Cambridge’s Science Magazine produced in association with
Issue 11 Lent 2008
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Synthetic Biology The Challenges of Engineering Life
Brain Barometer Saccades and Disease
Crowd Control Physics of Human Behaviour African Rock Art . Intelligent Plants . Physics of Rainbows Sci-fi . Human Nutrition Research . Fish Ecology
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Lent 2008
Issue 11
contents
Features Fishy Business
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Going with the Flow
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Intelligent Plants
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A Tangle of Rainbows
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Saccades
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Them’s the Breaks
Suzanne Cooke investigates translocations and their role in cancer ................................
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Editorial ..................................................................................................................... In Brief ....................................................................................................................... On the Cover .......................................................................................................... Book Reviews .......................................................................................................... Student Affairs .......................................................................................................... Focus .......................................................................................................................... A Day in the Life of ................................................................................................ Away from the Bench ............................................................................................ Initiatives ................................................................................................................... History ...................................................................................................................... Arts and Reviews .................................................................................................... Dr Hypothesis .........................................................................................................
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Oliver Jones explains how to save decreasing fish populations ..........................................
Sue Kirk walks us through the role of fluid dynamics in controlling crowds ..................
Mico Tatalovic investigates the case for plant intelligence ...................................................
James Bullock unravels the mystery of the rainbow .............................................................
Benjamin Pearson follows new efforts to map our thoughts as they happen .................
Regulars
Issue 11: Lent 2008
In Brief Team: Beth Ashbridge, Kat Austen, Thomas Kluyver, Andrew Morton, Abinand Rangesh Book Review Editors: Beth Ashbridge, Peter Basile Focus Editors: Peter Davenport, Tristan Farrow Focus Team: James Brown, Amy Chesterton, Michaela Freeland, Narin Hengrung, Alexandra Lopes, Will White Features Editors: Lynne Aitkenhead, Michaela Freeland, Nikiforos Karamanis, Hannah Price, Juliet Redhouse, James Shepherd A Day in the Life of... Editor: Chris Adriaanse Away from the Bench Editor: Matthew Yip Initiatives Editor: Chloe Stockford History Editor: Collette Johnson Arts and Reviews Editor: Natalie Vokes Dr Hypothesis: Mike Kenning Second Editors: Kat Austen, Tamara Evans Braun, Matt Cottingham, Michaela Freeland, Marlis Herberth, Fernando Ramos, Juliet Redhouse Pictures Team: Sonia Aguera, Agnes Becker, Jon Heras, Jamie Marland, Kelly Neaves, Tom Wilks, Sanne de Wit Production Team: Sonia Aguera, Amy Chesterton, Terry Evans, Nikiforos Karamanis, Alexandra Lopes, Hannah Price, Juliet Redhouse, Rose Spear, Chloe Stockford, Ashley Winslow Chairman: Steven Ortega ISSN 1748-6920
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From The Editor
Mico Tatalovic
Editor: Mico Tatalovic Managing Editor: Lorina Naci Production Manager: Lara Moss Pictures Editor: Adam Moughton Submissions Editor: Maya Tzur Publicity Officer: Collette Johnson
Welcome to the eleventh issue of BlueSci, your science magazine! Pollution, kidney transplants, graduate research funding, paranormal research, evolution of human sexuality, cuckoo trickery, defence of the natural selection theory, role of genomics and micro-antibodies in cancer research... None of these made it to the current issue. If these sound interesting though, read on, because we have included equally intriguing articles and worked with authors to make them an informative and easy read for you. Focusing on synthetic biology, a new field of bio-engineering at whose forefront in Europe are the researchers from the University of Cambridge, we bring you an insightful discussion about the benefits and drawbacks of this fascinating field in our Focus section.
Lorina Naci
Published by Varsity Publications Ltd
The Arts and Reviews article reviews the science fiction art. How our diet and lifestyle affect our health features in A Day in the Life of... where Dr Rosemary Hall explains her work and research interests.The History article brings you the etymology of the word ‘scientist’, which was coined in Cambridge at a revolutionary time for science.The Initiatives article looks into new plagiarism software used by the University of Cambridge, while the Away from the Bench article brings you adventures of an african rock art archaeologist. As usual, there is a host of complementary online material: films, podcasts, extended articles and further information about the topics covered. I hope you enjoy the new issue as much as we enjoyed preparing it. Mico Tatalovic issue-editor@bluesci.org
From The Managing Editor Happy New Year and welcome to a new issue of BlueSci! Many thanks to everybody in the CUSP team for their hard work, and to Varsity for its continued support. As Cambridge’s leading popular science magazine run by students and postdocs, BlueSci brings you cutting-edge scientific research and discoveries. An unusual highlight from our Cambridge notes is the University’s efforts to tractably enforce the ethical and academic standards at the backbone of our institutional pride. Turnitin, a new web-based software to fuel the University’s new offensive against plagiarism, is at the heart of controversy about intellectual property and our rights on it. On BlueSci news, this year brings the launch of BlueSci podcasts, a new prong to our multimedia science content, to be flexibly accessed by all. The BlueSci workshops are bringing in Cambridge science
media professionals from top-notch organizations, from Nature Network to New Scientist. Graham Lawton-chief feature editor at New Scientist-will kick start this term’s lecture series, on 23 January 2008. If you’d like to be part of BlueSci be it with writing, illustration, graphics, or production please do not hesitate to get in touch with us at enquiries@bluesci.org. We hope you will become involved in debating and communicating science within Cambridge and beyond. To check out our recent movie on synthetic biology and for other complimentary material to the printed edition of BlueSci, as well as weekly news, podcasts and other videos of high-impact Cambridge science events don’t forget to visit www.bluesci.org. Lorina Naci managing_editor@bluesci.org
Next Issue: 25 April 2008 Submissions Deadline: 20 February 2008 Lent 2008
In Brief
In Brief
For up-to-date news visit our website www.bluesci.org Cybernetworking: we are virtually working together University of Cambridge scientists have established a revolutionary networking site for scientists, based on advances in Web 2.0. Social networking sites such as MySpace, Facebook and Bebo have boomed in the last few years. Cambridge scientists have built a site that not only develops networks between users, but provides tools to facilitate research collaborations as well: SciSpace at www.scispace.net.
‘eMinerals scientists’ based in the Department of Earth Sciences realised how difficult it is to communicate between researchers who work at different length scales. In their case they needed a tool to span from the molecular to the global scale. SciSpace was born, merging the collaborative functionality of wikis with the communication capabilities of social networking sites. The site has now been
running for six months, and is already being used for European and trans-Atlantic collaborations and the production of a number of publications. SciSpace was built and is maintained by the National Institute for Environmental eScience and members of the eMinerals project, using Elgg technology. Access to the site is free and open to any scientist worldwide. KA
Scientists have identified the genetic code that affects the ripening of grapes. Despite the importance of the grapevine around the world, the factors affecting the biochemical and physical changes leading to fruit and flavour development have remained undiscovered until now. Researchers at the IASMA Research Centre, San Michelle, Italy, studied the Pinot Noir variety of grape over the course of three growing seasons and found more than 1400 genes that affect ripening – some of these are strongly affected by climate changes. They found that different internal transformations take place during the green (pre-véraison) and red (post-véraison) periods. Initially, light and chemicals such as auxin and ethylene play a critical role in the green grape’s metabolism reprogramming. As the grape moves towards véraison, enzyme anti-oxidant activity is controlled, metabolism slows down and photosynthesis is suppressed, leading to increases in the amount of sugar stored, flavour development and a change in colour. Meanwhile, American researchers independently identified seven growth phases in the Cabernet Sauvignon grape variety. They mapped out the factors that affected the expression of the genes during each phase and how they influenced processes such as circadian rhythm, aroma, flavour and colour.
Wikimedia Commons; Mick Stephenson
In Vino Veritas
These new advances may help grape growers to set the right conditions for grape growth such that vintage grade wine can be grown year after year. AR
A stripy pest blocks waterways no more The zebra mussel is a stripy, freshwater mussel and a public nuisance. At only around five centimetres long, this menace is ranked among the world’s 100 worst invasive species. In fact, the female zebra mussel is one of the most prolific reproductive organisms on the planet: they can produce a staggering 40,000 eggs per year. These pests account for millions of pounds in clean-up costs because, in the past, companies have pumped chlorine through their pipes to remove them. This has proved costly and environmentally unfriendly, so a new prize-winning
toxin, launched by the company BioBullets Ltd, has been an exciting solution to this problem. The first epidemic of zebra mussels colonizing Great Britain was reported in the 1820s in Cambridgeshire. From there the spread was rapid as these filter feeders opened up their shells to remove pollutants but also rapidly took over freshwater areas, migrating easily as they stick to the hulls of boats. Not only do they cover the underside of docks, boats and anchors, they can also grow so close together that they block off pipelines affecting water supplies to cities and hydroelectric power companies.
Dr David Aldridge, lecturer at the University of Cambridge in the Department of Zoology and director and cofounder of the spin off company BioBullets Ltd was thrilled with his prize of Entec Medal at the annual Institution of Chemical Engineers awards: “We are currently looking at how our invention can be applied to control some of the world’s other major pests.” Recognising and promoting organisations that make an outstanding contribution to chemical and bioprocess industries, BioBullets Ltd beat 32 other competitors to claim the top prize of the evening. BA
The Nature of Things to Come Matt Brown, Editor of Nature Network London, entertained BlueSci and friends in the cosy surroundings of The Anchor recently. In an informal discussion over drinks, Matt generously shared his insights on the scientific publishing industry, based on his experience of a conventional publishing house setting and his current role at the Nature Network website. Matt also told the assembled audience about the future plans for expansion of Nature Network and had some thought-provoking ideas about the future of peer-reviewed publishing in the coming age of which the Nature Network is an excellent exponent. BlueSci’s presence on Nature Network will help expose our coverage of science news and events in Cambridge to a wider audience equally passionate about science. To find out more, visit BlueSci’s forum, enter a discussion or read the BlueSci editor’s blog on Nature Network. Matt was even kind enough to write up his visit to Cambridge on his blog. We look forward to developing collaborations with Nature Network in 2008. AM http://network.nature.com/
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On the Cover
Filamentous Flu: a Muddle with Models
Dr P. Digard
Ed Hutchinson talks about his research interest of understanding the elusive influenza virus
E. Hutchinson
Influenza A virus is by far the most serious of the influenza viruses, infecting a wide range of different species and causing severe, acute disease in humans and livestock. It remains one of the world’s major uncontrolled diseases, causing serious illness in three to five million people and killing 250,000 to 500,000 people globally in a normal year. Typically, the symptoms are much worse than the mild cold commonly referred to as flu. Influenza A infection causes a fever that can land a patient in bed for a week, and severe cases can be fatal, particularly as the disease predisposes patients to secondary infections. Furthermore, because the virus infects so many different species of animal there is a constant possibility that viruses adapted to one host species will exchange genes with viruses from another host, producing novel viruses with the potential to cause devastating pandemics. The risk of this happening with the avian H5N1 virus is currently a very real cause for concern. The Digard group, based in the Virology Division of the University of Cambridge’s Department of Pathology, has a
research interest in the molecular biology of influenza infections. The group is particularly interested in how components of the virus are trafficked to different locations in the infected cell, how the virus replicates, and how new virus particles assemble. Much of our understanding of influenza virus comes from work in tissue culture–from infecting layers of cells growing in dishes. This has huge practical, financial and ethical advantages over animal work. However, as with any model system (an experimental scenario analogous to the situation we care about, but easier to work with), tissue culture has the problem that it differs from the original system in various respects. Influenza mutates extremely rapidly, which allows it to adapt to new environments. Consequently, although a virus studied in tissue culture will be broadly similar to the viruses found in real-world infections, it will have accumulated certain quirks not found in clinical isolates of virus. We normally think of influenza virus particles as being rounded, kidney-shaped blobs, roughly 100 nanometres across (about a fifth of the wavelength of visible light). When a tissue culture cell is infected, within eight hours 500 or so of these virus particles will have budded out of the membrane that surrounds the cell, wrapping themselves in a layer of membrane as they do so. They then float off and infect neighbouring cells, and the cycle of infection continues. It is a nice, fairly simple idea. Unfortunately it may not be the whole story. In clinical isolates of the virus, virus particles have been found as filaments– still roughly 100 nanometres wide, but anything up to 100 times this in length.
The spread of influenza through tissue culture. Cell nuclei are stained blue, and influenza infections are seen progressing across the dish. Viral protein is shown in green, and part of the viral genome is shown in red.
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Although viruses that grow in tissue culture tend to have lost their ability to form these filaments, they can regain their filament-forming potential if we introduce specific mutations into a viral protein called M1, which forms a shell just under the membrane layer and gives the virus its shape. The cover image shows a group of cells infected with a mutated, filament-forming virus: instead of throwing out hundreds of round viruses, filaments are growing from the cell surfaces. Individually they are too thin to see, but they bundle together like dreadlocks to give the hairy appearance seen.
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Flu remains one of the world’s major uncontrolled diseases
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Exactly what the filaments are doing is still something of a mystery, but there has been some speculation. Like most respiratory diseases, influenza has an ambivalent relationship with mucus (the virus family to which it belongs, the orthomyxoviruses, get their name from myxa, the Greek for mucus). The virus uses droplets of mucus to spread from host to host (unless a handkerchief gets in the way). On the other hand the host produces mucus in order to clear viruses and other potential pathogens away from the sensitive respiratory membranes. The surface of the upper respiratory tract secretes mucus and has countless tiny hairs, or cilia, which beat constantly to flush the mucus upwards into the throat where it can be swallowed or spat out. The cells that the virus emerges from are covered with a layer of thin mucus, and the thicker mucus that will carry the virus to new hosts lies above this. The thin mucus layer is roughly as deep as a filamentous virus is long, and one idea–as yet unconfirmed– is that filaments help the virus to reach mucus that will be coughed up and spread from host to host. Filamentous influenza viruses highlight the caution needed when generalising from experimental systems to the real world–under normal circumstances they would not be observed in tissue culture. For a full understanding of a disease such as influenza, results obtained using tissue culture models will always need to be compared with clinically relevant systems. Ed Hutchinson is a PhD student in the Department of Pathology
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Book Reviews
Book Reviews Peter Basile and Beth Ashbridge discuss some recent publications It is not often that one has an opportunity to elaborate upon orgasms without feeling awkward and perhaps a little guilty. However, Elizabeth A. Lloyd’s new book on evolutionary biology offers an intellectually irreproachable analysis of this frequently misunderstood topic with exemplary clarity and precision. According to Lloyd, orgasmologists have allowed sloppy science to lead them to the conclusion that female orgasms contribute to the reproductive success of our species. Her book systematically exposes the myth, bias and irrationality contaminating research in this area as it carefully constructs a coherent account of our current orgasmological knowledge. Lloyd’s premise is that women have orgasms for the same reason men have nipples. Apparently, primordial nipple cells are present in both male and female embryos. In adult women they become useful. In men they’re generally considered nice things to have but they serve no serious evolutionary purpose. Instead, they develop as a by-product of adaptive pressure on the female of our species. Lloyd considers female orgasms to be best understood as a developmental by-product too. In evolutionary terms, humans acquired orgasms as part of a sperm delivery system for men.
