Cambridge’s Science Magazine produced by
in association with
Hangover Hell The morning after the night before
Einstein 100 years of E=mc2
Our Origins The genes that make us human
• Robots: the Next Generation? • Mobile Medicine • • Climate Change • Forensic Science •
Features Outsmarting the Cheats
Emma McIlroy investigates the future of performance enhancing drugs in sport....................
Alistair Moore discusses the patenting of inventions arising from scientific research.............
Robots: the Next Generation?
Anna Lacey goes in search of artificial life..........................................................................................
The Genetic Origins of Humanity
Andrew Lin explains how small genetic changes go a long way towards making us human..
Charley Barber examines the remedies for the morning after......................................................
Katherine Borthwick finds out how a simple text message helps the medicine go down.....
Natureâ€™s Motor: Putting a Spanner in the Works
Jonathan Gledhill on interfering with ATP synthase, the motor that makes our cellular energy...
What Children Leave Behind
Joanna Maldonado-Saldivia investigates the long lasting effects of pregnancy.............................
Regulars Editorial ............................................ 03 Cambridge News ........................... 04 Events ............................................... 05 Focus ................................................. 06 On the Cover ................................. 20 A Day in the Life of... .................... 21
Away from the Bench ................... 22 Initiatives .......................................... 23 History ............................................. 24 Arts and Reviews .......................... 26 Dr Hypothesis ................................ 28
The front cover shows Paul Cuddonâ€™s image of a neuron (green) resting on a bed of astrocytes (red). The nuclei of both types of cell appear in blue.To find out more, turn to page 20.
Next Issue: May 2005 Want to write for BlueSci?
We are currently looking for submissions for our Easter Term issue. We need to receive submissions by 5pm on 28 February 2005. We want articles on all kinds of science, but in particular we are intereste d i n r e c e iv i n g c o n t r i b u t i o n s c o n c e r n i n g t h e p h y s i c al sciences. So whatever your scientific passion, why donâ€™t you share it with our readers?
Would you like to see your photograph on the front cover of BlueSci? With a print run of thousands, what better opportunity to have your work distributed throughout Cambridge? Microscopy, MRI, views of the galaxyâ€Ś the choice is yours! To enter, send your picture and a brief explanation to email@example.com by 28 February 2005.
Article enquiries:: firstname.lastname@example.org General enquiries:: email@example.com
New for 2005: BlueSci online Read all the articles on our website
Issue 2: Lent 2005
From The Editor
Produced by CUSP & Published by Varsity Publications Ltd Editor: Edwina Casebow
When the BlueSci team gathered to judge the photographs for our cover competition, we were impressed by the diversity of images we’d received. Cambridge’s scientific community is certainly very heterogeneous! With such a high standard of entry, it was difficult to pick a winner. I think you’ll agree that Paul Cuddon’s photograph of neurons is stunning. As always, you can learn more about it by reading our ON THE COVER article. The human brain, which contains billions of neurons, cannot fail to be one of the most captivating objects of scientific study. How though, does it make us different from our closest relatives in the animal world? Andrew Lin’s compelling article on THE GENETIC ORIGINS OF HUMANITY offers an intriguing insight into the biological basis of this complex problem. EINSTEIN is considered to be one of the most cerebrally gifted scientists of all time. 2005 marks the hundredth anniversary of his most ground-breaking papers. To mark this unique occasion, our HISTORY section has bro-
ken with its Cambridge connections to take a special look at the physicist’s remarkable life and work. Back in the scientific world of 2005, Katherine Borthwick reports on the latest innovative applications of modern technology in MOBILE MEDICINE; Emma McIlroy examines how scientists are researching new techniques to detect athletes who use PERFORMANCE ENHANCING DRUGS, and Alistair Moore considers the pros and cons of filing for PATENTS. If that’s not enough to whet your neuronal appetite, look beyond the human mind and enter the world of ARTIFICAL INTELLIGENCE in Anna Lacey’s insight into the next generation of robots. If your abstemious New Year’s resolutions have already been broken, take cheer, and turn to Charley Barber’s article on HANGOVER CURES to soothe your fragile nerve cells. I hope you enjoy this brain stimulating issue! Edwina Casebow firstname.lastname@example.org
