BlueSci Issue 08 - Lent 2007

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Cambridge’s Science Magazine produced by

in association with

www.bluesci.org

Issue 8 Lent 2007

The Future of Neuropsychiatry Unravelling the biological basis of mental health

Darwinian Chemistry Selection of the fittest molecules

Biological Warfare Does biodefence research make us safer?

• Poincaré Conjecture • Science Documentaries • Pharmaceuticals • • Human Uniqueness • The Whipple Museum • RNAi • • Stock Markets • Parliamentary Office of Science and Technology •

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The Deutsche Bank Bursary for First Years

Throughout the world, Deutsche Bank seeks opportunities to play a positive role in the student community by committing its financial resources, the talents of its personnel and the leadership of its management.

If you are a first year undergraduate who possesses outstanding academic ability combined with the ambition and drive to join the financial services industry, you could be rewarded a Deutsche Bank Bursary.

What does the Deutsche Bank Bursary offer?

I Substantial annual financial support I Ongoing mentoring I A summer internship opportunity Applications can be submitted online until March 15th 2007.

For more information visit www.db.ukbursary.co.uk Expect the better career

A Passion to Perform.

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Lent 2007

Issue 8

contents

Feature s

Chemistry Steals Tricks From Darwin

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Jonathan Gledhill explains why Darwin s dogma may revolutionize chemistry...........................

Are Humans Special?

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Mico Tatalovic questions the behavioural basis of human uniqueness...........................................

Black-Scholes: The Black Hole of Maths and Money

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Tristan Farrow tells the story of the formula that crashed the stock market.............................

Biodefence: Is Prevention Always Better Than Cure?

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Three authors debate the benefits and risks of furthering biowarfare research.......................

RNAi:Taking Control of the Gene

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Catherine Jopling describes a novel method of silencing gene expression...................................

The Dilemma of the Third Dimension

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Michaela Freeland discusses one of mathematics most alluring problems....................................

Regulars

Editorial .............................................................................................................................. 03 Focus ...................................................................................................................................04 In Brief ................................................................................................................................08 A Day in the Life of ...........................................................................................................20 Away from the Bench ..................................................................................................... 22 Initiatives ............................................................................................................................ 23 History ............................................................................................................................... 24 Arts and Reviews .............................................................................................................26 Dr Hypothesis .................................................................................................................. 28 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 a Xenopus laevis tadpole which was genetically tagged with a neuronal-specific alkaline phosphatase reporter. Because tadpole larvae develop externally, and are generally transparent once hatched, the brain of an intact tadpole is highly visible under a dissecting microscope. Here, the cranial nerve network was detected after an alkaline phosphatase reaction—a simple enzymatic reaction that causes the genetically labelled axons to turn blue."

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Visit www.bluesci.org Weekly science news stories Additional Bluesci articles Complementary material to the printed issue Podcasts of speakers, lectures, interviews, and more!

Schedule of CUSP software workshops Archives of all past issues of Bluesci Information on getting involved with Bluesci

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Issue 8: Lent 2007

From The Editor Happy New Year! Welcome back to Cambridge and to a fresh issue of BlueSci. Issue 8 presents an exiting set of articles.

Our FOCUS section opens a window into the future of mental health care, while our feature and regular articles discuss topics ranging from biodefence to science museums and science documentaries.

CHEMISTRY STEALS TRICKS FROM DARWIN explains how Darwin’s dogma may successfully quench the modern world’s voracious appetite for new molecules. BIODEFENCE: IS PREVENTION ALWAYS BETTER THAN CURE? discusses the benefits and perils of learning to engineer deadly bioagents. THE DILEMMA OF THE THIRD DIMENSION unravels the drama that ensued from Grigori Perelman’s cracking the Poincaré conjecture—one of the Millennium Prize Problems in mathemat-

ics. On the artistic end of the spectrum, ARTS AND REVIEWS illustrates how modern technology is enabling inspired individuals to bridge the gap between art and science.

Complementary material to the printed edition of BlueSci, as well as weekly news updates, podcasts and videos of highimpact science events in Cambridge can be found online at www.bluesci.org.

BlueSci is the product of dedicated work from Cambridge undergraduates, graduates, and postdocs who love science, communication and giving back to society. If you’d like to contribute to the magazine, be it in writing, editing, production, graphic design or online material, please don’t hesitate to get in touch. I hope you enjoy reading the eighth issue of BlueSci. Lorina Naci issue-editor@bluesci.org

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 the organization of CUSP and BlueSci. At the start of Michaelmas Term, we began running weekly training workshops, addressing all aspects of producing the magazine.

These have been very popular and we think the results, in terms of the standard of the magazine, speak for themselves. The workshops will be continuing throughout Lent Term, with a particular focus on graphic design and web development.

Anyone interested in coming along should visit our website for details.

On the web front, the BlueSci website has been redesigned with a sleeker look.

The website hosts our weekly news service, which runs throughout each term to keep you up-to-date on the latest scientific developments, in Cambridge and beyond. Over the last year the news serv-

ice has been heavily expanded and now has a large team of writers, many of whom are also involved with the print magazine.The news is also published, in an abbreviated form, in Varsity.

Alongside the news, at the BlueSci website you can find our podcasts and videos, produced by our film team led by Tristan Farrow. We were particularly pleased to be able to offer a podcast of Richard Dawkins’ speech at the Cambridge Union Society last term. Visit the website now for interviews with the TV psychiatrist Raj Persaud, Amnesty International’s Kate Allen and the environmentalist George Monbiot.

As ever we would like to thank the Varsity Business Manager,Adam Edelshain, for finding the time in his busy schedule to help us out, in more ways than we have space to list.

Michael Marshall CUSP Chairman

Next Issue: 27 April 2007 Submissions Deadline: 29 January 2007 www.bluesci.org

Produced by CUSP & Published by Varsity Publications Ltd Editor: Lorina Naci Managing Editor: Louise Woodley Production Manager: Ryan Roark Pictures Editor: Jon Heras Submissions Editor: Maya Tzur Business Manager: Adam Edelshain Focus Editors: Hannah Critchlow, Peter Davenport, Michael Marshall Features Editors: Sheena Gordon, Michelle Percharde, Sharon Tate A Day in the Life of... Editor: Si-houy Lao-Sirieix Away from the Bench Editor: Serena Scollen Initiatives Editor: Serena Scollen History Editor: Emily Tweed Arts and Reviews Editor: Mico Tatalovic Dr Hypothesis: Rob Young Second Editors: Lynne Aitkenhead, Beth Ashbridge, Chloe Hardman,Thomas Kluyver, Jonathan Zwart Copy Editors: Lynne Aitkenhead, Brendan D Arcy, Michael Marshall, Lorina Naci, Bojana Popovic, Jonathan Zwart 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 Rangesh Web News Team: Chris Adriaanse, Lynne Aitkenhead, Beth Ashbridge, Hannah Critchlow, Subhajyoti De, Michaela Freeland, Gurman Kaur,Thomas Kluyver, Lorina Naci, Michelle Percharde, Abinand Rangesh, James Shepherd, Mico Tatalovic, Emily Tweed CUSP Chairman: Michael Marshall ISSN 1748—6920

Varsity Publications Ltd 11/12 Trumpington Street Cambridge, CB2 1QA Tel: 01223 353422 Fax: 01223 352913 www.varsity.co.uk business@varsity.co.uk BlueSci is published by Varsity Publications Ltd and printed by Warners (Midlands) plc. All copyright is the exclusive property of Varsity Publications Ltd. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without the prior permission of the publisher.

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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

FOCUS The Coming Revolution in Psychiatry Mental illness is estimated to affect 450 million people worldwide.The effects for patients and their families can be devastating.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 provides satisfactory patient care. Many patients are misdiagnosed or remain undiagnosed for a long period, psychological therapy is not 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 neuropsychiatry and bring you exciting new research on the diagnosis and treatment of disorders such as schizophrenia and depression.

Problems With Current Diagnosis and Treatment To be diagnosed with a psychiatric disorder such as schizophrenia, a patient must display certain behavioural symptoms for most of a one-month period, if the symptoms are severe, or continuous signs, for at least six months, for less extreme symptoms.

Schizophrenia exhibits a diverse set of symptoms—ranging from delusions and hallucinations to disorganized speech and behaviours—and its underlying nature is hotly debated.

One theory, advanced by Professor Tim Crow, posits that schizophrenia is unique to humans, and, specifically, that schizophrenia is associated with an anomaly of the genetic mechanism that controls hemispheric lateralization. Lateralization is a property unique to human brains, in which language is controlled mainly by one hemisphere, usually the left. When language lateralization fails, the processes generating speech and those generating thought can be confounded in the brain. As a result, a person may fail to distinguish between oneself, other people and the environment.

Among the 327 mental illnesses currently recognized, many share the psychotic symptoms seen in schizophrenia. According to Dr Sabine Bahn, psychotic features can be present not only

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in mental disorders like schizophrenia, but also in drug-induced psychosis, neurological disorders such as epilepsy, Parkinson’s and Alzheimer’s, as well as in immunological disorders affecting the brain, such as systemic lupus erythematosus.

In Professor Bullmore’s opinion, “the problem with the current categorization system is that it’s the end product of a historical process of consensus building.” However, he points out that this internationally standardized diagnosis method has drastically improved reliability and comparability in psychiatric diagnosis.

In spite of these improvements, the current diagnostic criteria are often criticised by mental health professionals for poor scientific validity. For example, according to an article published in the American Journal of Psychiatry by McGorry and colleagues, the rate of agreement between any two psychiatrists when diagnosing schizophrenia is about 65%, at best. Dr Bahn argues that this is because the “current diagnosis is based on findings that are really 100 years old.”

Biologically-based diagnostic tests that can uniquely identify each psychiatric disorder don’t exit. Instead, the diagnosis is based on the patient’s self-reported experiences, in combination with secondary signs observed by a psychiatrist or clini-

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It’s really a whittling down of a most likely diagnosis, where you ask patients questions such as ‘are you hearing voices’; suggestive questions that are neither specific nor very sensitive - Dr Sabine Bahn

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the symptoms, patients must exhibit symptoms for up to several months, before they can be considered for diagnosis.“This can be a very big delay, especially since it is becoming increasingly clear that if you treat early on you can improve prognosis,” Dr Bahn adds.

Because of the large overlap in symptoms between different disorders and the inherent subjectivity of the diagnostic criteria, patients may not be correctly diagnosed for a long time.According to a European survey involving over 1000 individuals, patients with bipolar disorder wait on average 5.7 years before correct diagnosis. In the US, up to 69% of patients with bipolar disorder are initially misdiagnosed, and more than a third of patients experience an average of 10 years‘ delay before correct diagnosis.

“We have to start from scratch in terms of diagnosis,” Dr Bahn argues. “That means that we have to collect a lot of data in order to determine if there is a ‘biomarker’ for specific clinical features, for example, cognitive impairment, or a biomarker specifically correlating with persecutory ideas.”

According to Professor Bullmore, we need to “get psychiatry looking more like neuroscience”, where brain scans are routinely used to diagnose brain tumours. “If you believe in the biological opportunity for psychiatry, which I obviously do, then you’d like to imagine that 20-30 years down the line we’re not really going to be using the term schizophrenia as a diagnosis.What we’re calling schizophrenia at the moment will be much more deeply understood.

When someone comes along with schizophrenia syndrome, we’ll be able to make a more precise sub-diagnosis.”

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CBT is a powerful non-pharmacological technique for all kinds of psychiatric problems, but I have to say that blokes in particular are not good at it - Professor Ed Bullmore

Kelly Neaves

Our poor understanding of the biological basis of psychiatric disorders results not only in delayed, but also in inadequate treatment. Drugs do not always work effectively and often give rise to significant side effects, often resulting in the patients refusing to take the medication.

“At the moment, it is a hit and miss situation for the pharmacological treatment of psychiatric illness.We just pluck... one of the medications available and titrate them out. Often, for several months, we wait and see [that] they are not working.

Then we have to start with the next one.

If we had biomarkers to guide us… we would have a much more objective way of addressing the needs of the patient,” Dr. Bahn explains.

Another problem is that many patients do not have immediate access to therapy.

The standard waiting time for psychotherapy is 6-9 months.

One of the more successful forms of psychotherapy is cognitive behavioural therapy (CBT), which has been used with varying degrees of success in the treatment of schizophrenia, obsessivecompulsive disorder, anxiety and depression. CBT involves recognizing unhelpful or destructive patterns of thinking and reacting, and modifying or replacing these with more realistic or helpful ones.

