily available, and the existing medication is often ineffective and can give rise to significant side effects.
Hannah Critchlow, Peter Davenport and Michael Marshall spoke to a panel of four leading researchers in neuropsychia-try and bring you exciting new research on the diagnosis and treatment of disorders such as schizophrenia and depression.
The Coming Revolution in Psychiatry
450 million people throughout the world suffer from mental illness
16% of people aged 16-75 in the UK suffer from mental illness
25% of those with mental illness are receiving treatment
50% of people with schizophrenia will attempt suicide
10-13% of people with schizophrenia commit suicide
6-9 months is the standard waiting time for psychological therapy
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cal psychologist. Dr Bahn explains: “It’sreally a whittling down of a most likelydiagnosis, where you ask patients ques-tions such as ‘are you hearing voices’,‘doyou think someone is out to get you’,‘do you feel people are influencing yourideas and actions’. These are suggestivequestions that are neither specific norvery sensitive.”
Currently, it is impossible to accuratelyidentify individuals at high risk of devel-oping a mental illness, and, depending on
the symptoms, patients must exhibitsymptoms for up to several months,before they can be considered for diag-nosis.“This can be a very big delay, espe-cially since it is becoming increasinglyclear that if you treat early on you canimprove prognosis,” Dr Bahn adds.
Because of the large overlap in symp-toms between different disorders and theinherent subjectivity of the diagnosticcriteria, patients may not be correctlydiagnosed for a long time.According to aEuropean survey involving over 1000individuals, patients with bipolar disorderwait on average 5.7 years before correctdiagnosis. In the US, up to 69% ofpatients with bipolar disorder are initiallymisdiagnosed, and more than a third ofpatients experience an average of 10years‘ delay before correct diagnosis.
“We have to start from scratch in termsof diagnosis,” Dr Bahn argues. “Thatmeans that we have to collect a lot of datain order to determine if there is a ‘bio-marker’ for specific clinical features, forexample, cognitive impairment, or a bio-marker specifically correlating with per-secutory ideas.”
According to Professor Bullmore, weneed to “get psychiatry looking morelike neuroscience”, where brain scansare routinely used to diagnose braintumours. “If you believe in the biologi-cal opportunity for psychiatry, which Iobviously do, then you’d like to imaginethat 20-30 years down the line we’renot really going to be using the termschizophrenia as a diagnosis.What we’recalling schizophrenia at the momentwill be much more deeply understood.When someone comes along withschizophrenia syndrome, we’ll be ableto make a more precise sub-diagnosis.”
Our poor understanding of the bio-logical basis of psychiatric disordersresults not only in delayed, but also ininadequate treatment. Drugs do notalways work effectively and often giverise to significant side effects, oftenresulting in the patients refusing to takethe medication.
“At the moment, it is a hit and miss sit-uation for the pharmacological treatmentof psychiatric illness.We just pluck... oneof the medications available and titratethem out. Often, for several months, wewait and see [that] they are not working.Then we have to start with the next one.If we had biomarkers to guide us… wewould have a much more objective wayof addressing the needs of the patient,”Dr. Bahn explains.
Another problem is that many patientsdo not have immediate access to therapy.The standard waiting time for psy-chotherapy is 6-9 months.
One of the more successful forms ofpsychotherapy is cognitive behaviouraltherapy (CBT), which has been usedwith varying degrees of success in thetreatment of schizophrenia, obsessive-compulsive disorder, anxiety anddepression. CBT involves recognizingunhelpful or destructive patterns ofthinking and reacting, and modifyingor replacing these with more realisticor helpful ones.
According to the UK’s National Institutefor Health and Clinical Excellence(NICE),“it [CBT] is of equal effectivenessto antidepressants”. The NICE guidelineson depression also cite clear evidence that,although expensive at the early stages,CBTtreatment is very cost-effective in the longrun. Richard Layland, a member of theHouse of Lords, argues that “psychologicaltherapies like CBT, which are in heavy
demand, are not adequately available”. Heestimates that some 10,000 extra therapistsare needed to meet the current demand.
However, Professor Bullmore points outthat not all psychotic patients benefit frompsychotherapeutic approaches. “CBT is apowerful non-pharmacological techniquefor all kinds of psychiatric problems, but Ihave to say that blokes in particular are notgood at it. Our adults with psychosis don’treally want to sit around talking about stuff.Some of them do, but it doesn’t necessari-ly suit everybody.”
Professor Ed Bullmore is co-director ofthe Brain Mapping Unit at the Department ofPsychiatry and Clinical Director of the Behav-ioural and Clinical Neuroscience Institute atthe University of Cambridge. He uses MRIbrain scanning to investigate schizophreniaand other neurodevelopmental disorders.
Dr Sabine Bahn is a practising psychiatristand head of the Cambridge Centre for Neu-ropsychiatric Research. Her group useslarge-scale molecular profiling technologiesto define the molecular basis of schizophre-nia and bipolar disorder.
Professor Tim Crow is Honorary Directorof the Prince of Wales International Centre forResearch into Schizophrenia and Depressionat the University of Oxford. He uses geneticand neuroimaging techniques to examine theneural basis of schizophrenia.
Professor Trevor Robbins is head of theDepartment of Experimental Psychology andDirector of the Behavioural and ClinicalNeuroscience Institute at the University ofCambridge. He investigates the underlyingneural mechanisms of psychiatric and neuro-logical disorders.
It’s really a whittling down of a most likely
diagnosis, where you askpatients questions such as‘are you hearing voices’;suggestive questions thatare neither specific nor
very sensitive
- Dr Sabine Bahn
“
”
CBT is a powerful non-pharmacological
technique for all kinds ofpsychiatric problems, but I have to say that blokes
in particular are not good at it
- Professor Ed Bullmore
“
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The use of animals in neuropsychi-atric research is a source of endlesscontroversy.
Preclinical safety testing, whichinvolves testing drugs on animals, isrequired by UK law before a new drugcan be released for the human market.Professor Bullmore explains that “Idon’t see how you can develop drugssafely without some period of preclini-cal testing. Would people really ratherthat drugs went straight into humansfollowing Parexcel [the drug involved inthe July 2006 clinical trial scandal]?Even where you have an animalmodel… there are still risks. But. I thinkthese risks are mitigated a lot by pre-clinical testing.”
It is clear that in order to treat psy-chiatric disorders more effectively, weneed to better understand their biolog-ical basis. However, there is no consen-sus on the best way to do this. Thestudy of post-mortem brain tissue islimited by artefacts such as medicationand drug abuse, which affect the brainand can mask the underlying neural
features of the disease. Anotherapproach is to study the brains of livinghuman patients. However, ethical, legaland practical considerations severelyrestrict the information that can begathered from human patients. This iswhy scientists turn to animal testing inpsychiatric research.
Some experts argue that animal mod-els provide us with otherwise unattain-able insights, whereas others disputetheir relevance to human psychiatricdisorders.The key question is: how cananimal models be used to learn more
about psychiatric disorders and todesign innovative drugs? Can you actu-ally make a rat psychotic?
Dr Bahn is not convinced. “Whetherthese animal models are aetiologicallyrelated to schizophrenia has to be verydoubtful, as we don’t know the aetiolo-gy of the disorder at all.”
Professor Crow believes that “Thisapproach [of using animals] is potential-ly useful up to a point. It establisheswhat we know about neuroanatomyand neuropharmacology.” However, heargues that what critically matters aboutpsychiatric illnesses, such as psychosis, isthat they are “human-specific”, and thatneuropsychiatric research will eventual-ly “tell us a lot about what it means tobe human”.
In contrast, Professor Robbins feelsthat “[specific] symptoms can probablybe modelled in animals, as the samebasic brain systems—the neurotrans-mitter systems—are present in humansand they mediate much the same kindof behaviours. Even something as com-plex as schizophrenia can be brokendown into its constituent parts. Someaspects of schizophrenia… depend onvery ancient brain systems, which arepresent in other animals.”
Animal Controversies
Neuropsychiatric research will tell us a lot
about what it means to be human
- Professor Tim Crow
“
”
How Do SSRIs Work?
The neurotransmitter (serotonin, A)is stored in vesicles (B) within thepresynaptic neuron (terminal endshown, C) and is released into thesynaptic cleft (space betweenneurons). Some serotonin entersthe receptors (D) of the postsy-naptic neuron (E), causing thetransmission of a nerve impulse.
Some of the serotonin flowsback (upward arrows) and isrecycled within the presynapticnerve cell.This reuptake of sero-tonin from the presynaptic neu-ron impedes the transmission ofneural signals.
The selective serotonin reuptakeinhibitor (SSRI) drug molecules (F)fit and block the reuptake channels(G), causing more of the serotonin toremain in the synaptic cleft, and to influ-ence subsequent synaptic transmission.
A
B
C
D
E
F
G
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Text adapted from www.itmonline.org
Selective serotonin reuptake inhibitors (SSRIs)—one of the more successful classes of psychiatric drugs includingProzac, Paxil and Lexapro—mainly target the serotonin system and are used to treat a variety of mental disorders.
They work by allowing the neurotransmitter to remain in the synaptic cleft (the space between the pre and post-synaptic neurons) for a longer time, thereby stimulating neural transmission.
Although SSRIs are markedly more effective than previous drugs, many patients don’t respond positively to them,or become dependent on the medication. For example, a review of clinical studies using SSRIs found that 27% ofpatients withdrew from the studies, due to either adverse events or lack of efficacy.
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Recent research in neuropsychiatry ischarting new frontiers towards under-standing the biological underpinning ofspecific mental disorders. Although thisresearch area holds much promise, it isstill at a very early stage.
Professor Tim Crow was among thefirst to link changes in brain structurewith schizophrenia, in 1976. He cau-tions that “although schizophrenicpatients show an enlarged region of thebrain, termed the cerebral ventricles,when compared with healthy volun-teers, this finding is quantitative and nota discrete marker, as there is overlapbetween patient and control groups.”
In Professor Robbins’ view, biologicaltesting for the diagnosis of psychiatric ill-nesses is entirely possible. Indeed, he says:“I don’t necessarily think it will be limitedto biochemical markers; I think there arestrong behavioural and cognitive traits, andother types of social symptoms,which mayalso be predictive. This might have enor-mous therapeutic potential.”
A recent study from Dr Bahn’s group,published last year in PLoS Medicine,found elevated levels of glucose—themain energy source in our bodies—in thebrain and cerebrospinal fluid (CSF) ofschizophrenia patients. This may be a bio-marker for schizophrenia. Her groupfound that schizophrenic patients did notmetabolize glucose as well as controls, butappeared to use a different energy source,lactate, in their brains and CSF.
Professor Bullmore recently publishedresearch in Proceedings of the National Acad-emy of Sciences showing that, in non-psy-chotic individuals, early development ofmotor functions was linked to better‘executive functions’, such as planningand abstract thinking in adulthood, and toincreased amounts of grey matter in thebrain. By contrast, schizophrenia patientshad delayed motor development in earlylife and impaired executive functions inadulthood. However, these motor devel-opment abnormalities are not alwaysassociated with the development of psy-chosis in later life.
Professor Bullmore warns that carefulforethought is needed to ensure thatpatients benefit from new diagnostictechniques. He says: “If you believe thatlong-term neurodevelopmental abnor-malities lead up to development of psy-chiatric symptoms, you might argue that
there is something you might be able todo, to intervene perhaps 10 years earlier.Now that’s quite attractive as a concept,but we’re not there yet.”
Indeed, early intervention could comeat a high cost to patients and their fami-lies, especially in cases of misdiagnosis.“You can’t say to somebody:‘I think yourchild might develop schizophrenia in 10years’ time’, unless you can quantify theprobability that you’re wrong. Otherwise,you’re not really giving the parents or thechildren information, you’re just fright-ening them.Also, you’ve got to know thatthe intervention you’re going to offer isreally going to work.”
He argues: “My favourite for an earlyintervention would be more along thelines of physical therapy, rather than psy-chotherapy.Think about the observationsthat children who later go on to develop
schizophrenia are abnormal in terms ofmotor function and social function. [Helpwith] motor function, in particular forboys, is something that you could quiteeasily offer as a treatment withoutappearing too clinical.”
However, this type of early interven-tion suggested by Professor Bullmoredoes not convince Dr Bahn. She feelsthat a motor test would not be verysensitive or specific, as children oftenshow delayed development for otherreasons. Rather, she believes that bio-markers, such as the high glucose levelsin schizophrenia patients, have bettersensitivity, and “could enable us todevelop new, early or pre-symptomatictreatments to improve outcomes, or
even prevent disease symptoms”. Sheplans to commercially develop hernovel biomarker findings through aUniversity of Cambridge spin-outcompany called PsyNova Ltd.