From The Managing Editor The first issue of BlueSci was launched last term and was enthusiastically received.We are thrilled with the response, and are glad that you, the readers, agree with us that there’s a real niche for what we’re trying to achieve. We hope that in giving Cambridge scientists a chance to express themselves we have managed to entertain non-scientists and scientists alike, and have also provided a forum for everyone in Cambridge to find out about events across the University. We have no intention of restraining our ambitions this year, and have plenty of ideas to establish ourselves firmly in the Cambridge science community. Firstly, we’re hoping that improving our distribution will mean that there will be more copies in hands in all departments, so no more scowling across the
tea table at that postdoc who sneaked back to the lab with the last copy! Secondly, we’ve appointed a webmaster and have lots of ideas for improving our website (www.bluesci.org). Thirdly, we’re trying to broaden the scope of our articles to include both more on the physical sciences, and to appeal to budding science journalists out there. So if you are interested in contributing to BlueSci, especially in either of these areas, or have ideas for the coming year, then please get in touch. Finally, thanks again to Varsity and CUSP, without whose support the magazine would not exist. Looking forward to a scientifically enlightening 2005! Louise Woodley email@example.com
Managing Editor: Louise Woodley Submissions Editor: Ewan Smith Business Manager: Eve Williams Design and Production Production Managers: Tom Walters, Jonathan Zwart Pictures Editor: Sheena Gordon Production Team: Victoria Leung,Tasleem Samji, Helen Stimpson Webmaster: Mark Woodbridge
Section Editors Cambridge News: Laura Blackburn Events: Carolyn Dewey Focus: Ewan Smith Features: Joanna Maldonado-Saldivia, Helen Stimpson, Owain Vaughan On the Cover: Jonathan Zwart A Day in the Life of…: Nerissa Hannink Away from the Bench and Initiatives: Tamzin Gristwood History: Emily Tweed Arts and Reviews: Owain Vaughan Dr Hypothesis: Rob Young CUSP Chairman: Björn Haßler firstname.lastname@example.org PostScriptPicture (VarsityBlackEPSNewest.eps)
Varsity Publications Ltd 11/12 Trumpington Street Cambridge, CB2 1QA Tel: 01223 353422 Fax: 01223 352913 www.varsity.co.uk email@example.com BlueSci is published by Varsity Publications Ltd and printed by Cambridge Printing Park. All copyright is the exclusive property of Varsity Publications Ltd. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, without the prior permission of the publisher.
Dancing on the Brain
Role for Volcanoes in Origins of Life
An unusual collaboration between Dr McCarthy from the Rosaleen Department of Experimental Psychology and choreographer Wayne McGregor may lead to new insights into how the brain processes and comprehends movement. The Choreography and Cognition project, funded by the Arts and Humanities Research Board and Arts Council of England, examined how dancers retain movement and how they put movement together. When the dancers were asked to visualise a routine whilst repeating a word over and over, they found they could run the routine through in their minds with no interruption. However, when they repeated the visualisation whilst tapping a sequence of dots on a page, they found that the sequence in their minds became disrupted. Dr McCarthy hopes that this will help to understand how the brain thinks about movement whilst the body is carrying out different tasks, thus helping patients with brain injury or movement disorders.
Researchers from the Department of Earth Sciences have shown that volcanoes may have played an important role in the origin of life on Earth by fixing nitrogen. All life needs nitrogen to survive, but most organisms canâ€™t use atmospheric nitrogen as it is in the wrong form. Bacteria and fungi in the soil can fix nitrogen into a form that plants can use, which in turn is used by animals further up the food chain. In the primordial soup, however, no such bacteria existed, so where did the fixed nitrogen come from? Tamsin Mather and David Pyle measured the composition of gases above a hot lava lake at the Masaya Volcano in Nicaragua and found that there was a higher level of fixed nitrogen in the volcanic plume than elsewhere. The heat from the volcano allowed the formation of fixed nitrogen, and the results suggest that volcanoes could have been as important as lightning and asteroid impacts in fixing nitrogen for use by the earliest micro-organisms.