According to the UK’s National Institute for Health and Clinical Excellence (NICE),“it [CBT] is of equal effectiveness to antidepressants”. The NICE guidelines on depression also cite clear evidence that, although expensive at the early stages, CBT treatment is very cost-effective in the long run. Richard Layland, a member of the House of Lords, argues that “psychological therapies like CBT, which are in heavy

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cal psychologist. Dr Bahn explains: “It’s really a whittling down of a most likely diagnosis, where you ask patients questions such as ‘are you hearing voices’,‘do you think someone is out to get you’, ‘do you feel people are influencing your ideas and actions’. These are suggestive questions that are neither specific nor very sensitive.”

Currently, it is impossible to accurately identify individuals at high risk of developing a mental illness, and, depending on

Professor Ed Bullmore is co-director of the Brain Mapping Unit at the Department of Psychiatry and Clinical Director of the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. He uses MRI brain scanning to investigate schizophrenia and other neurodevelopmental disorders.

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Dr Sabine Bahn is a practising psychiatrist and head of the Cambridge Centre for Neuropsychiatric Research. Her group uses large-scale molecular profiling technologies to define the molecular basis of schizophrenia and bipolar disorder.

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Professor Trevor Robbins is head of the Department of Experimental Psychology and Director of the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. He investigates the underlying neural mechanisms of psychiatric and neurological disorders.

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demand, are not adequately available”. He estimates that some 10,000 extra therapists are needed to meet the current demand.

However, Professor Bullmore points out that not all psychotic patients benefit from psychotherapeutic approaches. “CBT is a powerful non-pharmacological technique for all kinds of psychiatric problems, but I have to say that blokes in particular are not good at it. Our adults with psychosis don’t really want to sit around talking about stuff.

Some of them do, but it doesn’t necessarily suit everybody.”

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Professor Tim Crow is Honorary Director of the Prince of Wales International Centre for Research into Schizophrenia and Depression at the University of Oxford. He uses genetic and neuroimaging techniques to examine the neural basis of schizophrenia.

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Animal Controversies The use of animals in neuropsychiatric research is a source of endless controversy.

Preclinical safety testing, which involves testing drugs on animals, is required by UK law before a new drug can be released for the human market.

Professor Bullmore explains that “I don’t see how you can develop drugs safely without some period of preclinical testing. Would people really rather that drugs went straight into humans following Parexcel [the drug involved in the July 2006 clinical trial scandal]?

Even where you have an animal model… there are still risks. But. I think these risks are mitigated a lot by preclinical testing.”

It is clear that in order to treat psychiatric disorders more effectively, we need to better understand their biological basis. However, there is no consensus on the best way to do this. The study of post-mortem brain tissue is limited by artefacts such as medication and drug abuse, which affect the brain and can mask the underlying neural

features of the disease. Another approach is to study the brains of living human patients. However, ethical, legal and practical considerations severely restrict the information that can be gathered from human patients. This is why scientists turn to animal testing in psychiatric research.

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Neuropsychiatric research will tell us a lot about what it means to be human - Professor Tim Crow

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Some experts argue that animal models provide us with otherwise unattainable insights, whereas others dispute their relevance to human psychiatric disorders. The key question is: how can animal models be used to learn more

about psychiatric disorders and to design innovative drugs? Can you actually make a rat psychotic?

Dr Bahn is not convinced. “Whether these animal models are aetiologically related to schizophrenia has to be very doubtful, as we don’t know the aetiology of the disorder at all.”

Professor Crow believes that “This approach [of using animals] is potentially useful up to a point. It establishes what we know about neuroanatomy and neuropharmacology.” However, he argues that what critically matters about psychiatric illnesses, such as psychosis, is that they are “human-specific”, and that neuropsychiatric research will eventually “tell us a lot about what it means to be human”.

In contrast, Professor Robbins feels that “[specific] symptoms can probably be modelled in animals, as the same basic brain systems—the neurotransmitter systems—are present in humans and they mediate much the same kind of behaviours. Even something as complex as schizophrenia can be broken down into its constituent parts. Some aspects of schizophrenia… depend on very ancient brain systems, which are present in other animals.”

How Do SSRIs Work?

The neurotransmitter (serotonin, A) is stored in vesicles (B) within the presynaptic neuron (terminal end B shown, C) and is released into the synaptic cleft (space between neurons). Some serotonin enters the receptors (D) of the postsy- C naptic neuron (E), causing the transmission of a nerve impulse.

Some of the serotonin flows F back (upward arrows) and is recycled within the presynaptic A nerve cell.This reuptake of serotonin from the presynaptic neuron impedes the transmission of E neural signals.

The selective serotonin reuptake inhibitor (SSRI) drug molecules (F) D fit and block the reuptake channels (G), causing more of the serotonin to remain in the synaptic cleft, and to influence subsequent synaptic transmission.

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Selective serotonin reuptake inhibitors (SSRIs)—one of the more successful classes of psychiatric drugs including Prozac, 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 postsynaptic 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% of patients withdrew from the studies, due to either adverse events or lack of efficacy.

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Text adapted from www.itmonline.org

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The Future of Diagnosis and Treatment Recent research in neuropsychiatry is charting new frontiers towards understanding the biological underpinning of specific mental disorders. Although this research area holds much promise, it is still at a very early stage.

Professor Tim Crow was among the first to link changes in brain structure with schizophrenia, in 1976. He cautions that “although schizophrenic patients show an enlarged region of the brain, termed the cerebral ventricles, when compared with healthy volunteers, this finding is quantitative and not a discrete marker, as there is overlap between patient and control groups.”

In Professor Robbins’ view, biological testing for the diagnosis of psychiatric illnesses is entirely possible. Indeed, he says: “I don’t necessarily think it will be limited to biochemical markers; I think there are strong behavioural and cognitive traits, and other types of social symptoms, which may also be predictive. This might have enormous therapeutic potential.”

A recent study from Dr Bahn’s group, published last year in PLoS Medicine, found elevated levels of glucose—the main energy source in our bodies—in the brain and cerebrospinal fluid (CSF) of schizophrenia patients. This may be a biomarker for schizophrenia. Her group found that schizophrenic patients did not metabolize glucose as well as controls, but appeared to use a different energy source, lactate, in their brains and CSF. Professor Bullmore recently published research in Proceedings of the National Academy of Sciences showing that, in non-psychotic individuals, early development of motor functions was linked to better ‘executive functions’, such as planning and abstract thinking in adulthood, and to increased amounts of grey matter in the brain. By contrast, schizophrenia patients had delayed motor development in early life and impaired executive functions in adulthood. However, these motor development abnormalities are not always associated with the development of psychosis in later life.

Professor Bullmore warns that careful forethought is needed to ensure that patients benefit from new diagnostic techniques. He says: “If you believe that long-term neurodevelopmental abnormalities lead up to development of psychiatric symptoms, you might argue that

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there is something you might be able to do, to intervene perhaps 10 years earlier.

Now that’s quite attractive as a concept, but we’re not there yet.”

Indeed, early intervention could come at a high cost to patients and their families, especially in cases of misdiagnosis.

“You can’t say to somebody:‘I think your child might develop schizophrenia in 10 years’ time’, unless you can quantify the probability that you’re wrong. Otherwise, you’re not really giving the parents or the children information, you’re just frightening them.Also, you’ve got to know that the intervention you’re going to offer is really going to work.”

He argues: “My favourite for an early intervention would be more along the lines of physical therapy, rather than psychotherapy.Think about the observations that children who later go on to develop

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I don’t think it will be limited to biochemical markers; I think there are strong behavioural and cognitive traits, and other types of social symptoms, which may also be predictive - Professor Trevor Robbins

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schizophrenia are abnormal in terms of motor function and social function. [Help with] motor function, in particular for boys, is something that you could quite easily offer as a treatment without appearing too clinical.”

However, this type of early intervention suggested by Professor Bullmore does not convince Dr Bahn. She feels that a motor test would not be very sensitive or specific, as children often show delayed development for other reasons. Rather, she believes that biomarkers, such as the high glucose levels in schizophrenia patients, have better sensitivity, and “could enable us to develop new, early or pre-symptomatic treatments to improve outcomes, or

even prevent disease symptoms”. She plans to commercially develop her novel biomarker findings through a University of Cambridge spin-out company called PsyNova Ltd. Highly sensitive biological diagnostic tests targeted to the treatment of mental disorders are already underway. In 2006, a biochemical company called LGC developed and marketed a DNA-based test, the first of its kind available in psychiatry, which, it claims, predicts whether a patient will respond well to the antipsychotic drug clozapine. The test is based on long-term genetic and psychotherapy studies conducted at the Institute of Psychiatry, King’s College London.

However, the government has not yet decided whether to fund such tests. If governmental funding for mental health does not increase, is there a potential for a two-tiered mental health system, in which the wealthy will be able to obtain individualized screening and tailored treatment, whereas society’s poor will not?

Professor Bullmore says: “I suppose it’s a potential [scenario]. There are a lot of unknowns in that equation. [What is] the level of NHS funding? How quickly will existing therapies come off patent and be replaced by much cheaper generics? Will that produce headroom in NHS pharmacy budgets for investing in newer, more expensive things?

Suppose a drug company had really understood what was going on in the brain as someone becomes psychotic, [developed] a new drug targeted to a faulty mechanism, and it was shown that a year or two’s treatment with this entirely new kind of drug was sufficient to prevent the emergence of chronic psychosis. If you had a drug like that, it would have to cost a lot to be more expensive than the long-term costs of untreated psychosis. So, the argument of a two-tiered mental health system may not be relevant.”

Hannah Critchlow is a PhD student in the Department of Physiology, Development and Neuroscience Peter Davenport is a PhD student in the Department of Biochemistry Michael Marshall is a Scientific Literature Curator in the Sanger Institute

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In Brief

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In Brief Access to Essential Medicines The development and delivery of drugs for ‘diseases of poverty’ could be revolutionized by a new patent scheme, according to the economist and philosopher Professor Thomas Pogge from Columbia University in New York City.

Pogge outlined his proposal in Cambridge on 22 November at the first annual Routledge Philosophy Lecture, describing his scheme as “simply hanging the carrot in the right place”.

Under the current system of drug licensing, the world’s poorest are left without the lifesaving drugs readily available in richer countries. To solve this, Pogge proposes a new system of adminis-

tering intellectual property (IP), to run alongside the current scheme. IP rights are the rules that govern the reproduction, sale and use of ideas and inventions, from new technologies to music.

Under Pogge’s plan, firms would not have proprietary rights over a drug but would instead receive an annual financial reward proportional to the impact it has on relieving the global disease burden.

These rewards would be underwritten by governments, with different countries contributing according to their means.As a result, serious but neglected diseases would become a more attractive target for drug companies, because of the

potential for a big impact and big money.

At the moment a World Trade Organization treaty, the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), sets the international standards for IP rights. TRIPS was meant to provide incentives for pharmaceutical companies to invest in drug development, by granting them a 20-year monopoly to fix the prices of their new drugs.

Pogge argued that this system imposes a huge health burden on poor populations, by pricing new medicines out of their reach and by discouraging research into drugs for diseases of poverty. ET

Detecting Pollution on the Go

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A new research project called MESSAGE will use cyclists and pedestrians wearing environmental sensors to track pollution levels. MESSAGE is a £3.5million, three-year initiative set up in October 2006. It aims to use state-ofthe-art sensors attached to people and vehicles to monitor air pollution.

The scheme, organized by Professor John Polak at Imperial College London, will study the impact that buildings, streets and local weather have on pollution levels in Cambridge.

According to the MESSAGE project aims, cheap and easily available sensor devices can be attached to people or

vehicles.These will act as ‘mobile environmental probes’ studying how pollution levels change in real time.

The team plans to analyze how traffic pollution changes in particular locations and under different environmental conditions. Individuals out in Cambridge during the day, on bicycles or walking, will be particularly suited to carrying sensors to record pollution levels. Other participating cities include Newcastle, Leeds and Southampton.

If you are interested in volunteering for the scheme, please contact Michael Simmonds (mps48@dpmms.cam.ac.uk) of the Cambridge eScience Centre. MP

Environmentally Friendly Fashion

Artificial Pancreas for Children

Around one trillion US dollars were spent on clothing last year alone. However, a recent study from the Cambridge Institute for Manufacturing may have prompted a pause for thought in the fashion industry.

The study suggests that manufacturers should increase the use of organic cotton, place more emphasis on the durability of their clothes and raise prices to encourage fewer purchases. It also calls for research into less environmentally damaging materials and production methods, and the introduction of an ‘eco tax’ on purchases.

The study also outlines how consumers can help to reduce the environmental impact of the clothes they buy. It emphasises buying fewer clothes and using them for longer.

Clothes should be washed less often, at lower temperatures, using ecologically-friendly detergent. Old clothes should be recycled rather than discarded.

It is hoped that these measures will reduce carbon emissions from the production and washing of clothes, as well as the landfill space occupied by discarded clothing. LA

Cambridge scientists report that the development of an artificial pancreas for children with Type 1 diabetes is underway.