Compiled by the Intergovernmental Panel on Climate Change, Cambridge University Press, 2007 With the current furore of interest in our global climate change problem, it was time for the Intergovernmental Panel on Climate Change (IPCC) to publish their knowledge for all to see. This takes
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While women sometimes have orgasms, Lloyd points out that no one has ever discovered a good reason for this. Women who have orgasms are not more fertile, they do not have sex more often, they do not attract better mates and while female orgasms might be nice things to have, plenty of women get by without them. That is, as long as one is talking about heterosexual intercourse. Lloyd assures her reader that the average time to orgasm for a female masturbator is a mere four minutes, which is just as quick as the average male. Somewhat unsettling are this book’s descriptions of sex research methodology. It seems that highly regarded laboratory researchers regularly perform unnatural acts on wide-eyed stumptail and rhesus macaques with complete impunity. I do not consider myself an Animal Rights advocate but the “manual stimulation” of presumably helpless primate clitorises and “artificial penetration” of what I fear are unwilling vaginas seems unnecessary given that human volunteers might consent to the same kind of experimental stimulation in the name of science. It may seem a high price to pay, but clearly, our understanding of this puzzling phenomenon will remain incomplete until difficult questions are asked, easy
the form of a four-piece report Climate Change 2007 – The Physical Science Basis set to be complete by December of the same year. The first of the texts was released in early October with promise of “representing the first major global assessment of climate change science in six years”; policymakers and the general public alike were keen to get a glimpse. This sought-after report has received much interest with so much media coverage focused on climate change and last year’s Nobel Peace Prize being awarded to Al Gore and the IPCC for their ongoing efforts to raise awareness in the area. So does it deliver? The first work reads like an academic textbook with over 1000 pages and several appendices with supplementary information. This may well put off some potential readers but if you are interested in the worldwide debate on whether or not the climate change problems are founded in science then this report is the only text worth reading. Written by 152 coordinating lead authors from over 30 countries and reviewed by over 600 experts, it will not fail to give you a better appreciation of where we are in terms of our scientific understanding. The report is structured into ten chapters, each one covering a different aspect of the assessment. Chapter one is an introductory chapter with an aim of covering the ways in which climate change
Written by Elizabeth A. Lloyd Harvard University Press, 2005 assumptions are challenged and a great deal more practical research has been duly undertaken. Peter Basile is a graduate student in the Faculty of English
science has progressed over the years, including an overview of the science that has been developed in the last six years. Chapters two to seven detail the changes in the atmospheric constituents that affect the Earth’s climate, including carbon dioxide, methane and the other Kyoto Protocol gases. The final chapters investigate the use of current climate models to project future patterns of climate change together with their inevitable uncertainties. Note that this book is not for the fainthearted but it does offer a vast and deep analysis into the current state of art in this field, on a global scale. Anyone wishing to learn more about the science behind climate change and to critically analyse the endless information they are bombarded with in the media, will certainly gain from buying this book. The images and layout are easy to manage and, as with any academic report, all references are listed for further reading. For a complete appreciation of the complex climate change issues and where we stand, globally, on the science of the Earth’s fragile climate, this is the most extensive assessment to date, with contributions from the greatest minds working in this field. Beth Ashbridge is a PhD student in the Department of Chemistry
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Student Affairs
Student Science Publishing in the UK Mico Tatalovic reviews student science publications currently produced by various UK universities Science magazines have an important role in disseminating scientific knowledge into the public sphere and in discussing the broader scope affected by scientific research such as technology, ethics and politics. Student-run science magazines afford opportunities for future scientists, communicators and leaders to practise communicating science. The ability to translate ‘scientese’ into a jargon-free discussion is rarely easy, it requires practice, and student magazines are the best practice ground for undergraduate science students wishing to improve their communication skills. However, publishing research articles in peer reviewed journals is also not self-explanatory and many undergraduate students lack the knowledge, confidence and skills to publish their work. Once again, practice is available in student peer-reviewed journals. These are popular in the USA and have recently made an entrance to the UK universities. These journals are usually aimed at undergraduates interested in staying in academia, and allow them to publish their research while learning about science publishing.
Magazines I, Science is produced by students at Imperial College London, in association with The Felix student newspaper. It provides information on science at Imperial College and beyond. It has been coming out termly on 32 pages, both online and in print, since the first issue in 2005. It features imaginative cover art and sophisticated, modern-looking layout. Its main sections are: features, reviews, interviews, opinions, news and events. Apart from its cool design, the main strength of this magazine is the variety of intriguing topics covered as well as amazingly readable style of writing. Cleverly abbreviated to FSM (echoing popular men’s magazine FHM), Faculty Science Magazine is a student science magazine produced by the undergraduate students studying for BSc Science and Media at the University of Plymouth. The first issue appeared in January 2006 on 12 pages and can be found online. The magazine hopes to encourage the readers to “keep up to date with
the developments in science, create an opinion and expand on ideas and work already approached”. All of the articles are brief and most focus on work done at the University of Plymouth, but, overall, it is an informative read, with a few
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Science magazines allow students to practise communicating science, while learning how to publish
enjoyable trivia such as ‘unusual facts’ and ‘quiz corner’. Unfortunately, this first issue also seems to be the only one ever published. At the University of Oxford, for a long time the only science found in student magazines was an occasional article in
I, science Issue 5 Summer 2006
The Imperial College Science Magazine
Genius or Madness?
I, Science (left) and Nudibranch Biology Magazine (right) are student-run magazines at Imperial College, London, and the University of Oxford respectively
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the science section of The Owl Journal. In 2006 however, Nudibranch Biology Magazine was launched. This was a student-run magazine dedicated to the life sciences. The first issue came out both online and in print on 32 pages,
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featuring articles, comics and even a science poem. The second issue only came out online. After the first two issues the magazine switched emphasis to all sciences and changed the name to The Element Science Magazine. In 2007 a group of students formed O?, a science magazine aimed at undergraduate students. Since both magazines wanted to affiliate with OSSL, the publisher of The Oxford Student newspaper, they decided to merge into a single publication called Bang! Science Magazine. The first issue came out in November on 40 glossy and unusually artsy pages. The Triple Helix: a global forum for science in society is a global student magazine with various chapters at universities in several countries. It started out in the USA and recently spread out to Europe and Asia. The existing chapters in the UK are at the University of Cambridge, University of Oxford, University College London, London School of Economics and Political Studies and King’s College London, with the Cambridge chapter coming out with the first UK issue in spring 2007. This magazine produces online and print issues covering various aspects of science and its influences on society. Interestingly, the print version contains a global section with the best articles from across all the chapters and a local section with the articles written at the topical university. The Triple Helix is printed twice a year.
Lent 2008
Biolog-e is the University of Leed’s undergraduate bioscience research journal publishing 1st class undergraduate research projects and aiming to “publicise undergraduate bioscience research to a wide audience, but it is also a medium for students to get more from the academic environment.” Biolog-e is an online journal only and has been coming out since 2003. Earth and E-nvironment is another research journal for undergraduate and taught postgraduate research at the University of Leeds. Only 1st class and distinction research qualifies for submission to the journal, the first issue of which was published in 2005. Biosciences Undergraduate Research at Nottingham (BURN) started in 2006 as an online journal showcasing research by the final year undergraduates and graduates, drawn from submissions recommended by the supervisors. The research articles featured vary in complexity, but are generally aimed at a lay audience. BURN also encourages the use of video and interactive media to be included with the articles.
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Origin: Journal of Undergraduate Research in Biological Sciences has been published annually since 2001 by the University of Chester. It is published in print with some sleek cover art, and the abstracts can also be found online. Origin’s ethos is that “publication of results is the natural, concluding stage of any successful research project and serves as a reward for the student researcher as well as passing the knowledge gained from the researcher’s efforts to a wider audience”. The University of Warwick and Oxford Brookes University are working on a similar joint venture journal that would come out in print and online with the possible name Emergence. SEPS Undergraduate Research Journal is published by the University of Surrey’s School of Electronics and Physical Sciences to provide their students with experience in the academic writing process. Volume 1 was published online in 2006. Bioscience Horizons is the first national undergraduate bioscience journal published by Oxford University Press, with the first issue due to come out in early
2008. Recognising the current trend in the increase in the number of student science journals and their importance for science communication and training, the OUP states: “The journal provides a forum for students, their supervisors and universities, to showcase high quality undergraduate research work, strengthening the link between teaching and research in higher education. All papers are written by students and based on final year research projects.” This journal will accept up to two submissions per faculty from the Universities from the UK and the Republic of Ireland, and it might become the most prestigious of the UK student science journals. Apart from these student peer-reviewed journals in the UK there is the Journal of Young Investigators (JYI), which is an international journal based in the USA. It has been coming out since 1998 and articles can be found online.
Student Affairs
Journals
Mico Tatalovic is a graduate student in the Department of Zoology
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Equinox Graphics
Synthetic Biology Classical biology has traditionally tried to understand existing life. But in the last five years, a brand new science has emerged that turns the paradigm on its head. If I were a microbe, my favourite novelist would be Mary Shelley. In her most famous novel, she terrifies people with a creature cobbled together from spare human parts. I like scaring people too with tales from my microscopic world. I know it is considered very bad form among human scientists to use that word, dare I say it, but where I come from, microscopic Fff…, ‘Frankenbugs’, are almost a banality. So far, nature and evolution have been the sole authors of the rapid succession mutants, but something very different is happening today. Classical biology has traditionally tried to understand existing life. But in the last five years, a brand new science has emerged that turns the paradigm on its head. Synthetic biology, as this new branch of science is called, tries to create new life by cobbling together artificial microorganisms from a ‘Lego set’ of off-the-shelf genetic building bricks. Each brick has a predesigned function and contributes to a new metabolic pathway. Synthetic biology is as multi-disciplinary as a science can get. It brings
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together biochemistry and genetic engineering, and surprisingly, finds inspiration in electronic engineering, as an article below explains. Pioneers in the field are as likely to be computer scientists, electronic engineers or physicists as they are to be biochemists. Traditional wet-bench biologists are oddly absent from the ranks. ‘Genetic engineering’ is a catch-all expression, but broadly it is a toolkit of methods for cutting and pasting genes together, analysing gene sequences and their functions with computers, and modelling how they behave at the level of a single cell. Synthetic biology is at the top of the genetic engineering hierarchy. It uses the tools of genetic engineering to create genetic building bricks endowed with a designer function.Those bricks can then be assembled into whole new artificial biological systems. Every century brings about its own revolution. The 18th century brought us the humanist ideals of Voltaire and Rousseau, the 19th gave us the mechanised revolution, steam trains, ships, factories. Physics defined the 20th century,
yielding the secrets of the atom, electronics and computers. Making predictions is at best an educated guess, but one thing that seems clear is that the 21st century too will leave its mark, and biology appears poised on the cusp of momentous discoveries. In the following set of articles we explore the principles behind synthetic biology, the expectations and fears it raises. The field holds out the promise of revolutionary impact, such as replacing the fossil fuel economy with clean hydrogen power, insulin-producing cells grafted directly into diabetics, ‘sentinel’ microbes actively patrolling our bodies and repairing tissues, or even blisteringly fast computers made from DNA strands. But every new science also raises deep-rooted and healthy apprehensions about its dangers and unintended consequences. The race for patents could drive some research under wraps, whereas transparency and a genuine public dialogue could go a long way towards ensuring the best outcomes. Tristan Farrow
Lent 2008
Engineering Meets Biology But scientists are not content with adding new characters to the alphabet but are also trying to translate forbidden words of the natural genetic code into new amino acids, the building blocks of proteins (see diagram). The aim is to increase the repertoire of proteins, for example enzymes, inside the cell and explore new useful properties that could for instance make them more effective as drugs. And if you think that is pushing biology too far, be prepared for more tricks. The holy grail of the field is to endow engineered devices with life, to create machines in symbiosis with living cells. The idea is to make cells programmable through a device integrated within the cell at a molecular level. As complex as it may seem, the first steps taken towards this goal have been fairly simple and are inspired from electronic components. Scientists are creating DNA components–nicknamed BioBricks– that perform logic functions, such as turning a gene on or off, and that could be combined into more complex genetic circuits to produce a final output. The potential outcomes of applying this approach borrow from science fiction. One can imagine devices built
into human cells that perform ‘surveillance’ functions: a mechanism counting the number of times a cell divides and instructing it to self-destruct at a set number to prevent tumours. Another would sense damaged tissue and repair it. A new generation of drugs consisting of a synthetic molecular assembly could sense molecules associated with certain diseases and make diagnoses by activating the drug. Perhaps more ambitious still is the promise of achieving a more efficient programming of human stem cells to manufacture insulinproducing ‘beta cells’ to be transplanted into the liver of diabetic patients. But, the manipulation of biological systems is complicated and this challenge will keep scientists busy in decades to come. Apart from satisfying the curiosity of tinkering with life, the new technologies based on DNA are also appealing because they are cheap. Moreover, industries based on them can be easily implemented locally, in the developing world, regulatory and patenting framework permitting. Alexandra Lopes
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Biology is full of fascinating marvels, performing complex processes at the nanoscale and with low energy demand. A new generation of engineers is now adding design and intention to biology by crafting newly built genetic parts into microorganisms and living cells. They promise a vast range of applications, from biomedicine to energy production, and the emergent field–synthetic biology–has the potential to bring about a major revolution in the technological landscape of the future. The most popular aspiration of synthetic biology is the production of microbes with custom-made genomes that synthesize natural products of commercial interest. Engineered yeast cells that produce a highly effective anti-malarial compound known as artemisin, which is only found in small quantities in plants, are their current trophy. The challenge now is to broaden the range of products, the set of genetic instructions inserted into host microorganisms to code new biosynthetic pathways and fine-tune the efficiency of the processes. The principle could then be applied to the cheap production of biopharmaceutical compounds and more general industrial chemicals, or even pave the way to the development of new biomaterials with useful properties. One of the most exciting possibilities is the potentially positive impact on the environment by enabling sustainable energy production–engineered bacteria may well be turned into powerhouses of the future, producing biofuels or even filling the ranks of a green army designed to degrade toxic waste. The radical approach of this new discipline is to build from scratch organisms from a biological Lego set. And what better way to start than rewriting the code of life? By adding artificial nucleotide bases to the existing four letter alphabet (A, T, C, G) scientists are creating an artificial genetic code with potentially interesting applications. To date this innovative idea has been exploited in healthcare and in the development of more sensitive diagnostics of infectious agents. But the possibilities are expanding as new types of DNA–called TNA and xDNA–are more stable and thus are attractive raw materials for laying out the genetic information to be delivered into microorganisms and living cells.