Minute Microcages Developed
The Cambridge based company Light Blue Optics has developed a tiny video projector, the size of a cigarette packet, without the need for expensive light bulbs or bulky lenses. Traditional digital projectors use a bulb, a wheel of colour filters and a lens to magnify the image. However, the bulbs can cost up to ÂŁ400 and have a short life. Not only is the new projector more robust, but it is also smaller and more costeffective. It works by creating a 2-D holographic image of a picture, using diffracted light from a laser that illuminates a small liquid-crystal-on-silicon microdisplay inside the unit. Sharp images are produced without the need for bulky lenses, and the hologram chip inside the projector can generate 200 frames per second. It might be possible to downsize even further and integrate the projector into mobile phones.The company expects the projectors to be in the shops in two to four years.
Medical student Chris Zagorski has set up a company with colleagues from his Cambridge MIT Institute exchange studies that has great potential to help breast cancer sufferers. Chris came up with the idea of developing a tissue scaffold that could help breast cancer sufferers who had undergone mastectomies to grow new breast tissue. This idea has great benefits as it will help heal the physical and psychological wounds caused by intense cancer treatment, as well as negating the need for artificial implants. Along with MBA student Harry Sloan and Prof. Ioannis Yannas, Zagorski founded the company BioScaffolds.The team is hoping to develop the technology in the UK, followed by Europe and the US. It will take at least five years for the technology to be available, although once prototypes have been developed and undergone clinical trials it is hoped that this will pave the way for technology to help regenerate other body tissues, such as the liver.
Light Blue Optics
The development of multi-fingered microcages by Dr Jack Luo and colleagues in the Department of Engineering could offer a much better alternative to the instruments currently available for holding minute objects such as biological cells. The device is made from a metal and Diamond-Like Carbon (DLC) bimorph layer deposited by a process used in industrial microelectronics. The DLC layer forces the fingers to curl inward, forming a cage 20-40 microns in diameter, the width of a wool fibre. The microcage opens when a pulsed current is applied to the device, which can be used for holding specimens without applying direct force, thus avoiding damage. Specimens can then be tested, probed, injected or transported. Currently, the operating temperature is too high for use on biological specimens, but development of the device is ongoing to make it more suitable. The new technology could have applications not only in biology and medicine, but also in nanoscience.
E ve n t s
Events EINSTEIN YEAR
THE NAKED SCIENTISTS
This year celebrates the 100th anniversary of the publication of three of Einstein’s ground-breaking papers: Brownian motion, the photoelectric effect and special relativity. To find out more, turn to the History section on pages 24-25. Events in Cambridge include: 27 January To the 5th Dimension and Beyond Professor Andy Parker 24 February The Physics of Music Wendy Sadler 5 March Exploring Universes Professor John Barrow All at the Cavendish Laboratory, Pippard Lecture Theatre. For details see wwwoutreach.phy.cam.ac.uk 17 January From Particles to Strings: Can we Fulfil Einstein’s Dream? Dr David Berman 5-6pm, Centre for Mathematical Sciences. Free, but ticket only, email firstname.lastname@example.org Part of the Millennium Maths Project. For further details of this and other events go to www.mmp.maths.org 16-23 March Evening lectures as part Cambridge Science Week. See below for details.
CAMBRIDGE SCIENCE FESTIVAL: TIME TRAVEL 16-23 March From Archaeology to Zoology, scientists and students will offer activities exploring millions of years of the Earth’s history. This year, the festival travels to the future, exploring advances in medical science and looking at the possibilities of some well-known science fiction stories becoming a reality. There will be over 100 laboratory tours, demonstrations, hands-on activities and public lectures. Hands-on activities include making green slime, turning coins gold and extracting DNA from bananas. Kids are also given the chance to build a hovercraft, a dancing robot or a model of the solar system. Visit www.cambridgescience.org to find out more, email email@example.com to get involved.
CAMBRIDGE UNIVERSITY ENGINEERING SOCIETY See www.cuesonline.org for details of events.