Type 1 diabetes destroys the cells in the pancreas that produce insulin, the hormone needed to control sugar levels in the blood.

Diabetics must manually test their blood sugar level and give themselves 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 the Department of Paediatrics at the University of Cambridge. His team is working on an accurate, automated and painless solution.

The artificial pancreas will measure blood sugar level on a minute-to-minute basis via glucose monitors. The signal will be transmitted wirelessly to a hand-held computer that calculates the amount 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. It may also significantly reduce the risk of hypoglycaemia, a complication associated with low blood sugar levels that in extreme cases can lead to coma. SD

SciSoc Events The Scientific Society has several high-profile speakers lined up for Lent Term. Professor Ross Anderson from the Computer Laboratory in Cambridge will describe his work on ID cards and nationwide databases. Later in the term, UCL’s Professor Lewis Wolpert, one of the key figures in developmental biology, will give a talk. Other speakers include crystallographer Professor Sir Tom Blundell FRS, protein engineer Professor Sir Greg Winter and stem cell biologist Professor Miodrag Stojkovic. MM www.scisoc.com

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Lakshmi Harihar and Jon Heras

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Chemistry Steals Tricks from Darwin Jonathan Gledhill explains why Darwin’s dogma may revolutionize chemistry The inefficiency of the drug design process is a consequence of our limited understanding of the subtleties of molecular recognition—the process by which a molecule binds to a target.This inefficiency has both a time and a financial penalty. It can take up to 12 years and close to $1 billion to develop a drug and take it to market. The enormity of

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The modern world is constantly crying out for new molecules. Professor Sanders’ philosophy is simple: why not let nature do the work for us?

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this problem has led scientists to seek out more elegant solutions that can make drug design quicker and cheaper.

Professor Jeremy Sanders is a pioneer of a solution based on the principles of evolution and called Dynamic Combinatorial Chemistry (DCC). DCC is based on the observation that evolution has successfully moulded organisms to fit their environment; thus, it seems feasible that, in the right conditions, a molecule could evolve to bind to a specific target. “We have developed an entirely new approach, inspired by the example of evolution and selection in biology”, explains Professor Sanders, who has set out the essential features of DCC as early as 1992, and is a leader in this ever-growing field.

DCC requires a diverse molecule population, known as a dynamic combinato-

Jeremy Sanders and Tom Walters

Charles Darwin gave biology its central dogma: the concept of natural selection. He believed that those organisms best suited to their environment would survive and reproduce.

Scientists such as Professor Jeremy Sanders from the University of Cambridge are currently asking if this principle can be applied to the development of new chemicals. Professor Sanders’ philosophy is simple: why not let nature do the work for us?

The modern world is constantly crying out for new molecules. Health services demand new drugs to combat the ever increasing number of pathogens that have developed immunity to established treatments. Traditional chemistry is struggling to keep up with these demands.

Early approaches to drug discovery involved a degree of serendipity. Nowadays, scientists design drugs to interact with particular proteins or nucleic acids, referred to as ‘targets’.A trial and error approach is generally adopted to isolate a molecule that associates with the target and elicits a druglike effect.The isolated molecule must not bind indiscriminately to other targets, nor should it be toxic. A molecule that satisfies these criteria is called a lead.

Once a lead is identified it must be optimised to bind very tightly and specifically to the target. The potency and physiological effect of the optimised lead is subsequently assayed in the test tube, prior to conducting tests in animals and, finally, in human subjects. Each stage involves the lengthy and repetitive process of chemical design, synthesis and evaluation. For each drug on the market today, at least 10,000 related molecules were scrupulously synthesised and tested.

A collection of molecules (coloured blocks) reversibly bind to form a dynamic mixture of assorted receptors. The addition of a template molecule (purple object) selects the “fittest” receptor from the dynamic library.

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rial library (DCL), and a selection pressure to distinguish a lead so that it becomes more numerous. The immune system provides an example of such a selection occurring naturally. It contains a large library of different antibodies; of these, only those antibodies that bind to, and thereby neutralise, the infecting pathogen become selected and amplified.

A DCL contains thousands of unique molecules. Each molecule is assembled from a different number of basic building blocks in different orientations. Thus, the molecules vary in size, shape, stability and charge. Only a subset of a diverse DCL will be able to interact with the target.

A key feature of a DCL is that the assembly of the molecules is totally reversible. This means that the library is constantly changing as molecules swap building blocks.These exchange reactions must meet a number of stringent requirements, such as occurring on a practical timescale, being able to be frozen, and to not require an extreme temperature, pressure or pH. Extreme conditions may disrupt the delicate interactions within the target, as well as between the target and a binding molecule.

A DCL can be described as ‘dynamic and adaptive’, because the assembly of the molecules is influenced by the presence of a target. When a molecule in a DCL binds the target, this molecule is stabilised, and the equilibrium becomes biased toward the formation of this molecule. In evolutionary terms, this molecule is the fittest. It is selected and enriched in the population at the expense of all other molecules. “The beauty of our approach is that we design the experiment rather than the molecule. The molecules design themselves,” comments Professor Sanders.

Theoretically, DCC appears to be the solution to the enormous demand for new molecules. In practice, however, there is still a lot of work to be done.

For example, increasing the number of the reversible reactions and the size of the combinatorial library are significant challenges. Despite these difficulties, Darwin’s dogma may transform the way we make new chemicals. Chemistry, it would seem, is set to evolve.

Jonathan Gledhill is a PhD student in the MRC-Dunn Human Nutrition Unit

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Are humans special?

Mico Tatalovic questions the behavioural basis of human uniqueness The principles of evolution suggest that humans are nothing more than another animal species. Yet, we have always had the tendency to identify ourselves as different, in some way special and separate from the rest of the animal kingdom. Among the main differences between humans and other animal species are our use of technology and our highly complex societies, which display a division of labour unmatched in any other animal group. But, why are humans, and not other species, able to develop technology and complex societies?

Traditionally, scientists have considered three main behavioural features to be uniquely human: tool usage, language and our ability to teach. However, recent research, which points towards the presence of these behaviours in other animal species, prompts the need to revise our understanding of what is at the basis of human uniqueness.

Studies of animal tool use, predominantly looking at primates, have suggested that chimpanzees can use tools.

One notable example is Jane Goodall’s

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Scientists have considered three main behavioural features to be uniquely human: tool usage, language and our ability to teach

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observation that, in their natural environment, chimpanzees fish for termites to feed on by using sticks. An example of tool use in other animal species is the

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New Caledonian crow, a bird species that uses a range of tools in the wild.

These crows are capable of producing tools de novo from natural materials, such as twigs and plant leaves. The range of tools found in their habitat shows that the knowledge of tool usage may be transmitted culturally between different birds and bird populations.

Research led by Professor Kacelnik at the University of Oxford suggests that crows use problem-solving skills when acquiring food. The crows appear to

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eties. Language is thought to be necessary for the development of self-awareness and our understanding of the minds of others—so-called, ‘theory of mind’.

Having a theory of mind enables us to reason about the intentions, thoughts and emotions of other people, and, possibly, to put ourselves in their shoes.

Language is regarded as a vital part of this reasoning process, traditionally considered to be uniquely human.

Among the key characteristics of the human language are its recursive grammar

Crows are capable of producing tools de novo from natural materials, such as twigs and plant leaves

choose tools of an appropriate length, diameter and shape to obtain the food from holes and traps. One celebrated crow, named ‘Betty’, was observed to create a hook from a straight wire in order to reach for food. In contrast, chimps and two-year old toddlers do not understand how to use hooks.

Studies indicate that the birds may use tools sequentially: first, use a tool to reach for another tool, and, then, use the secondary tool to reach for the food. Such an instance of ‘rational’ behaviour suggests that crows understand the consequences of their actions, and may even plan ahead. This line of research has led some scientists to conclude that birds may have intelligence comparable to the intelligence of primates. Although more research is needed to corroborate these findings, these studies already suggest that the ability to use tools is not an exclusively human trait.

As the main medium for the transmission of culture and expertise to future generations, language is another component crucial to the development of soci-

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and its vast lexicon (tens of thousands) of arbitrary, learned words, representing long-term associations between memory and structured pronunciations. Some scientists have argued that the sole distinguishing feature of human language is recursion, or the process that a rule undergoes when one of the steps of that rule involves rerunning the entirety of the same rule. Recursion allows the unlimited extension of language by embedding sentences within sentences. For example, ‘Mary kissed Tom’ could be embedded into a frame of 'X verb Y' to make 'Jon said Mary kissed Tom’, which can further be embedded to give 'Jane heard, Jon said, Mary kissed Tom’. Noam Chomsky has argued that “no species other than humans has a comparable capacity to recombine meaningful units into an unlimited variety of larger structures, each differing systematically in meaning”.

However, a recent study published in Nature suggests that other animal species may also use recursive grammar.

Gentner and colleagues trained European starlings to recognize acoustic

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patterns defined by recursive grammar, to classify new patterns defined by this grammar, and, then, to exclude agrammatical (non-recursive) patterns. Based on these results, they argued that “the capacity to classify sequences from recursive, centre-embedded grammars, is not uniquely human”. Undoubtedly, these findings must be replicated to establish the validity of Gentner’s claim.

However, these findings suggest that the elements, which traditionally have given language its privileged status as a human faculty, may not be solely the domain of human beings.

Our ability to teach is another strong candidate for the X-factor that separates us from other animal species. Social learning is commonplace in most animal species. However, until 2006, limited data existed to support the idea that members of another animal species actively teach their kin at no apparent, immediate benefit to themselves, but, rather, mainly to the benefit of the animals being taught. However, Professor Clutton-Brock and colleagues at the University of Cambridge have collected extensive data on meerkats in the

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The evidence for what has been considered uniquely human behaviour is not as clear-cut as previously thought

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Chimpanzees photographed on one of Jane Goodall’s research expeditions. Left: A chimpanzee fishing for termites. Right: Fifi and an infant chimpanzee.

shares the tasks of guarding its members against predators and digging communal holes used to escape any threat.

Meerkats’ use of specific calls for identifying different types of predators, as well as threat levels, suggests that they have a ‘language’ of their own. Pups use calls to beg for food—mainly invertebrates—and adults can tell the age of the pups by their calls. Adult meerkats have been found to respond differently to begging calls from pups of different ages. Meerkats have recently gained much popularity due to evidence that they teach their young how to deal with prey, by giving pups more challenging prey, as they get older. The youngest pups are given dead prey, whereas the most dangerous prey, the scorpion, is first given to pups with the deadly stings removed. Adults also nudge their pups to encourage them to examine the prey, and to learn what

behaviour to expect from the prey, before having to deal with a potentially deadly one.

It is becoming apparent that the evidence for what has been considered uniquely human behaviour is not as clear-cut as previously thought, or hoped. Current research suggests that we are not the only animals to adapt tools, to communicate via a complex language, and to teach one another.

Perhaps, it is the combination of these three characteristics, not yet found to occur in any other animal species, that makes us so different from the rest of the animal kingdom. Just how important these characteristics are, separately or together, for making us what we are remains a mystery that will continue to drive further study.

Mico Tatalovic is a PhD student in the Department of Zoology

Alex Thornton

Kalahari Desert, South Africa that oppose this idea. Meerkats are social, carnivorous mammals that live in family groups of up to 40 members. Group members co-operate in rearing, babysitting and feeding their pups. The group

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Left: A baby meerkat. Right: Meerkats in a social setting.

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Black-Scholes The black hole of maths and money Tristan Farrow tells the story of the formula that crashed the stock market The use of mathematical equations to model complex patterns plays a vital role in science, physics and economics. However, there are also dangers in putting too much trust in one simplified formula. Occasionally these dangers become a dreadful reality, as happened in 1987, when stock markets worldwide suffered one of the biggest financial crashes of the century. More recently, in 1998, thousands of investors in the Long-Term Capital Management (LTCM) hedge fund saw their monies disappear, as LTCM lost over $4.6 billion in less than four months. Who was to blame for these disastrous losses?

Few mathematical equations form the subject of popular articles and books, and fewer still are credited with crashing a stock market. In the 1990s, Forbes business magazine pointed its finger directly at the Black-Scholes equation, as the formula behind the disastrous miscalculation of the stock market prices. In recognition of the importance of this equation, the Nobel committee awarded its 1997 Economics prize “for a new method to determine the value of derivatives”, to Myron Scholes and Robert Merton.

Fischer Black, who also gave his name to the formula, became ineligible for the award, due to premature death in 1995.

The Black-Scholes equation was developed to calculate a fair price for the financial derivatives called options. These

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are contracts that can be bought just like insurance policies, which give you the right to buy or sell a share, at a future date and for a pre-agreed price.This practice is as ancient as trade itself; merchants from the Phoenicians to the Romans frequently traded options on their goods.