Transcription is the process by which genetic information from DNA is transferred into RNA. The protein-encoding section of the DNA strand is unwound enzymatically, and copied to produce a complementary messenger RNA strand (mRNA). The information in the mRNA is made into a protein chain (a linear string of amino acids) via transfer RNA (tRNA). Codons in the DNA sequence are three bases long, and there are therefore 64 possible variations of C,T, A and G. In nature, 61 of these are used to produce amino acids, and the remaining three are non-coding (termed ‘stop’ codons). The work of Jason Chin (see next page) has made use of the TAG stop codon, and forced it to code for a novel amino acid, the first time this has been done.
DNA computing? Far from the living world, DNA is equally a contender for a surprising potential technological novelty: biocomputing. Information can be stored very efficiently in the DNA molecule (in quaternary code) and is naturally compact, or ‘zipped’, due to the tight spatial distribution of its constituent bases. It has been demonstrated over a decade ago that even a complex computational problem can be solved using DNA. At present a molecular computer is little more than a ‘soup’ of several strands of DNA in which different inputs interact to produce a certain output. Its most appealing features are an astonishing computing speed, several orders of magnitude faster than a supercomputer, and a natural capacity for parallel processing along several different DNA strands.
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Current research in synthetic biology typically takes one of two approaches: assembling known natural systems into networks to perform specific tasks, and creating artificial modules to expand the range of organism function. Researchers have, for example, constructed biological logic gates, which take two (or more) biochemical input signals and control the cellular response accordingly. Logic gates form the core of traditional computing, and so would be essential if we were to ‘program’ the biological networks we create–the first steps toward ‘genetic computing’. The AND gate designed by Anderson, Voigt and Arkin at the University of California uses the fact that two inputs–the gene itself, and a ‘nonsense suppressor’–are required in order for a cell to express the protein T7 RNA polymerase. Only when both inputs are supplied is the polymerase expressed which activates a chemical output from the cell. The logic gates could have medical applications, too–the same researchers have also designed a version which, when switched on, causes E. coli cells to express the invasin gene, and thereby acquire the ability to invade mammalian cells, which they cannot do if the gate is off. Similarly, by randomly rearranging the genes for three different repressors of transcription, and five promoters these control, Stanislas Leibler and co-workers at Rockefeller University created 512 different networks, which exhibited logical properties including NAND, NOR and NOT IF–with the surprising observation that circuits with very similar connectivity can demonstrate diverse logical properties. This emphasises the fact that in biological networks, the underlying molecular interactions of the components, rather than just the overall setup, is fundamentally important.
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Synthetic biologists have been attempting to create life from scratch
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Excitingly, if the external stimuli are switched off, cell populations have been shown to ‘remember’ the state set by the last stimulus applied. James Collins at Boston University designed a ‘genetic toggle switch’ and used it to set the level of protein expression from a cell. When the molecules acting to initiate the toggle were
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Away From The Bench
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Intelligent Design
removed, after subsequent generations, daughter cells continued to express the same levels of protein as set for the original cell. These developments allow the creation of cell networks having very high sensitivity to large numbers of external conditions and stimuli–important steps toward biosensor devices. Increasingly, too, techniques of synthetic biology are being applied to enhance and extend the functioning of organisms. In nature, for example, only 20 different amino acids occur in the genetic codes of all life forms– limiting the varieties of proteins that can be assembled from them, possibly limiting the function of the entire organism. In November 2007, however, scientists led by Jason Chin, of the Laboratory for Molecular Biology at the University of Cambridge, succeeded in adding artificial amino acids into the genetic code of the yeast Saccharomyces cerevisiae. Inserted amino acids which are metal-binding or photoisomerisable, for example, could confer useful properties such as lightsensitivity on the cells, which could then be incorporated into a synthetic network. Not only this, but, theoretically, the technique used (using a synthetase from E. coli bacterium to insert the artificial amino acids) could also be directly applied to enhance function in higher organisms–possibly even humans. Taking this enhancement to extremes, a number of synthetic biologists–notably, those led by Craig Venter, the owner of Celera Genomics, the private corporate challenger to the Human
Genome Project–have been attempting to create ‘synthetic life’, building a living organism from scratch.
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The technique could enhance function in humans
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Inspired by the fact that, in nature, cells can exchange genetic information–either by ‘transduction’, in which viruses act as chromosome-carrying intermediaries, or ‘conjugation’, when DNA is passed directly between cells in contact–Venter’s team have performed a full ‘genome transplant’. Donor cells of the M. mycoides bacterium are suspended in agarose blocks, immobilising the intact chromosomes inside the cell, but digesting the proteins, lipids, RNAs and other cellular components which are then siphoned off. The agarose is then melted away, leaving a solution of naked M. mycoides DNA, which is mixed with cells of M. capricolum and yeast transfer RNA. The resulting bacteria are incubated and grown into colonies which display all the characteristics (such as antibiotic resistance) of the donor organism. Though the transplant mechanism is still poorly understood, and highly inefficient (about one success per 150,000 cells), if biologists can eventually initiate processes analogous to transduction
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construct a living cell. Transposons, or ‘jumping genes’–sequences of DNA which move around to different positions on the genome within the cell– are inserted in 2500 different sites of the genomes of M. genitalium bacteria, creating ‘knockout mutant’ variants of the bacterium. By identifying which of these mutants survived, the scientists found 100 ‘dispensable’ genes out of M. genitalium’s already small total of 470 (around 600,000 base pairs). Though such a minimal organism would only be able to survive under
ideal conditions–surrounded by all the necessary nutrients and free from external stresses, adapting to which might require some of the ‘extraneous’ genes– it gives an insight into exactly which functions (or phenotypes) are essential to life. For example, no genes coding for proteins in the cytoskeleton of M. genitalium were found to be dispensable, suggesting that the membrane is essential for the organism’s survival no matter how good the going gets.
Inititatives
and conjugation, and transmute one species into another, they may ultimately be able to construct microorganisms specifically to perform given tasks in medicine, environmental regulation or energy generation–perhaps even by transplanting the artificial, laboratorysynthesised chromosomes which the Chin group suggests are possible. Venter’s team have also recently been working on developing a ‘minimal organism’–stripping organisms down to their very basics to determine how few elements it actually takes to
Michaela Freeland
Building with Biology Genetic engineering is often described as more of an art than an engineering discipline. The difficult and time consuming methods of transferring individual genes between organisms are unpredictable and often rely on luck. But a revolution could well be under way with synthetic biology, and the standardisation of genetic parts. These standard genetic parts are collectively known as BioBricks, DNA segments encoding particular functions. They are designed to be easily assembled, to communicate by a universal biochemical language, and to fit together like Lego bricks to form working systems. In this respect synthetic biology is very much engineering, and uses these BioBricks to interact with living systems in an analogous way to an electrical engineer assembling components to form a working circuit. In many ways, synthetic biology is analogous to electrical engineering, where circuits are assembled from individual parts that shunt back and forth inputs and outputs in the form of electrical pulses. In synthetic biology we have an organic circuit where the signals are chemicals. Any synthetic biologist is able to search for parts in an online catalogue and pick BioBricks tailored to specification. The designer does not need to understand how each component was synthesised, just how it will perform when pieced
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Components
Genes
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together. In both biological and electrical engineering disciplines there is a hierarchy of complexity with basic parts at the bottom and complex systems at the top. Each level requires specialist knowledge, but without necessarily needing any knowledge of the other levels. Electrical engineers begin with a toolbox of components. These range from transistors to diodes and include resistors and LEDs. Each performs a certain task, which is of little use in isolation. However, when the components are linked together they form devices which can attend to more complex tasks, such as computations. A synthetic biologist uses DNA, RNA and proteins as basic parts. Together they form devices able to complete discrete functions, such as a transformation of a chemical regulating a biochemical signal. As these parts are put together, the complexity increases until a system like an integrated circuit is formed. The genetic part can be regarded as the software of the system, and the cellular host as the hardware. But that is where the analogy ends. The engineering system is able to work independently of its surroundings, but the biological system goes on to interact with the environment, moving, responding and reproducing. Amy Chesterton
Modules
Computers
Pathways
Cells
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Through accidental or malicious use, synthetic biology poses potential risks. Can those risks be managed effectively? The new engineering discipline creates novel organisms and gives life to designs that bypass evolution. In a way that is reassuring, because left to its own devices in a non-laboratory environment, a synthetic system would struggle to survive longer than a few hours. But scientists will naturally work to create much more persistent organisms. Anyone with access to the internet can easily download the DNA sequence of their chosen pathogen and order the required synthetic DNA to tailor-produce their favourite organism. Not only are scientists rebuilding viruses, they are improving them by editing out redundancies as well as creating new designs. It is hard to predict how they will behave. As scientists
become increasingly bold and adventurous they could produce more complex and potentially dangerous organisms. Development has led to the production of synthetic bacterial cells and the leap has already been made from bacterial to mammalian cells. According to engineering professor Drew Endy of Massachusetts Institute of Technology (MIT) “there is no technical barrier to synthesising plants and animals, it will happen as soon as anyone pays for it”. To date the synthetic biology community has taken the initiative in addressing these questions and has striven to keep research transparent. They reserved a third of their latest international conference, which took place in Boston last October, to a discussion about the ethics and risks of their research. The public remains uncertain about how best to manage risks associated with the health hazards of research on the nano-scale. Ironically, in a study published in the November issue of Nature Nanotechnology, scientists were shown to be more concerned
than the lay public about those risks. The advent of the privatisation of research, the proliferation of patents, and fierce competition in the race for publication pose a serious challenge to transparency in this field. Amy Chesterton and Tristan Farrow
Adam Moughton
Away From The Bench
Potential Biorisks
The iGEM Competition
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Can simple biological systems be built from standard, interchangeable parts and operated in living cells? Or is biology simply too complicated to be engineered in this way? The international Genetically Engineered Machine Competition (iGEM) is an open design challenge for student teams that addresses this difficult question. Using a library of standardised biological components known as BioBricks, groups of undergraduates from around the world spend their summers designing and assembling biological devices to build genetic machines. The engineering of new biological systems is a new frontier, with opportunities for collaboration between biologists, computer scientists and engineers. The iGEM competition throws together students from different disciplines, requires them to initiate a novel scientific programme over the summer, and challenges them to learn and share different skills. The competition has provided a new educational model in this exciting new field. As well as learning challenging new scientific skills, the competition allows students to experience project management, teamwork, presentation and other skills that are normally missed by undergraduate curriculums. The competition provides a powerful educational tool, exposing students to engineering challenges and a modern research environment. The iGEM competition tripled in size since 2006 when 37 teams from North and South America, Europe, India and Japan took part.
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In the 2007 competition, 57 teams and 750 participants proposed ever more impressive projects at the cutting edge of synthetic biology research. The iGEM competition helps to draw new students from a multitude of disciplines into synthetic biology. This growth looks set to continue, in numbers of iGEM teams, geographical spread and diversity of BioBricks. Significantly, established laboratories have started to contribute to the BioBrick collection through their day-to-day research and in doing so look set to provide a range of better characterised parts and devices. iGEM 2008 will get under way in June with an anticipated 100 teams participating from all over the world. Ahead of them lies an exciting summer of hard work and enjoyment as they strive to design and build new biological systems. Here is what one Cambridge student who took part in the 2007 iGEM competition had to say: “At first, our ideas of what to build were grandiose and overambitious. Among the early frontrunners was the proposal to construct a system that allowed bacteria to solve a maze built from walls of chemical attractants and repellents. Other suggestions were three-dimension-forming bacteria. As the end of our initial two weeks of lectures and brainstorming loomed, reality began to set in, which focussed everyone on a more realistic project that would see the light of day. In the end we developed a new chemical signalling system inside cells. We ordered off-the-shelf genes and launched ourselves enthusiastically into lab work. Over the months we all experienced some of the hard graft and frustration that goes hand in hand with scientific research. But we kept going, driven by the excitement of working towards a goal we had set ourselves and the satisfaction when things worked out.” “By the time of the Jamboree held at Massachusetts Institute of Technology, we could proudly present what we had accomplished. Our Cambridge team scooped the ‘Best BioBrick Part’ award jointly with University of Melbourne. Overall it was a great experience and I was very lucky to have been able to participate.” www.synbio.org.uk James Brown and Narin Hengrung
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BlueSci Film Team is offering ideal opportunities for people interested in producing, filming and directing science-related films and podcasts. No experience is necessary and training will be provided. Get involved as a project editor or as a general member to work on short film projects, news interviews for the BlueSci website and podcasts, from conception to filming and post-production with industry standard software. You will be free to take on as much or as little as your free time and enthusiasm allow, but whatever you do put in is guaranteed to be enjoyable and worthwhile. Whether filming or podcasting are your hobby, or you are considering a career in the media, BlueSci is highly respected in the science media industry for its quality output and has alumni working presently at Nature and New Scientist magazines and the BBC, among many other outlets. For further information on how to get involved contact: Head of BlueSci Film, Chloe Stockford (cas84@cam.ac.uk) www.bluesci.org
Adam Moughton
Fishy Business
Oliver Jones explains how to use knowledge of individual behaviour and an ageing technique to save entire populations of ever decreasing fish populations “Fish populations in crisis”, announces one headline. “Only 50 years left for sea fish” declares another. According to most fisheries’ scientists, fish stocks around the world are in trouble. Despite bigger boats, better nets and new technology for spotting fish, the world’s fishing fleets are actually catching less (the global catch fell by 13% between 1994 and 2003). In order to manage fish stocks in a more sustainable manner a better understanding of fish ecology is needed. But how can one obtain such an understanding? Curiously enough, some of the answers may be found by studying a small freshwater fish which does not even taste very nice. At first glance, the European bitterling (Rhodeus sericeus) does not look like a particularly interesting fish. It is fairly small (they grow up to 10 centimetres long), it has no fancy colours (the exception being the males in mating season) and, despite being food for a variety of predators, such as perch (Perca fluviatilis) and pike (Esox lucius), it is not endangered. What is very interesting about bitterling, however, is their mating strategy. Members of the bitterling subfamily are unique among fish species because they have an obligate spawning relationship with living freshwater mussels. During the breeding season males defend territories around mussels and perform courtship displays to attract females for spawning.