On the radio, Sundays 6-7pm on 96.0FM www.thenakedscientists.com/listen 16 January Cyborgs Professor Kevin Warwick from the University of Reading discusses the creation of man-machine interfaces and his own personal experience of embedding microchips in his body. 27 January Jurassic Park: Fact or Fiction? David Norman, paleontologist, and Alan Cooper, expert on ancient DNA, explore the feasibility of recovering DNA from ancient remains and recreating the dinosaurs. 6 March Hypnosis Peter Naish, psychologist and hypnotist, discusses the art of hypnotism, and demonstrates it live on air. Live in Cambridge: 17 January Cyborgs 8-9.30pm Borders Bookstore. 1 February Parallel Universes 8-9.30pm Borders Bookstore.
ENGINEERS WITHOUT BORDERS A charitable organisation based at British universities. Run by students with the backing of expert academics and professionals, EWB aims to find technical solutions to developing world problems and to involve engineering students and professionals in development work. For talks, project lectures, and information about overseas placements, go to www.ewb-uk.org/cambridge/events.php
CRASH, BANG, SQUELCH SCIENCE FESTIVAL 19 March Free, fun, hands-on science for all. CHaOS are looking for enthusiastic science students to demonstrate fun experiments to the public for just three hours at the end of term. Email firstname.lastname@example.org or go to www.chaosscience.org.uk
PETERHOUSE KELVIN CLUB Regular talks will be given, with speakers including Dr James Martin, Professor Richard Frackowiak and Professor Andrew Briggs. Email Jamie Muir Wood email@example.com for further details.
THE STUDENT PUGWASH SOCIETY Concerned with the ethical, social and global implications of science and technology, they hold regular meetings to discuss these issues and invite guest speakers to talk on related topics. For details visit www.cam.ac.uk/societies/pugwash
INSTITUTE OF ASTRONOMY Every Wednesday from 7.30pm is open night. Use telescopes to see the sky and enjoy a 30-minute talk from a member of the department.
THINKING OUTSIDE THE BOX For talks on everything from Philosophy and SPS to Chemical Engineering, go to: www.cam.ac.uk/societies for all societies available in Cambridge; www.cam.ac.uk/cambuniv/seminars.html for the University’s departmental seminar list, and www.srcf.ucam.org/scisoc/links for the CU Scientific Society lists.
STOKES SOCIETY OF PEMBROKE 10 March Tinnitus, the Phenomenon of Phantom Auditory Sensation Dr Ian Winter 8.45pm, the Nihon room at Pembroke. Contact firstname.lastname@example.org
JESUS COLLEGE SCIENCE SOCIETY Talks held every second Thursday during full term at 6.30pm. For more information, see www.jcsu.jesus.cam.ac.uk/jcss
MEDSOC 10 February Talk by Dr Tim Hunt, Nobel Prize winner for Medicine 3 March Talk by The Governmental Advisor for Science Date To Be Arranged The (In)famous Wonky Willies Talk by Mr Whittaker For more on these and other talks go to www.srcf.ucam.org/medsoc
Kyoto: a Cure for Carolyn Dewey discusses the science behind one of the The Earth’s climate is changing, causing dramatic alterations to the natural landscape. With potentially catastrophic events predicted by the UN’s Intergovernmental Panel on Climate Change (IPCC) that may affect billions of people, governments from around the world have become actively involved in attempts to remedy the problem. Preparing to spend billions of pounds, many have signed up to the Kyoto Protocol, which becomes legally binding on 16 February 2005.