In 1900, this ancient system stood on the brink of revolution driven by the application of scientific options pricing.

Louis Bachelier, a PhD student of the famous mathematician Jules Henri Poincaré, decided to apply ‘random walk theory’ to options, in his thesis Théorie de la Spéculation. This was the notion that

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For the first time in history, it seemed that you could play the markets risk-free

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stock market prices fluctuate randomly without being affected by past price movements, simulating the same jagged price variation in options. Remarkably, his work came five years prior to Einstein’s paper that applied random walk theory to so-called ‘Brownian motion’, to describe the random movements of gas particles.

Bachelier’s scientific model of pricing options presented a new approach to an old problem. Unfortunately, it was flawed

in several ways. Firstly, it failed to take into account catastrophic events such as stock market crashes, because it assumed that the probability of extreme price fluctuations was negligible. Crashes may be infrequent, but they are all too real. This flaw is inherent in a model based on random walk theory, where the distribution of probabilities is said to be ‘normal’. A normal distribution with price on the horizontal axis and probability on the vertical assumes a bell shape, with a sharp ski-jump drop followed by a gentle short tail—too short, in fact, to accurately reflect the reality of extreme share price movements. Crucially, when calculating an option’s price, Bachelier’s model was also unable to calculate the risk premium, or the financial value of risk. This problem remained unsolved for many years, as the amount of risk investors are willing to accept is anyone’s guess.

It was Black and Scholes, 70 years later, who realized that the risk premium calculation could be avoided altogether.

Their inspiration came from gamblers who covered their losses by betting in opposite directions. In a portfolio with a mixture of shares and options, Black and Scholes saw that they could create a riskfree investment, since the movement of shares and option prices would offset each other. The underlying point is that the prices of shares in companies move completely randomly. If you try picking shares by throwing darts at the financial

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Bachelier’s model from 1900, and that the volatility is constant during the lifetime of the option. Neither assumption is quite true. The assumption of a normal distribution for share values fails to predict extreme price fluctuations and market crashes, while volatility itself can follow a ‘random walk’. Blindly trusting the formula to calculate option prices gives one a rosy picture of the world.

Despite the warnings of Forbes magazine, this costly lesson was driven home

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

in 1998 to thousands of investors. The formula’s inventors were directly to blame. In 1994 Robert Merton and Myron Scholes set up a company, Long Term Capital Management (LTCM), intending to play the markets using the models that would eventually earn them the Nobel Prize. LTCM was a “gigantic vacuum cleaner sucking up nickels from all over the world”, according to Scholes. Cashing in on their iconic status as the fathers of modern finance, the start-up raised three billion dollars, which the company set forth to multiply, with average returns of 35% in the first three years.

Then, the unpredictable happened.

The economies of South-East Asia skidded to a halt in a domino effect, sparked by the collapse of property prices in Thailand in 1997. Banks went out of business and loans went unpaid worldwide. Yet this was only a foretaste. The big shock came in August 1998, when Russia suddenly announced it would

S is the current share price, σ is the share price volatility, r is the interest rate, T is the time before an option’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 be higher when S, σ, r,T, N are all high. N is assumed to follow a normal distribution, since it depends on the expected share price on the date of the option’s maturity, L. The lower the share price at maturity, the higher the option’s overall price.

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cease all foreign debt payments.

Pandemonium reigned in the financial world, with all indicators jittering furiously back and forth, reflecting the panic in the market. By this time, LTCM had bets topping one trillion dollars, with its models now as useful as a dud compass.

Models based on the normal distribution work well on calm days, but they simply could not predict such catastrophic events, nor could they point the way out of the rut. Finally, the US

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Financial Times

pages, as a group of US academics tried to do in the 1930s, you may discover that your portfolio will perform as well as any professionally managed fund.

After further refinement by Robert Merton, who adapted the equation for a fast-paced market, the formula was finally unveiled in 1973. Its impact was virtually immediate, spawning a trilliondollar market for financial derivatives such as options, as well as the growth of giant hedge funds managing shareoption portfolios. When Texas Instruments began making calculators with an inbuilt Black-Scholes button to allow traders to calculate option prices, they were snapped up like candy in a playground. The world was bedazzled and, for the first time in history, it seemed that traders could play the markets risk-free.

The Black-Scholes formula is obtained by solving a differential equation that closely resembles the equation describing the diffusion of heat, which emphasizes its relationship to physics. The original formula is then converted to the expression used for ‘call’ options, which allow one to buy a share at a specific date in the future. A modified expression is also used for ‘put’ options, for selling shares.

The equation takes as its inputs the price of the share it underwrites, the length of time before the date on which the option can be used, the interest rate, and, significantly, the so-called ‘volatility’, or the amount by which a share price can be expected to fluctuate. It can be likened to the jitter of particles in a gas, which bang into each other ever more violently with higher temperatures.

The formula relies on a number of assumptions.The most significant of these is that fluctuations in the share price follow a normal distribution, like in

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Federal Reserve stepped in to bail out LTCM, preventing it from taking all of Wall Street down along with it.

Today, the Black-Scholes formula is still used millions of times each day by derivative traders and fund managers worldwide.Astonishingly, it is used more than ever before, but with a significant difference: Black-Scholes no longer predicts option prices. Instead, it is being used in reverse. The option’s price is taken as a given, and is plugged into the equation in order to calculate the volatility of the share price. This does not address the problem that volatility itself does not follow a genuine normal distribution for large fluctuations.

However, it does relieve the equation’s Achilles’ heel of direct option pricing for extreme share price fluctuations.

Investment decisions can now be made with a very useful tool that complements, rather than replaces, the qualities that traders value above all—instinct, gut feeling and experience.

Outside the world of finance, large companies have also found a way of adapting the Black-Scholes equation. It is used to calculate the cost of business decisions, such as closing down plants or buying new equipment, by treating them as options.The trend of modelling economics, and even certain social and historical phenomena, is booming, and looks set to spawn new fields of interdisciplinary research. Econophysics, a field barely in existence ten years ago, now features in several dedicated academic departments around the globe.

Despite all this, the next time a magic formula is unleashed on us, we would do well to remember how the BlackScholes equation, with its beauty and apparent simplicity, lulled many into an unjustified sense of confidence. Albert Einstein once said that “if you are out to describe the truth, leave elegance to the tailor”. The costly lesson that Black and Scholes gave, teaching us how intractable the human element can be, is as valuable as the equation itself.

Tristan Farrow is a PhD student in the Cavendish Laboratory

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Biodefence: Is prevention always better than cure?

Three authors debate the benefits and risks of furthering biowarfare research October 2001 saw the first real example of a new kind of biological attack.The notorious ‘anthrax letters’ incident in the US caused panic and confusion. Biological and chemical weapons are not new phenomena, but this was. Bioterror, the suggestion that 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 plotting to use ricin, a lethal toxin that can be extracted from castor bean oil, as a bioagent in the UK. Governments have responded by 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? Collette Johnson, James Shepherd and Rebecca Arkell all believe ‘no’—but for very different reasons.

Predicting Threat, Preventing Panic The recent increase in biodefence spending, while a step in the right direction, is not enough. Among UK scientists, bioterror expertise is a taboo, an area some scientists avoid altogether. We need dedicated scientists and state of the art laboratories, equipped to handle the most pathogenic bioagents, in order to gain the expertise needed to counteract bioterror attacks. To best prepare for any medical, political and social crises that might ensue, biodefence needs to be a financial priority for the government.

In Britain, only a handful of scientists work on bioagents, with most biodefence

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With so few scientists developing methods of prevention and treatment, no one can feel prepared for a bioterror attack

research occurring at the Health Protection Agency (HPA), which is part of the NHS, and at the Defence Science and Technology Laboratory (DSTL), in the Ministry of Defence. DSTL has approximately 200 scientists working on biodefence. Only one third of these investigate pathogens for which limited treatment is available, and only ten work with life-threatening pathogens for which no treatment is known. HPA has only 70 scientists working in biodefence, on an emergency response program, and only 20 of these work with the most hazardous pathogens.

In the months following the 9/11 attacks, anthrax letters became the standard biological threat. However, anthrax is only one of many bioagents, some of which, like the viruses that cause Ebola haemorrhagic fever, can pose much more serious risks. Animals are thought to be the natural reservoir of these viruses, and it is not known how they

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are transmitted to humans in the first instance. The incubation period of the viruses ranges from two to 21 days, with internal and external bleeding among the worst symptoms seen in infected individuals.There is no direct treatment and most of the infected people die.

Ebola and anthrax head a long list of potential bioagents, and with so few scientists developing methods of prevention and treatment, no one can feel prepared for a bioterror attack.

The problem becomes even larger when we consider the multitude of ways that bioagents can spread through the population. They can be transmitted by

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aerosol, via the water or the food supply, or by person-to-person contact. It has been assumed that most bioagents would likely be delivered in the form of aerosol clouds; hence, aerosol transmission has been a main focus of research. Another biodefence research focus has been vaccine development. There are many more areas that require attention, yet only very few research facilities dedicated to biodefence exist in the UK. Possibly the most important, albeit controversial, aspect of biodefence research is the modification of pathogens to anticipate both evolution and the bioterrorists. Outside of the laboratory, many pathogens have short life cycles and evolve considerably between generations.

This means that a treatment effective in the laboratory may not be effective in a real life scenario. Bioterrorists could genetically modify pathogens to make them more dangerous, and baffle doctors and scientists, as SARS in 2002 baffled

the scientific community worldwide.

Nevertheless, biodefence research involving the modification of pathogens is essential for improving our chances of predicting the ‘worst-case scenarios’ and, possibly, of preparing for them.

One worst-case scenario involves undetectable agents, which may fool our current security systems until it is too late. Although it can be argued that terrorists prefer increased disruption to increased casualties, it would be in our best interest to be able to detect the presence of a bioagent immediately.The earlier a bioagent is detected, the fewer deaths it is likely to cause. Recent bioagent detection techniques developed by DSTL have aided the survival of troops in war. However, more biodefence research is needed make these techniques more versatile and applicable to a wider number of bioagents.

For example, one bioagent that poses a particularly big threat is Burkholderia pseudomallei.This pathogen does not present unique clinical features. It causes either an acute pulmonary infection or a blood infection. Its incubation period ranges from two days to up to 10 years, making it ideal for a ‘silent’ bioagent attack.

Researching diseases and scientific problems other than biodefence is essential for the health and economic wellbeing of a country. However, the immense threat posed by bioterror should make biodefence research a top priority for both the government and the scientific community. Increased financial investment for biodefence research and commitment from the scientific community will improve our protection against the potential severity of any bioterror attack. Biodefence research must prepare for the worst-case scenarios, whether they are silent attacks, bioagents modified for maximum lethality, or both.

Collette Johnson is a PhD student at Clare College

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Defending the Nation, or Draining the Drug Cabinet?

At face value, investing in biodefence research seems like a reasonable strategy for protection against bioterror. To date, worldwide biodefence spending has produced positive results. For instance, a safe ricin vaccine and a quick test for anthrax infection are on the way. However, we should be sceptical about research that engineers deadly bioagents. One rationale for biodefence research is to pre-empt any terroristic attempts to modify existing pathogens for maximum lethality. However, there are several arguments against it.

Creating pathogens in laboratories for research purposes gives rise to many dangers. Bioagents could fall into the wrong hands, either by theft or through their increased availability to non-scientific staff. This could lead to incidents such as that in 2002, when the poliovirus was

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of individuals approved to handle live bioagents has increased tenfold since 2001, and, with it, possibly also the risk of terrorist infiltrating these programs.

While there are security tests, Richard Ebright, a professor from Rutgers University, claims that “Mohammed Atta would have passed those tests without difficulty” (taken from M. Williams (2006) Technology Review: An MIT Enterprise). This was exemplified by the link between the 2001 anthrax letters and a biodefence community insider.

Moreover, when biodefence laboratories undertake their research, where should the information go? Whether it is through the media, the Internet or academic journals, information about engineering deadly bioagents could be made available to the public. There is no consensus regarding how to ade-

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

recreated from mail-ordered DNA. Regulation to control these risks has been met with discord, because many scientists perceive it as burdensome red tape.

A related risk is that of accidental exposure, as in the case of the accidental anthrax release at a military biology centre in Russia, in 1979, which caused 68 deaths.This type of public health risk has prompted locals to try to block the construction of a new $178 million biodefence laboratory in the Boston area.

Given the inherent dangers of handling pathogens, intensifying biodefence research may unwittingly cause more harm than good.

Further, creating technical expertise in engineering deadly pathogens means enhancing the chances that terrorists could exploit this expertise. The number

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quately censure the dissemination of this highly sensitive information.