Highly sensitive biological diagnostictests targeted to the treatment of mentaldisorders are already underway. In 2006, abiochemical company called LGC devel-oped and marketed a DNA-based test, thefirst of its kind available in psychiatry,which, it claims, predicts whether a patientwill respond well to the antipsychotic drugclozapine. The test is based on long-termgenetic and psychotherapy studies con-ducted at the Institute of Psychiatry, King’sCollege London.
However, the government has not yetdecided whether to fund such tests. Ifgovernmental funding for mental healthdoes not increase, is there a potential for atwo-tiered mental health system, in whichthe wealthy will be able to obtain individ-ualized screening and tailored treatment,whereas society’s poor will not?
Professor Bullmore says:“I suppose it’sa potential [scenario].There are a lot ofunknowns in that equation. [What is]the level of NHS funding? How quicklywill existing therapies come off patentand be replaced by much cheaper gener-ics? Will that produce headroom in NHSpharmacy budgets for investing innewer, more expensive things?
Suppose a drug company had reallyunderstood what was going on in thebrain as someone becomes psychotic,[developed] a new drug targeted to afaulty mechanism, and it was shown thata year or two’s treatment with thisentirely new kind of drug was sufficientto prevent the emergence of chronicpsychosis. If you had a drug like that, itwould have to cost a lot to be moreexpensive than the long-term costs ofuntreated psychosis. So, the argument ofa two-tiered mental health system maynot be relevant.”
Hannah Critchlow is a PhD student in theDepartment of Physiology, Development and
Neuroscience
Peter Davenport is a PhD student in the Department of Biochemistry
Michael Marshall is a Scientific LiteratureCurator in the Sanger Institute
I don’t think it will be limited to biochemicalmarkers; I think there arestrong behavioural and
cognitive traits, and othertypes of social symptoms,
which may also be predictive
- Professor Trevor Robbins
“
”
The Future of Diagnosis and Treatment
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The development and delivery of drugsfor ‘diseases of poverty’ could be revolu-tionized by a new patent scheme, accord-ing to the economist and philosopherProfessor Thomas Pogge from ColumbiaUniversity in New York City.
Pogge outlined his proposal inCambridge on 22 November at the firstannual Routledge Philosophy Lecture,describing his scheme as “simply hangingthe carrot in the right place”.
Under the current system of druglicensing, the world’s poorest are leftwithout the lifesaving drugs readily avail-able in richer countries. To solve this,Pogge proposes a new system of adminis-
tering intellectual property (IP), to runalongside the current scheme. IP rightsare the rules that govern the reproduc-tion, sale and use of ideas and inventions,from new technologies to music.
Under Pogge’s plan, firms would nothave proprietary rights over a drug butwould instead receive an annual financialreward proportional to the impact it hason relieving the global disease burden.These rewards would be underwritten bygovernments, with different countriescontributing according to their means.Asa result, serious but neglected diseaseswould become a more attractive targetfor drug companies, because of the
potential for a big impact and big money.At the moment a World Trade
Organization treaty, the Agreement onTrade-Related Aspects of IntellectualProperty Rights (TRIPS), sets the inter-national standards for IP rights. TRIPSwas meant to provide incentives forpharmaceutical companies to invest indrug development, by granting them a20-year monopoly to fix the prices oftheir new drugs.
Pogge argued that this system imposesa huge health burden on poor popula-tions, by pricing new medicines out oftheir reach and by discouraging researchinto drugs for diseases of poverty. ET
InBri
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08 Lent 2007
In Brief
Artificial Pancreas for Children
The Scientific Society has several high-profile speakers lined up for Lent Term. Professor Ross Anderson from the ComputerLaboratory in Cambridge will describe his work on ID cards and nationwide databases. Later in the term, UCL’s Professor LewisWolpert, one of the key figures in developmental biology, will give a talk. Other speakers include crystallographer Professor SirTom Blundell FRS, protein engineer Professor Sir Greg Winter and stem cell biologist Professor Miodrag Stojkovic. MM
www.scisoc.com
SciSoc Events
Access to Essential Medicines
A new research project called MES-SAGE will use cyclists and pedestrianswearing environmental sensors to trackpollution levels. MESSAGE is a £3.5-million, three-year initiative set up inOctober 2006. It aims to use state-of-the-art sensors attached to people andvehicles to monitor air pollution.
The scheme, organized by ProfessorJohn Polak at Imperial CollegeLondon, will study the impact thatbuildings, streets and local weather haveon pollution levels in Cambridge.
According to the MESSAGE projectaims, cheap and easily available sensordevices can be attached to people or
vehicles.These will act as ‘mobile envi-ronmental probes’ studying how pollu-tion levels change in real time.
The team plans to analyze how trafficpollution changes in particular locationsand under different environmental con-ditions. Individuals out in Cambridgeduring the day, on bicycles or walking,will be particularly suited to carryingsensors to record pollution levels. Otherparticipating cities include Newcastle,Leeds and Southampton.
If you are interested in volunteering forthe scheme, please contact MichaelSimmonds ([email protected])of the Cambridge eScience Centre. MP
Detecting Pollution on the Go
Cambridge scientists report that the development of an artificialpancreas for children with Type 1 diabetes is underway.
Type 1 diabetes destroys the cells in the pancreas that produceinsulin, the hormone needed to control sugar levels in the blood.Diabetics must manually test their blood sugar level and givethemselves an insulin injection up to six times a day.
The Juvenile Diabetes Research Foundation has provided£500,000 to support research led by Dr Roman Hovorka in theDepartment of Paediatrics at the University of Cambridge. Histeam is working on an accurate, automated and painless solution.
The artificial pancreas will measure blood sugar level on aminute-to-minute basis via glucose monitors. The signal will betransmitted wirelessly to a hand-held computer that calculates theamount of insulin needed and delivers it with an insulin pump.
The device will be trialled on diabetic children from January.If successful, this device will considerably improve their lives. Itmay also significantly reduce the risk of hypoglycaemia, a com-plication associated with low blood sugar levels that in extremecases can lead to coma. SD
Vin
nyR
Around one trillion US dollars were spent on clothing lastyear alone. However, a recent study from the CambridgeInstitute for Manufacturing may have prompted a pause forthought in the fashion industry.
The study suggests that manufacturers should increase theuse of organic cotton, place more emphasis on the durabil-ity of their clothes and raise prices to encourage fewer pur-chases. It also calls for research into less environmentallydamaging materials and production methods, and the intro-duction of an ‘eco tax’ on purchases.
The study also outlines how consumers can help toreduce the environmental impact of the clothes they buy. Itemphasises buying fewer clothes and using them for longer.Clothes should be washed less often, at lower temperatures,using ecologically-friendly detergent. Old clothes should berecycled rather than discarded.
It is hoped that these measures will reduce carbon emis-sions from the production and washing of clothes, as well asthe landfill space occupied by discarded clothing. LA
Environmentally Friendly Fashion
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9www.bluesci.org
Jonathan Gledhill explains why Darwin’s dogma may revolutionize chemistry
Charles Darwin gave biology its cen-tral dogma: the concept of naturalselection. He believed that thoseorganisms best suited to their environ-ment would survive and reproduce.Scientists such as Professor JeremySanders from the University ofCambridge are currently asking if thisprinciple can be applied to the devel-opment of new chemicals. ProfessorSanders’ philosophy is simple: why notlet nature do the work for us?
The modern world is constantly cryingout for new molecules. Health servicesdemand new drugs to combat the everincreasing number of pathogens that havedeveloped immunity to established treat-ments.Traditional chemistry is strugglingto keep up with these demands.
Early approaches to drug discoveryinvolved a degree of serendipity.Nowadays,scientists design drugs to interact with par-ticular proteins or nucleic acids, referred toas ‘targets’.A trial and error approach is gen-erally adopted to isolate a molecule thatassociates with the target and elicits a drug-like effect.The isolated molecule must notbind indiscriminately to other targets, norshould it be toxic.A molecule that satisfiesthese criteria is called a lead.
Once a lead is identified it must beoptimised to bind very tightly andspecifically to the target. The potencyand physiological effect of the optimisedlead is subsequently assayed in the testtube, prior to conducting tests in animalsand, finally, in human subjects. Each stageinvolves the lengthy and repetitiveprocess of chemical design, synthesis andevaluation. For each drug on the markettoday, at least 10,000 related moleculeswere scrupulously synthesised and tested.
The inefficiency of the drug designprocess is a consequence of our limitedunderstanding of the subtleties ofmolecular recognition—the process bywhich a molecule binds to a target.Thisinefficiency has both a time and a finan-cial penalty. It can take up to 12 yearsand close to $1 billion to develop a drugand take it to market. The enormity of
this problem has led scientists to seekout more elegant solutions that canmake drug design quicker and cheaper.
Professor Jeremy Sanders is a pioneer ofa solution based on the principles of evo-lution and called Dynamic CombinatorialChemistry (DCC). DCC is based on theobservation that evolution has successful-ly moulded organisms to fit their environ-ment; thus, it seems feasible that, in theright conditions, a molecule could evolveto bind to a specific target. “We havedeveloped an entirely new approach,inspired by the example of evolution andselection in biology”, explains ProfessorSanders, who has set out the essential fea-tures of DCC as early as 1992, and is aleader in this ever-growing field.
DCC requires a diverse molecule pop-ulation, known as a dynamic combinato-
rial library (DCL), and a selection pres-sure to distinguish a lead so that itbecomes more numerous. The immunesystem provides an example of such aselection occurring naturally. It contains alarge library of different antibodies; ofthese, only those antibodies that bind to,and thereby neutralise, the infectingpathogen become selected and amplified.
A DCL contains thousands of uniquemolecules. Each molecule is assembledfrom a different number of basic buildingblocks in different orientations. Thus, themolecules vary in size, shape, stability andcharge.Only a subset of a diverse DCL willbe able to interact with the target.
A key feature of a DCL is that theassembly of the molecules is totallyreversible. This means that the library isconstantly changing as molecules swapbuilding blocks.These exchange reactionsmust meet a number of stringent require-ments, such as occurring on a practicaltimescale, being able to be frozen, and tonot require an extreme temperature, pres-sure or pH. Extreme conditions may dis-rupt the delicate interactions within thetarget, as well as between the target and abinding molecule.
A DCL can be described as ‘dynamicand adaptive’, because the assembly ofthe molecules is influenced by the pres-ence of a target. When a molecule in aDCL binds the target, this molecule isstabilised, and the equilibrium becomesbiased toward the formation of this mol-ecule. In evolutionary terms, this mole-cule is the fittest. It is selected andenriched in the population at theexpense of all other molecules. “Thebeauty of our approach is that we designthe experiment rather than the mole-cule. The molecules design themselves,”comments Professor Sanders.
Theoretically, DCC appears to be thesolution to the enormous demand fornew molecules. In practice, however,there is still a lot of work to be done.For example, increasing the number ofthe reversible reactions and the size ofthe combinatorial library are significantchallenges. Despite these difficulties,Darwin’s dogma may transform the waywe make new chemicals. Chemistry, itwould seem, is set to evolve.
Jonathan Gledhill is a PhD student in theMRC-Dunn Human Nutrition Unit
A collection of molecules (coloured blocks) reversibly bind to form a dynamic mixture ofassorted receptors.The addition of a template molecule (purple object) selects the “fittest”receptor from the dynamic library.
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Chemistry Steals Tricks from DarwinChemistry Steals Tricks from Darwin
The modern world is constantly crying out fornew molecules. Professor
Sanders’ philosophy issimple: why not let nature
do the work for us?
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The principles of evolution suggestthat humans are nothing more thananother animal species. Yet, we havealways had the tendency to identifyourselves as different, in some wayspecial and separate from the rest ofthe animal kingdom.Among the maindifferences between humans andother animal species are our use oftechnology and our highly complexsocieties, which display a division oflabour unmatched in any other animalgroup. But, why are humans, and notother species, able to develop technol-ogy and complex societies?
Traditionally, scientists have consideredthree main behavioural features to beuniquely human: tool usage, language andour ability to teach. However, recentresearch, which points towards the pres-ence of these behaviours in other animalspecies, prompts the need to revise ourunderstanding of what is at the basis ofhuman uniqueness.
Studies of animal tool use, predomi-nantly looking at primates, have sug-gested that chimpanzees can use tools.One notable example is Jane Goodall’s
observation that, in their natural envi-ronment, chimpanzees fish for termitesto feed on by using sticks. An exampleof tool use in other animal species is the
New Caledonian crow, a bird speciesthat uses a range of tools in the wild.These crows are capable of producingtools de novo from natural materials,such as twigs and plant leaves. Therange of tools found in their habitatshows that the knowledge of tool usagemay be transmitted culturally betweendifferent birds and bird populations.