The scale of the issue During the last 100 years, the Earth’s temperature has risen by a global average of 0.6ºC. The IPCC predicts that it will continue to rise by between 1.4ºC and 5.8ºC over the next century. This means that the Earth is already warming faster than at any other time in the last thousand years, with the 1990s the warmest decade since records began. Even if the Earth does warm up by only a further 1.4ºC, this increase would mark the most rapid change in 10 millennia. Although a 0.6ºC rise in temperature may not sound significant, in 2004 the Arctic Climate Impact Assessment (ACIA) stated that this has already been enough to melt glaciers and icecaps, and to cause a decrease in summer Arctic sea ice by 20% over the past 30 years. This in turn has warmed and acidified oceans, caused a rise in sea levels and produced extreme weather phenomena across the globe, including hurricanes, heat waves and prolonged droughts. These changes are all consistent with a warming climate near the Earth’s surface. Furthermore, according to scientists at the National Institute of Health and Medical Research, there were nearly 15,000 additional deaths during August 2003 in France alone, as a direct result of the soaring temperatures that summer. A 1.4ºC increase in temperature would result in even greater catastrophes. The IPCC predicts increasingly violent storms, droughts and flooding
and disruption of water supplies. Most of those who would suffer are in poorer countries, particularly Latin America, Africa and Asia, as it is these countries that will bear the brunt of the climate changes. After reviewing the available scientific data, the IPCC concluded that, “there is new and stronger evidence that most of the observed warming observed over the last 50 years is attributable to human activities”, especially the increase of greenhouse gases in the atmosphere. These findings have been confirmed by other committees of experts, such as the United States National Assessment Synthesis team set up by the US Congress. While human activity has increased the concentration of all greenhouse gases, of particular concern is that atmospheric concentrations of carbon dioxide are rising faster than at any time in Earth’s history. Although it is accepted that carbon dioxide levels naturally fluctuate, current levels have been increasing over 200 times faster than the background rate, a fact clearly demonstrated by ice core studies like the Law Dome Ice Core project. This increase is mainly the result of burning fossil fuels, such as coal, oil and natural gas, which release carbon dioxide into the atmosphere. These energy sources are used for almost everything we do – from powering our cars and heating our homes, to fuelling the power stations on which we rely for everyday life. Carbon dioxide, methane, nitrous oxide and water vapour all occur naturally in the atmosphere, and all play an important role in keeping the Earth some 33ºC warmer than it would be otherwise by acting as a layer of insulation, trapping some of the heat reflected off the Earth. However, humans have dramatically altered the natural balance of greenhouse gases through increasing atmospheric concentrations of carbon dioxide, methane and nitrous oxide. Indeed, according to data from NASA, humans release over 6.5 billion tonnes of carbon dioxide a year into the
During the last 100 years, the Earth’s temperature has risen by a global average of 0.6°C
atmosphere. The increase in concentration of greenhouse gases leads to greater insulation around the Earth, resulting in the rise in temperature.The atmosphere allows solar energy through, but as it is reflected off the Earth, the wavelength of the radiation alters so it cannot pass back out through the atmosphere into space. Instead, it remains trapped causing an increase in temperature. In an attempt to combat climate change, many countries, including the UK, are preparing to invest substantial resources to reduce the levels of greenhouse gases that are emitted, particularly carbon dioxide. The Kyoto Protocol is the result of a meeting of over 160 nations, who agreed in 1997 that industrialised countries would reduce their collective emissions of greenhouse
Fo c u s
major challenges for global politics in the 21st Century
gases by 5.2% compared to the year 1990. However, although signed in 1997, the Kyoto Protocol will only become legally binding on 16 February 2005,with those that have ratified the Protocol having until 2012 to achieve this reduction. In the UK, the government is attempting to achieve its targets by, for example, using less coal for electricity generation, and replacing this method with renewable energy sources such as wind power.
amongst both scientists and politicians. In the past, this controversy was partly centred on the question of whether human activity was responsible for climate change, or whether it was the result of variation in solar radiation.
the change in climate is the result of both human and natural activity
Is Kyoto the cure? Some countries, including the US, have refused to ratify the Kyoto Protocol. This lack of commitment demonstrates that the implementation of global policy to combat climate change has not been without international dispute,
course, climate change is not just caused by humans. Since the Earthâ€™s climate system is driven by the sun, it is affected by solar variability. Another important factor affecting the climate is volcanic eruptions, which can inject
Those who believed that human activity was to blame thought that if manmade emissions were cut, then the effects of climate change could be radically reduced. This is one of the key ideas behind the Kyoto Protocol. Of
large amounts of dust into the atmosphere. The IPCC have more recently concluded that the change in climate is the result of both human and natural activity. Their 2001 results illustrate that
Focus anthropogenic influences, such as greenhouse gases and sulphate aerosols, provide a plausible explanation for a substantial part of the temperature changes over the past century.They find that the best agreement between model simulations and observations is obtained when both anthropogenic influences and natural influences, such as solar variation and volcanic activity, are combined. The IPCC also cautions that although the influences included in their study are sufficient to explain the observed changes, this does not exclude the possibility that other influences may have also contributed. The climate changes on many different timescales, some of them millions of years long. It is well-known that there are processes that affect climate change over such times, and this is the subject of paleoclimatology. For instance, the Earth’s position and orientation relative to the sun are not fixed, but vary in what are known as Milankovitch cycles. Milankovitch cycles play an important role in explaining ice ages and other climate variability over thousands of years. However, for the prediction of climate change in the 21st century, long-term effects like the Milankovitch cycles are thought to be much less important than the aforementioned anthropogenic and natural influences. The climate is a very complex system, and the warming of the globe may affect it in unexpected ways. A particular worry is that global warming may disrupt the global circulation system,
ous illnesses like cholera. This raises many questions, perhaps most significantly that if the Kyoto Protocol will not stop climate change, but merely delay it, would the money needed to implement it be more beneficially spent on providing global access to clean water, and maybe preparing for the inevitable?