Reservations similar to those expressed towards biodefence research can be applied to some conventional research. For example, in 2001, before the anthrax attacks, Dr Ron Jackson, from the Australian National University, created an immune system evading strain of mousepox, whilst working on a contraceptive vaccine to be used for pest control. The same technique applied to smallpox would undoubtedly have potential bioweapon applications. This research poses the same potential threats as biodefence research.

Should this kind of apparently innocuous research be paralyzed for the same reasons?

Should all the laboratories working with pathogens be checked to ensure that they are not at risk of developing bioagents?

Surely the only thing separating Jackson from the biodefence scientists is their motives. Where terror and national security are concerned, public perception is crucial. The public never perceived Jackson to be potentially aiding bioterror. They might not be so lenient when judging scientists deliberately trying to develop a more potent version of smallpox.

Furthermore, it should be noted that, although the threat of bioterror is real and the hazard great, the risk itself is tiny even when compared with the risk of avian flu, which while small, is far larger.

Biodefence funding could be spent on higher risk public health problems, or channelled into public health funding for diseases already present in the population.

These arguments were unfruitfully voiced in 2003, when $34 million was diverted to biodefence research and away from medical research into diseases such as HIV. Similarly, US microbiologists in 2005 wrote to the NIH warning that biodefence spending was draining money from necessary research into tuberculosis and hepatitis.

Even if the risk of bioterror outweighed the risks from more present threats, the chances of predicting and manipulating the same bioagents as those used by the terrorists would be abysmal.

This seems especially true, given that the proponents of the ‘increased spending’ strategy eagerly warn us that there are a myriad potential bioterror agents.

Even if the predictive powers of biodefence research were greater than they are, the risks associated with increased availability and expertise of bioagents are too great to justify increased biodefence spending. Despite aiming to make us feel safer, biodefence research may actually increase the risk of a bioterror attack.

James Shepherd is a second year Natural Scientist, specializing in biochemistry Rebecca Arkell is a PhD student in the Babraham Institute

ANTHRAX has a mortality rate of 90-100%, partly due to its diagnosis being confused with a variety of viral and fungal infections. Vaccines are available against some forms of anthrax, but their efficacy against unpredictably high exposure levels is uncertain.

EBOLA is one of the most virulent diseases known to man, with a mortality rate of 50-90%. Symptoms include a sudden onset of fever, vomiting and internal and external bleeding. No treatment or vaccine exists.

Kelly Neaves

RICIN blocks protein synthesis by altering the cells’ RNA. Symptoms include the rapid onset of nausea and severe diarrhoea. High doses can cause pulmonary damage severe enough to cause death. There is no antitoxin available.

Immunisation methods are under study.

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Federation of American Scientists

BOTULISM is caused by neurotoxins that attack the nervous system, resulting in symptoms similar to food-borne botulism.The mortality rate can be constrained to <5% with appropriate treatment. A vaccine that provides 90% protection up to after 1 year is available.

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RNAi

Taking Control of the Gene Catherine Jopling describes a novel method of silencing gene expression Information provided by our genes defines how our cells function from development to death. It is therefore no surprise that changes in our genes can have serious effects. Disease can arise from genes being switched on at the wrong time, being on for too long, or being present in a modified form.

In the past, we have had very limited methods of controlling gene expression, both in vivo and in vitro. However, a recently discovered technique called RNA interference (RNAi) has expanded our ability to turn off genes to reveal their function, and has the potential to facilitate the treatment of some diseases.

In October 2006 the Nobel Prize for Medicine was awarded to two Americans, Andrew Fire and Craig Mello, for their discovery of RNAi.Working at the Carnegie Institute in Washington and the University of Massachusetts respectively, they found a method to silence specific genes in the nematode worm. In a seminal paper pub-

thymine (T). Each base in one DNA strand pairs with its specific partner—A binds to T and G binds to C—in the other DNA strand, creating a doublestranded DNA helix.When the cell needs to make a particular protein, the DNA helix is unwound and the sequence of the bases that constitute the gene is read and used as a template to make a complementary messenger RNA (mRNA). mRNA is similar to DNA, but is normally singlestranded, has a shorter lifespan, and, as the name suggests, acts as a messenger. mRNA travels out of the nucleus into the cytoplasm, where molecular machines called ribosomes bind it and convert the RNA code to protein.

As early as 1984, researchers tried to inactivate genes using RNA molecules that had a complementary sequence to a stretch of mRNA of interest. This is known as antisense RNA, and it was thought that it would bind to its single-stranded mRNA partner and prevent it interacting with the ribosome, so that no protein would be

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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

lished in Nature in 1998, Fire and Mello showed that they could inactivate a muscle gene by injecting a nematode worm with a particular double-stranded RNA containing the exact information encoded by the gene. This technique has been named RNAi, and, in the short time since its discovery, it has become a vital asset to scientists in the laboratory.

Every gene is made up of a unique DNA code formed from a pattern of four different chemical bases known as adenine (A), guanine (G), cytosine (C), and

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made. The results of these experiments were mysterious. Sometimes they were relatively successful, sometimes woefully ineffective. Strangely, in 1995, Guo and Kemphues found that sense RNA, which had exactly the same sequence as the gene they were trying to silence, was as effective as antisense in preventing the production of a particular protein.

Around the same time, researchers working on plants and fungi discovered a phenomenon they called post-transcriptional gene silencing (PTGS) or quelling, in

which putting a second copy of a gene into a cell stopped the protein being made. Fire and Mello’s stroke of genius was to test the effect of double-stranded RNA, made of one sense and one antisense strand, like the DNA. The double-stranded RNA proved very effective at turning off protein production in nematode worm, whereas single-stranded RNA did nothing.

We now know that RNAi, PTGS, and quelling are all the same process, and that RNAi is not unique to nematode worms, but occurs in insects, fish and mammals.

Even more importantly, we now know how RNAi works. Fire and Mello noticed that injecting even very small quantities of double-stranded RNA induced destruction of the mRNA, preventing protein production. This suggested that sensitive detection of doublestranded RNA led to the activation of a range of protein enzymes. This is indeed the case, as a complex machinery of proteins exists in the cell to carry out RNAi. Double-stranded RNA is recognised in the nematode worm by the protein Dicer, which cuts the RNA into small, 21-base pieces.These are known as short interfering RNAs (siRNAs), and are recognised by a protein complex called the RNAiinduced silencing complex (RISC).

As well as binding siRNAs in mammals, RISC contains a protein called Ago2, which acts as a pair of molecular scissors. These scissors first destroy one strand of siRNA, whilst the other strand forms part of RISC. RISC can now pair with any complementary mRNA it encounters. Successful pairing with mRNA activates Ago2 and the mRNA is cut into two pieces.These two pieces are unstable in the cell and are rapidly degraded, leaving no message for the ribosomes. Thus, the gene can no longer trigger the production of its protein.

Hundreds of studies have been published that use RNAi to turn off a particular

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gene, enabling scientists to decipher the function of its protein product. RNAi is particularly useful now that the complete genome of many organisms has been sequenced, as we often have very little idea of what each gene product or protein does.

Norbert Perrimon’s group at Harvard University has developed a screening system with which they can individually inactivate every gene in the fruit fly, by using RNAi.The screen has been used to identify genes involved in fundamental processes, such as cell growth and viral infection.

As well as enhancing our understanding of how different genes function, RNAi can help to identify drug targets.

Fotis Kafatos and colleagues at the EMBL in Heidelberg used RNAi to identify three genes in the mosquito that help or hinder the life cycle of the malaria parasite. This knowledge is very useful for designing malaria treatments, allowing the development of drugs that target essential genes and their protein products.

The potential medical benefits of inactivating specific genes are immense.

Philip Zamore and his colleagues at the University of Massachusetts used RNAi to selectively destroy a mutant version of the gene SOD1, which causes a neurodegenerative disease in humans. In cultured

no RNAi

RNAi

Brock et al. (2006)

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Fluorescent photographs of the roundworm (Caenorhabditis elegans).Three genes (fat-5, fat-6, and fat-7) are bound to green fluorescent protein (GFP) using empty vector control bacteria.The worm then glows green where the genes are active.The effect of RNAi can therefore be visualized.

protein, it is not accessible to traditional drug therapies. Preventing ApoB protein from being made by siRNA may provide a new way of reducing high levels of cholesterol.

Despite the promise of RNAi as a new weapon for fighting disease, there are still many questions regarding its safety. One concern is the delivery of the siRNA into the cell. An inherent hurdle is that negatively charged siRNAs do not pass easily

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It will be some time before safe, reliable RNAibased medicines become available, but the technique has enormous therapeutic promise for the future

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through the cell membrane. One approach to overcoming this is to encase the siRNA in a hydrophobic membrane known as a liposome.This method is very effective in the cell culture and, encouragingly, was used successfully by the Alnylam researchers to deliver siRNA to monkey liver cells. An alternative, currently being explored by researchers, is to chemically modify the RNA backbone with uncharged molecules, such as cholesterol, to allow it to interact with the hydrophobic membrane and enter the cell.

In an entirely different method, the DNA itself can be delivered to cells.

Instead of using siRNA directly, it is possible to introduce DNA that will

Catherine Jopling is a postdoc in the Department of Biochemistry

Tom Walters

human cells the specificity of the siRNA was such that the normal version of the mRNA, which differs by only a single base, was unaffected.This point is significant, as some siRNAs are not entirely specific and induce ‘off-target’ effects. By careful design of the siRNA, Zamore was able to avoid this problem.

Many other disease genes have been targeted with varying levels of success, both in cultured cells and in mice.

Researchers at Alnylam Pharmaceuticals were recently able to reduce cholesterol levels in monkeys using a siRNA against the mRNA for ApoB gene. ApoB has an essential role in the transport and metabolism of cholesterol, and, as a large

subsequently produce a short doublestranded ‘hairpin’ RNA. This is then recognised and processed by the Dicer enzyme to make an siRNA. The DNA is introduced into the cell using a suitable virus such as adeno-associated virus (AAV). AAV is harmless to cells, and has the advantage of coming in a number of different varieties that can infect different tissues. However, it is particularly important to regulate the dose delivered by the virus, to avoid interfering with normal cellular functions. It will be some time before safe, reliable RNAibased medicines become available.

The recent interest in RNAi has given rise to questions as to why cells have evolved such a process. In plants and insects, RNAi seems to work as a defence against viruses. Most viruses produce double-stranded RNA at some point during their life cycle.Viral genes inside cells can therefore be recognised and destroyed.

Mammals, however, have different systems to deal with viruses, making unclear the reason why we have RNAi. It may be an evolutionary artefact, it may provide yet another tool for antiviral defence, or it may serve some other important purpose that remains to be discovered. Whatever the reasons for the existence of RNAi, there is no doubt about its enormous potential, both for the study of gene function and the treatment of disease.

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The Dilemma of the Third Dimension Michaela Freeland discusses one of mathematics’ most alluring problems Mathematics hit the headlines in May 2006 with the awarding and subsequent rejection of the Fields Medal, the ‘Nobel Prize of Maths’, for a proof of the Poincaré conjecture. Named as one of seven Millennium Prize Problems, proof of the Poincaré conjecture has remained elusive for almost 100 years, although spurious proofs have frequently been announced. The mathematician Grigori Perelman was awarded the coveted prize for his apparent proof of the Poincaré conjecture. The unprecedented drama that unfolded following the announcement has largely overshadowed Perelman’s achievement in conquering one of mathematics’ most significant unsolved problems.

Jules Henri Poincaré, a noted mathematician and theoretical physicist, lived during the latter half of the nineteenth and early twentieth centuries. Regarded as one of the founders of the mathematical field of topology, he is also recognised for formulating the basis of chaos theory. His famous conjecture was first

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The Poincaré conjecture was first proposed in 1904, as a concluding note on the last page of a 67-page paper

proposed in 1904, as a concluding note on the last page of a 67-page paper. The Poincaré conjecture was subsequently identified as one of the fundamental questions in topology.

The Poincaré conjecture is concerned with how the properties of an object depend not on its exact shape, but on the way its parts are joined together. The standard introduction to the idea is to think of a ring doughnut and a teacup.

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These shapes are regarded as topologically equivalent, since one can be manipulated to resemble the other.When distorted, the hole in the centre of the doughnut becomes the loop in the mug handle.

Topology deals with mathematical objects called ‘manifolds’—mathematical spaces that on a small scale look like ordinary, flat space.This idea can be likened to an ant living on a jam doughnut.The ant, being so small, would be unaware of the doughnut’s curvature, instead perceiving its world to be flat.

In mathematical terms, a jam doughnut is considered simply as a connected, twodimensional sphere. If an elastic band is placed on the jam doughnut (the manifold) and tightened, the jam doughnut will shrink down to a point without tearing, since its surface is connected.