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Interestingly, like many other fish species, some males prefer to employ the alternative strategy of sneaking into the territory of another fish rather than going to the trouble of defending their own. Mussels are filter feeders: they feed by drawing a current of water in through an inhalant siphon and out through an
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Answers may be found by studying a small freshwater fish which does not even taste very nice
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exhalent siphon, and filtering out food particles. During the mating season female bitterling develop long egg tubes, ovipositors, which may extend to the end of their tail. They use these to place their eggs into the gills of a mussel. Males fertilise the eggs by releasing sperm into the inhalant siphon, so that the water current generated by the mussel carries the sperm to the eggs.The young then develop inside the mussel for about a month, eventually leaving as actively swimming
larvae. As an interesting aside, this behaviour was once used as a pregnancy test for humans, since the female bitterling’s ovipositor would often extend upon exposure to the hormones in a pregnant woman’s urine. However, it was not an especially reliable test, sometimes predicting men were pregnant, and quickly fell out of favour. Four species of unionid freshwater mussel (Unio pictorum, Unio tumidus, Anodonta anatinea and Anodonta cygnea,) are commonly used as spawning hosts by bitterling (although females have been shown to prefer to spawn in the first three while avoiding A. cygnea where possible). The catch for all this free parenting is that the mussels release their own larvae, known as glochidia, into the water column. During their early development these attach themselves to adult bitterlings in the vicinity, before dropping off and settling in the substrate to metamorphose into young mussels sometime later. This relationship has previously been thought of as symbiotic, since each side gains something. Interestingly however, recent work indicates that bitterling may in fact be parasitic.This is because they go to elaborate lengths to avoid becoming hosts to mussel larvae whilst imposing an energetic cost on the mussels forced to act as foster parents to young bitterling. Because bitterling are totally reliant on freshwater mussels for their survival they are a valuable model species in
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behavioural, population and evolutionary ecology studies, especially those dealing with the links between behaviour and population dynamics. This is
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Recent work indicates that bitterling may in fact be parasitic
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because their spawning sites can be easily quantified, manipulated and assessed for quality, while the fish themselves are easily observed in both the natural environment and under laboratory conditions. Nevertheless, ascertaining population data is difficult without a reliable way of ageing individual fish. Luckily there is a reasonably easy way to do this, through what is known as otolith analysis (see text box).
Using otolith analysis it is possible to calculate and compare growth rates among fish from different populations and from different habitats within populations. One study carried out a few years ago applied this to bitterling populations in the Czech Republic, which is the centre of their natural range in Europe. What was curious was that the results of the study indicated that growth rates of fish of the same age from both high and low quality habitats were the same. This was despite the fact that individuals in low quality habitats were both considerably more vulnerable to predation and had less available food than those in high quality habitats. This apparent anomaly can be explained by considering the type of competition operating within the system. There are two types of competition that are likely to operate in fish communities. Exploitative competition (also called scramble or resource competition) involves the removal of resources by one, which reduces the availability of resources for others but implies no direct interaction amongst individuals. Interference competition (also called contest competition) involves a direct behavioural
How to age a fish Otoliths (literally ear stones) are a calcium carbonate mass located in the inner ear of many fish species.They supply the individual with information about changes in direction, position and speed, help them balance and are also capable of detecting sound. Otoliths grow via the continual deposition of calcium carbonate over a 24 hour period. At night, when the fish is inactive or asleep (and hence not feeding) this deposition slows down to a very slow rate and it is this that causes the dark rings. In contrast, faster calcium carbonate deposition during the day causes the wider white bands. Much like ageing a tree by counting the rings in its trunk, by counting the rings in an otolith one can calculate the age of the fish. This is an especially useful test when checking commercial catches to make sure fishermen are not catching immature fish. To do this, the otoliths must first be dissected out from the fish and examined under a light microscope, with a video camera attached. The camera allows the image of the otolith to be projected onto a screen to allow a more accurate ring count.
interaction between competitors, which reduces the net energy gain of one or both interactors. If interference competition is operating within a system, competitively superior individuals will occupy high quality habitats and competitively inferior individuals will be relegated to low quality habitats (referred to as despotic distribution). Conversely, if exploitative competition is in operation, ecological theory indicates that
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It was not an especially reliable test, sometimes predicting men were pregnant
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individuals will choose the habitat with the highest net profitability. As a consequence, individuals will be spread out among all available habitat types so that the fitness of all remains approximately equal. Since the growth rates of juvenile bitterling in the study were determined to be equal in both habitat types (and assuming growth rate gives a useful indication of overall fitness) it is reasonable to assume that exploitative competition operates in this particular system, at least for fish of the same age group. Increased competition in the high quality habitat meant that there was less food available to the individuals present; hence the decision of some fish to feed in the lower quality areas is reasonable. Although there were fewer, or lower quality, food items present, the competition for resources was reduced in trade-off for the higher risk involved in utilising them. Now, bitterling are not a particularly important fish for humans so you could be forgiven for wondering what all this has to do with fish stocks. Well, the simple answer is that the rules governing the population dynamics of bitterling are also likely to hold true for (or at least be similar to) those governing the population dynamics of other types of fish that are harder to study, for example open ocean species. The more we can understand about how fish behave and how that behaviour affects population dynamics and other aspects of their ecology, the more successful our management of fisheries and marine reserves is likely to become. With many fish species on the verge of extinction but more people than ever reliant on them as a food source, that can only be a good thing.
Oliver Jones
A short film on a related topic called Cinequarium is available online at http://mediaplayer.group.cam.ac.uk/ A bitterling otolith viewed under 100X magnification. The dark and light bands are clearly visible.
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Oliver Jones is a postdoc in the Department of Biochemistry
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Jamie Marland
Sue Kirk walks us through the role of fluid dynamics in controlling crowds Walking through Cambridge on a Saturday afternoon, most of us have experienced dynamic crowd behaviour, navigating a maze of bikes, pedestrians and lamp posts without a second thought. However, sometimes this flow behaviour breaks down, as anyone who has arrived at Sainsbury’s around 5pm can testify. But, annoying as it is snaking slowly around the aisles, this is nothing compared to the serious consequences that can occur when crowds become more densely packed. Many people are killed every year as a result of panic stampedes and trampling at mass gatherings such as religious pilgrimages, festivals, or simply in busy train stations or the rush for seats at a concert. One of the worst such events in recent times took place during the Hajj pilgrimage in 2006, where over 300 people were killed as a result of crushing and trampling in an extremely dense crowd. Dirk Helbing and physicists at the University of Köln were invited by the Saudi government to study video footage of the period leading up to these events. Analyzing crowd flow in this footage has allowed them to help establish the reasons for the observed behaviour by analogy to other flow systems studied in physics. By identifying key warning signs in the way the crowd moves, their suggestions have helped to ensure a safe Hajj in 2007 and may have implications for other crowd situations.
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The study of pedestrian flow dynamics has been an active area of research since 1995, when the first computational models were applied to human crowds. It had been thought that the decision-making capacity of humans would make it difficult to model the behaviour of crowds, but in large groups, individual thought is often superseded by a herd mentality, meaning that a relatively simple analysis can explain many commonly observed phenomena. For example, consider walking down a busy corridor. Flow seems to segregate naturally into two lanes moving in opposite directions without any prior
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Many people are killed every year as a result of panic stampedes
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planning. Similarly, where two corridors cross, flow in the perpendicular directions can be maintained without any need for direct communication. This self-organization behaviour can be simulated using many-particle models,
similar to those which would be used in a range of physical problems from granular flow (the interaction of small particles such as sand, which bears strong analogy with pedestrian dynamics) to the emergence of superconductivity in crystal lattices. Each person is modelled as a unit which responds in a defined way to the situation in which it finds itself, which is in turn defined by the motion and position of the surrounding people. But defining this behaviour is not always simple, and requires some understanding of the people within the crowd. For example, cultural factors are important, as the personal space which someone from Cambridge would consider comfortable is likely to be much larger than that for a person used to the crowds of Delhi or Bangkok. Similarly, the age composition of the crowd will be important in determining how fast the average pedestrian would wish to move. A group of people at a train station, which will typically have a mix of ages including families and elderly people, will tend to move slower than a crowd leaving a football match. This approach has allowed researchers to reproduce well-known behaviour, but the availability of experimental data from extreme crowd situations against which the models can be tested has always been limited for ethical reasons. Some experimental data exist from studies of the behaviour of animals. Altshuler
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Supplicating Pilgrim at Masjid Al Haram. Mecca, Saudi Arabia.
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Wikimedia Commons; Sureyya Aydin
dynamics model, the flow rate is given by the product of the density of people and their velocity. However, velocity is dependent on the density and will fall to zero when people can no longer move as they are too tightly packed. Modelling crowd behaviour in this way reproduces stop and go flow at high densities. However, Helbing found that even at high crowd densities, local movement within crowds did not tend towards zero, contradicting a key assumption of these models. In fact, at much higher densities of around 9 people per square metre (equivalent to packing seven and a half people into a phone box!), there was a second transition to a new type of motion which they termed ‘turbulent’ by analogy to similar behaviour in, for example, granular materials. As a result of the close packing, people start to try and push neighbours to gain more space. Under these conditions, people are moved randomly in all directions as a result of waves of pushing within the crowd. These shock waves and irregular flows in all directions cause people to trip and fall. As the people behind them are also subject to the wave of motion, they cannot stop moving to allow people to get back up, so people become trampled by those behind them. Under these conditions, people also overheat or become unable to breathe, and with no means by which to remove them from the congested environment, they are more likely to fall when moved randomly by the crowd. Fallen people act as an obstacle to the remaining crowd, making further tripping and trampling events more likely such that the situation rapidly escalates. These events of sudden, uncontrollable stress release can be analogised to earthquakes, where the build up of pressure over an extended period results in one violent quake. Helbing extended this analogy to look at the pressure within the crowd, which he defined as the local
Wikimedia Commons; Ali Mansuri
and co-workers from the University of Havana studied the behaviour of ants in a confined space with two equivalently located exits. Both exits were roughly equally favoured in normal circumstances, but when panic was generated by the insertion of repellent, one exit became favoured over another. Researchers at the University of the Philippines also studied the behaviour of mice escaping from a water pool through a single exit, the size of which was varied. They found that queuing behaviour was seen as the mice self-organized to efficiently escape the water and confirmed other findings from the models, such as the rate of increase of escape with increased door size, which follows a power law. The observation of human behaviour in crowds has only recently been possible through the developments of high throughput video analysis software. This was used by Helbing’s group to look at the crowd behaviour at the 2006 Hajj disaster. They recorded the position and velocity of people in an area 20 metres by 12 metres over a period of 45 minutes prior to the events described. By analysing small-scale variations in crowd density they were able to identify two key transition points which led to panic behaviour in the crowd. In normal crowd situations, people tend to move in a laminar flow pattern, walking at a steady rate in one direction. However, if crowd density increases, the number of people becomes too high to maintain this steady motion and the first transition to stop-and-go flow takes place. In this regime, people move in waves, continually stopping and starting. This is similar to what is observed in long queues at traffic lights, where cars have periods of movement and then periods where they are stationary. This kind of transition had been predicted from conventional models which liken pedestrian dynamics to fluid-dynamic flow-behaviour. In this fluid
The Kaaba in Mecca, and the directions of the ritual walk during Hajj
density multiplied by the local velocity variation, and found that this was the critical factor in determining the transition to dangerous turbulent behaviour.
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Since 1995 computational models were applied to human crowds
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So how can these findings be applied to prevent dangerous crowd behaviour? Once crowd panic and trampling starts, it is uncontrollable and little can be done to prevent death and injury. But Helbing’s team found that there were warning signs. The event at Hajj 2006 occurred around 10 minutes after turbulent motion set in and more than 30 minutes after the onset of stop and go flow. In Hajj 2007, one of the methods employed was automated video surveillance, programmed to recognise stop and go flow, giving an advance warning in time for the organisers to take preventative measures such as flow control, pressure relief and separation of the crowd to prevent shockwave propagation. These measures helped to ensure that the event passed with no serious incidents. However, this method requires some prior knowledge of likely crowd hotspots to set up the appropriate surveillance systems. At present, no model exists which can simulate both transitions from laminar, through stop and go flow, to turbulent flow. To fully understand crowd behaviour and prevent future crowd disasters, further work needs to be done to create complete models of the behaviour of crowds at extreme densities. Sue Kirk is a third year PhD student in the Department of Physics
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Sanne de Wit
Mico Tatalovic investigates the case for plant intelligence Plants are considered to be living organisms; they grow, reproduce, interact with their environment and eventually die. However, when it comes to interactions with their environment, some plant biologists have argued that plants act in an intelligent way. Professor Malcolm Wilkins, one of the proponents of the view that plants are more intelligent than people generally think, says: “When it comes down to it, there is not much an animal can do that a plant cannot do, except, perhaps, walk around.” But it turns out that some plants can even slowly walk away from trouble… Plants, just like animals, are exploited by a variety of micro- and macro-parasites such as viruses, bacteria, fungi and worms. But plants are not just sitting ducks for malicious microbes: they employ a series of defense strategies in order to prevent the entry of pathogens (such as tough surfaces and thick cellulose cell walls). They also counteract the spread of microbes once they breach the primary defences and facilitate the clearance of pathogens from the plant (by killing and dropping off the infected part of the plant). There are numerous genes that have evolved in order to convey resistance to specific pathogens that attack different plants.The ever growing field of plant disease and resistance is important to our general understanding of disease processes and the evolution of resistance; some resistance genes seem to be shared by plants and animals, implying that they evolved before the evolutionary split of the two ‘kingdoms’. The research is also important for protecting our crops from losses due to pathogens (the annual loss of rice to pathogens worldwide is enough to feed the UK for a year).