if the Kyoto Protocol will not stop climate change would the money be more beneficially spent on providing global access to clean water?
Conveyor will shut down, as the exact critical concentration of salt water on which it depends is not yet known. So in the longer term, the Northern Hemisphere at least may be heading towards a cooling climate, rather than a warmer one.
So, what now? Most national governments are committed to the Kyoto Protocol, and to reducing the emission of man-made greenhouse gases. But is the Kyoto protocol good enough? A model by Tom Wigley, one of the authors of the IPCC reports, shows that an expected temperature increase of 2.1ºC by 2100 would
the introduction of the Kyoto Protocol may cost up to one trillion US dollars worldwide
known as the ‘Ocean Conveyor’. This can contribute significantly to the warming and cooling of the Earth. The Ocean Conveyor transports vast amounts of heat around the planet via the Gulf Stream, warming the North Atlantic region by as much as 9ºC, and resulting in milder winters and warmer summers. For the Ocean Conveyor to function, there must be a critical concentration of salt water, but as the Earth warms up and glaciers and ice caps melt, increasing amounts of fresh water are released into the oceans, diluting the salt water. As a result, the Conveyor shuts down, causing substantial cooling throughout the North Atlantic region. Records from a variety of sources show
that this shutdown has happened several times before, and appears to be happening again. Data collected in 2002 found that the North Atlantic had been diluted dramatically by fresh water, with evidence of a slow-down of the Ocean Conveyor reported in 2001. However, it is difficult to make an actual prediction as to when the Ocean
be diminished by the Kyoto Protocol to an increase of 1.9ºC.This latter temperature is the predicted increase for 2094 without emission reduction. Therefore, the temperature increase that the planet would have experienced in 2094 would simply be postponed by six years. The statistician Bjørn Lomborg has estimated that the implementation of the Kyoto Protocol may cost up to one trillion US dollars worldwide. He believes that the cost in the US alone would be greater than that of providing global access to clean drinking water and sanitation – a measure that could prevent two million deaths a year and protect half a billion people from seri-
It is clear that the Earth is getting warmer, with potentially devastating consequences for billions of people, especially those in developing countries and those who live in low-lying areas. Human activity has been shown to cause an increase in the amount of greenhouse gases in the atmosphere, most notably carbon dioxide, and there is robust scientific evidence that demonstrates that the change in global temperature is connected to both human influences, like the increase in greenhouse gases, and natural influences, such as solar variability. So, what are we to do? Should developed nations try to do something about climate change? Should there be a stricter Kyoto-style protocol? Or should we just accept that climate change is inevitable, and work on alleviating its adverse effects? If there is a balance, what is it? If you had to spend the money, what would you do? Carolyn Dewey is a medical student based at Addenbrooke’s Hospital. Additional research and writing by Björn Haßler
Further Reading The Intergovernmental Panel on Climate Change www.ipcc.ch United Nations Framework Convention on Climate Change http://unfccc.int EU carbon trading scheme http://europa.eu.int/comm/ environment/climat/emission.htm
Outsmarting the Cheats Emma McIlroy investigates the future of performance enhancing drugs in sport Mushrooms, plant seeds, dried figs and dogs’ testicles might not appear to have much in common. Yet for Greek Olympians 2000 years ago, these were the equivalent of doping. Times have changed though, and in what has become a highly lucrative business, the methods and drugs available to enhance athletic performance are becoming increasingly sophisticated. The scandals of Athens may have left the front pages, but the problem remains. Modern day cheats have tricks up their sleeves, but scientists are working hard to find methods to catch them out. Will they have outsmarted the cheats by the time the Olympics reach Beijing in 2008?