However, if the elastic band were placed around a three-dimensional sphere such as a ring doughnut, then it could not shrink to a single point without the doughnut tearing. The Poincaré conjecture asks whether three-dimensional

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spheres can be characterized by connectivity like two-dimensional spheres. If a loop on a three-dimensional manifold can be tightened to a point, is the manifold necessarily equivalent to a sphere?

An analogous statement can be formulated for higher dimensions, for which the proof is, surprisingly, simpler. Stephen Smale proved the conjecture for more than five dimensions, and Michael Freedman for four. Both mathematicians

were awarded Fields Medals for their work, in 1966 and 1986 respectively.

The three-dimensional case presents a more complicated challenge. Essentially, there are too few dimensions to remove problematic regions of the manifold, a mathematical process known as ‘surgery’.

Since its proposal, the conjecture has motivated many advances in the field of topology. In recognition of this, and in acknowledgment of its famous intractability, the Clay Mathematics Institute named the Poincaré conjecture as one of the Millennium Prize Problems. One million US dollars were offered as prize money for the solution. Seven Millennium Prize problems were proposed, intended to represent the most significant challenges currently facing mathematics and theoretical physics.

Other problems include proving the famous Riemann hypothesis, establishing the existence of the Yang-Mills theory in quantum physics, and solving the ‘P versus NP’ problem. No claim has yet been made on any of the other problems.

Grigori Perelman, a Russian mathematician, is at the heart of the recent controversy. Perelman first came to the attention of the mathematics community at the age of 16, when he achieved a perfect score in the International Mathematical Olympiad. He embarked on a promising career at the Steklov Institute of Mathematics in St Petersburg, interspersed with periods at New York University and the University of California, Berkeley.

Increasingly, he appeared to shun contact with other mathematicians, earning himself a reputation as a recluse.

Colleagues felt that he had become obsessed with the Poincaré conjecture. In 2003, Perelman surprised the mathematics’ community by taking the unconven-

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tional step of publishing on the internet three papers, in which he is believed to have proven the Poincaré conjecture.

Perelman’s approach to solving the Poincaré problem involved a property known as the Ricci flow, which describes the curvature of the manifold.The Ricci flow had long been identified as a promising approach for proving the Poincaré

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paper entitled ‘The Hamilton-Perelman Theory of Ricci Flows:The Poincaré and Geometrisation Conjectures’ and published in the Asian Journal of Mathematics in April 2006. Yau allegedly dismissed Perelman’s work as “written in such a messy way that we didn’t understand”.

An article entitled ‘Manifold Destiny’, published in August 2006 by the New

Perelman’s techniques are used to investigate the properties of space-time, and to describe its shape

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Yorker magazine, further fanned the flames of discord. The article suggested that Yau, a renowned mathematician and Fields medallist, had violated mathematics’ internal ethical code. It accused him of discrediting Perelman’s claims, and furthermore of seeking to claim the credit for proving the Poincaré conjecture through his students, Zhu and Cao. Furthermore, the article implied that Perelman was caught in the middle of a territorial struggle for the position of pre-eminent Chinese mathematician,

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Having left his post at the Steklov Institute of Mathematics, Perelman has since lived with his elderly mother, declining virtually all interview requests

between Yau and Gang Tian, a former student of Yau. The finding that Tian had been appointed to produce a guide and review of Perelman’s proof heightened this supposition.

Perelman himself has subsequently done little to cement his claim to have been the first to prove the conjecture.

He unveiled his results in an unconventional manner, making them available

Left: www.wikipedia.org; Right: International Congress of Mathematicians

conjecture. Richard Hamilton of Cornell University carried out much of the groundwork for this; his approach was crucial to Freedman’s proof of the fourdimensional case. Perelman’s proof adapted Hamilton’s ideas to prove the Poincaré conjecture in three dimensions.

The presence of singularities, regions of infinite density on the manifold, means that a straightforward approach to the Ricci flow is insufficient to provide proof of the Poincaré conjecture in three dimensions. Instead, Perelman performed multiple surgeries to replace singularities with well-behaved and understood mathematical components. Rather than working with just the Ricci flow, he used the ‘Ricci flow with surgery’.

Perelman’s breakthrough was to show that the number of surgeries required to make a given manifold tractable is finite.

If the ‘Ricci flow with surgery’ satisfies Hamilton’s theorem, Perelman proved that so too does the original Ricci flow.

Hence, the Poincaré conjecture holds true for the manifold. of the publication Following Perelman’s proof, the Chinese mathematicians Shing-Tung Yau, Xi-Ping Zhu and Huai-Dong Cao disputed his claim that the Poincaré conjecture had been solved. Their position was advanced in a

Jules Henri Poincaré (left) and Grigori Perelman (right)

www.bluesci.org

only on the online arXiv archives. His three papers do not contain any mention of either the Poincaré or Geometrization conjectures, the wider theorem of which the Poincaré conjecture is a special case. This in itself creates an obstacle to awarding him the Millennium Prize, which requires that any proof be published in a traditional, peer-reviewed journal. However, many mathematicians argue that the scrutiny to which Perelman’s papers have been subjected since their 2003 release is more than equivalent to the peerreview process.

In October 2006, at a Cambridge General Relativity/High Energy Physics seminar, Dr Gabriel Paternain of the Department of Pure Mathematics and Statistics discussed the Poincaré conjecture. Dr Paternain’s seminar highlighted the technique that he considered to be the most elegant aspect of Perelman’s proof: the coupling of the Ricci tensor, which describes the Ricci flow, with a surgery scale function.

The seminar, organized by the High Energy Physics and General Relativity groups, emphasized the relevance of both the Poincaré conjecture and

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Perelman’s techniques outside pure mathematics, in particular to the fields of gravitation and cosmology. The Universe itself is a manifold, and Ricci flows are standard tools of general relativity. They are used to investigate the topological properties of space-time, and to describe its shape.

However, the Poincaré dispute appears to have brought little but misfortune for those involved. After rejecting the Fields Medal in August 2006, Perelman is believed to have given up mathematics entirely. Having left his post at the Steklov Institute of Mathematics, he has since lived with his elderly mother, declining virtually all interview requests and contact with fellow mathematicians.

Perelman’s rejection stands in stark contrast to the excitement and interest generated only 10 years ago, by Andrew Wiles’ unveiling in Cambridge of his proof of Fermat’s last theorem. It is the aim of the Millennium Prizes, not only to encourage the solution of intractable problems of mathematics, but also, in doing so, to widen the appeal of the discipline. Sadly, it seems that in the case of the Poincaré conjecture, amid the twists of controversy, the ugly legal wrangling and the personal attacks, the true beauty of mathematics has been lost.

Michaela Freeland is a second year undergraduate in the Faculty of Mathematics

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A D ay i n t h e L i f e o f …

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A Pharmaceuticals Scientist Si-houy Lao-Sirieix talks to Matthew Thomas about the pros and cons of working for a pharmaceutical company How many academic scientists have wondered what it is like to work for a big pharmaceutical company? As an insider, Matthew Thomas agreed to share his experiences with us.

Kelly Neaves

How did you find the transition?

After a few high-profile publications, together with collaborative work, conference travel and a promotion offer with a permanent contract, I was convinced that the move I had made was a good one. I found the availability of resources and expertise within the company very attractive. My previous academic group, although successful, could not compete with all the state-of-the-art equipment and tools available to me here. The rewards available to a successful scientist within this environment are generally better than those in academia.

However, I confidently predict that any-

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one making a similar career move would find the way science is practised in the pharmaceutical industry to be very different from academia.

Can you tell us about your job and responsibilities?

I work within the respiratory diseases area (RDA) of the NIBR. I manage a small group of scientists whose current focus is to investigate drug leads in lung diseases. My daily routine involves designing experiments to develop the optimum route for a project, liaising with various groups of specialists, assisting in the interpretation of results and giving recommendations for future directions. I then present the results to the project team or to the higher disease area management. It is important for me to be involved to some extent at every stage of the process. Apart from these core responsibilities, I act as a consultant for other projects or disease areas. I also sit on a board that reviews how all the respiratory disease projects are run. As this is a research position, I frequently study the literature to keep abreast of developments and publish as much as I can.

What do you particularly enjoy about working in this kind of environment?

I enjoy the variety. Eighteen months ago I was working on asthma—a far cry scientifically from my current project.

This gives rise to a challenging but exciting environment. However, despite the high pressure within scientific research, there is a well-developed career advancement system, which can provide flexibility between the various disciplines of a large drug company.

There are usually ways and means to enable employees to move within the company to another disease area, country or career path.

Are there any drawbacks though?

Indeed there are. I don’t believe pharmaceutical science would suit everyone: there is a comparative lack of autonomy within pharmaceutical research. It is my experience that the science one does must provide the results required to move the project ahead, or it must cease completely. Interesting discoveries made along the way may be pursued as a ‘spare time’ activity, but this must come second to achieving what is required for the project. A path change or rethink in a project can be a drastic decision. Such decisions are not made lightly, but are usually dealt

Matthew Thomas, NIBR

What attracted you to work for a big pharmaceutical company?

A more appropriate question is, “What persuaded me to stay working for a big pharmaceutical company?” My move from academia to pharmaceutical science was an exercise more in reconnaissance than in career change. I knew little of how a big pharmaceutical company worked, but was curious to learn and willing to give it a try. As an academic post-doctoral researcher, I was wary of a future of frantic grant writing, isolation and financial frustration, although I was perhaps being a little down-beat at the time. I resolved to determine whether pharmaceutical science was suited to me, and was fortunate enough to gain a twoyear post-doctoral position within the Novartis Institutes for Biomedical Research (NIBR), in Horsham, West Sussex, as a researcher of respiratory disease-relevant systems.

with both deftly and swiftly. This can be different from the typical academic situation, in which a person can devote themselves to an area and, assuming the science is good enough and the funding bodies are suitably impressed, they can largely determine what they want to do and how. This seems like a major drawback until you bear in mind that such a scientific policy in the pharmaceutical industry does not tolerate ‘ivory tower’ science.

The experiments being performed must contribute to a process specifically designed to create a product treating or curing a disease.

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I don’t believe pharmaceutical science would suit everyone: there is a comparative lack of autonomy within pharmaceutical research

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In your opinion, is the fact that you have to stick to a ‘bigger picture’ set by the company a source of frustration, or the way forward?

It is both. I certainly believe that it is the way forward for a pharmaceutical firm and for a scientist like me. I think it would be fair to say that you are more in control of your own direction in academia than in a big drug company.

However, it is necessary to focus on a

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What are the fundamental skills someone needs to work for a pharmaceutical company?

Firstly, I would say it is rather difficult to find a position within a large pharma-

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The standards are very high and this gives me confidence that, with whomever I collaborate in the company, they are likely to be the best in their field

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ceutical firm, so you would need to be at the ‘top of your game’. Secondly, I would say that the ability to adapt is fundamental as you are often required to take on a new project or a whole new disease target at a moment’s notice. If

you can do that, if you can use every tool and resource available to achieve the objectives set for the project, then such qualities would be quickly groomed for further responsibilities within the company and beyond.

Do you have any advice to give to someone who wishes to work within a big pharmaceutical firm?

The standards are very high and this gives me confidence that, with whomever I collaborate in the company, they are likely to be the best in their field.

Becoming as informed as possible about the particular company you wish to work for is useful. Contacting a current employee would be a good way to find out more and to really discover if it is indeed the career for you.

A D ay i n t h e L i f e o f …

successful strategy for the treatment of a disease and for this to happen, other discoveries or directions must take a back seat. What is important is that the experiments performed to validate a project must be of sufficient depth to determine the ‘correct’ path of a given study. The ever-present search for a novel therapeutic strategy has led to more expansive validation studies. The end result may be that the strategy does not and cannot fulfil the aim of the project, leading to a change in direction.

This can be seen as a refreshing opportunity to expand knowledge and expertise, or as a frustrating contraction to a body of work that required immense effort. In truth, it is always a little of both.

Matthew Thomas was interviewed by Sihouy Lao-Sirieix, a Clinical Research Associate in Papworth Hospital

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Keeping you POSTed Sam Dolan enters Westminster to help inform MPs about science This time last year, I was idly flicking through the pages of Physics World wondering what I should do when, or if, I finished my PhD. A career in industry? Or perhaps in finance? To be honest, neither option really appealed.

Then, a small advertisement for a placement at the Parliamentary Office of Science and Technology (POST) in Westminster caught my eye. This sounded more like it: short, sweet, and scientific.The placement would allow me to take a three-month break from my research. It would be perfect for me, so naturally I concluded that I had no chance of winning the placement. Thankfully I applied anyway, and, as it transpired, the starting

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Writing coherently is a skill—and one I wish I had acquired before writing my thesis

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Sam Dolan

date of 2 October became the fixed deadline for writing up my PhD. POST is Parliament’s in-house source of independent and accessible analysis of public policy issues related to science and technology. It produces ‘POSTnotes’: four-page information sheets that are sent out to MPs, peers and other interested parties. Each note is intended to be a self-contained introduction to an area of science and technology, aimed at a nonspecialist audience. These notes cover a wide range of topical subjects, from avian flu and computer crime, to nanoscience.