Research led by Professor Kacelnik atthe University of Oxford suggests thatcrows use problem-solving skills whenacquiring food. The crows appear to
choose tools of an appropriate length,diameter and shape to obtain the foodfrom holes and traps. One celebratedcrow, named ‘Betty’, was observed to cre-ate a hook from a straight wire in orderto reach for food. In contrast, chimps andtwo-year old toddlers do not understandhow to use hooks.
Studies indicate that the birds may usetools sequentially: first, use a tool to reachfor another tool, and, then, use the sec-ondary tool to reach for the food. Suchan instance of ‘rational’ behaviour sug-gests that crows understand the conse-quences of their actions, and may evenplan ahead. This line of research has ledsome scientists to conclude that birdsmay have intelligence comparable to theintelligence of primates. Although moreresearch is needed to corroborate thesefindings, these studies already suggestthat the ability to use tools is not anexclusively human trait.
As the main medium for the transmis-sion of culture and expertise to futuregenerations, language is another compo-nent crucial to the development of soci-
eties. Language is thought to be neces-sary for the development of self-aware-ness and our understanding of the mindsof others—so-called, ‘theory of mind’.Having a theory of mind enables us toreason about the intentions, thoughtsand emotions of other people, and, pos-sibly, to put ourselves in their shoes.Language is regarded as a vital part ofthis reasoning process, traditionally con-sidered to be uniquely human.
Among the key characteristics of thehuman language are its recursive grammar
and its vast lexicon (tens of thousands) ofarbitrary, learned words, representinglong-term associations between memoryand structured pronunciations. Some sci-entists have argued that the sole distin-guishing feature of human language isrecursion, or the process that a rule under-goes when one of the steps of that ruleinvolves rerunning the entirety of thesame rule. Recursion allows the unlimitedextension of language by embedding sen-tences within sentences. For example,‘Mary kissed Tom’ could be embeddedinto a frame of 'X verb Y' to make 'Jonsaid Mary kissed Tom’, which can furtherbe embedded to give 'Jane heard, Jon said,Mary kissed Tom’. Noam Chomsky hasargued that “no species other thanhumans has a comparable capacity torecombine meaningful units into anunlimited variety of larger structures, eachdiffering systematically in meaning”.
However, a recent study published inNature suggests that other animal speciesmay also use recursive grammar.Gentner and colleagues trainedEuropean starlings to recognize acoustic
10 Lent 2007
Mico Tatalovic questions the behavioural basis of human uniqueness
Scientists have considered three main
behavioural features to beuniquely human: tool usage,
language and our ability to teach
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Are humans special?
Crows are capable of producing tools de novofrom natural materials, such as twigs and plant leaves
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patterns defined by recursive grammar,to classify new patterns defined by thisgrammar, and, then, to exclude agram-matical (non-recursive) patterns. Basedon these results, they argued that “thecapacity to classify sequences fromrecursive, centre-embedded grammars,is not uniquely human”. Undoubtedly,these findings must be replicated toestablish the validity of Gentner’s claim.However, these findings suggest that theelements, which traditionally have givenlanguage its privileged status as a humanfaculty, may not be solely the domain ofhuman beings.
Our ability to teach is another strongcandidate for the X-factor that separatesus from other animal species. Sociallearning is commonplace in most ani-mal species. However, until 2006, limit-ed data existed to support the idea thatmembers of another animal speciesactively teach their kin at no apparent,immediate benefit to themselves, but,rather, mainly to the benefit of the ani-mals being taught. However, ProfessorClutton-Brock and colleagues at theUniversity of Cambridge have collectedextensive data on meerkats in the
Kalahari Desert, South Africa thatoppose this idea. Meerkats are social,carnivorous mammals that live in familygroups of up to 40 members. Groupmembers co-operate in rearing, babysit-ting and feeding their pups. The group
shares the tasks of guarding its membersagainst predators and digging commu-nal holes used to escape any threat.
Meerkats’ use of specific calls foridentifying different types of predators,as well as threat levels, suggests that theyhave a ‘language’ of their own. Pups usecalls to beg for food—mainly inverte-brates—and adults can tell the age ofthe pups by their calls. Adult meerkatshave been found to respond differentlyto begging calls from pups of differentages. Meerkats have recently gainedmuch popularity due to evidence thatthey teach their young how to dealwith prey, by giving pups more chal-lenging prey, as they get older. Theyoungest pups are given dead prey,whereas the most dangerous prey, thescorpion, is first given to pups with thedeadly stings removed. Adults alsonudge their pups to encourage them toexamine the prey, and to learn what
behaviour to expect from the prey,before having to deal with a potentiallydeadly one.
It is becoming apparent that the evi-dence for what has been considereduniquely human behaviour is not asclear-cut as previously thought, orhoped. Current research suggests thatwe are not the only animals to adapttools, to communicate via a complexlanguage, and to teach one another.Perhaps, it is the combination of thesethree characteristics, not yet found tooccur in any other animal species, thatmakes us so different from the rest ofthe animal kingdom. Just how impor-tant these characteristics are, separatelyor together, for making us what we areremains a mystery that will continue todrive further study.
Mico Tatalovic is a PhD student in the Department of Zoology
Left: A baby meerkat. Right: Meerkats in a social setting.
Chimpanzees photographed on one of Jane Goodall’s research expeditions. Left: A chim-panzee fishing for termites. Right: Fifi and an infant chimpanzee.
11www.bluesci.org
The evidence for what has been considereduniquely human behaviour
is not as clear-cut as previously thought
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The use of mathematical equations tomodel complex patterns plays a vitalrole in science, physics and econom-ics. However, there are also dangers inputting too much trust in one simpli-fied formula. Occasionally these dan-gers become a dreadful reality, as hap-pened in 1987, when stock marketsworldwide suffered one of the biggestfinancial crashes of the century. Morerecently, in 1998, thousands ofinvestors in the Long-Term CapitalManagement (LTCM) hedge fundsaw their monies disappear, as LTCMlost over $4.6 billion in less than fourmonths. Who was to blame for thesedisastrous losses?
Few mathematical equations form thesubject of popular articles and books, andfewer still are credited with crashing astock market. In the 1990s, Forbes busi-ness magazine pointed its finger directlyat the Black-Scholes equation, as the for-mula behind the disastrous miscalculationof the stock market prices. In recognitionof the importance of this equation, theNobel committee awarded its 1997Economics prize “for a new method todetermine the value of derivatives”, toMyron Scholes and Robert Merton.Fischer Black, who also gave his name tothe formula, became ineligible for theaward, due to premature death in 1995.
The Black-Scholes equation was devel-oped to calculate a fair price for thefinancial derivatives called options.These
are contracts that can be bought just likeinsurance policies, which give you theright to buy or sell a share, at a future dateand for a pre-agreed price.This practice isas ancient as trade itself; merchants fromthe Phoenicians to the Romans frequent-ly traded options on their goods.
In 1900, this ancient system stood onthe brink of revolution driven by theapplication of scientific options pricing.Louis Bachelier, a PhD student of thefamous mathematician Jules HenriPoincaré, decided to apply ‘random walktheory’ to options, in his thesis Théorie dela Spéculation. This was the notion that
stock market prices fluctuate randomlywithout being affected by past pricemovements, simulating the same jaggedprice variation in options.Remarkably, hiswork came five years prior to Einstein’spaper that applied random walk theory toso-called ‘Brownian motion’, to describethe random movements of gas particles.
Bachelier’s scientific model of pricingoptions presented a new approach to anold problem. Unfortunately, it was flawed
in several ways. Firstly, it failed to takeinto account catastrophic events such asstock market crashes, because it assumedthat the probability of extreme price fluc-tuations was negligible. Crashes may beinfrequent, but they are all too real.Thisflaw is inherent in a model based on ran-dom walk theory, where the distributionof probabilities is said to be ‘normal’. Anormal distribution with price on thehorizontal axis and probability on thevertical assumes a bell shape, with a sharpski-jump drop followed by a gentle shorttail—too short, in fact, to accuratelyreflect the reality of extreme share pricemovements. Crucially, when calculatingan option’s price, Bachelier’s model wasalso unable to calculate the risk premium,or the financial value of risk. This prob-lem remained unsolved for many years, asthe amount of risk investors are willing toaccept is anyone’s guess.
It was Black and Scholes, 70 years later,who realized that the risk premium cal-culation could be avoided altogether.Their inspiration came from gamblerswho covered their losses by betting inopposite directions. In a portfolio with amixture of shares and options, Black andScholes saw that they could create a risk-free investment, since the movement ofshares and option prices would offseteach other. The underlying point is thatthe prices of shares in companies movecompletely randomly. If you try pickingshares by throwing darts at the financial
12 Lent 2007
Tristan Farrow tells the story of the formula that crashed the stock market
For the first time in history, it seemed that
you could play the markets risk-free
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Black-ScholesThe black hole of maths and money
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pages, as a group of US academics tried todo in the 1930s, you may discover thatyour portfolio will perform as well as anyprofessionally managed fund.
After further refinement by RobertMerton, who adapted the equation for afast-paced market, the formula wasfinally unveiled in 1973. Its impact wasvirtually immediate, spawning a trillion-dollar market for financial derivativessuch as options, as well as the growth ofgiant hedge funds managing share-option portfolios. When TexasInstruments began making calculatorswith an inbuilt Black-Scholes button toallow traders to calculate option prices,they were snapped up like candy in aplayground. The world was bedazzledand, for the first time in history, itseemed that traders could play the mar-kets risk-free.
The Black-Scholes formula is obtainedby solving a differential equation thatclosely resembles the equation describingthe diffusion of heat, which emphasizesits relationship to physics. The originalformula is then converted to the expres-sion used for ‘call’ options, which allowone to buy a share at a specific date inthe future. A modified expression is alsoused for ‘put’ options, for selling shares.The equation takes as its inputs the priceof the share it underwrites, the length oftime before the date on which theoption can be used, the interest rate, and,significantly, the so-called ‘volatility’, orthe amount by which a share price canbe expected to fluctuate. It can belikened to the jitter of particles in a gas,which bang into each other ever moreviolently with higher temperatures.
The formula relies on a number ofassumptions.The most significant of theseis that fluctuations in the share price fol-low a normal distribution, like in
Bachelier’s model from 1900, and that thevolatility is constant during the lifetimeof the option. Neither assumption isquite true. The assumption of a normaldistribution for share values fails to pre-dict extreme price fluctuations and mar-ket crashes, while volatility itself can fol-low a ‘random walk’. Blindly trusting theformula to calculate option prices givesone a rosy picture of the world.
Despite the warnings of Forbes maga-zine, this costly lesson was driven home
in 1998 to thousands of investors. Theformula’s inventors were directly toblame. In 1994 Robert Merton andMyron Scholes set up a company, LongTerm Capital Management (LTCM),intending to play the markets using themodels that would eventually earn themthe Nobel Prize. LTCM was a “giganticvacuum cleaner sucking up nickels fromall over the world”, according toScholes. Cashing in on their iconic sta-tus as the fathers of modern finance, thestart-up raised three billion dollars,which the company set forth to multi-ply, with average returns of 35% in thefirst three years.
Then, the unpredictable happened.The economies of South-East Asia skid-ded to a halt in a domino effect, sparkedby the collapse of property prices inThailand in 1997. Banks went out ofbusiness and loans went unpaid world-wide. Yet this was only a foretaste. Thebig shock came in August 1998, whenRussia suddenly announced it would
cease all foreign debt payments.Pandemonium reigned in the financialworld, with all indicators jittering furi-ously back and forth, reflecting the panicin the market. By this time, LTCM hadbets topping one trillion dollars, with itsmodels now as useful as a dud compass.Models based on the normal distribu-tion work well on calm days, but theysimply could not predict such cata-strophic events, nor could they point theway out of the rut. Finally, the US
Federal Reserve stepped in to bail outLTCM, preventing it from taking all ofWall Street down along with it.
Today, the Black-Scholes formula isstill used millions of times each day byderivative traders and fund managersworldwide.Astonishingly, it is used morethan ever before, but with a significantdifference: Black-Scholes no longer pre-dicts option prices. Instead, it is beingused in reverse. The option’s price istaken as a given, and is plugged into theequation in order to calculate thevolatility of the share price. This doesnot address the problem that volatilityitself does not follow a genuine normaldistribution for large fluctuations.However, it does relieve the equation’sAchilles’ heel of direct option pricingfor extreme share price fluctuations.Investment decisions can now be madewith a very useful tool that comple-ments, rather than replaces, the qualitiesthat traders value above all—instinct, gutfeeling and experience.