Modern day cheats have tricks up their sleeves, but scientists are working hard to find methods to catch them out
‘designer’ drugs are either almost identical to those naturally produced by our body… or are so recently developed that they are virtually unheard of
Dr Holt’s research group has been pioneering the downstream markers approach. Unlike the isoform method, this test looks at the secondary effects of HGH on the body, and is concerned with the stimulation of protein production, particularly IGF-1 and procollagen type 3. The fundamental principle behind the test is that subjects injecting
exogenous HGH will have unusually high concentrations of these two markers. “The beauty of this method is that although it takes longer for these markers to rise, it also takes longer for them to fall. So we have a greater chance of catching the cheats,” says Dr Holt. This research is encouraging but Dr Holt and his colleagues at WADA may soon face another hurdle: gene doping, the altering of an individual’s genetic make up to gain genes that will ultimately enhance their performance. Gene doping can be achieved in two ways: either by directly injecting the gene into the muscle or tissue, or by delivering it to all the tissues via a virus. Although talk of gene doping may conjure images of ‘super-humans’, and the topic is often treated as futuristic, there is no escaping the fact that mice and baboons have already proved successful subjects for gene therapy. So, just how ridiculous is the idea that athletes might use it? “Sadly, gene doping is a real possibility,” sighs Dr Richard Budgett, Director of Medical Services at the British Olympic Association. “Therapeutic genetic treatments are rapidly improving, which is great. Unfortunately there’s very little to stop someone injecting a gene for EPO instead.” Research into finding a test for gene doping is already under way, but the problem scientists face seems almost insurmountable: how do you detect which genes the athlete was born with and which they weren’t? “I’ve no doubt there will be those willing to use gene therapy for non-therapeutic applications,” says Dr Rabin. According to a recent statement from the International Olympic Committee, antigen detection, gene chips and protein identification are all being used to try and find effective tests. Despite this, one is left with the feeling that there will always be those who will stop at nothing to go stronger, higher and faster.
n Zwart Jonatha
Among the most popular performance enhancing drugs are peptide hormones, including erythropoietin (EPO), human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1). These are all naturally made by the body, but cheats inject an almost identical synthetic form, which augments the body’s natural levels and potentiates their effects. EPO is naturally produced by the kidneys and stimulates erythropoiesis; the production of red blood cells. By injecting EPO, athletes can increase their red blood cell count and thus improve their ability to carry oxygen, which is an attractive prospect in endurance events. HGH is naturally produced in the brain by the pituitary gland, and stimulates the growth of muscle, cartilage, and bone. Cheats commonly use it to increase muscle size and reduce muscle fatigue. Of course, all this doesn’t come without a price. Aside from the prospect of a lifetime ban, there are plenty of downsides to doping. HGH, for example, can cause heart, liver and kidney damage, various cancers and abnormal growth of the hands and face. These are the hard-hitting consequences, which are often forgotten in the pursuit of glory. These ‘designer’ drugs are either almost identical to those naturally produced by our body, making it impossible to detect them as synthetic, or are so recently developed that they are virtually unheard of in the scientific community. Scientists at the World AntiDoping Agency (WADA) are faced with the challenging task of developing tests to detect chemicals which either appear to be invisible or they don’t even know exist! “Urine is cur-
rently the main matrix we use for drug testing, but blood will be increasingly used as we develop tests for previously undetectable substances. Hair, saliva and sweat detection methods are being considered for future use,” explains Dr Olivier Rabin, Scientific Director for WADA. The main area of research at present is the development of a reliable test for HGH, but it’s not an easy task as Dr Richard Holt, Head of the Growth Hormone 2004 project, discovered: “The first problem we came up against was that HGH isn’t excreted in our urine, so we couldn’t use urine testing. Secondly, HGH is secreted in pulses, meaning that levels within the body can vary tremendously. Thirdly, both stress and exercise increase HGH levels, so you can imagine that during a major competition, an athlete’s HGH will naturally increase. Finally HGH that the cheats administer is identical to naturally produced growth hormone. All this makes our job of finding an accurate test very difficult indeed.” To date, two approaches have been followed to detect exogenous growth hormone: the isoform method and the downstream markers method.The isoform method relies upon the fact that our body naturally produces many molecules of growth hormone, which vary in weight. These are known as isoforms, and the naturally predominant one weighs 22 kiloDaltons (kDa). The injected form of HGH consists purely of the 22 kDa form, and causes all the other isoforms to disappear from the circulation. Thus, by looking at the ratio of the different isoforms, the presence of exogenous HGH can be detected. Unfortunately, this method only detects HGH injected up to 24 hours before, a risk very few athletes are willing to take. Instead, they are more likely to take HGH in training several weeks before competition.