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Plants are living organisms with an immune system. But are they also intelligent? We often think of consciousness as being integral to intelligence, but this does not have to be so. In his book The Evolution of Intelligence (1973), Stenhouse defines intelligence as ‘Adaptively variable behaviour within the lifetime of the individual’. Since most behaviours exhibited by plants are mediated by growth and development, adaptive variation in growth and development during the lifetime of any plant individual should be considered intelligent. Adaptive in biological terms simply means that the behaviour results in better survival and eventually more offspring that the individual can contribute to the next generation. Plants make up 99% of
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Plants are not just sitting ducks for malicious microbes
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the entire biomass of the planet excluding bacteria, making them extremely evolutionarily successful. Given that plant habitats often contain varied availability of light, water and minerals, it is obvious that plants that could exploit their habitats in an intelligent way would have an edge over the ‘stupider’ plants, so to speak. But does this happen? Is there any evidence that plants behave as different individuals and in a smart way? Professor Anthony Trewavas from
the University of Edinburgh seems to believe there is. Plants develop in a plastic way; their development depends on signals they receive from the environment. A plant growing in the shade may grow tall to reach sunlight, while the same plant individual grown in sunlight may remain shorter and dedicate more resources to reproduction. If re-grown from a bud or a leaf, the plant may develop differently depending on its environment. So plants can respond to a variety of environmental cues in order to make the best use of available resources. This is what intelligence is all about in animals as well. Intelligence is an evolved property allowing better adaptation to changing or uncertain environments. Plants have been shown to navigate mazes, developing more leaves in parts of mazes with more sunlight or more roots in parts of the maze with more nutrients in the soil. Plants are able, then, to detect rich patches of resources and preferentially develop leaves and roots to exploit the newly sensed resource; this requires sensing and communicating with various plant parts. A further example of ‘intelligent’ adaptive behaviour is that plants have to learn which way to grow. For example, a seed can fall on the ground with various orientations, yet the seedling must grow its root into the soil, and its stem towards the light source if it is going to survive. Intriguingly, if a growing root is turned away from its proper direction, it starts growing back towards the original direction but often ‘overshoots’: it ends up initially growing too far in the opposite direction. Also, plants exposed to mild drought or cold become better equipped to withstand more extensive drought or cold than
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Further examples of intelligence in plant behaviour come from dodder plants, which attack other plants and use them as nutrient sources. Most dodders reject a host plant after sensing its potential as a bad nutrient source. Many can be fooled into accepting a host plant if the host is treated with nitrogen, which is a crucial nutrient for dodder. It appears that dodder plants make an active choice of which plants they are going to parasitise, which is also an intelligent choice. Both the choice of hosts and the number of coils used to attach to the host depend on the reward expected from the host, such that hosts with more nutrients are chosen by more plants and are attacked by more coils than hosts with low nutrient levels. Some plants, such as the stilt palm, literally escape competitors who would otherwise leave them in the dark. These plants grow stems on top of roots and if they sense a competitor plant growing in the vicinity, they grow new roots directed away from the competitor and allow the ones closest to the competitor to wilt away; this effectively allows them to walk away from trouble, and the intentionality of this adaptive behaviour seems to demonstrate intelligence. There are other examples where plants exhibit individual differences in their behaviour and seem to show intentionality of behaviour in such a way as to make an intelligent choice that will increase their probability of survival. Recent research by Josef Stuefer, at the University of Radboud in Nijmegen, Netherlands, shows that plants can ‘chat’ and exchange useful information. Many plant species, such as strawberry and clover have a network of runners connecting
Tom Wilks
plants that have never experienced harsh environments. These examples illustrate that plants learn how to deal with the changing environment. Although it appears very different from animal intelligence, there are many similarities between certain molecules in plants and those present in animal nerve cells, suggesting that similar chemical pathways are involved in both animal and plant intelligence; the emergent properties of these cells and their communications may represent intelligent response and learning. There are also suggestions that plasmodesmata (connections between plant cells otherwise separated by rigid cellulose cell walls) can act in a similar way to nerve connections in animals, controlling the flow of information within a plant. Plants also have memories of their developmental stages, as the same stimulus may lead to different responses at different stages of development. So a certain wavelength, say red, may initiate growth, budding or flowering at different stages of a plant’s life. In a single population, individual plants will respond in different ways to a single stimulus. A feature of intelligent behaviour is that it differs for different individuals. For example, stomata (small openings underneath leaves which allow carbon dioxide and oxygen to move in and out) close in response to abscisic acid, but different plant individuals close different numbers of stomata in response to the same concentration of abscisic acid. This may result in differences in carbon dioxide acquisition, which can have adaptive effects, and this is, in a sense, a feature of the intelligence of plants.
individual plants and allowing exchange of information. Stuefer found that when one individual in the network was attacked by a herbivorous enemy such as a caterpillar, others were warned by a signal travelling along these networking runners. This warning signal results in an early preparation for the attack and the warned plants deploy mechanical and chemical reinforcements to prevent the same attacker from infecting them as well. This has been shown to reduce damage to other plants in the network and either way one looks
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Plants can ‘chat’ and exchange useful information
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at it, as a spy plant informing its conspecifics of a terrorist attack so they can prepare for it or as an altruist plant helping its kin, this behaviour certainly shows that plant lives are more complex and intriguing than we generally think. Stuefer said in a press release for the Netherlands Organisation for Scientific Research: “We were very surprised how communicative plants really are. We looked at the common clover and discovered that they ‘talk’ through networks to warn of approaching attackers such as caterpillars.This has very interesting parallels to electronic networks and early warning systems for military defence purposes.” However, just as computer networks are susceptible to attack by viruses, so are plant networks, and some viruses spread from plant to plant using these channels of runners, exploiting the plant communication system. Stuefer continues: “It appears that plants lack firewalls, so they become easily and quickly infected by viruses.” Antony Trewavas refers to plant intelligence as ‘Mindless Mastery’ since plants seem to show intelligence without possessing a brain or a nervous system. Just as in animals, though, intelligence in plants seems to be an emergent property of communication between cells. Perhaps the next question in line is whether plants feel pain and, as some believe, emotion. The fact that their surface is covered in electrolytes just like human skin lead some to believe that plants do indeed have feelings. Others have found that plants exposed to herbivory by insects release volatile chemicals which alert other plants in their vicinity of the danger.These chemicals also attract natural enemies of the herbivorous insects that attack plants. Is this intelligence or emotion? Perhaps future research will give us answers and further inform vegetarians about the morality of their lifestyle. www.botanic.cam.ac.uk www.plantsci.cam.ac.uk
Plants respond to many environmental stimuli with surprisingly sophisticated mechanisms
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Mico Tatalovic is a graduate student in the Department of Zoology
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Tom Wilks
James Bullock unravels the mysteries of the rainbow
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Nature always likes to play with simple designs
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So what exactly is the science that “unweaves” the rainbow? The answer evokes the simple principles of classical ray optics. Sunlight enters a rain droplet and slows down as it encounters a denser medium, as a result light is refracted and bent. The different wavelengths that make up white light are slowed by different amounts and the colours begin to separate. This dispersed light ray reflects from the back of the water droplet and exits as a rainbow spectrum over a narrow range of angles around 42º. This explains why the rainbow always appears in the direction opposite to the sun, as the brain sums up all the droplets into an arc of colour, projecting away from the raindrops. Each observer will therefore always see their own unique rainbow, which stays with them as they move (meaning that the pot of gold can
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never be reached). A secondary bow can also often be observed and is the result of a further set of reflections within the water droplet, flipping the colours around and exiting at a higher angle (52º). This gives a beautiful, if rather faint, band above the first. Following the same logic, higher order bows are also possible but they are increasingly faint and so are seldom seen. Nature always likes to play with simple designs and the rainbow has many variations. At sunset for example, when all but the red light has been scattered from the sky, an entirely red rainbow can be formed from the crimson light. On particularly bright nights, a pale ‘moonbow’ can form, appearing ghostly white due to the inability of our eyes to accurately observe colour in poor light. A further effect may occur with a large body of water around, where the sunlight can be reflected. This allows a second rainbow to take to the sky, appearing as if the first had split in two. All these phenomena can be explained by Newton’s use of classical ray optics as detailed in his 1704 work, Opticks. However, although his approach generally predicts the correct results, it fails to explain several detailed features of the rainbow. In particular, it does not predict the supernumerary bows, which are faint rainbows observed inside the primary bow and the mysterious ‘glory’, a circle of colour emitted directly from the back of the raindrops (back in the direction from which the light has come). The search for an answer to these phenomena ended up inspiring one of the great breakthroughs of nineteenth century physics, wave optics. Originally proposed by Huygens in 1678 and later adopted by Young, wave physics could explain the supernumerary bows as a series of interference patterns produced by diffracting light waves. The final piece of the puzzle came with James Clerk Maxwell (University of Cambridge’s first Clarendon Professor) and the immensely important theory of electromagnetism. This meant that by the end of the 1800s, light was no longer seen as a simple stream of ‘corpuscular’ particles, but also as a propagating electromagnetic wave. Finally, a set of tools was available
with which to reveal the actual mechanisms behind the rainbow. An electromagnetic wave will not simply reflect from the raindrop as assumed by Newton, but will be scattered by it. In this process, the water droplet behaves somewhat like a magnet, interacting with the incoming light wave, removing energy from it and re-radiating it as a new wave (this is known as Rayleigh scattering). Maxwell’s equations predict that the longer the wavelength, the less the light will be scattered. This explains why the sky is blue: atmospheric dust particles scatter the shorter, blue wavelengths of light across the sky, so this is the colour that reaches our eyes. But, at sunset, when the sun is low and the light is coming directly towards us, the blue light is scattered away, leaving only the longer red wavelengths. However, this model is a good approximation only when the water droplet size is much smaller than the wavelength of the incident light. If this is not so (for example in the droplets of rain or fog), the drop behaves instead as a ‘multipole’ (imagine a magnet with several norths and souths). There results a more complicated interaction, described by Mie scattering, which produces several new waves. These all interfere with each other, giving bright bands of colour at certain angles–the rainbow.The supernumerary bows mentioned above correspond to secondary bands occurring at larger scattering angles than the primary bow. The glory is a further result of Mie scattering, and is predicted by a complex
Sonia Aguera
Optical atmospheric phenomena can be stunning events that transform the sky. They are as varied as they are beautiful, impressing with both striking colour displays and their dramatic scale. Even simple clouds can grow to 19 kilometres tall and stretch across entire countries. It is not surprising then that these heavenly displays have been used as powerful metaphors in both religion and science. The magnitude of a rainbow lends itself easily to divine images whilst its artistic appeal prompted Keats to famously accuse Newton of “unweaving” it, dispelling its mysteries and reducing it down to cold mathematics. Despite Keats’ criticism, the rainbow in many ways unites the disciplines. Newton himself split the rainbow into seven colours through a belief that it should share the same number of divisions as a musical scale (hence the slightly dubious separation of ‘indigo’ and ‘violet’).
Light is refracted as it enters a rain droplet
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The glory is a far more complicated effect than the rainbow
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A shimmering nacreous cloud observed over Lón in Eastern Iceland
the potential of glories in determining the molecular-scale properties of their parent clouds.The optical properties, droplet radii, and even the size distribution of drops can all be inferred remotely from observations of the angular size of the glory. Available computer algorithms can even simulate a glory given these parameters. Last year, Anatoly Nevzorov of the Russian Central Aerological Observatory even suggested that the presence of certain glories could confirm the discovery of a special phase state of water known as ‘amorphous water’ in cold clouds, although this finding has recently been disputed. Rainbows and glories are also far from being the only atmospheric spectacles, another particularly elegant example being the nacreous clouds of the polar winter. These stratospheric clouds exhibit a subtle yet striking mother of pearl effect, and their height allows them to stay illuminated with light diffracting through ice crystals to produce the colour. The clouds themselves are formed in a rather unusual way, and feature strongly in the scientific debate over the ozone layer depletion in the 1980s. As temperatures drop over the polar winter, steep differences between northern and southern temperatures develop. As in all weather systems, this difference causes a pressure imbalance, resulting in a stable vortex as the wind rushes in. However rather than restoring equilibrium, the vortex isolates
the air inside it and temperatures drop even further. Below -78ºC the air becomes cold enough to condense and then freeze the small amount of water vapour and nitric acid available and the polar, stratospheric clouds form. The clouds provide a large surface area upon which reactions take place, liberating CFC halogens from their otherwise stable forms. As the gaseous nitric acid is frozen inside the clouds, it cannot react with the halogens, removing an essential pathway back to stability. As the sunlight returns, photons enable the reaction cycles between the halogens and ozone. Ozone depletion then continues until the temperature becomes warm enough to break up the polar vortex and the clouds disperse, explaining the seasonal change in the Antarctic ozone layer hole. The rainbow has, since its early description by Aristotle, borne witness to many of man’s greatest scientific works – from Newton’s ray optics to the wave-particle duality of light and Maxwell’s electromagnetism. It has inspired art and literature, religion and science and somehow symbolises an important respect for Nature. It will also never fail to attract the attention of mountain climbers, astronauts or simply passers-by, who are just lucky enough to be in the right place at the right time. James Bullock is a PhD student in the Department of Zoology
James Bullock
Wikimedia Commons; Mila Zinkova
where it was often observed. A mountaineer emerging from the mist below him would turn to see a ghostly figure, its head gleaming with a brightly coloured halo. The glory is a far more complicated effect than the rainbow. Whereas the rainbow was easily explained by ray optics and waves, the glory has no precise physical explanation save through the detailed mathematics of Mie theory, a set of analytical solutions to Maxwell’s equations. As a result, the glory is still an active area of research. For example, in a 2004 paper by Bernhard Mayer and colleagues from the German Aerospace Centre, they discussed
James Bullock
mathematical argument. In essence, further reflections within the drop guide light along the air-water boundary, giving rise to yet another electromagnetic wave, which travels along the surface of the drop. This can be seen experimentally as a shining ring of light around the water drop’s exterior. This travels along the drop and exits as a backscattered cone of rainbow light.As it is seen from the top of the clouds (where the sunlight hits), rather than underneath as for rainbows, an observer must be between the sun and the cloud to see it. This is most commonly the case from the side of a mountain or a plane, but has even been observed from space. The very first occurrence of this was recorded on 23 January 2003 by the MEIDEX instrument of the doomed space shuttle Columbia. It was named the ‘Astronaut’s glory’, in honour of the lost crew. The glory appears as small, bright circles of colour surrounding the head of the observer’s shadow projected onto cloud or fog. This halo effect created the legend of the Brocken spectre, named after the peak in the Harz Mountains of Germany
Left: Spray rainbow from Gullfoss, one of Iceland’s waterfalls. Right: A fog bow, solar glory and Brocken spectre observed at the Golden Gate Bridge in San Francisco.