Outside the world of finance, largecompanies have also found a way ofadapting the Black-Scholes equation. It isused to calculate the cost of business deci-sions, such as closing down plants or buy-ing new equipment, by treating them asoptions.The trend of modelling econom-ics, and even certain social and historicalphenomena, is booming, and looks set tospawn new fields of interdisciplinaryresearch. Econophysics, a field barely inexistence ten years ago, now features inseveral dedicated academic departmentsaround the globe.
Despite all this, the next time a magicformula is unleashed on us, we woulddo well to remember how the Black-Scholes equation, with its beauty andapparent simplicity, lulled many into anunjustified sense of confidence. AlbertEinstein once said that “if you are out todescribe the truth, leave elegance to thetailor”.The costly lesson that Black andScholes gave, teaching us howintractable the human element can be, isas valuable as the equation itself.
Tristan Farrow is a PhD student in theCavendish Laboratory
13www.bluesci.org
The next time a magic formula is unleashed on us,we should remember how the Black-Scholes equation
lulled many into an unjustified sense of confidence
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S is the current share price, σ is the share pricevolatility, r is the interest rate, T is the time before anoption’s exercise date,N is the probability of exercise,and L is the expected share price on maturity.
The equation says that the option price, C, will behigher when S, σ, r,T, N are all high. N is assumedto follow a normal distribution, since it depends onthe expected share price on the date of the option’smaturity, L. The lower the share price at maturity,the higher the option’s overall price.
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The recent increase in biodefencespending, while a step in the rightdirection, is not enough. Among UKscientists, bioterror expertise is ataboo, an area some scientists avoidaltogether. We need dedicated scien-tists and state of the art laboratories,equipped to handle the most patho-genic bioagents, in order to gain theexpertise needed to counteract bioter-ror attacks. To best prepare for anymedical, political and social crises thatmight ensue, biodefence needs to be afinancial priority for the government.
In Britain, only a handful of scientistswork on bioagents, with most biodefence
research occurring at the HealthProtection Agency (HPA), which is partof the NHS, and at the Defence Scienceand Technology Laboratory (DSTL), inthe Ministry of Defence. DSTL hasapproximately 200 scientists working onbiodefence. Only one third of theseinvestigate pathogens for which limitedtreatment is available, and only ten workwith life-threatening pathogens forwhich no treatment is known. HPA hasonly 70 scientists working in biodefence,on an emergency response program, andonly 20 of these work with the most haz-ardous pathogens.
In the months following the 9/11attacks, anthrax letters became the stan-dard biological threat. However, anthraxis only one of many bioagents, some ofwhich, like the viruses that cause Ebolahaemorrhagic fever, can pose muchmore serious risks. Animals are thoughtto be the natural reservoir of theseviruses, and it is not known how they
are transmitted to humans in the firstinstance. The incubation period of theviruses ranges from two to 21 days, withinternal and external bleeding amongthe worst symptoms seen in infectedindividuals.There is no direct treatmentand most of the infected people die.Ebola and anthrax head a long list ofpotential bioagents, and with so few sci-entists developing methods of preven-tion and treatment, no one can feel pre-pared for a bioterror attack.
The problem becomes even largerwhen we consider the multitude of waysthat bioagents can spread through thepopulation. They can be transmitted by
aerosol, via the water or the food supply,or by person-to-person contact. It hasbeen assumed that most bioagents wouldlikely be delivered in the form of aerosolclouds; hence, aerosol transmission hasbeen a main focus of research. Anotherbiodefence research focus has been vac-cine development.There are many moreareas that require attention, yet only veryfew research facilities dedicated to biode-fence exist in the UK.
Possibly the most important, albeitcontroversial, aspect of biodefenceresearch is the modification of pathogensto anticipate both evolution and thebioterrorists. Outside of the laboratory,many pathogens have short life cycles andevolve considerably between generations.This means that a treatment effective inthe laboratory may not be effective in areal life scenario. Bioterrorists couldgenetically modify pathogens to makethem more dangerous, and baffle doctorsand scientists, as SARS in 2002 baffled
the scientific community worldwide.Nevertheless, biodefence research involv-ing the modification of pathogens isessential for improving our chances ofpredicting the ‘worst-case scenarios’ and,possibly, of preparing for them.
One worst-case scenario involvesundetectable agents, which may fool ourcurrent security systems until it is toolate. Although it can be argued that ter-rorists prefer increased disruption toincreased casualties, it would be in ourbest interest to be able to detect thepresence of a bioagent immediately.Theearlier a bioagent is detected, the fewerdeaths it is likely to cause. Recent bioa-gent detection techniques developed byDSTL have aided the survival of troopsin war. However, more biodefenceresearch is needed make these tech-niques more versatile and applicable to awider number of bioagents.
For example, one bioagent that poses aparticularly big threat is Burkholderiapseudomallei.This pathogen does not pres-ent unique clinical features. It causes eitheran acute pulmonary infection or a bloodinfection. Its incubation period rangesfrom two days to up to 10 years, making itideal for a ‘silent’ bioagent attack.
Researching diseases and scientificproblems other than biodefence is essen-tial for the health and economic well-being of a country. However, theimmense threat posed by bioterrorshould make biodefence research a toppriority for both the government and thescientific community. Increased financialinvestment for biodefence research andcommitment from the scientific commu-nity will improve our protection againstthe potential severity of any bioterrorattack. Biodefence research must preparefor the worst-case scenarios, whetherthey are silent attacks, bioagents modifiedfor maximum lethality, or both.
Collette Johnson is a PhD student at Clare College
14 Lent 2007
Three authors debate the benefits and risks of furthering biowarfare research
Biodefence:Is prevention always better than cure?
With so few scientists developing methods of prevention and treatment, no one can feel
prepared for a bioterror attack
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October 2001 saw the first real example of a new kind of biological attack.The notorious ‘anthrax letters’ incident in the UScaused panic and confusion. Biological and chemical weapons are not new phenomena, but this was. Bioterror, the suggestionthat threats to national security by terrorists could be perpetrated by the use of so-called bioagents, was born.
Since then, the perceived threat of bioterrorism has increased.This is especially so since Kamel Bourgass was caught plottingto use ricin, a lethal toxin that can be extracted from castor bean oil, as a bioagent in the UK. Governments have respondedby increasing biodefence spending. Most notably, the US National Institutes of Health (NIH) increased biodefence spending from$50 million in 2001 to $1.6 billion dollars in 2005.The question is, can our current strategy keep us safe from bioterror? ColletteJohnson, James Shepherd and Rebecca Arkell all believe ‘no’—but for very different reasons.
Predicting Threat, Preventing Panic
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At face value, investing in biodefenceresearch seems like a reasonable strate-gy for protection against bioterror. Todate, worldwide biodefence spendinghas produced positive results. Forinstance, a safe ricin vaccine and a quicktest for anthrax infection are on theway. However, we should be scepticalabout research that engineers deadlybioagents. One rationale for biodefenceresearch is to pre-empt any terroristicattempts to modify existing pathogensfor maximum lethality. However, thereare several arguments against it.
Creating pathogens in laboratories forresearch purposes gives rise to many dan-gers. Bioagents could fall into the wronghands, either by theft or through theirincreased availability to non-scientificstaff.This could lead to incidents such asthat in 2002, when the poliovirus was
recreated from mail-ordered DNA.Regulation to control these risks has beenmet with discord, because many scientistsperceive it as burdensome red tape.
A related risk is that of accidentalexposure, as in the case of the accidentalanthrax release at a military biology cen-tre in Russia, in 1979, which caused 68deaths.This type of public health risk hasprompted locals to try to block the con-struction of a new $178 million biode-fence laboratory in the Boston area.Given the inherent dangers of handlingpathogens, intensifying biodefenceresearch may unwittingly cause moreharm than good.
Further, creating technical expertise inengineering deadly pathogens meansenhancing the chances that terroristscould exploit this expertise.The number
of individuals approved to handle livebioagents has increased tenfold since2001, and, with it, possibly also the risk ofterrorist infiltrating these programs.While there are security tests, RichardEbright, a professor from RutgersUniversity, claims that “Mohammed Attawould have passed those tests withoutdifficulty” (taken from M. Williams(2006) Technology Review: An MITEnterprise). This was exemplified by thelink between the 2001 anthrax letters anda biodefence community insider.
Moreover, when biodefence labora-tories undertake their research, whereshould the information go? Whether itis through the media, the Internet oracademic journals, information aboutengineering deadly bioagents could bemade available to the public. There isno consensus regarding how to ade-
quately censure the dissemination ofthis highly sensitive information.
Reservations similar to those expressedtowards biodefence research can beapplied to some conventional research. Forexample, in 2001, before the anthraxattacks, Dr Ron Jackson, from theAustralian National University, created animmune system evading strain of mouse-pox, whilst working on a contraceptivevaccine to be used for pest control. Thesame technique applied to smallpox wouldundoubtedly have potential bioweaponapplications.This research poses the samepotential threats as biodefence research.Should this kind of apparently innocuousresearch be paralyzed for the same reasons?Should all the laboratories working withpathogens be checked to ensure that theyare not at risk of developing bioagents?
Surely the only thing separatingJackson from the biodefence scientistsis their motives. Where terror andnational security are concerned, publicperception is crucial. The public neverperceived Jackson to be potentially aid-ing bioterror. They might not be solenient when judging scientists deliber-ately trying to develop a more potentversion of smallpox.
Furthermore, it should be noted that,although the threat of bioterror is realand the hazard great, the risk itself is tinyeven when compared with the risk ofavian flu, which while small, is far larger.Biodefence funding could be spent onhigher risk public health problems, orchannelled into public health funding fordiseases already present in the population.These arguments were unfruitfullyvoiced in 2003, when $34 million wasdiverted to biodefence research and awayfrom medical research into diseases suchas HIV. Similarly, US microbiologists in2005 wrote to the NIH warning thatbiodefence spending was draining moneyfrom necessary research into tuberculosisand hepatitis.
Even if the risk of bioterror out-weighed the risks from more presentthreats, the chances of predicting andmanipulating the same bioagents as thoseused by the terrorists would be abysmal.This seems especially true, given that theproponents of the ‘increased spending’strategy eagerly warn us that there are amyriad potential bioterror agents.
Even if the predictive powers of biode-fence research were greater than they are,the risks associated with increased avail-ability and expertise of bioagents are toogreat to justify increased biodefencespending. Despite aiming to make us feelsafer, biodefence research may actuallyincrease the risk of a bioterror attack.
James Shepherd is a second year NaturalScientist, specializing in biochemistry
Rebecca Arkell is a PhD student in theBabraham Institute
Defending the Nation, or Draining the Drug Cabinet?
With the number of individuals approved to handle live bioagents increasing tenfold since 2001,
the risk of a terrorist infiltrating these programs is much higher
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ANTHRAX has a mortality rate of 90-100%, partly due toits diagnosis being confused with a variety of viral and fungalinfections. Vaccines are available against some forms ofanthrax, but their efficacy against unpredictably high expo-sure levels is uncertain.
BOTULISM is caused by neurotoxins that attack the nerv-ous system, resulting in symptoms similar to food-bornebotulism.The mortality rate can be constrained to <5% withappropriate treatment. A vaccine that provides 90% protec-tion up to after 1 year is available.
EBOLA is one of the most virulent diseases known toman, with a mortality rate of 50-90%. Symptoms include asudden onset of fever, vomiting and internal and externalbleeding. No treatment or vaccine exists.
RICIN blocks protein synthesis by altering the cells’ RNA.Symptoms include the rapid onset of nausea and severediarrhoea. High doses can cause pulmonary damage severeenough to cause death. There is no antitoxin available.Immunisation methods are under study.
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Information provided by our genesdefines how our cells function fromdevelopment to death. It is thereforeno surprise that changes in our genescan have serious effects. Disease canarise from genes being switched on atthe wrong time, being on for too long,or being present in a modified form.In the past, we have had very limitedmethods of controlling gene expres-sion, both in vivo and in vitro. However,a recently discovered technique calledRNA interference (RNAi) hasexpanded our ability to turn off genesto reveal their function, and has thepotential to facilitate the treatment ofsome diseases.
In October 2006 the Nobel Prize forMedicine was awarded to two Americans,Andrew Fire and Craig Mello, for their dis-covery of RNAi.Working at the CarnegieInstitute in Washington and the Universityof Massachusetts respectively, they found amethod to silence specific genes in thenematode worm. In a seminal paper pub-
lished in Nature in 1998, Fire and Melloshowed that they could inactivate a musclegene by injecting a nematode worm witha particular double-stranded RNA con-taining the exact information encoded bythe gene.This technique has been namedRNAi, and, in the short time since its dis-covery, it has become a vital asset to scien-tists in the laboratory.