Sam Dolan at Westminster

meetings with anyone who might be able to contribute. So far, I have interviewed 10 individuals from across the academia, industry and Government. At first I was apprehensive, but learning to interview busy and often quite senior people has definitely boosted my overall confidence.

One of the best things about working at POST is meeting the other interns, and exploring Parliament together. Some interns hope to pursue a career in public policy. Others, like me, just want to find out a bit more about how science affects the way the world works.We are given a free rein to explore.

In our first week, we were given a guided tour of the debating chamber by a security guard who had an encyclopaedic knowledge of its history. It is amazing how many of the origins of common phrases can be traced to Parliamentary customs. For instance, did you know that to be ‘out of order’ is to overstep the lines that separate the front benches in the House of Commons? Or that the phrase ‘it’s in the bag’ comes from the custom of putting petitions in the bag on the back of the Speaker’s chair?

So, what next? I will finish at POST

by Christmas. The note will be published in the new year, after undergoing an extensive review. It is intended to anticipate the forthcoming energy White Paper. In the meantime, I have passed my PhD and, from January, will continue research at University College Dublin. While electricity networks may have little to do with my research on black hole physics, I now know much more about the way the world works than I did just three months ago. www.parliament.uk/parliamentary_offices/ post.cfm

POST members, with Sam second from right.

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I am presently researching a note on the UK’s electricity networks.There is a concern among politicians about the UK’s increasing dependence on imported gas.

Following the recent publication of the Stern Review on climate change, energy policy is once again at the top of the political agenda. The Government has launched an Energy Review giving a potential green light to nuclear power.

Against the back-drop of November’s large-scale electricity blackouts across Europe, the UK’s record on the security of the electricity supply is relatively good.

However, the existing electricity network is not configured to make the most of renewable energy sources. The national grid is strong in former coal-mining regions, but weak in rural areas like North-West Scotland and mid-Wales, where the renewable energy resources are greatest. Difficulties in obtaining planning consent and grid connections could mean the Government is likely to miss its 2010 target of generating 10% of the electricity from renewable sources.

After writing a 45,000-word PhD thesis, one might think that producing a four-side note would be easy.

Unfortunately, any fantasies of knocking off the note in an afternoon, and taking the remaining three months off, have long since evaporated.The real challenge is to distil 40 or so pages of technical detail into four sides of comprehensible, jargon-free prose.Writing coherently is a skill—and one I wish I had acquired before writing my thesis.

It is important that POSTnotes represent a balance of opinion. My supervisor identified contacts that could help me at an early stage. She encouraged me to arrange

Kelly Neaves

Away from the Bench

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Sam Dolan recently completed a PhD in the Department of Physics

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Cambridge News

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I n i t i at i ve s

Cambridge Neuroscience Initiative Cambridge has a strong tradition of world-leading achievements in neuroscience research, or the study of the functioning of the brain and the nervous system in health and disease.

Despite a strong history of excellence in the field, current neuroscience research is less renowned as a Cambridge strength. To tackle this problem, several recent efforts aim to achieve â&#x20AC;&#x2DC;one voiceâ&#x20AC;&#x2122; that will raise the profile of Cambridge neuroscience research and create an international centre of excellence.

Historically, Cambridge breakthroughs in neuroscience have been recognized by Nobel prizes on a wide range of topics. In the early 1930s, Matthews and Adrian carried out the first neural signalling analysis, at the University of Cambridge.This work won Adrian a Nobel Prize in Physiology or Medicine in 1932. In 1963, Hodgkin and Huxley earned the Nobel Prize in Physiology or Medicine, for determining the mechanisms of the action potential.

Around the same time, the identification of noradrenaline by Vogt facilitated a revolution in the treatment of mental illnesses.

Also in the 1960s, Marr and Barlow developed some of the early theoretical approaches to the functioning of the neural circuitry. More recently, in 2002, Brenner was awarded the Nobel Prize in Physiology or Medicine, for investigating the development and function of the nervous system, by applying genetic analysis to cell division in the nematode worm. today Cambridge neuroscience involves over 150 principal investigators and encompasses a much wider range of subjects than the traditional biological sciences.Yet the fractioning of research in many departments across and beyond the University does not foster collaborative work. It is difficult to identify researchers with common interests in particular neuroscience-related fields and to keep pace with their work. Perhaps most importantly, the lack of fully developed centralized visions for neuroscience research jeopardizes the ability to attract large funding opportunities.

Recently, the University of Cambridge has begun strengthening the competitive1930: Matthews and Adrian carry out the first neural signalling analysis

Jon Heras

Katharine Hartley reports on interdisciplinary neuroscience partnerships in Cambridge

Neuroscience research at the University of Cambridge and associated units and institutes

ness of its neuroscience research on the international stage, by creating a closely interlinked neuroscience research community.Two major first steps in this direction have been the creation of the Department of Clinical Neurosciences and of the Behavioural and Clinical Neurosciences Institute (BCNI), in 2004 and 2005 respectively. The Department of Clinical Neurosciences was established in the School of Clinical Medicine, to subsume the former Neurology and Neurosurgery units, as well as the Brain Repair Centre and the Wolfson Brain Imaging Centre.

The BCNI, created within the School of Biological, Medical and Veterinary Sciences, brought together internationally recognized basic and clinical neuroscience researchers aiming to identify the neural systems underlying cognitive dysfunction and psychopathology.

The most ambitious initiative so far is the creation of a virtual institute called Cambridge Neuroscience, which will be launched in September 2007 with a prestigious international symposium. Cambridge 1960s: Marr and Barlow develop theoretical approaches to the functioning of the neural circuity

1954:Vogt characterizes the regional distribution of noradrenaline and adrenaline in the cortex

Neuroscience hopes to create a Cambridge-wide, interacting neuroscience community involving researchers across disciplines, departments and institutes.

Shared equipment, techniques and resources, such as new seminar series, enhanced courses and workshops, and a neuroscience website encompassing all Cambridge research, are proposed to facilitate new partnerships. Novel intellectual partnerships are expected to arise from combined efforts across the mathematics, engineering, computer science and nanotechnology disciplines. Ultimately, it is hoped that the expansion of the Cambridge neuroscience community will integrate, alongside more traditional areas, sub-fields at the cutting-edge of research such as neurophysics, neurophilosophy, social neuroscience, neuroeconomics and neuroethics, towards a better understanding and treatment of neurological and psychological disorders.

Katharine Hartley is a postdoc in the Department of Zoology 2002: Brenner wins Nobel Prize in Physiology or Medicine, for genetic analysis of cell division in C. Elegans

1963: Hodgkin and Huxley win the Nobel Prize in Physiology or Medicine, for investigating the action potential

Time-line of the main Cambridge breakthroughs in neuroscience

initiatives@bluesci.org

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History

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Instruments of the past

Whipple Museum of the History of Science, University of Cambridge

It was the Grand Orrery that caught my attention on my first visit to the Whipple Museum, and it continues to captivate me now. This fascinating contraption, with its arching metal ribbons and tiny rotating planets, is a centre-piece of the Museum’s extensive collection of scientific instruments, which ranks among the most important in the world.

Orreries, which demonstrate the movement of the planets and their satellites around the sun, reflected eighteenthcentury ideas of a ‘clockwork universe’, whose workings were dictated by Newtonian mechanics. These devices were a must-have in contemporary polite society, given its fascination for amateur astronomy. This fashion is most famously depicted in a painting of the era by Joseph Wright of Derby, showing a philosopher demonstrating an orrery, his audience’s eager faces illuminated by the lamp representing the sun.

As with many scientific instruments, understanding the orrery reveals much about contemporary science: in this case, about the prevailing theories and public perceptions of, and engagement with, science in the eighteenth century.

Robert Stewart Whipple was a keen believer in understanding the history of science through its tools, apparatus and models. It was for this reason that he donated his extensive private collection of scientific instruments to the University of Cambridge in 1944, to establish what is now the Whipple Museum of the History of Science.

The eponymous Mr Whipple had spent his life working for the Cambridge Scientific Instrument Company, first as a personal assistant to its founder, and later as Managing Director and Chairman.

The Grand Orrery

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Whipple had a keen interest in science and its history, and was a founder and fellow of both the Institute of Physics and the British Society for the History of Science. His collecting career began in the 1910s, his first acquisition being an antique telescope he bought in France for 10 francs. By the 1940s, his collection had grown to around 1000 instruments, models and pictures, and a similar number of books, which he gave to the University, in order to create a museum for the history of science.

But this was not to be a dimly lit, rarely visited corner in which artefacts slowly gathered dust. As the memorandum that proposed the move stated, both Whipple and his contemporaries at the University felt it important "that the Museum should be more than just a well-arranged repository of historic scientific apparatus. It should be designed and maintained as a teaching instrument and accessory to modern research." This idea remains one of the guiding principles in the museum’s work today, as its curator, Liba Taub, explains in the interview on the next page.

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Andrew Dunn

Emily Tweed explores the extraordinary collections of the Whipple Museum

An 18th-century Persian astrolabe

Main Gallery—that was previously part of the Departments of Engineering and of Physical Chemistry.

The original Whipple collection has since expanded, thanks to donations from the colleges and departments of the University. These include a number of physical instruments from the early years of the Cavendish Laboratory, astronomical apparatus from the observatory of St

Whipple’s collecting career began with an antique telescope he bought in France for 10 francs

The items presented to the University

by Whipple were initially displayed in an exhibition at the Old Schools site on Trinity Lane, but were moved a number of times in the following years due to lack of space. It was not until 1959 that the collection found a permanent home in the Department of History and Philosophy of Science on Free School Lane, in a high-ceilinged hall—now the

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John’s College, and many sundials, astrolabes and perpetual calendars from the Fitzwilliam Museum. Nowadays, the museum’s artefacts reside in a number of galleries throughout the department, allowing as much of the collection to be on display as possible.

Another part of the donation was a collection of scientific books. These formed the foundation for the Whipple Library, and reflected Whipple’s interest in instruments and instrument making.

They include Renaissance books of astronomy and practical mathematics, as well as seventeenth and eighteenth century books by Descartes, Hooke and Leeuwenhoek on the new instruments of optics and philosophy.

Though the Museum houses a diverse array of gadgets, gizmos and models relating to different branches of the sciences, its particular strength is an internationally recognized collection of mathematical, astronomical, navigational and surveying instruments.

One of the instruments that particularly stands out is the astrolabe. The Museum has a number of astrolabes from England, Europe and Persia, dating from the fourteenth to the eighteenth centuries. These intricately engraved brass circles are multifunctional instruments central to medieval astronomy, consisting of a map of the heavens, with

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History

overlaid rings, and bars marking the positions of the stars and the annual path of the sun through the sky. Astrolabes were used to tell the time, to calculate important dates on the medieval calendar, and to measure the positions of celestial bodies or the heights of buildings. Often they were extraordinarily beautiful, as shown in the picture.

As well as the galleries themselves, the Museum offers a range of electronic resources for those interested in the history of science. The ‘Explore’ section of its website allows a closer inspection of the exhibits, with articles and interactive items focusing on the Museum’s astronomical instruments, microscopes and teaching models.Visitors to one interactive page can perform a ‘virtual dissection’ using a nineteenth century anatomical model.This recently acquired exhibit was made from papier mâché by the French doctor Louis Auzoux, to circumvent the shortage of cadavers available for teaching anatomy to medical students.

In line with Whipple’s wishes, the Museum is a central part of University teaching and research in the history of science. Many of the cases have been designed by students, who have helped with exhibitions, written booklets, and made models of their own.

The Museum’s enduring value and appeal are captured well by the words of

Kelly Neaves

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A “universal mechanical ring dial”, a type of sun-dial, made by John Rowley in 1715

Sir Henry Dale, then President of the Royal Society, on opening the first exhibition of Whipple’s gift to the University in 1944: “This collection of historic scientific instruments and old books is not only of significant interest, but it possesses a great deal of artistic work of beauty, and such a collection gives us the feeling of living in sympathetic contact with the great men of science who lived before.”

The Whipple Museum for the History of Science (edited by Liba Taub and Frances Willmoth), a book of essays and illustrations charting the museum’s history, is available from the museum website or from the Main Gallery. www.hps.cam.ac.uk/whipple Emily Tweed is a recent graduate in Natural Sciences, specialising in Pathology

On the Front Line in the Museum Emily Tweed speaks to Liba Taub, Director and Curator of the Whipple Museum 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 about those sorts of messages.Through examining the history of science, we learn that it isn’t as simple as that. My own period of research is Ancient Greek and Roman science. I think that science, historically, is not just about having a practical solution to things, but about wanting to answer basic questions about the world around us. It is part of our human experience to want to have the answers and to want to explore the ways that we know about the world around us.The creativity of art and of literature, for instance, is often celebrated. I think the creativity of trying to explain the natural world can be just as beautiful and interesting.