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Equinox Graphics
The Brain Barometer: Where to Look Next? How we make decisions has recently become one of the hottest topics in brain science. Information enters our senses from the outside world, and the underlying neural mechanisms weigh up probabilities based on this often fuzzy data. Being based on probability, the mechanisms are hard to study, but an approach that has proved very successful is to look at the most frequent decision any of us make: where to look next. The eye movements we use to concentrate on a particular object are called saccades. We make two or three of them every second of our waking lives, so they are more frequent than even a heartbeat. Each is the outcome of a decision to select one of the host of visual objects around us for closer examination. Modern technology allows us to study these tiny movements ever more closely through the use of a non-invasive infrared sensor. In the simplest case, a subject looks at a small visual target on a display screen and saccadic latency–how long they take to respond when it suddenly moves–is measured. Strangely, it is found that this latency is around 200 milliseconds. In neuron time this is an age–enough for a fast nerve to conduct over 20 metres, far longer than the shortest neural path from retina to eye muscles (via a midbrain nucleus called the colliculus). Even more bizarrely, the delay varies dramatically from saccade to saccade, apparently at random. Neuroscientists wondered why this would occur.
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We are seeing the grinding gears of high-level cortical decision
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Although the colliculus does an excellent job of translating the directions of visual targets into appropriate commands to the eye muscles, what it cannot do is decide which target is worth looking at. Only the cerebral cortex (the centre of brain function) has access to the information needed to recognise an object and assess its behavioural importance. Hence, in saccadic latency, rather than the duration of a lowly reflex, we are seeing the
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grinding gears of high-level cortical decision. Analysing the variability in latency over hundreds of saccades allows investigators to guess at the kind of process that must be giving rise to it, one model for which is called LATER (Linear Approach to Threshold with Ergodic Rate). In this model the reciprocal of latency obeys a normal or Gaussian distribution, so that the mean and variance neatly describe an individual’s rate of cerebral function. Precise mathematical description of this kind is rare in behavioural neuroscience. It allows the effects of visual stimulus type, probability, motivation and reward to be studied quantitatively. For the clinician, it provides a tool for identifying and quantifying a wide array of neurological conditions, which may have different effects upon the statistical distribution of the patient’s brain function. This brings with it the possibility of improved diagnosis and, more importantly, improved quantitative comparisons between different treatments. Such clinical work, however, requires less expensive and more portable versions of the equipment used in research laboratories. Indeed, what has made much of the recent clinical work on saccades possible is the ‘saccadometer’, a portable, self-contained infrared eye tracker developed as a collaboration between Dr Roger Carpenter (from the University of Cambridge’s Department of Physiology, Development and Neuroscience) and Dr Jan Ober (Director of the Institute of Biocybernetics, Poznañ, Poland). Subjects wear the device like a pair of glasses, and follow targets projected by miniature lasers built into the headpiece. Many hundreds of latencies can be recorded in just a few minutes anywhere there is a blank area of wall or ceiling. This makes saccadometry an attractive proposition compared with neuropsychological tests that can take hours yet generate relatively unreliable data, or the expense of neuroimaging, which in any case does not as yet provide any functional assessment. In fact, it has already been applied in a wide range of clinical situations to gauge latency variation with brain function.Very low levels of anaesthetic, as might occur a few days after surgery, increase latency even when the subject is unaware of any sedative effect. In surgical interventions to improve the cerebral blood supply, latency is either reduced, as blood flow to the cortex is improved, or increased–often dramatically–as debris from surgery lodges in arteries and reduces brain oxygenation. At the Cambridge Brain Repair Centre,
Chrystalina Antoniades
Benjamin Pearson follows new efforts to map our thoughts as they happen
The ‘saccadometer’
saccadometry is being used to quantify the progress of Parkinson’s disease and Huntington’s disease, whilst at the University of Maastricht it has been shown to provide a good measure of the effectiveness of deep brain stimulation therapy in patients suffering from Parkinson’s disease. The portability of the device also makes it ideal for studying concussion. A preliminary trial showed that latency was greatly increased in some university boxers immediately after a fight, though it completely recovered within a few days. Professional jockeys in Newmarket are now regularly having their saccadic latencies measured. They are sometimes known to slow their responses down in traditional pre-season testing, to be sure that later on they will pass even if concussed after a fall, but eye movements cannot be manipulated so easily. Portability was important on a recent expedition to Everest base camp where researchers assessed the effects of altitude on the brain. One can foresee a development of portable altitude sickness warning system for climbers, and possibly something similar detecting the impaired judgement of nitrogen narcosis in SCUBA divers. Other conditions that are not primarily neurological, such as liver damage, can also be assessed by saccadometry. The cumulative effects of ageing take their toll. Latencies rise steadily throughout life, and a recent study suggests that they begin to rise more rapidly a few years before death. Perhaps in the future every family will own a saccadometer, with checks for brain-decay over breakfast. www.cudos.ac.uk/later.htm Benjamin Pearson is a PhD student in the Department of Physiology, Development and Neuroscience
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Equinox Graphics
Them’s the Breaks Suzanne Cooke investigates translocations and their role in cancer
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Balanced translocations occur without loss of DNA
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Chromosomal translocations in solid tumours are often considered to be ‘unbalanced’.This means that there is loss of chromosomal material in the process of breaking and fusing with another chromosome. Previously, it was thought that the resulting loss of DNA causes the effects of chromosomal translocations in cancer development. Genes that would normally be present on the chromosomes are lost during translocations thereby changing the cell’s genetic identity. However, it has recently emerged that many more translocations than expected are actually ‘balanced’. Balanced translocations can occur without any associated loss of DNA when two chromosomes break and each piece of one chromosome fuses to a piece of the other.When these types of translocations occur the only change that could be contributing to cancer development is the point of fusion. Since all the genetic material is still present, the point of fusion is the only affected region where some change would have happened. The importance of chromosomal translocation, including balanced translocation,
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in liquid tumours such as leukaemias and lymphomas, is well established. This was first observed in chronic myeloid leukaemia (CML), where 90% of cases have a balanced translocation of chromosomes 9 and 22. Chromosomal translocations are traditionally expected to be products of a fusion between the broken ends of two different chromosomes. However, they can be more complex and this can correlate with poor prognosis. Given the prevalence of this 9-22 fusion in CML, one would predict that this fusion were crucial for disease development. Studies have revealed that the translocation fuses the front end of one gene, BCR, to the tail end of another gene, ABL. The ABL gene encodes an enzyme (tyrosine kinase) that has a role in cell division and differentiation. The translocation results in its constitutive activation. This means that, instead of becoming functional white blood cells, cells with the translocation divide continuously, never developing enough to carry out their specialised function. This defines them as tumour cells. The ubiquity of this translocation in CML, and its importance to malignancy, make it an ideal therapeutic target. The drug imatinib mesylate (known commercially as Glivec) was designed to inhibit the activity of this fusion protein and has proved to be one of the most successful anti-cancer drugs ever developed. This highlights the main advantage of using fusion genes as therapeutic targets: they are unique to the cancer cells and therefore allow more selective targeting of culprit cells than the standard chemotherapy agents. Recent research has begun to show that chromosomal translocations may be just as important in the development of solid tumours as they are in leukaemias and lymphomas. In 2005, scientists at the University of Michigan showed that around 80% of
prostate cancers have a fusion of TMPRSS2, a gene which is highly expressed in the prostate, to either the ERG or ETV1 genes, which act to control the expression of dozens of other genes.This results in high production of the ERG and ETV proteins in the prostate cells, where they are not usually found, thus contributing to malignant changes. This study clearly demonstrated the existence of genes commonly affected by fusion and recurrent chromosomal rearrangements in solid tumours. The general aims of cancer research are three-fold. The ultimate aim is to identify new therapeutic targets and develop new therapies that will allow successful treatment of the disease. However, at this stage in our battle against cancer, it is also important to identify new diagnostic and prognostic markers. Early diagnosis dramatically increases the chances of successful treatment. The accurate prediction of disease course and outcome increases the treatment options available to the patient. Patients with a naturally less aggressive form of cancer can be treated more conservatively, thus avoiding the side effects of intensive treatment. Patients with the most aggressive forms of disease can be given more informed decisions about whether to pursue treatment, with serious side effects, when it is unlikely to have any significant impact on survival. The recent discovery of chromosome translocations that contribute to the development of solid tumours has the potential to impact both cancer therapy and prognostics. The resulting fusions provide unique targets for therapy. The presence and structure of a translocation can correlate with disease course and outcome. This furthers our understanding of the causes and potential treatments of cancer. Suzanne Cooke is a PhD student in the Department of Pathology
Equinox Graphics
The DNA of solid tumours, such as breast, colorectal and lung cancers, undergoes many alterations compared to that of normal cells. One example of this is the rearrangement of DNA (translocation), rather than changes to the DNA code (mutation). DNA in healthy human cells is arranged into 23 pairs of chromosomes, whilst the DNA in cancer cells can undergo chromosomal rearrangement as a result of translocations. These chromosomal translocations join sequences from two different chromosomes. Historically, the importance of this particular type of rearrangement in solid tumours has been disregarded since translocations usually result in loss of material from the chromosomes involved and it was this loss, rather than the junction where the two chromosomes fuse, that was assumed to be important.
A balanced translocation between chromosomes 9 and 22 is the most common cause of chronic myeloid leukaemia
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A Day in the Life of...
You Are What You Eat Chris Adriaanse talks to Dr Rosemary Hall about her research on human nutrition and risks of obesity and diabetes Dr Rosemary Hall is a clinical research scientist in the Nutrition and Health Research Group at the Medical Research Council’s Human Nutrition Research Unit (MRC HNR) based in Cambridge. She tells us about her work to help reduce the risk of obesity, diabetes and heart disease.
Jamie Marland
50 years and the public health burden is really significant. It is important to work out how we can reduce it, and particularly how we can reduce the number of people who develop diabetes and heart disease as a result of their excess body fat. We’re trying to find out which factors predispose people to being overweight, with the aim of being able to alter their metabolic risk by altering their diet.
Tell me a bit about the MRC HNR. The MRC HNR is one of 40 MRC units throughout the country. Our unit was formed just under 10 years ago when the MRC Dunn Nutrition Research unit, based at Addenbrooke’s Hospital, was restructured. Our role is to advance the knowledge of the relationships between human nutrition and health. What research does the HNR conduct? We carry out research into the relationships between nutrition and health that are considered a national or international priority, and work with governments, industry and academic groups. The unit is involved in translating the research we do into important public health and nutrition messages for the population, by acting as an independent source of advice and information. In practice this means a number of different research groups working towards the common goal of determining how nutrition affects various aspects of health. What is your group’s focus? My group, led by Dr Susan Jebb, is called Nutrition and Health Research and we are looking at the link between obesity and metabolic diseases. We’re interested in why some people become overweight– what causes it? How does it occur? And then, more importantly, why do some overweight people develop metabolic and cardiovascular diseases? We look at what is termed the ‘metabolic syndrome’: a cluster of factors that predict your risk of developing these diseases.Those at high risk typically have a large waist circumference, high blood-glucose levels, high cholesterol and high blood pressure.The rate of obesity in the UK, and in fact worldwide, has increased dramatically over the last
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How did you become involved in nutrition research? Why did you specialise in this particular area? I am a specialist physician in diabetes and endocrinology, the medicine of metabolic diseases and hormone-related diseases. This is an interesting area for a number of different reasons. One of these is that it is preventative medicine–treating people with diabetes is treating essentially healthy people (with established risks for future problems) in order to prevent them from becoming unwell. There is fascinating medicine and physiology involved, and it’s a growing area–which is obviously not a great thing–so it’s important to have people who can provide treatment. I worked as a physician in New Zealand before coming to Cambridge. What brought me to the MRC HNR was the desire to do some research outside of New Zealand and gain a thorough understanding of nutrition in order to help my patients. In the majority of the patients I saw, an important factor in their disease management was improving their lifestyle risk factors, particularly diet and exercise.