Every gene is made up of a uniqueDNA code formed from a pattern of fourdifferent chemical bases known as ade-nine (A), guanine (G), cytosine (C), and
thymine (T). Each base in one DNAstrand pairs with its specific partner—Abinds to T and G binds to C—in theother DNA strand, creating a double-stranded DNA helix.When the cell needsto make a particular protein, the DNAhelix is unwound and the sequence of thebases that constitute the gene is read andused as a template to make a complemen-tary messenger RNA (mRNA). mRNAis similar to DNA, but is normally single-stranded, has a shorter lifespan, and, as thename suggests, acts as a messenger.mRNA travels out of the nucleus intothe cytoplasm, where molecularmachines called ribosomes bind it andconvert the RNA code to protein.
As early as 1984, researchers tried toinactivate genes using RNA molecules thathad a complementary sequence to a stretchof mRNA of interest. This is known asantisense RNA, and it was thought that itwould bind to its single-stranded mRNApartner and prevent it interacting with theribosome, so that no protein would be
made. The results of these experimentswere mysterious. Sometimes they were rel-atively successful, sometimes woefully inef-fective. Strangely, in 1995, Guo andKemphues found that sense RNA, whichhad exactly the same sequence as the genethey were trying to silence, was as effectiveas antisense in preventing the productionof a particular protein.
Around the same time, researchers work-ing on plants and fungi discovered a phe-nomenon they called post-transcriptionalgene silencing (PTGS) or quelling, in
which putting a second copy of a gene intoa cell stopped the protein being made. Fireand Mello’s stroke of genius was to test theeffect of double-stranded RNA, made ofone sense and one antisense strand, like theDNA.The double-stranded RNA provedvery effective at turning off protein pro-duction in nematode worm, whereas sin-gle-stranded RNA did nothing.
We now know that RNAi, PTGS, andquelling are all the same process, and thatRNAi is not unique to nematode worms,but occurs in insects, fish and mammals.Even more importantly, we now knowhow RNAi works. Fire and Mellonoticed that injecting even very smallquantities of double-stranded RNAinduced destruction of the mRNA, pre-venting protein production.This suggest-ed that sensitive detection of double-stranded RNA led to the activation of arange of protein enzymes. This is indeedthe case, as a complex machinery of pro-teins exists in the cell to carry out RNAi.Double-stranded RNA is recognised inthe nematode worm by the protein Dicer,which cuts the RNA into small, 21-basepieces.These are known as short interfer-ing RNAs (siRNAs), and are recognisedby a protein complex called the RNAi-induced silencing complex (RISC).
As well as binding siRNAs in mam-mals, RISC contains a protein calledAgo2, which acts as a pair of molecularscissors. These scissors first destroy onestrand of siRNA, whilst the other strandforms part of RISC. RISC can now pairwith any complementary mRNA itencounters. Successful pairing withmRNA activates Ago2 and the mRNA iscut into two pieces.These two pieces areunstable in the cell and are rapidlydegraded, leaving no message for theribosomes.Thus, the gene can no longertrigger the production of its protein.
Hundreds of studies have been publishedthat use RNAi to turn off a particular
16 Lent 2007
Catherine Jopling describes a novel method of silencing gene expression
Hundreds of studies have been published that use RNAi to turn off a particular gene, enabling scientists
to decipher the function of its protein product
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gene, enabling scientists to decipher thefunction of its protein product. RNAi isparticularly useful now that the completegenome of many organisms has beensequenced, as we often have very little ideaof what each gene product or protein does.Norbert Perrimon’s group at HarvardUniversity has developed a screening sys-tem with which they can individually inac-tivate every gene in the fruit fly, by usingRNAi.The screen has been used to iden-tify genes involved in fundamental process-es, such as cell growth and viral infection.
As well as enhancing our understand-ing of how different genes function,RNAi can help to identify drug targets.Fotis Kafatos and colleagues at the EMBLin Heidelberg used RNAi to identifythree genes in the mosquito that help orhinder the life cycle of the malaria para-site. This knowledge is very useful fordesigning malaria treatments, allowingthe development of drugs that targetessential genes and their protein products.
The potential medical benefits of inac-tivating specific genes are immense.Philip Zamore and his colleagues at theUniversity of Massachusetts used RNAito selectively destroy a mutant version ofthe gene SOD1, which causes a neurode-generative disease in humans. In cultured
human cells the specificity of the siRNAwas such that the normal version of themRNA, which differs by only a singlebase, was unaffected.This point is signifi-cant, as some siRNAs are not entirelyspecific and induce ‘off-target’ effects. Bycareful design of the siRNA, Zamore wasable to avoid this problem.
Many other disease genes have beentargeted with varying levels of success,both in cultured cells and in mice.Researchers at Alnylam Pharmaceuticalswere recently able to reduce cholesterollevels in monkeys using a siRNA againstthe mRNA for ApoB gene. ApoB has anessential role in the transport andmetabolism of cholesterol, and, as a large
protein, it is not accessible to tradition-al drug therapies. Preventing ApoB pro-tein from being made by siRNA mayprovide a new way of reducing highlevels of cholesterol.
Despite the promise of RNAi as a newweapon for fighting disease, there are stillmany questions regarding its safety. Oneconcern is the delivery of the siRNA intothe cell. An inherent hurdle is that nega-tively charged siRNAs do not pass easily
through the cell membrane.One approachto overcoming this is to encase the siRNAin a hydrophobic membrane known as aliposome.This method is very effective inthe cell culture and, encouragingly, wasused successfully by the Alnylamresearchers to deliver siRNA to monkeyliver cells. An alternative, currently beingexplored by researchers, is to chemicallymodify the RNA backbone withuncharged molecules, such as cholesterol,to allow it to interact with the hydropho-bic membrane and enter the cell.
In an entirely different method, theDNA itself can be delivered to cells.Instead of using siRNA directly, it ispossible to introduce DNA that will
subsequently produce a short double-stranded ‘hairpin’ RNA. This is thenrecognised and processed by the Dicerenzyme to make an siRNA. The DNAis introduced into the cell using a suit-able virus such as adeno-associated virus(AAV).AAV is harmless to cells, and hasthe advantage of coming in a number ofdifferent varieties that can infect differ-ent tissues. However, it is particularlyimportant to regulate the dose deliveredby the virus, to avoid interfering withnormal cellular functions. It will besome time before safe, reliable RNAi-based medicines become available.
The recent interest in RNAi has givenrise to questions as to why cells haveevolved such a process. In plants andinsects, RNAi seems to work as a defenceagainst viruses. Most viruses produce dou-ble-stranded RNA at some point duringtheir life cycle.Viral genes inside cells cantherefore be recognised and destroyed.
Mammals, however, have different sys-tems to deal with viruses, making unclearthe reason why we have RNAi. It may bean evolutionary artefact, it may provideyet another tool for antiviral defence, or itmay serve some other important purposethat remains to be discovered. Whateverthe reasons for the existence of RNAi,there is no doubt about its enormouspotential, both for the study of gene func-tion and the treatment of disease.
Catherine Jopling is a postdoc in theDepartment of Biochemistry
17www.bluesci.org
Fluorescent photographs of the roundworm (Caenorhabditis elegans).Three genes (fat-5, fat-6, andfat-7) are bound to green fluorescent protein (GFP) using empty vector control bacteria.The wormthen glows green where the genes are active.The effect of RNAi can therefore be visualized.
no RNAi RNAi
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It will be some time before safe, reliable RNAi-based medicines become available, but the technique has
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Mathematics hit the headlines in May2006 with the awarding and subsequentrejection of the Fields Medal, the‘Nobel Prize of Maths’, for a proof ofthe Poincaré conjecture. Named as oneof seven Millennium Prize Problems,proof of the Poincaré conjecture hasremained elusive for almost 100 years,although spurious proofs have fre-quently been announced. The mathe-matician Grigori Perelman was award-ed the coveted prize for his apparentproof of the Poincaré conjecture. Theunprecedented drama that unfoldedfollowing the announcement has large-ly overshadowed Perelman’s achieve-ment in conquering one of mathemat-ics’ most significant unsolved problems.
Jules Henri Poincaré, a noted mathe-matician and theoretical physicist, livedduring the latter half of the nineteenthand early twentieth centuries. Regardedas one of the founders of the mathemat-ical field of topology, he is also recog-nised for formulating the basis of chaostheory. His famous conjecture was first
proposed in 1904, as a concluding noteon the last page of a 67-page paper.ThePoincaré conjecture was subsequentlyidentified as one of the fundamentalquestions in topology.
The Poincaré conjecture is concernedwith how the properties of an objectdepend not on its exact shape, but on theway its parts are joined together. Thestandard introduction to the idea is tothink of a ring doughnut and a teacup.
These shapes are regarded as topological-ly equivalent, since one can be manipu-lated to resemble the other.When distort-ed, the hole in the centre of the dough-nut becomes the loop in the mug handle.
Topology deals with mathematicalobjects called ‘manifolds’—mathematicalspaces that on a small scale look like ordi-nary, flat space.This idea can be likened toan ant living on a jam doughnut.The ant,being so small, would be unaware of thedoughnut’s curvature, instead perceivingits world to be flat.
In mathematical terms, a jam doughnutis considered simply as a connected, two-dimensional sphere. If an elastic band isplaced on the jam doughnut (the mani-fold) and tightened, the jam doughnutwill shrink down to a point without tear-ing, since its surface is connected.
However, if the elastic band wereplaced around a three-dimensional spheresuch as a ring doughnut, then it could notshrink to a single point without thedoughnut tearing. The Poincaré conjec-ture asks whether three-dimensional
spheres can be characterized by connec-tivity like two-dimensional spheres. If aloop on a three-dimensional manifoldcan be tightened to a point, is the mani-fold necessarily equivalent to a sphere?
An analogous statement can be formu-lated for higher dimensions, for whichthe proof is, surprisingly, simpler. StephenSmale proved the conjecture for morethan five dimensions, and MichaelFreedman for four. Both mathematicians
were awarded Fields Medals for theirwork, in 1966 and 1986 respectively.
The three-dimensional case presents amore complicated challenge. Essentially,there are too few dimensions to removeproblematic regions of the manifold, amathematical process known as ‘surgery’.
Since its proposal, the conjecture hasmotivated many advances in the field oftopology. In recognition of this, and inacknowledgment of its famous intract-ability, the Clay Mathematics Institutenamed the Poincaré conjecture as oneof the Millennium Prize Problems. Onemillion US dollars were offered as prizemoney for the solution. SevenMillennium Prize problems were pro-posed, intended to represent the mostsignificant challenges currently facingmathematics and theoretical physics.Other problems include proving thefamous Riemann hypothesis, establish-ing the existence of the Yang-Mills the-ory in quantum physics, and solving the‘P versus NP’ problem. No claim hasyet been made on any of the otherproblems.
Grigori Perelman, a Russian mathe-matician, is at the heart of the recent con-troversy. Perelman first came to the atten-tion of the mathematics community atthe age of 16, when he achieved a perfectscore in the International MathematicalOlympiad. He embarked on a promisingcareer at the Steklov Institute ofMathematics in St Petersburg, inter-spersed with periods at New YorkUniversity and the University ofCalifornia, Berkeley.
Increasingly, he appeared to shun con-tact with other mathematicians, earninghimself a reputation as a recluse.Colleagues felt that he had becomeobsessed with the Poincaré conjecture. In2003, Perelman surprised the mathemat-ics’ community by taking the unconven-
18 Lent 2007
Michaela Freeland discusses one of mathematics’ most alluring problems
The Dilemma of
The Poincaré conjecture was first proposed in 1904, as a concluding note on
the last page of a 67-page paper
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tional step of publishing on the internetthree papers, in which he is believed tohave proven the Poincaré conjecture.
Perelman’s approach to solving thePoincaré problem involved a propertyknown as the Ricci flow, which describesthe curvature of the manifold.The Ricciflow had long been identified as a prom-ising approach for proving the Poincaré
conjecture. Richard Hamilton of CornellUniversity carried out much of thegroundwork for this; his approach wascrucial to Freedman’s proof of the four-dimensional case. Perelman’s proof adapt-ed Hamilton’s ideas to prove the Poincaréconjecture in three dimensions.
The presence of singularities, regions ofinfinite density on the manifold, meansthat a straightforward approach to theRicci flow is insufficient to provide proofof the Poincaré conjecture in threedimensions. Instead, Perelman performedmultiple surgeries to replace singularitieswith well-behaved and understood math-ematical components. Rather than work-ing with just the Ricci flow, he used the‘Ricci flow with surgery’.
Perelman’s breakthrough was to showthat the number of surgeries required tomake a given manifold tractable is finite.If the ‘Ricci flow with surgery’ satisfiesHamilton’s theorem, Perelman provedthat so too does the original Ricci flow.Hence, the Poincaré conjecture holdstrue for the manifold.