What can the material culture of science—its instruments, its models and its tools—tell us about its history?

The practice of science isn’t just about reading books or journal articles, sitting in front of a computer, or spending time in the laboratory. Science involves interacting with the world at a number of levels, and there have been various tools, historically, that have been devised to do this. So we can’t just learn about the history of science by reading about it; we have to 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 collecting experience—that of Robert Whipple. It also represents collecting activity and scientific work in the different Cambridge colleges. One example is the fume cupboard from

www.bluesci.org

Newnham College, purpose-built in the 1870s when the women of the college could not use the laboratories at St John's or Trinity Colleges, and the University did not have its own. The museum also has a number of interesting models, such as the botanical teaching models. One of the things I have pursued in my life as a curator is increasing our collection of models, 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 the history of science in the University, but there was no formal department. Now, the Museum is physically in the centre of the Department—an ‘embedded’ museum—and we have a very close relationship with the Department.

One of the things I think the Museum is about is to be here as a resource for students, from second and third years right up to postgraduates.We have examples of undergraduate and postgraduate students’ work on display; so, when visitors come to the Museum, we want them to understand that this is a living museum. It is actively being used as a source of evidence about how we do history and philosophy of science. One of the messages we’re trying to convey is that the Museum is about the work that students within the University 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 grand orrery. I used to carry a picture of them in my wallet!

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Arts & Reviews

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Science documentary at the cinema

Catherine Williams and Lakshmi Harihar

Mico Tatalovic examines the rising popularity of science documentaries

Until recently, science seemed to occupy a rather sober and well-defined place in television, in the genre of science documentaries. Although fictional films have occasionally drawn inspiration from science, for the most part they have avoided it as a main topic.

However, a recent boom in featurelength science documentaries intended for the big-screen has catapulted science into a somewhat different domain of popular interest, one that blends emotional narrative with scientific investigation. The two main examples of this phenomenon, March of the Penguins and The Besieged Fortress, may leave some viewers wondering whether this cinematic popularization of science comes at the cost of sacrificing scientific rigour.

For a long time mainstream cinema was devoid of science films.The short science films of Jean Painlevé, shown as preludes to artistic feature films in French cinemas as early as the mid-twentieth century, were the exception rather than the rule.

On some occasions, artistic films crossed paths with science. For example, in Illumination (Illuminacja 1972), by the Polish director Krzysztof Zanussi, the film’s cinéma vérité style seems to open up the scientist’s inner world and examine anew the social impact of science. In this film one scene depicts young physicists discussing the dangers of scientific inventions such as atomic bombs and genetic engineering, and brushing off any personal responsibility in the name of pragmatic concerns such as supporting their families.

Science documentaries have often successfully penetrated the realm of popular interest—think of David Attenborough’s documentaries and the Discovery Channel—and brought science to the wider

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public. However, recent feature-length science documentaries have had an unparalleled large-scale appeal to audiences. The blurring of the line between scientific fact and fiction may in part explain the wide appeal of these films.

The hugely successful documentary, March of the Penguins (Luc Jacquet, 2005), is an excellent example of an anthropomorphic portrayal of animals. This film, about the yearly migration of Emperor penguins in Antarctica, and narrated from a human perspective, was shown in cinemas around the globe and won an

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The cinematic popularization of science may come at the cost of sacrificing scientific rigour

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Oscar in 2006, for Best Documentary.

Advancing the belief that animals experience emotions, the narrator claims that the Emperor penguins migrate for months, braving below-freezing temperatures and snow-storms for the love of their partners and children. Small humanoid penguins are portrayed as stoically defying the brutality of the Antarctic winter in order to see their children nourished. Whether animals have emotions or not, is a controversial issue in the scientific world. However, influenced by this film, many people may readily accept that animals have emotions, without carefully considering the opposing view.

Recently, a new French documentary has been released: The Besieged Fortress (Philippe Calderon, 2006). Anthropomorphizing its subject in a similar manner to March of the Penguins, the film depicts the lives of termites and their attempt to defend their ‘metropolitan city’ from the invasion of killer ants. In spite of the almost Hollywood-style action, some close-up scenes, such as ants forming a living bridge over a water stream or attacking the termites by dropping from branches in large groups like miniature paratroopers, are remarkably well rendered and a pleasure to watch.

However, focusing more on the storyline than the science, the film fails to provide a deeper understanding of these intriguing insect behaviours. The narrator does not even name the species featured.

So far, it seems that French cinema dominates the niche of big-screen science documentaries; however, the BBC is about to change this picture. A crew is currently in the Kalahari Desert filming a feature documentary about meerkats. Meerkats’ communal behaviours, especially their cooperation in rearing their young and teaching them how to feed themselves, are strikingly reminiscent of human communities.

Previous documentaries about meerkats, such as Meerkat Manor, have been popular both in the UK and the US. Their popularity may in part come from the research that a group at the Department Zoology in Cambridge has conducted trying to understand their social lives and interactions. Be it March of the Meerkats or Besieged Meerkat Manor, audiences are looking forward to a good story, and, hopefully, there will be good science behind it.

Mico Tatalovic is a PhD student in the Department of Zoology

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A r t s & R ev i ew s

Science Film Festival at Cambridge Film festivals are well known events, whereas science film festivals are less so. However, there are various science film festivals taking place around the world, screening science education films that raise awareness about scientific and environmental issues. One example is SCINEMA in Sydney, which incorporates a variety of films and also organizes discussions about scientific film.These events are intended to serve as a tool for communication between scientists and the public.

SCINEMA is a travelling film festival, screening some of its films in different cities, even countries. In 2006, SCINEMA made it to Cambridge.

At Cambridge, the CUSP film crew produces various science related recordings and films each year. However, until recently, a science film festival had not been organized at the University of Cambridge. In Michaelmas Term 2006, I contacted the director of SCINEMA, Cris Kennedy, about showing some of the films from the 2006 SCINEMA festival at the University of Cambridge.The screenings, the first showing of SCINEMA in Britain, were supported by the Cambridge University Scientific Society and the Graduate Union, who provided the facilities and advertising for Cambridge’s science film event. Subsequently, I spoke to Cris Kennedy about SCINEMA and science film festivals in general.

What are you trying to achieve with SCINEMA? We just want to make science accessible. Bringing two fields together, we hope to create new audiences for both filmmaking and the sciences.We have a wonderful partner in Cosmos Magazine, and together, we hope to build SCINEMA into an international festival that will raise the profile of science filmmaking and reward excellence in the field. We run a short film competition for students, to promote interest in science and build up the numbers of students enrolling in science subjects in high school. In Australia, we are a part of National Science Week.

How long has the film festival been running for?

This will be our seventh year running SCINEMA. It began in 2000 as an epic event at a local Canberra cinema, with paid entry. The big draw card the first year was called Sexy Skivvy Science, and featured the two stars of The Curiosity Show, a 1970s Aussie children’s science show. The presenters were famous for their colourful skivvies, way before The Wiggles made them famous all over again. Our second festival was a much lower-profile event, just a few screenings at the National Museum of Australia, and

Catherine Williams and Lakshmi Harihar

Mico Tatalovic speaks with film festival director Cris Kennedy

progressively we’ve built up into a national event... and now, international.

Do the screenings attract many viewers?

Our 2006 Festival screened at 90 venues across Australia and New Zealand, to over 10,000 people. Some venues are small: local libraries, schools, town halls in regional centres, where only two or three people might be at a screening.We’re also in major venues like Sydney’s Powerhouse Museum and the National Museum of Australia.

What are the plans for the future of SCINEMA? World domination! SCINEMA is really a labour of love; just a bunch of people who like science and film, putting it all together in our spare time and using resources borrowed from our understanding companies. We dream of a nice big fat sponsor that would allow us the luxury of working on it fulltime. There are so many things we could do with it: podcasting films, live streaming and online voting. These would make it truly an international festival.

Are there plans to show the festival’s films in the UK as well?

I’m chuffed enough that you guys at Cambridge saw them.We’ve put the Festival together so that it’s very easy for any group or venue anywhere to take part.

We compile our films onto a set of DVDs and produce a generic programme, so anyone with the drive to put the screenings on can take them anywhere... I’d love to see SCINEMA Reykjavik, Edinburgh, Dubrovnik...

Are you aware of any other similar science film festivals?

There’s quite a list of science-themed film festivals, the biggest of which is

Images Et Sciences, which the French government seem to put a lot of money into. It’s a biennial event that screens in the theatre on the Eiffel Tower. Any festival would find it hard to top that for a sexy location.

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SCINEMA is really a labour of love; just a bunch of people who like science and film, putting it all together in our spare time

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What would be your message to the Cambridge students interested in making science films?

If you’re interested in filmmaking, my only advice is to get out there and make films. Learning on the job is the only way to learn, and technology has become so cheap and accessible that filmmaking isn’t an elitist art form any more, rather an expression tool for the common man.

Look at the YouTube phenomenon. As a science communicator, it really excites me to see people using film, using Flash, using YouTube; telling their stories and finding an audience. If you’re interested in science and film, like I am, then drop me a line. We could use a helping hand putting SCINEMA together, no matter where you are. www.csiro.au/scinema scinema@csiro.au Mico Tatalovic is a PhD student in the Department of Zoology

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Dr Hypothesis

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Dr Hypothesis

Lakshmi Harihar

Dear Dr Hypothesis, I have liked this girl at work for several months and last week I built up the courage to ask her out. To my surprise, she said yes! Simply going to the cinema seems a bit of a cliché, so I would like to impress her by taking her to the new IMAX® cinema that has opened in my town.

Could you tell me the differences between an IMAX® cinema and a regular cinema, so that I might impress my date?

Movie Mark

DR HYPOTHESIS SAYS: The first thing you’ll notice about an IMAX® cinema, Mark, is that the screen is much larger than in a normal cinema and it may even be dome-shaped. The screen fills your entire field of vision, immersing you in the film and enhancing any motion. In order to fill this screen, the film format is much larger than usual, which makes the picture exceptionally clear. Much larger cameras are used to capture the detail. These can only hold a three-minute spool, and require 20 minutes to change spools.

These special features increase the cost of making an IMAX® film, so they are usually only about 40–50 minutes long.

Hopefully, Mark, this will help you have something to talk about after the film.

Good luck!

Dear Dr Hypothesis, I know that you normally only answer serious, science-related problems, but I have a more superficial query with which I was hoping you could help me. Due to the lack of natural sunlight over the last few months, I have resorted to self-tanning to maintain the year-round colour I love so much. Do you know how this works, and whether there is any difference in the action of the various products available?

Colourless Carmel

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DR HYPOTHESIS SAYS: Most cosmetic tanning products work immediately by applying a colour to the skin, and are easily washed off. If you are looking for a longer-lasting tan, you may wish to use a lotion or spray containing dihydroxyacetone, which is a sugar that causes a colour change in the epidermis, the upper layer of skin cells. These products can last for up to a week. It is also possible to purchase ‘tanning accelerators’, which contain the amino acid tyrosine, so as to stimulate the production of the natural tanning pigment melanin. However, I am yet to be convinced that these latter products actually produce visible results.

One word of caution, however, Carmel: although you may get that natural-looking glow, a fake tan will not protect you from ultraviolet radiation in the same way as a natural tan, so you will still need to use sunscreen when summer finally arrives.

Dear Dr Hypothesis, My wife is pregnant with our first child.

I’m very excited, but also slightly concerned. I’ve heard from friends that sleepless nights are likely to become a regular fixture of my life. As I work shifts, I’m worried that this could affect my performance at work, which could affect my chances of promotion, which could affect the life I can provide for my new family.What are the effects of sleep deprivation?

Narcoleptic Nigel

Lakshmi Harihar

Please email your queries to drhypothesis@bluesci.org for your chance to win a £10 book voucher

DR HYPOTHESIS SAYS: As you’re asking this question, I can safely assume that you’ve never been a student! After a couple of nights of missed sleep, you are likely to become more irritable and make more mistakes, but it is after three consecutive nights of missed sleep that your problems will become more acute. You will find it almost impossible to think clearly and will probably begin to hallucinate— perhaps that you’re asleep? The importance of sleep was clearly demonstrated by an experiment on rats: they died when prevented from sleeping for an extended period of time. Remember, though, that these effects will only happen if you get absolutely no sleep at all during the night—unlikely in your situation I think, Nigel.

Moving Money Start by arranging 6 coins as shown on the left. By moving one coin 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 with at least 2 others, arrange the coins as shown on the right.

Agnes Becker

Visit www.bluesci.org for the answer

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