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The rate of obesity in the UK has increased dramatically over the last 50 years
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What can you tell me about your current research interests? I am looking at how particular aspects of diet impact upon energy regulation. If we’re not gaining or losing weight we are in energy balance. What goes in equals what goes out; energy from food is equal to our energy expenditure from physical
activity, expenditure at rest and our basal metabolic rate. I am doing experimental work to see whether particular types of food have any impact on this balance and also whether they affect body composition: the ratio of fat to lean tissue to bone. It is not just weight as such that puts you at risk of metabolic diseases, but whether your weight is made up of lean or fat tissue. Stored fat is one of the biggest producers of hormones–previously we thought fat was inert and just sat there as a storage depot. In fact, it produces a lot of different hormones, many of which we don’t really know much about. And if you reduce the fat, particularly central (or abdominal) fat, it appears that you change
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Stored fat is one of the biggest producers of hormones
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the ratio of circulating hormones. These can interact with your hypothalamus (the centre in your brain that controls appetite) to regulate your body weight. Reducing weight, particularly abdominal fat can reduce your metabolic risk and risk of developing diabetes and heart disease. You need volunteers for research. How does that work? In my current project we have volunteers who come to the MRC HNR for a week at a time on three different occasions to allow us to look at the effects of diet on energy balance. Being able to compare the same person over time makes for a much more meaningful study. During the week we provide all of the food they eat and measure energy expenditure; both metabolic rate and body composition are measured, culminating in time spent in a room calorimeter where we can very carefully calculate energy expenditure under controlled conditions. If you can change the type of food that people eat to help increase their energy expenditure this could help to either maintain their weight or prevent weight gain by adjusting the energy balance equation. If we can establish whether different macronutrients can alter energy balance following a meal,
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Jamie Marland
we can advise people on an appropriate diet to help maintain their body weight. The other component is the important process of glucose metabolism, which, when it goes wrong, leads to diabetes and a major risk of heart disease. If we can affect the way we metabolise glucose, particularly after a meal, then that can reduce the risk of metabolic disease. When you eat a meal your glucose value rises quite substantially and then falls back to your baseline. This pattern changes quite significantly for different amounts and types of food. Your risk of metabolic diseases is increased by longer and higher excursions from the baseline glucose levels. If we can alter the ratio of macronutrients to even out the post-meal glucose levels we can reduce this risk, or help people to manage their diabetes. It must take quite a lot of work to prepare the food. It does take quite a bit of time. We have a research kitchen with all the facilities to prepare and cook the food. All of the food has been carefully calculated so we know exactly what goes into everything we
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make. The way it is cooked is standardised, the way it is stored is standardised and the way it is heated is standardised. It’s just like being in a lab but these carefully controlled conditions mean that we can really pinpoint any existing differences. You hold certain information back from volunteers about the aims of the study. Why is this? We are trying to measure particular factors that would be altered if people knew they were being measured. We are trying to find out how our physiology, rather than the brain, controls what we do. If we tell people exactly what is going on all the time then their brain may override their natural response. For example if we told participants that we were looking at fruit and vegetable intake they may alter their usual intake of these foods because they know it is the focus of the study, rather than behaving naturally. It’s the same with any drug trial. You don’t tell people what drug they are taking to avoid the placebo effect. However the study is explained in detail to participants when it has been completed.
A Day in the Life of...
How does your week unfold? Before the volunteers come for the week we ensure we have all the food and equipment prepared, making sure everything is carefully labelled and everyone knows what is happening.When volunteers come it is really a matter of making sure they are comfortable in the volunteer suite and then continuing with food preparation and provision. When the volunteers are not around we upload all the collected information onto the database. Much of the analysis, including blood test and data analysis, will be done later when this year’s group of volunteers is finished. Feeding experiments were popular over 100 years ago. What can technology bring and why repeat them? In order to be sure that what you found the first time is actually correct, it is always necessary to repeat experiments. That said, at the MRC HNR we are obviously trying to do something new as well. One of the major factors that has changed in the past 100 years is the realisation of the importance of having enough people in a study. We will be looking at about 20 people over two years, and because they come for three visits each this increases the statistical power and accuracy of the study. There is an enormous amount of new information on metabolites and hormones and the ease with which we can analyse them just wasn’t there in the past. At Addenbrooke’s Hospital we have some very sophisticated room calorimeters. They allow us to measure energy expenditure very accurately-we can break it down into how much energy is used sleeping, after meals, at rest or exercising. What have you learnt from your own research? Any take-home messages? My research and my involvement in the Nutrition and Health Research group has emphasised to me the importance of a good diet in maintaining good health and reducing future risk of disease. It is important for everyone to know what they are eating and to enjoy nutritious food in an appropriate quantity. www.mrc-hnr.cam.ac.uk Chris Adriaanse is a PhD student in the Department of Chemistry
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Away From The Bench
An Old Fashioned Tent-Story
Marcelle Olivier
Marcelle Olivier takes us to the heart of Africa in her quest to catalogue prehistoric rock art
Marcelle Olivier
Marcelle Olivier
Everyone I know who works in the field has a favourite tent-story. The tent blew away. The tent flooded. The tent was invaded by ants. The tent was lost somewhere between Heathrow and the Third World. My favourite tent-story, however, involves a hippopotamus. My fieldwork took place over two years in two locations in Zambia, bordering the South Luangwa National Park. On the Muchinga Escarpment, the first research area, many of the larger species of wildlife have been hunted out, bar the elusive leopards, or an occasional roaming lion or hyena, there are no other dangerous animals to avoid. It does help to keep an eye on the ground for snakes and fire ants, and to check that shelters are free of bees or porcupines before sticking your head in, but otherwise it is a soothing landscape of shy antelopes and colourful birds. My days here were spent walking either on my own or with my guide and assistant, climbing the magnificent inselbergs (large isolate granite outcrops) imposingly scattered between swathes of miombo forest, looking for and recording rock art.
For the most part, this art is found on the walls of relatively small shelters or overhangs: red, finger-painted images showing various geometric shapes. Often, they are in places overlooking rich grazing and rivers, with breathtaking views across the landscape. There is archaeology on the ground too–stone tools made on quartz or chert from the Later Stone Age, and fragmented pottery remaining from the ceramics used by Iron Age peoples. There is no direct evidence to tell us who made the art, but suggested artists include southcentral African hunter-gatherers, herders or early farmers. The paintings are probably anywhere between 500 and 8000 years old (depending on who you believe) and many are deteriorating rapidly, so recording them before they completely disappear is imperative. Part of my project was to re-evaluate the various theories about the identity of the artists, as well as their motives. But interpreting prehistoric rock art is a speculative and intellectually risky business, so it is good to get the most out of enjoying your fieldwork to make up for the months of agonising over the validity of your arguments during the write-up! And in order to enjoy your time in the field, you have to know what you’re up against. At my second research site, lying next to the Luangwa River in the Valley itself, the animals have benefited from the government’s protection. Thus, in contrast to the relatively safe escarpment environment, my Health-and-Safety form had to list avoiding dangerous situations such as walking into an illegal poaching camp, or a herd of buffalo–both surprisingly reasonable things to be worried about. I was accompanied at all times by an armed scout in case outrunning an elephant or out-staring a lion did not work and further emergency tactics were needed. Luckily, such occasions were rare, but the constant vigilance did take its toll, so a
Left: A large granite boulder balances on top of an inselberg at Mutinondo. Right: A typical example of the red geometric rock art tradition from south-central Africa.
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cold drink and a recuperative sleep were always much welcomed. Which brings me back to the hippopotamus. Out here you soon get used to the night sounds of hippos grazing around your tent, hyenas laughing and mosquitoes buzzing. One evening I was awakened by a hippo munching just beyond the canvas. I had a small tent at the time, and, as I stretched my neck to look behind me, I could see its shadow almost completely dwarfing my little camper. When the hippo’s stomach rumbled ominously and gave an echoing belch, my imagination finally got the better of me. I had to move, and the only place to move to was the opposite side of the tent. There I sat with my knees drawn to my chest, berating myself for completely overreacting to a normal situation and vowing not to mention this moment of weakness to anyone.
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2000 kilograms of hippo buttocks sat on my tent
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Then, out of the blue, the hippopotamus sat down on my tent. The tent tilted, the pegs lifted from the ground and the tent-poles bent inwards. More than 2000 kilograms of buttocks were now placed exactly where my head had been a few seconds earlier, the hippo relieving itself of what I presumed was a slight itch. It felt like hours before it stood up again. My tent returned to an upright position and the tent-poles popped back into their original shape. Then the hippo sauntered off as a disappearing shadow, leaving me to contemplate my destiny in the dark. I eventually got back to sleep, and the next morning nothing but the loosened tentpegs and some scuff-marks on the canvas showed the hippo had been there at all. This might not be the most thrilling tale of escape ever, but for a regular old tentstory I reckon it is pretty darn good. Incidentally, I am still amazed the tent made it through the experience unscathed, eventually succumbing instead to that age-old bugbear: a broken zip. My rock artists might have had to deal with hippos in their days as well, but they should be thankful they were spared the irritation of zippers! To read the longer article with Marcelle’s further adventures, visit our website www.bluesci.org Marcelle Olivier is a DPhil student at the University of Oxford, and a visiting student in the Department of Archaeology, University of Cambridge
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Inititatives
Should You Turn It In? Are you a cheat? No, of course not! You would not lift text from the net and call it your own. Not even when you are anxiously trying to think of a way to explain that confounding calculation the night before a report is due? According to The Daily Telegraph, one in four students have admitted to cheating their way through their degrees, using either material taken from the Internet or copied from friends. “Because we use the Internet so much in teaching and learning these days, there is the potential for it to be a bigger issue,” explains Gill Rowell of the Joint Information Systems (JISC) Plagiarism Advisory Service. Once upon a time, copying and pasting text from the Internet was hard to detect and easy to get away with. Now, the computer you thought was your best friend turns foe with the development of a piece of plagiarism software, somewhat threateningly called Turnitin. Like many other UK universities, the University of Cambridge has taken action on plagiarism by subscribing to use the new software. Watch out, as according to The Guardian, use of such computer programs has led to hundreds of students at UK universities being disciplined or even expelled. Gill Rowell suggests that before the development of this program universities were acting as if plagiarism was a problem that did not exist. Now they are serious.
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The University of Cambridge has taken action on plagiarism
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The Turnitin software was designed by iParadigm, a Californian company that started out in 1996. It all began when a group of computing graduates decided to develop some software that would allow them to assess similarities
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between their work. They succeeded and due to popular demand, they created the website ‘plagiarism.org’. By 1998, their website and products had gained international attention. Turnitin is a web based program which allows you to upload pieces of work to be checked for plagiarism. For each piece of work that is uploaded a digital fingerprint is created. This digital fingerprint is then checked against an extensive database. The results are returned in the form of originality reports where any text matches are highlighted, allowing your examiners to determine whether plagiarism has occurred and whether further action needs to be taken. Of course, the similarity of your text to someone else’s alone does not count as plagiarism; it is the failure to cite that source as such that is plagiarism. The database used by Turnitin is composed of millions of previously submitted student papers, along with copious numbers of commercial publications. As the largest source of plagiarism is now the Internet, a web crawler is also used. This archives digital material to allow continual updating of the database. Storage of submitted papers aids plagiarism detection but has also caused some controversy as some people believe it infringes the student’s intellectual property rights. The for-profit organisation keeps the student’s work for re-use and so some feel this is breaking their copyright to their own work. Some objections by students in the USA are so strong that they have petitioned for the right not to submit work to Turnitin and even sued the company. One example is McLean High School, Virginia, which tracks its litigation progress on the website ‘dontturnitin.com’! Despite the objections, universities (including the University of Cambridge) seem to view Turnitin as the way forward in the war against plagiarism. They are quickly adopting the software and are easily finding cheaters. Although the University of Cambridge is still finalising its policy for routine use of Turnitin for
Sanne de Wit
Chloe Stockford discusses newly employed plagiarism software
Poor Timmy was about to get bitten by the hand that fed him...
examination purposes, if plagiarism is suspected, the software is employed. Cracking down on plagiarism may sound scary and it is easy to be paranoid that you might accidentally do something wrong. Do not worry, this software is not just there to catch you out. Gill Rowell offers us some reassurance “We encourage it to be used in more of a preventative way than a policing way. If a student has a draft of their work, they can run it through the software to see if there are any issues and ask for help with referencing.” So why not give it a go, see what all the fuss is about. Just remember, no more copying and pasting from Wikipedia (or any other source for that matter). www.admin.cam.ac.uk/offices/ exams/plagiarism/ Chloe Stockford is a PhD student in the Department of Chemistry
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History
Where Does the ‘Scientist’ Come From?
Adam Moughton
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Wikimedia Commons; Frans Hals (1648)
What is a scientist? Ask one and they are most likely to reel off a list of features of their day job like “experiment…analysis…double-blind trials… repeatable results”. In truth, the sheer diversity of science today means that the term defies easy definition. But the word has an intriguing history of its own and retelling the story helps illuminate something of what it really means to be a scientist. The word is widely thought to have been coined in 1833 by William Whewell, a fellow of Trinity College, University of Cambridge. But why did he coin it? Was it merely an attempt to simplify clumsy existing monikers like ‘man of science’? Far from it. The invention of the new term was closely tied to a wider programme, a programme that came to redefine what it meant to do science. This revolution remains a major talking point in the history of science. In the early 19th century, Cambridge was at the forefront of a Europe-wide wave of change in the ideology and methodology of science. Before the 19th century there was ‘natural philosophy’, and its exponents called themselves philosophers. It was never a profession: we are talking about a small, elite group of (mostly) men, living off inherited wealth or crown patronage.At the heart of natural philosophy lay a presumption that God’s purpose was writ large in his Creation; to do natural philosophy was to interpret the Book of Nature, a process analogous to interpreting the Bible. A good natural philosopher would be pious, solitary and in tune with God. Discoveries, when they came, would be logical and beautiful: feats of careful contemplation, not ‘eureka’ moments.
Wikimedia Commons; Godfrey Kneller (1702)
Jonathan Birch explains how the modern scientist arrived from Cambridge some 170 years ago
From Aristotle to Descartes (left) to Newton (right), philosophers had always adopted this logical argument approach.
With this approach came the assumption that there was an art to discovery. New science had always been spelled out in the form of step-by-step, logical arguments. From Aristotle to Descartes to Newton, philosophers had always adopted this manner. These philosophers were revered as masters of an art. They were not revered as geniuses or as experts in a technical discipline. Around the start of the 19th century, the field of natural philosophy began to fragment.The French Revolution of 1789 was critical in this, as was the role of PierreSimon Laplace. Already a noted mathematician, he used the political turmoil to push for the institutionalisation of a new discipline, mathematical physics. With his scientific programme embodied in the new Institut de France, Laplace showed that training cadres of researchers in a highly specialised field could yield amazing
results. Laplacian celestial mechanics was the most complete theory of the solar system yet formulated, while new mathematical treatments of gases, light, heat, electricity and chemical reactions were the envy of European science. All this without a mention of God. “I have no need of that hypothesis,” claimed Laplace.