Following the publication ofPerelman’s proof, the Chinese mathe-maticians Shing-Tung Yau, Xi-Ping Zhuand Huai-Dong Cao disputed his claimthat the Poincaré conjecture had beensolved. Their position was advanced in a
paper entitled ‘The Hamilton-PerelmanTheory of Ricci Flows:The Poincaré andGeometrisation Conjectures’ and pub-lished in the Asian Journal of Mathematicsin April 2006. Yau allegedly dismissedPerelman’s work as “written in such amessy way that we didn’t understand”.
An article entitled ‘Manifold Destiny’,published in August 2006 by the New
Yorker magazine, further fanned theflames of discord. The article suggestedthat Yau, a renowned mathematician andFields medallist, had violated mathemat-ics’ internal ethical code. It accused himof discrediting Perelman’s claims, andfurthermore of seeking to claim thecredit for proving the Poincaré conjec-ture through his students, Zhu and Cao.Furthermore, the article implied thatPerelman was caught in the middle of aterritorial struggle for the position ofpre-eminent Chinese mathematician,
between Yau and Gang Tian, a formerstudent of Yau. The finding that Tianhad been appointed to produce a guideand review of Perelman’s proof height-ened this supposition.
Perelman himself has subsequentlydone little to cement his claim to havebeen the first to prove the conjecture.He unveiled his results in an unconven-tional manner, making them available
only on the online arXiv archives. Histhree papers do not contain any men-tion of either the Poincaré orGeometrization conjectures, the widertheorem of which the Poincaré conjec-ture is a special case. This in itself cre-ates an obstacle to awarding him theMillennium Prize, which requires thatany proof be published in a traditional,peer-reviewed journal. However, manymathematicians argue that the scrutinyto which Perelman’s papers have beensubjected since their 2003 release ismore than equivalent to the peer-review process.
In October 2006, at a CambridgeGeneral Relativity/High Energy Physicsseminar, Dr Gabriel Paternain of theDepartment of Pure Mathematics andStatistics discussed the Poincaré conjec-ture. Dr Paternain’s seminar highlightedthe technique that he considered to bethe most elegant aspect of Perelman’sproof: the coupling of the Ricci tensor,which describes the Ricci flow, with asurgery scale function.
The seminar, organized by the HighEnergy Physics and General Relativitygroups, emphasized the relevance ofboth the Poincaré conjecture and
Perelman’s techniques outside puremathematics, in particular to the fieldsof gravitation and cosmology. TheUniverse itself is a manifold, and Ricciflows are standard tools of general rela-tivity. They are used to investigate thetopological properties of space-time,and to describe its shape.
However, the Poincaré dispute appearsto have brought little but misfortune forthose involved.After rejecting the FieldsMedal in August 2006, Perelman isbelieved to have given up mathematicsentirely. Having left his post at theSteklov Institute of Mathematics, he hassince lived with his elderly mother,declining virtually all interview requestsand contact with fellow mathematicians.
Perelman’s rejection stands in starkcontrast to the excitement and interestgenerated only 10 years ago, by AndrewWiles’ unveiling in Cambridge of hisproof of Fermat’s last theorem. It is theaim of the Millennium Prizes, not onlyto encourage the solution of intractableproblems of mathematics, but also, indoing so, to widen the appeal of the dis-cipline. Sadly, it seems that in the case ofthe Poincaré conjecture, amid the twistsof controversy, the ugly legal wranglingand the personal attacks, the true beautyof mathematics has been lost.
Michaela Freeland is a second year under-graduate in the Faculty of Mathematics
19www.bluesci.org
Having left his post at the Steklov Institute ofMathematics, Perelman has since lived with his elderly
mother, declining virtually all interview requests
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Jules Henri Poincaré (left) and Grigori Perelman (right)
Perelman’s techniques are used to investigate theproperties of space-time, and to describe its shape
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20 Lent 2007
A Pharmaceuticals ScientistSi-houy Lao-Sirieix talks to Matthew Thomas about the pros and cons of working for a pharmaceutical company
What attracted you to work for a big phar-maceutical company?
A more appropriate question is,“Whatpersuaded me to stay working for a bigpharmaceutical company?” My movefrom academia to pharmaceutical sciencewas an exercise more in reconnaissancethan in career change. I knew little ofhow a big pharmaceutical companyworked, but was curious to learn andwilling to give it a try. As an academicpost-doctoral researcher, I was wary of afuture of frantic grant writing, isolationand financial frustration, although I wasperhaps being a little down-beat at thetime. I resolved to determine whetherpharmaceutical science was suited to me,and was fortunate enough to gain a two-year post-doctoral position within theNovartis Institutes for BiomedicalResearch (NIBR), in Horsham, WestSussex, as a researcher of respiratory dis-ease-relevant systems.
How did you find the transition?After a few high-profile publications,
together with collaborative work, con-ference travel and a promotion offerwith a permanent contract, I was con-vinced that the move I had made was agood one. I found the availability ofresources and expertise within the com-pany very attractive. My previous aca-demic group, although successful, couldnot compete with all the state-of-the-artequipment and tools available to mehere.The rewards available to a success-ful scientist within this environment aregenerally better than those in academia.However, I confidently predict that any-
one making a similar career move wouldfind the way science is practised in thepharmaceutical industry to be very dif-ferent from academia.
Can you tell us about your job and respon-sibilities?
I work within the respiratory diseasesarea (RDA) of the NIBR. I manage asmall group of scientists whose currentfocus is to investigate drug leads in lungdiseases. My daily routine involvesdesigning experiments to develop theoptimum route for a project, liaising withvarious groups of specialists, assisting inthe interpretation of results and givingrecommendations for future directions. Ithen present the results to the projectteam or to the higher disease area man-agement. It is important for me to beinvolved to some extent at every stage ofthe process. Apart from these coreresponsibilities, I act as a consultant forother projects or disease areas. I also sit ona board that reviews how all the respira-tory disease projects are run. As this is aresearch position, I frequently study theliterature to keep abreast of developmentsand publish as much as I can.
What do you particularly enjoy aboutworking in this kind of environment?
I enjoy the variety. Eighteen monthsago I was working on asthma—a far cryscientifically from my current project.This gives rise to a challenging butexciting environment. However, despitethe high pressure within scientificresearch, there is a well-developedcareer advancement system, which canprovide flexibility between the variousdisciplines of a large drug company.There are usually ways and means toenable employees to move within thecompany to another disease area, coun-try or career path.
Are there any drawbacks though?Indeed there are. I don’t believe phar-
maceutical science would suit everyone:there is a comparative lack of autonomywithin pharmaceutical research. It is myexperience that the science one doesmust provide the results required to movethe project ahead, or it must cease com-pletely. Interesting discoveries made alongthe way may be pursued as a ‘spare time’activity, but this must come second toachieving what is required for the proj-ect.A path change or rethink in a projectcan be a drastic decision. Such decisionsare not made lightly, but are usually dealt
with both deftly and swiftly.This can bedifferent from the typical academic situa-tion, in which a person can devote them-selves to an area and, assuming the scienceis good enough and the funding bodiesare suitably impressed, they can largelydetermine what they want to do andhow. This seems like a major drawbackuntil you bear in mind that such a scien-tific policy in the pharmaceutical indus-try does not tolerate ‘ivory tower’ science.The experiments being performed mustcontribute to a process specificallydesigned to create a product treating orcuring a disease.
In your opinion, is the fact that you haveto stick to a ‘bigger picture’ set by the com-pany a source of frustration, or the wayforward?
It is both. I certainly believe that it isthe way forward for a pharmaceuticalfirm and for a scientist like me. I thinkit would be fair to say that you are morein control of your own direction in aca-demia than in a big drug company.However, it is necessary to focus on a
I don’t believepharmaceutical sciencewould suit everyone:
there is a comparativelack of autonomy
within pharmaceuticalresearch
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How many academic scientists have wondered what it is like to work for a big phar-maceutical company? As an insider, Matthew Thomas agreed to share his experienceswith us.
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successful strategy for the treatment of adisease and for this to happen, other dis-coveries or directions must take a backseat. What is important is that theexperiments performed to validate aproject must be of sufficient depth todetermine the ‘correct’ path of a givenstudy. The ever-present search for anovel therapeutic strategy has led tomore expansive validation studies. Theend result may be that the strategy doesnot and cannot fulfil the aim of theproject, leading to a change in direction.This can be seen as a refreshing oppor-tunity to expand knowledge andexpertise, or as a frustrating contractionto a body of work that requiredimmense effort. In truth, it is always alittle of both.
What are the fundamental skills someoneneeds to work for a pharmaceutical company?
Firstly, I would say it is rather difficultto find a position within a large pharma-
ceutical firm, so you would need to be atthe ‘top of your game’. Secondly, Iwould say that the ability to adapt is fun-damental as you are often required totake on a new project or a whole newdisease target at a moment’s notice. If
you can do that, if you can use everytool and resource available to achievethe objectives set for the project, thensuch qualities would be quicklygroomed for further responsibilitieswithin the company and beyond.
Do you have any advice to give to someonewho wishes to work within a big pharma-ceutical firm?
The standards are very high and thisgives me confidence that, with whomev-er I collaborate in the company, they arelikely to be the best in their field.Becoming as informed as possible aboutthe particular company you wish to workfor is useful. Contacting a currentemployee would be a good way to findout more and to really discover if it isindeed the career for you.
Matthew Thomas was interviewed by Si-houy Lao-Sirieix, a Clinical Research
Associate in Papworth Hospital
The standards are very high and thisgives me confidence that, with whomever I collaborate in thecompany, they are
likely to be the best in their field
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This time last year, I was idly flickingthrough the pages of Physics Worldwondering what I should do when, orif, I finished my PhD. A career inindustry? Or perhaps in finance? To behonest, neither option really appealed.
Then, a small advertisement for aplacement at the Parliamentary Office ofScience and Technology (POST) inWestminster caught my eye.This sound-ed more like it: short, sweet, and scientif-ic.The placement would allow me to takea three-month break from my research. Itwould be perfect for me, so naturally Iconcluded that I had no chance of win-ning the placement.Thankfully I appliedanyway, and, as it transpired, the starting
date of 2 October became the fixed dead-line for writing up my PhD.
POST is Parliament’s in-house sourceof independent and accessible analysis ofpublic policy issues related to science andtechnology. It produces ‘POSTnotes’:four-page information sheets that aresent out to MPs, peers and other interest-ed parties. Each note is intended to be aself-contained introduction to an area ofscience and technology, aimed at a non-specialist audience. These notes cover awide range of topical subjects, from avianflu and computer crime, to nanoscience.
I am presently researching a note on theUK’s electricity networks.There is a con-cern among politicians about the UK’sincreasing dependence on imported gas.Following the recent publication of theStern Review on climate change, energypolicy is once again at the top of thepolitical agenda. The Government haslaunched an Energy Review giving apotential green light to nuclear power.Against the back-drop of November’slarge-scale electricity blackouts acrossEurope, the UK’s record on the securityof the electricity supply is relatively good.However, the existing electricity networkis not configured to make the most ofrenewable energy sources. The nationalgrid is strong in former coal-miningregions, but weak in rural areas likeNorth-West Scotland and mid-Wales,where the renewable energy resources aregreatest. Difficulties in obtaining planningconsent and grid connections could meanthe Government is likely to miss its 2010target of generating 10% of the electricityfrom renewable sources.
After writing a 45,000-word PhD the-sis, one might think that producing afour-side note would be easy.Unfortunately, any fantasies of knockingoff the note in an afternoon, and takingthe remaining three months off, havelong since evaporated.The real challengeis to distil 40 or so pages of technicaldetail into four sides of comprehensible,jargon-free prose.Writing coherently is askill—and one I wish I had acquiredbefore writing my thesis.
It is important that POSTnotes representa balance of opinion. My supervisor iden-tified contacts that could help me at anearly stage. She encouraged me to arrange
meetings with anyone who might be ableto contribute. So far, I have interviewed 10individuals from across the academia,industry and Government. At first I wasapprehensive, but learning to interviewbusy and often quite senior people has def-initely boosted my overall confidence.
One of the best things about workingat POST is meeting the other interns,and exploring Parliament together. Someinterns hope to pursue a career in publicpolicy. Others, like me, just want to findout a bit more about how science affectsthe way the world works.We are given afree rein to explore.
In our first week, we were given aguided tour of the debating chamber by asecurity guard who had an encyclopaedicknowledge of its history. It is amazinghow many of the origins of commonphrases can be traced to Parliamentarycustoms. For instance, did you know thatto be ‘out of order’ is to overstep the linesthat separate the front benches in theHouse of Commons? Or that the phrase‘it’s in the bag’ comes from the custom ofputting petitions in the bag on the backof the Speaker’s chair?
So, what next? I will finish at POSTby Christmas. The note will be pub-lished in the new year, after undergoingan extensive review. It is intended toanticipate the forthcoming energyWhite Paper. In the meantime, I havepassed my PhD and, from January, willcontinue research at University CollegeDublin. While electricity networks mayhave little to do with my research onblack hole physics, I now know muchmore about the way the world worksthan I did just three months ago.
www.parliament.uk/parliamentary_offices/post.cfm
Sam Dolan recently completed a PhD in theDepartment of Physics
POST members, with Sam second from right.
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Keeping you POSTedSam Dolan enters Westminster to help inform MPs about science
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Time-line of the main Cambridge breakthroughs in neuroscience
Cambridge has a strong tradition ofworld-leading achievements in neuro-science research, or the study of thefunctioning of the brain and the nerv-ous system in health and disease.Despite a strong history of excellencein the field, current neuroscienceresearch is less renowned as aCambridge strength. To tackle thisproblem, several recent efforts aim toachieve ‘one voice’ that will raise theprofile of Cambridge neuroscienceresearch and create an internationalcentre of excellence.
Historically, Cambridge breakthroughsin neuroscience have been recognized byNobel prizes on a wide range of topics. Inthe early 1930s, Matthews and Adrian car-ried out the first neural signalling analysis,at the University of Cambridge.This workwon Adrian a Nobel Prize in Physiologyor Medicine in 1932. In 1963, Hodgkinand Huxley earned the Nobel Prize inPhysiology or Medicine, for determiningthe mechanisms of the action potential.Around the same time, the identification ofnoradrenaline by Vogt facilitated a revolu-tion in the treatment of mental illnesses.Also in the 1960s, Marr and Barlow devel-oped some of the early theoreticalapproaches to the functioning of the neu-ral circuitry. More recently, in 2002,Brenner was awarded the Nobel Prize inPhysiology or Medicine, for investigatingthe development and function of the nerv-ous system, by applying genetic analysis tocell division in the nematode worm.
Cambridge neuroscience todayinvolves over 150 principal investigatorsand encompasses a much wider range ofsubjects than the traditional biologicalsciences.Yet the fractioning of research inmany departments across and beyond theUniversity does not foster collaborativework. It is difficult to identify researcherswith common interests in particular neu-roscience-related fields and to keep pacewith their work. Perhaps most impor-tantly, the lack of fully developed central-ized visions for neuroscience researchjeopardizes the ability to attract largefunding opportunities.
Recently, the University of Cambridgehas begun strengthening the competitive-
ness of its neuroscience research on theinternational stage, by creating a closelyinterlinked neuroscience research commu-nity.Two major first steps in this directionhave been the creation of the Departmentof Clinical Neurosciences and of theBehavioural and Clinical NeurosciencesInstitute (BCNI), in 2004 and 2005respectively. The Department of ClinicalNeurosciences was established in theSchool of Clinical Medicine, to subsumethe former Neurology and Neurosurgeryunits, as well as the Brain Repair Centreand the Wolfson Brain Imaging Centre.The BCNI, created within the School ofBiological, Medical and VeterinarySciences, brought together internationallyrecognized basic and clinical neuroscienceresearchers aiming to identify the neuralsystems underlying cognitive dysfunctionand psychopathology.
The most ambitious initiative so far is thecreation of a virtual institute calledCambridge Neuroscience, which will belaunched in September 2007 with a presti-gious international symposium. Cambridge
Neuroscience hopes to create aCambridge-wide, interacting neurosciencecommunity involving researchers acrossdisciplines, departments and institutes.Shared equipment, techniques andresources, such as new seminar series,enhanced courses and workshops, and aneuroscience website encompassing allCambridge research, are proposed to facili-tate new partnerships. Novel intellectualpartnerships are expected to arise fromcombined efforts across the mathematics,engineering, computer science and nan-otechnology disciplines. Ultimately, it ishoped that the expansion of theCambridge neuroscience community willintegrate, alongside more traditional areas,sub-fields at the cutting-edge of researchsuch as neurophysics, neurophilosophy,social neuroscience, neuroeconomics andneuroethics, towards a better understandingand treatment of neurological and psycho-logical disorders.
Katharine Hartley is a postdoc in theDepartment of Zoology
Initiatives
Cambridge Neuroscience InitiativeKatharine Hartley reports on interdisciplinary neuroscience partnerships in Cambridge
Jon
Her
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Neuroscience research at the University of Cambridge and associated units and institutes
1930: Matthews and Adriancarry out the first neural sig-nalling analysis
1954:Vogt characterizes the region-al distribution of noradrenaline andadrenaline in the cortex
1960s: Marr and Barlow developtheoretical approaches to thefunctioning of the neural circuity
1963: Hodgkin and Huxley win theNobel Prize in Physiology or Medicine,for investigating the action potential
2002: Brenner wins Nobel Prize inPhysiology or Medicine, for geneticanalysis of cell division in C. Elegans
25 Initiatives_LN 11/1/07 16:18 Page 22
It was the Grand Orrery that caughtmy attention on my first visit to theWhipple Museum, and it continues tocaptivate me now. This fascinatingcontraption, with its arching metal rib-bons and tiny rotating planets, is a cen-tre-piece of the Museum’s extensivecollection of scientific instruments,which ranks among the most impor-tant in the world.
Orreries, which demonstrate themovement of the planets and their satel-lites around the sun, reflected eighteenth-century ideas of a ‘clockwork universe’,whose workings were dictated byNewtonian mechanics. These deviceswere a must-have in contemporary politesociety, given its fascination for amateurastronomy.This fashion is most famouslydepicted in a painting of the era byJoseph Wright of Derby, showing aphilosopher demonstrating an orrery, hisaudience’s eager faces illuminated by thelamp representing the sun.
As with many scientific instruments,understanding the orrery reveals muchabout contemporary science: in this case,about the prevailing theories and publicperceptions of, and engagement with,science in the eighteenth century.
Robert Stewart Whipple was a keenbeliever in understanding the history ofscience through its tools, apparatus andmodels. It was for this reason that hedonated his extensive private collectionof scientific instruments to the Universityof Cambridge in 1944, to establish whatis now the Whipple Museum of theHistory of Science.
The eponymous Mr Whipple hadspent his life working for the CambridgeScientific Instrument Company, first as apersonal assistant to its founder, and lateras Managing Director and Chairman.
Whipple had a keen interest in scienceand its history, and was a founder and fel-low of both the Institute of Physics andthe British Society for the History ofScience. His collecting career began inthe 1910s, his first acquisition being anantique telescope he bought in Francefor 10 francs. By the 1940s, his collectionhad grown to around 1000 instruments,models and pictures, and a similar num-ber of books, which he gave to theUniversity, in order to create a museumfor the history of science.
But this was not to be a dimly lit, rarelyvisited corner in which artefacts slowlygathered dust. As the memorandum thatproposed the move stated, both Whippleand his contemporaries at the Universityfelt it important "that the Museum shouldbe more than just a well-arranged reposi-tory of historic scientific apparatus. Itshould be designed and maintained as ateaching instrument and accessory tomodern research." This idea remains oneof the guiding principles in the museum’swork today, as its curator, Liba Taub,explains in the interview on the next page.
The items presented to the Universityby Whipple were initially displayed in anexhibition at the Old Schools site onTrinity Lane, but were moved a numberof times in the following years due to lackof space. It was not until 1959 that thecollection found a permanent home inthe Department of History andPhilosophy of Science on Free SchoolLane, in a high-ceilinged hall—now the
Main Gallery—that was previously partof the Departments of Engineering andof Physical Chemistry.
The original Whipple collection hassince expanded, thanks to donations fromthe colleges and departments of theUniversity. These include a number ofphysical instruments from the early yearsof the Cavendish Laboratory, astronomi-cal apparatus from the observatory of St
John’s College, and many sundials, astro-labes and perpetual calendars from theFitzwilliam Museum. Nowadays, themuseum’s artefacts reside in a number ofgalleries throughout the department,allowing as much of the collection to beon display as possible.
Another part of the donation was acollection of scientific books. Theseformed the foundation for the WhippleLibrary, and reflected Whipple’s interest ininstruments and instrument making.They include Renaissance books ofastronomy and practical mathematics, aswell as seventeenth and eighteenth cen-tury books by Descartes, Hooke andLeeuwenhoek on the new instruments ofoptics and philosophy.
Though the Museum houses a diversearray of gadgets, gizmos and modelsrelating to different branches of the sci-ences, its particular strength is an inter-nationally recognized collection ofmathematical, astronomical, navigationaland surveying instruments.
One of the instruments that particu-larly stands out is the astrolabe. TheMuseum has a number of astrolabesfrom England, Europe and Persia, datingfrom the fourteenth to the eighteenthcenturies. These intricately engravedbrass circles are multifunctional instru-ments central to medieval astronomy,consisting of a map of the heavens, with
His
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24
Instruments of the pastEmily Tweed explores the extraordinary collections of the Whipple Museum
Whipple’s collecting career began with an antique telescope he bought in France for 10 francs
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Why is studying the history of science important? Often people tend to associate science with progress, with
welfare, or with making profit. I have mixed views aboutthose sorts of messages.Through examining the history of sci-ence, we learn that it isn’t as simple as that. My own period ofresearch is Ancient Greek and Roman science. I think thatscience, historically, is not just about having a practical solu-tion to things, but about wanting to answer basic questionsabout the world around us. It is part of our human experienceto want to have the answers and to want to explore the waysthat we know about the world around us.The creativity of artand of literature, for instance, is often celebrated. I think thecreativity of trying to explain the natural world can be just asbeautiful and interesting.
What can the material culture of science——its instruments, itsmodels and its tools——tell us about its history?
The practice of science isn’t just about reading books orjournal articles, sitting in front of a computer, or spendingtime in the laboratory. Science involves interacting with theworld at a number of levels, and there have been various tools,historically, that have been devised to do this. So we can’t justlearn about the history of science by reading about it; we haveto see how people did it.
What is particularly special about the Whipple collection?The Whipple collection is special in many ways. One is that
so many items represent one individual’s collection and col-lecting experience——that of Robert Whipple. It also representscollecting activity and scientific work in the differentCambridge colleges. One example is the fume cupboard from
Newnham College, purpose-built in the 1870s when thewomen of the college could not use the laboratories at StJohn's or Trinity Colleges, and the University did not have itsown. The museum also has a number of interesting models,such as the botanical teaching models.One of the things I havepursued in my life as a curator is increasing our collection ofmodels, rather than just collecting in the traditional areas of‘brass and glass’, as they are known.
What is the role of the museum in teaching and research? The Museum was founded before the Department of
History and Philosophy of Science.There were lectures in thehistory of science in the University, but there was no formaldepartment. Now, the Museum is physically in the centre ofthe Department—an ‘embedded’ museum—and we have avery close relationship with the Department.
One of the things I think the Museum is about is to behere as a resource for students, from second and third yearsright up to postgraduates.We have examples of undergradu-ate and postgraduate students’ work on display; so, when vis-itors come to the Museum, we want them to understandthat this is a living museum. It is actively being used as asource of evidence about how we do history and philosophyof science. One of the messages we’re trying to convey isthat the Museum is about the work that students within theUniversity are doing.
What is your favourite item in the collection?There are a few, but one that first comes to mind is a set of
Euclidean models, by the same instrument-maker as the grandorrery. I used to carry a picture of them in my wallet!
overlaid rings, and bars marking thepositions of the stars and the annual pathof the sun through the sky. Astrolabeswere used to tell the time, to calculateimportant dates on the medieval calen-dar, and to measure the positions ofcelestial bodies or the heights of build-ings. Often they were extraordinarilybeautiful, as shown in the picture.
As well as the galleries themselves, theMuseum offers a range of electronicresources for those interested in the his-tory of science. The ‘Explore’ section ofits website allows a closer inspection ofthe exhibits, with articles and interactiveitems focusing on the Museum’s astro-nomical instruments, microscopes andteaching models.Visitors to one interac-tive page can perform a ‘virtual dissec-tion’ using a nineteenth century anatom-ical model.This recently acquired exhib-it was made from papier mâché by theFrench doctor Louis Auzoux, to circum-vent the shortage of cadavers available forteaching anatomy to medical students.
In line with Whipple’s wishes, theMuseum is a central part of Universityteaching and research in the history ofscience. Many of the cases have beendesigned by students, who have helpedwith exhibitions, written booklets, andmade models of their own.
The Museum’s enduring value andappeal are captured well by the words of
Sir Henry Dale, then President of theRoyal Society, on opening the first exhibi-tion of Whipple’s gift to the University in1944:“This collection of historic scientif-ic instruments and old books is not only ofsignificant interest, but it possesses a greatdeal of artistic work of beauty, and such acollection gives us the feeling of living insympathetic contact with the great men ofscience who lived before.”