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Scientific progress was like a staircase
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Before long, Cambridge had picked up the mathematical physics baton. In 1812, Robert Woodhouse, an astronomy professor, founded the Analytical Society (now the Cambridge Philosophical Society) with the aim of integrating the esoteric mathematics of calculus into the Cambridge curriculum. Mathematics teaching at Cambridge was gradually overhauled. The great hope was that the next generation of astronomers would arrive with a strong background in calculus and that the mathematical rigour of astronomy would become a paradigm for science in general. Graduating in 1816, Whewell was a late arrival in this movement but rapidly became a key protagonist. Science under the new Cambridge model was fundamentally different from the natural philosophy that had held sway in past centuries. It brought a new approach to practising science and a new way of seeing scientific progress. The new picture was explained best by Whewell himself in the plentiful works on the history and philosophy of science he published during the 1830s and 1840s. Scientific progress, to paraphrase the argument, was like a staircase. Every now
Lent 2008
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by Samuel Taylor Coleridge who had observed, quite rightly, that these men were in no way philosophers. In the famous biographies by David Brewster, past philosophical achievements such as those of Newton were reinvented
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Scientific discovery was seen as producing pieces of visionary mental guesswork
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as the revelatory, irrefutable insights of a unique genius. Newton would never have called himself a genius or a scientist but was made into these things as a model for future generations. Such biographies were meant to inspire scientists, to show them why their laborious work (increasingly done in labs and museums, increasingly centred on experiment) was, often despite appearances, worthwhile. Any scientist could become a genius; every horizontal
step was a platform for a vertical leap.This was the new way of seeing science that paved the way for the development of the professional scientist, an ongoing process throughout the 19th century. The word itself took a long time to catch on (Michael Faraday notably rejected it), but now it is as engrained in our language as Whewell’s ideas are engrained in science. There is still a perceived distinction between discovery and justification. There is still a tendency to admire geniuses (usually Nobel laureates) and to see scientists as potential future geniuses, waiting for their big idea to arrive. Whewell’s views may not sum up (except in the vaguest sense) what it is to be a scientist but they do say something fundamental about the profession, and its conception of itself. The modern ‘scientist’, then, is about two hundred years old. And if we want to find a worldview that unites all scientists our best hope is surely to go back to the beginning, to those years when– largely within the walls of Trinity College–that worldview was spelled out for the first time.
History
and again a vertical jump occurred: a profound, heroic insight into the truth perceived by a genius. The ‘eureka’ moment. Meanwhile, the horizontal stages were equally necessary. These stages between discoveries were stages of data gathering, justification of discoveries and dissemination of these discoveries. It was vital that knowledge of the latest discoveries filtered down to a large, educated bedrock of gentleman-researchers, auxiliaries to the geniuses. No one could know when or from whom the next great leap forward might come. Thus, it was of great importance that a large platform of precise research was built up in advance. The new discoveries could then build on this. Progress via leaps was integral to Whewell’s view. Scientific discovery was seen not as interpreting the Book of Nature but as producing pieces of visionary mental guesswork, brand new ideas that would then be justified retrospectively and disseminated as truth. And the ‘scientist’? This was the name given to the members of that educated, mathematically fluent bedrock. Not philosophers, not geniuses, but data gatherers and justifiers. Whewell coined the word at a meeting of the British Association for the Advancement of Science, the society for this new clerisy of intellectuals. He had been challenged
http://www.hps.cam.ac.uk/ Jonathan Birch is a third year undergraduate studying Natural Sciences.
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Arts and Reviews
Science Fiction: Less Fictitious than We Think? genre it is inevitable that some of it will, in retrospect, prove to have predicted real events. Is there then any indication as to what this material is? The three Terminator films centre on a war between an army of robotic soldiers (called Terminators) and their underdog human adversaries. The key feature of the Terminators is that they obey no master – they fight for no individual, private corporation or state, but for themselves.This concept may well be with us before long. The United States Air Force (along with over 30 other countries) has employed UAVs (Unmanned Aerial Vehicles) in reconnaissance roles, with heavy deployment in Iraq and Afghanistan. These are remote-controlled aircraft, operated by a human controller often many miles from the action. A more recent tactical version of these passive observation drones is the UCAV (Unmanned Combat Aerial Vehicle), essentially a UAV with a weapons payload, such as the Predator drone used in a CIA assassination attempt on a senior Al-Qaeda leader in Pakistan in 2002. The latest generation of experimental UCAVs includes the Boeing X-45, a unique aircraft that offers a glimpse of the future of warfare. Not only is this pilotless hunter-killer jet invisible to radar, it is in principle completely
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autonomous. In early 2005, two prototype X-45s took off on a test-flight where a simulated threat was presented, which was destroyed by one of the aircraft before a second threat was presented. Here the two aircraft communicated with one another
Hand C3 greeting Hand C5. For more information on the Shadow Robot Company and their products, visit www.shadowrobot.com.
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Hand C5 holding an egg
to determine the optimal approach to neutralise the (initially disguised) threat, completely independent of the human operators, who were maintained in the control loop only to provide permission to fire. These two machines successfully worked together to defend themselves from danger, autonomously making judg-
Science fiction has a long history of accurately predicting future inventions
The Shadow Robot Company
Science fiction is often regarded as a paragon of the ridiculous, from the warp-drives and dubiously made-up aliens of Star Trek to the computerinitiated nuclear holocaust of The Terminator. Yet these two franchises alone offer visions of the future that are, respectively, now commonplace or soon to become so. The earliest science fiction literature has also proven to be among the most prophetic. Jules Verne, often hailed as one of the fathers of the genre, has postulated many developments that have since come to pass, some within the great author’s lifetime. In his 1863 novel Paris in the 20th Century, Verne portrays a dystopian Paris of 1960 that features petrol-fuelled cars, calculators, the internet and, curiously, the electric chair (which made its real-world debut in 1890). Verne also authored From the Earth to the Moon, in which three men ascended to the moon from a launch site in Tampa, Florida, in an aluminium vessel nine feet in diameter, which, like many of the other details of the story, was remarkably close to a Saturn V command module and the Apollo 11 mission, when man actually set foot on the moon. One of the most commonly quoted examples of science fiction foreshadowing reality is the ‘communicator’ from the original series of Star Trek.This instrument, a hand-held wireless communications device, was a clear forerunner of the mobile phone. Interestingly, this series also featured a Russian (Chekov) and an American (Kirk) working side by side in space (preceding cooperation between the two nations on the International Space Station by 40 years). Thus, in some instances science fiction has portrayed events before they occurred with alarming accuracy. But what of today’s science fiction? With the vast quantity of material currently published in the
The Shadow Robot Company
Stewart Carnally discusses science fiction and its potentially accurate predictions
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ments that, in a real combat situation, could have seen a machine make the decision to end human life. Returning to Star Trek, popular villains in the more recent Next Generation series are the Borg, a race of zombie-like cyborgs (man-machines). They are endowed with massively enhanced physical strength by numerous artificial body-parts, and are devoid of individuality. Every Borg’s mind is connected to every other to form a delocalised collective consciousness. This first conception of super-powerful prosthetics is a common theme in sci-fi, from Dr Octopus’ mechanical arms in Spiderman, to Darth Vader in Star Wars, and Robocop. The concept of a decentralised collective consciousness is less prevalent in popular science-fiction, but was mentioned in print as far back as 1930 in Olaf Stapledon’s First and Last Men. At first glance, it seems unlikely that either of these traits could come to exist in real life. First, a reliable human-machine interface would have to be developed and second, a means of linking every individual to every other would be required.
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Revolutionizing Prosthetics 2009’ program, which aims to develop a fully responsive robotic arm capable of fine motion and tactile, sensory feedback. But Warwick’s most recent endeavour is also his most ambitious and has the most far-reaching implications for cybernetics and transhumanism. In 2002, in a highly publicised experiment,Warwick and his wife both had electrode arrays implanted into their median nerves. These were then used to transmit neural stimuli
Some of today’s seemingly far-fetched science fiction may be quite close to realization
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directly between their two nervous systems via the internet, which, Warwick noted, was in this case acting as an extension of their mutual nervous systems. This experiment was expressly intended as a proof-ofconcept study into direct brain-brain communication: not just of sensory stimuli and motor signalling but of ‘telequalic’ communication – the direct exchange of thoughts and memories. Warwick also considers the possibility of linking two or more minds for direct mental communication over the internet. Thus, the potential for replacement and eventually enhancement of body parts and the interconnection of vast numbers of human minds must both be considered
www.srcf.ucam.org/cusfs/ Stewart Carnally is a postdoc in the Department of Pharmacology
Adam Moughton
with each other. The leading proponent of contemporary cybernetics is widely considered to be Kevin Warwick of the University of Reading. He has undergone a series of experimental surgical procedures wherein synthetic devices were directly interfaced with his nervous system, outlined in his book I, Cyborg. The first of these involved the attachment of an array of electrodes directly to the median nerve in his forearm which he successfully used to remotely operate a robotic arm. This work is similar in concept to an ongoing Defence Advanced Research Projects Agency’s (the Pentagon’s high-tech research wing) program called ‘Project 1 of the
more of a feasible future development than a fictional curiosity. Another feature of many great works of science fiction (Back to the Future, Star Wars and The Fifth Element, to name but a few) is flying cars. There were a number of attempts in the 1960s to build commercially viable miniature aircraft that were also roadworthy, but these were essentially cars with wings and none proved practical. Professor Paul Moller of the University of California, Davis, is currently developing the M400 SkyCar, a four-person flying car. Powered by eight rotary engines, the SkyCar hovers 30 metres off the ground and has a projected top speed of nearly 600 kilometres per hour. Once market forces and economies of scale are brought to bear on what is at the moment a million-dollar rich-boy’s toy, large numbers of people may eventually be able to own what, if the concept proves feasible, is a highly advantageous mode of transport in an increasingly congested urban environment. It is unclear whether these and other scientific developments will materialise, and even less clear as to what role they may play in everyday life. It is clear, however, that the worlds described by science fiction may approach us faster than we anticipate– we may all need to be prepared for the day when the sky will be full of cars.
Arts and Reviews
Whilst it could be argued that a mobile phone is an ‘implant’ worn outside the body (few of us are beyond arm’s reach of our phones, night or day), and artificial hearts increase in sophistication every year, neither of these are capable of direct two-way information exchange with the human body and thus cannot be considered cybernetic. Nonetheless, there are ongoing efforts to create a cybernetic relationship between humans and machines, and humans
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Dr Hypothesis
Dr Hypothesis Please email your queries to drhypothesis@bluesci.org for your chance to win a £10 book voucher
“I’m sure there was one round ‘ere somewhere…”
Dear Dr Hypothesis, I’m a James Bond fiend, and take great pleasure in building working replicas of all his gadgets and gizmos. However, one that’s really got me stumped is that disappearing car of his, it would certainly help to reduce those speeding fines! Is there no way science can offer me some assistance? Bond, Arnold Bond DR HYPOTHESIS SAYS: Dear Arnold, in the film, the car relies on cameras and directed LEDs to project the image from behind the car. However, the most cursory piece of thought reveals the entire premise as flawed and unworkable–think about the variety of angles and distances that viewing might take place from. One answer to this is to use phased array optics, essentially making a 3D hologram of the background around the camouflaged object. However, a different and more radical solution may soon be on the way in the form of metamaterials. Metamaterials consist of nano-scale layers of alternating substances, which can be permeable to electromagnetic radiation (for example light). By shaping these materials, it’s theoretically possible to tunnel light around an object, merely spitting out on one side what came in the other. In 2006, scientists showed that this could be achieved in the microwave wavelength. The most recent study has extended the range of wavelengths, although not yet into the optical spectrum. The main problem is that to get down to smaller wavelengths, the nanolayers have to be even thinner. However, work continues, so you may yet get your invisible car–you’ll just be left with the problem of remembering where you parked it! Dear Dr Hypothesis, Please help me settle a long standing dispute within our MCR. Some know-itall, whose only trip into the sunshine was one week on safari in South Africa, claims that springbok, despite being South Africa’s national animal, cannot be found anywhere in the Kruger
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DR HYPOTHESIS SAYS: Dear Nadia, my usual methods have resulted in as conflicting results as your own. My null hypothesis is that there are no springbok in the KNP and the only sure way to find out is to test this empirically. My suggestion is to get on the next flight to South Africa and see for yourself. Dear Dr Hypothesis, I spent most of the summer holidays trekking through the Andes hoping to discover a lost civilization. What I was really intrigued by was the variety of different methods that my travelling companions used to purify their water while we were away. From simply drinking only from clean-looking streams, to carefully measuring out iodine drops, I saw the lot! Which method is the best? Thirsty Thelma DR HYPOTHESIS SAYS: Dear Thelma, I definitely would not recommend drinking out of streams just because they look clean, as it is impossible to judge how many microorganisms may be growing there. Boiling is the best way to sterilise water as it has been estimated that most pathogens will be killed by only a few minutes at 85˚C, so should die in the time it takes water to boil. I realise that this may be impractical at times, and so iodine tablets would be my second choice, although it is important to store these in a dark bottle as they are lightsensitive. An alternative chemical method
for purification is chlorine, which is recommended for those allergic to iodine. I hope that hasn’t muddied the waters even more for you. Dear Dr Hypothesis, I think I may have a slight problem, as I am unable to leave the house without my trusty Walkman (call me old fashioned but I prefer to think of myself as ‘retrosexual’). I just don’t seem to be able to face my daily commute without blocking out the hectic world around me and I often get panicky if my batteries die before I reach the office. However, sometimes, I am able to turn my Walkman back on as I leave work and the batteries seem to have recovered. Do you have any idea why this could be happening? Musical Muriel DR HYPOTHESIS SAYS: Muriel, this recovery is due to a fairly simple chemical process. In a common zinc/carbon battery, the zinc and carbon rods are immersed in sulphuric acid and connected by a wire so that electrons can flow from the zinc to the carbon and create an electrical circuit, thereby powering your personal stereo. During this reaction, hydrogen gas is produced as a byproduct at the carbon rod and this can completely coat the rod, preventing the further flow of electrons. If this battery is allowed to rest for a few hours (while you’re at work), the gas will dissipate and the connection between the carbon rod and the wire will be restored. In larger batteries, such a those in a car in which the drain on the battery is quite high, the hydrogen gas builds up more quickly and so, once given time to rest, the battery will show a more pronounced recovery as there will still be a greater charge stored within it.
Adam Moughton
Adam Moughton
National Park (KNP) because the habitat is wrong. This argument goes against two zoologists and one South African citizen. Please end this feud and give us a definitive answer so my friends will speak to each other again. Naturalist Nadia
Bond dodges yet another speeding fine…
Lent 2008
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