The Whipple Museum for the Historyof Science (edited by Liba Taub and FrancesWillmoth), a book of essays and illustrationscharting the museum’s history, is available fromthe museum website or from the Main Gallery.
www.hps.cam.ac.uk/whipple
Emily Tweed is a recent graduate in NaturalSciences, specialising in Pathology
Histo
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25www.bluesci.org
A “universal mechanical ring dial”,, a type of sun-dial,, made by John Rowley in 1715
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Emily Tweed speaks to Liba Taub, Director and Curator of the Whipple Museum
On the Front Line in the Museum
26-27 History_LN 11/1/07 16:28 Page 26
Until recently, science seemed to occu-py a rather sober and well-definedplace in television, in the genre of sci-ence documentaries.Although fictionalfilms have occasionally drawn inspira-tion from science, for the most partthey have avoided it as a main topic.However, a recent boom in feature-length science documentaries intendedfor the big-screen has catapulted sci-ence into a somewhat different domainof popular interest, one that blendsemotional narrative with scientificinvestigation. The two main examplesof this phenomenon, March of the Pen-guins and The Besieged Fortress, mayleave some viewers wonderingwhether this cinematic popularizationof science comes at the cost of sacrific-ing scientific rigour.
For a long time mainstream cinema wasdevoid of science films.The short sciencefilms of Jean Painlevé, shown as preludesto artistic feature films in French cinemasas early as the mid-twentieth century,were the exception rather than the rule.On some occasions, artistic films crossedpaths with science. For example, in Illumi-nation (Illuminacja 1972), by the Polishdirector Krzysztof Zanussi, the film’s ciné-ma vérité style seems to open up the scien-tist’s inner world and examine anew thesocial impact of science. In this film onescene depicts young physicists discussingthe dangers of scientific inventions such asatomic bombs and genetic engineering,and brushing off any personal responsibil-ity in the name of pragmatic concernssuch as supporting their families.
Science documentaries have often suc-cessfully penetrated the realm of popularinterest—think of David Attenborough’sdocumentaries and the Discovery Chan-nel—and brought science to the wider
public. However, recent feature-lengthscience documentaries have had anunparalleled large-scale appeal to audi-ences. The blurring of the line betweenscientific fact and fiction may in partexplain the wide appeal of these films.
The hugely successful documentary,March of the Penguins (Luc Jacquet, 2005),is an excellent example of an anthropo-morphic portrayal of animals. This film,about the yearly migration of Emperorpenguins in Antarctica, and narratedfrom a human perspective, was shown incinemas around the globe and won an
Oscar in 2006, for Best Documentary.Advancing the belief that animals expe-rience emotions, the narrator claims thatthe Emperor penguins migrate formonths, braving below-freezing temper-atures and snow-storms for the love oftheir partners and children. Smallhumanoid penguins are portrayed as sto-ically defying the brutality of the Antarc-tic winter in order to see their childrennourished. Whether animals have emo-tions or not, is a controversial issue in thescientific world. However, influenced bythis film, many people may readily acceptthat animals have emotions, withoutcarefully considering the opposing view.
Recently, a new French documentaryhas been released: The Besieged Fortress(Philippe Calderon, 2006). Anthropo-morphizing its subject in a similar man-ner to March of the Penguins, the filmdepicts the lives of termites and theirattempt to defend their ‘metropolitancity’ from the invasion of killer ants. Inspite of the almost Hollywood-styleaction, some close-up scenes, such as antsforming a living bridge over a waterstream or attacking the termites by drop-ping from branches in large groups likeminiature paratroopers, are remarkablywell rendered and a pleasure to watch.However, focusing more on the storylinethan the science, the film fails to providea deeper understanding of these intrigu-ing insect behaviours. The narrator doesnot even name the species featured.
So far, it seems that French cinema dom-inates the niche of big-screen science doc-umentaries; however, the BBC is about tochange this picture. A crew is currently inthe Kalahari Desert filming a feature doc-umentary about meerkats. Meerkats’ com-munal behaviours, especially their cooper-ation in rearing their young and teachingthem how to feed themselves, are striking-ly reminiscent of human communities.Previous documentaries about meerkats,such as Meerkat Manor, have been popularboth in the UK and the US.Their popu-larity may in part come from the researchthat a group at the Department Zoology inCambridge has conducted trying tounderstand their social lives and interac-tions. Be it March of the Meerkats or BesiegedMeerkat Manor, audiences are looking for-ward to a good story, and, hopefully, therewill be good science behind it.
Mico Tatalovic is a PhD student in theDepartment of Zoology
Arts
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Science documentary at the cinema
The cinematicpopularization of
science may come atthe cost of sacrificing
scientific rigour
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Mico Tatalovic examines the rising popularity of science documentaries
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Film festivals are well known events,whereas science film festivals are lessso. However, there are various sciencefilm festivals taking place around theworld, screening science educationfilms that raise awareness about scien-tific and environmental issues. Oneexample is SCINEMA in Sydney,which incorporates a variety of filmsand also organizes discussions aboutscientific film.These events are intend-ed to serve as a tool for communica-tion between scientists and the public.SCINEMA is a travelling film festival,screening some of its films in differentcities, even countries. In 2006, SCINE-MA made it to Cambridge.
At Cambridge, the CUSP film crewproduces various science related record-ings and films each year. However, untilrecently, a science film festival had notbeen organized at the University ofCambridge. In Michaelmas Term 2006, Icontacted the director of SCINEMA,Cris Kennedy, about showing some of thefilms from the 2006 SCINEMA festival atthe University of Cambridge.The screen-ings, the first showing of SCINEMA inBritain, were supported by the Cam-bridge University Scientific Society andthe Graduate Union, who provided thefacilities and advertising for Cambridge’sscience film event. Subsequently, I spoketo Cris Kennedy about SCINEMA andscience film festivals in general.
What are you trying to achieve withSCINEMA?
We just want to make science accessi-ble.Bringing two fields together,we hopeto create new audiences for both film-making and the sciences.We have a won-derful partner in Cosmos Magazine, andtogether, we hope to build SCINEMAinto an international festival that will raisethe profile of science filmmaking andreward excellence in the field. We run ashort film competition for students, topromote interest in science and build upthe numbers of students enrolling in sci-ence subjects in high school. In Australia,we are a part of National Science Week.
How long has the film festival beenrunning for?
This will be our seventh year runningSCINEMA. It began in 2000 as an epicevent at a local Canberra cinema, withpaid entry. The big draw card the firstyear was called Sexy Skivvy Science, andfeatured the two stars of The CuriosityShow, a 1970s Aussie children’s scienceshow. The presenters were famous fortheir colourful skivvies, way before TheWiggles made them famous all overagain. Our second festival was a muchlower-profile event, just a few screeningsat the National Museum of Australia, and
progressively we’ve built up into anational event... and now, international.
Do the screenings attract many viewers?Our 2006 Festival screened at 90 ven-
ues across Australia and New Zealand, toover 10,000 people. Some venues aresmall: local libraries, schools, town halls inregional centres, where only two or threepeople might be at a screening.We’re alsoin major venues like Sydney’s Power-house Museum and the National Muse-um of Australia.
What are the plans for the future ofSCINEMA?
World domination! SCINEMA isreally a labour of love; just a bunch ofpeople who like science and film, put-ting it all together in our spare time andusing resources borrowed from ourunderstanding companies.We dream ofa nice big fat sponsor that would allowus the luxury of working on it full-time. There are so many things wecould do with it: podcasting films, livestreaming and online voting. Thesewould make it truly an internationalfestival.
Are there plans to show the festival’sfilms in the UK as well?
I’m chuffed enough that you guys atCambridge saw them.We’ve put the Fes-tival together so that it’s very easy for anygroup or venue anywhere to take part.We compile our films onto a set of DVDsand produce a generic programme, soanyone with the drive to put the screen-ings on can take them anywhere... I’d loveto see SCINEMA Reykjavik, Edinburgh,Dubrovnik...
Are you aware of any other similar sci-ence film festivals?
There’s quite a list of science-themedfilm festivals, the biggest of which is
Images Et Sciences, which the Frenchgovernment seem to put a lot of moneyinto. It’s a biennial event that screens inthe theatre on the Eiffel Tower.Any festi-val would find it hard to top that for asexy location.
What would be your message to theCambridge students interested in mak-ing science films?
If you’re interested in filmmaking, myonly advice is to get out there and makefilms. Learning on the job is the only wayto learn, and technology has become socheap and accessible that filmmaking isn’tan elitist art form any more, rather anexpression tool for the common man.Look at the YouTube phenomenon. As ascience communicator, it really excitesme to see people using film, using Flash,using YouTube; telling their stories andfinding an audience. If you’re interestedin science and film, like I am, then dropme a line. We could use a helping handputting SCINEMA together, no matterwhere you are.
www.csiro.au/[email protected]
Mico Tatalovic is a PhD student in theDepartment of Zoology
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SCINEMA is really a labour of love; just abunch of people wholike science and film,putting it all together
in our spare time
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Science Film Festival at CambridgeMico Tatalovic speaks with film festival director Cris Kennedy
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DR HYPOTHESIS SAYS:As you’re asking this question, I cansafely assume that you’ve never been astudent! After a couple of nights ofmissed sleep, you are likely to becomemore irritable and make more mistakes,but it is after three consecutive nights ofmissed sleep that your problems willbecome more acute. You will find italmost impossible to think clearly andwill probably begin to hallucinate—perhaps that you’re asleep? The impor-tance of sleep was clearly demonstratedby an experiment on rats: they diedwhen prevented from sleeping for anextended period of time. Remember,though, that these effects will only hap-pen if you get absolutely no sleep at allduring the night—unlikely in your situ-ation I think, Nigel.
DR HYPOTHESIS SAYS:Most cosmetic tanning products workimmediately by applying a colour to theskin, and are easily washed off. If you arelooking for a longer-lasting tan, you maywish to use a lotion or spray containingdihydroxyacetone, which is a sugar thatcauses a colour change in the epidermis,the upper layer of skin cells. These prod-ucts can last for up to a week. It is also pos-sible to purchase ‘tanning accelerators’,which contain the amino acid tyrosine, soas to stimulate the production of the natu-ral tanning pigment melanin. However, Iam yet to be convinced that these latterproducts actually produce visible results.One word of caution, however, Carmel:although you may get that natural-lookingglow, a fake tan will not protect you fromultraviolet radiation in the same way as anatural tan, so you will still need to usesunscreen when summer finally arrives.
Dear Dr Hypothesis,My wife is pregnant with our first child.I’m very excited, but also slightly con-cerned. I’ve heard from friends thatsleepless nights are likely to become aregular fixture of my life. As I workshifts, I’m worried that this could affectmy performance at work, which couldaffect my chances of promotion, whichcould affect the life I can provide for mynew family.What are the effects of sleepdeprivation?
Narcoleptic Nigel
Dear Dr Hypothesis,I have liked this girl at work for sev-eral months and last week I built upthe courage to ask her out. To mysurprise, she said yes! Simply goingto the cinema seems a bit of a cliché,so I would like to impress her bytaking her to the new IMAX® cine-ma that has opened in my town.Could you tell me the differencesbetween an IMAX® cinema and aregular cinema, so that I mightimpress my date?
Movie Mark
DR HYPOTHESIS SAYS:The first thing you’ll notice about anIMAX® cinema, Mark, is that the screenis much larger than in a normal cinemaand it may even be dome-shaped. Thescreen fills your entire field of vision,immersing you in the film and enhanc-ing any motion. In order to fill thisscreen, the film format is much largerthan usual, which makes the pictureexceptionally clear. Much larger camerasare used to capture the detail.These canonly hold a three-minute spool, andrequire 20 minutes to change spools.These special features increase the costof making an IMAX® film, so they areusually only about 40–50 minutes long.Hopefully, Mark, this will help you havesomething to talk about after the film.Good luck!
Dear Dr Hypothesis,I know that you normally onlyanswer serious, science-related prob-lems, but I have a more superficialquery with which I was hoping youcould help me. Due to the lack ofnatural sunlight over the last fewmonths, I have resorted to self-tan-ning to maintain the year-roundcolour I love so much. Do you knowhow this works, and whether there isany difference in the action of thevarious products available?
Colourless Carmel
Moving MoneyStart by arranging 6 coins as shown on the left. By moving onecoin at a time such that it does not disturb any of the others,and that at the end of every move each coin is in contact withat least 2 others, arrange the coins as shown on the right.
Visit www.bluesci.org for the answer
Dr
Hyp
othe
sis
28 Lent 2007
Dr HypothesisPlease email your queries to [email protected] for your chance to win a £10 book voucher
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