Emma McIlroy is a third year Natural Scientist specialising in Experimental Psychology
Patent Pending Alistair Moore examines what is involved in patenting inventions arising from scientific research
for patent an unattractive prospect. Finally, while filing at the Patent Office is free, paying an attorney, assessing the application internationally and renewing a granted patent cost thousands of pounds. Cambridge Enterprise, part of the University’s Research Services Division, helps University members to file for a patent, handle legal details and suggests sponsorship sources to defray the costs. Part of its mission is to “enhance the University’s contribution to society through knowledge transfer from the University to the community”. Certainly, while the rights to a patented invention can be licensed for commercial production, an unpatented invention may never get off the drawing board because it lacks financial backing. The legally defensible monopoly granted by a patent is the all-important prerequisite for commercial development. Andrew Thomas, a Cambridge PhD graduate, patented part of his doctoral research work with a pharmaceutical firm. He says, “It’s gratifying that what I did in the lab may now be developed commercially. It could become a real product benefiting real people.” Soon after starting tumour research, I was asked what I would do if I invented a cure for cancer. Setting aside the improbability of such an event, I was forced to admit that I didn’t know. Would I write to Nature and present my idea to the world? Or write to the Patent Office and secure the invention as my own? As cynical as it sounds to think of legal ownership before potential benefit, an invention lacking legal protection may never be funded, and without funding it may never be more than just a good idea.The question of whether to
The question of whether to patent faces many researchers during their career
patent faces many researchers during their career. Although in industry it may be second nature, in academia the choice is more difficult and not always understood. So what is involved? And what are the pros and cons for scientists in academia? The ‘intellectual property’ generated by many kinds of creative endeavour can be protected in a number of ways, from copyright to patents, design rights and trademarks. For inventions emerging
from scientific research, patenting is a useful way to secure ownership and protection. Under UK law, invention ownership is acknowledged by letters patent, in which the inventor publicly discloses details of the invention. In return, a limited monopoly is granted allowing the invention to be ‘exploited’ (manufactured and sold) for a defined period (usually 20 years) in the UK. Crucially, the monopoly can be defended to stop competitors developing similar products. An invention need not be a wonder drug or revolutionary gadget to qualify for patent. Even the simplest idea can be filed, so long as it is ‘novel’ (has not been documented before), ‘inventive’ (is not an obvious advance) and has commercial application. However, filing is not an overnight process and there is no guarantee of success.Applications are made in writing to the Patent Office specifying what is being claimed, and a patent attorney is usually required to draft this precisely worded document. Securing UK rights takes around a year, and international protection a further 18 months or more. Importantly, although successful applications are published publicly, details of the work must be kept secret prior to filing so that the invention is considered novel. Public disclosure before this date invalidates the application. For researchers who make their name through publishing in academic journals, this requirement may make filing
Even the simplest idea can be filed
Dr Charles Smith of the University’s Cavendish Laboratory agrees. His group established a spin-out company to develop technology arising from their work in semiconductor physics. “One way of doing academic research is to move on to other projects if it becomes too applied,” says Smith. “Many researchers don’t know how to make the commercial leap. But it’s just as interesting, and now it has applications. Perhaps we can start solving problems.” Patenting may not be the natural choice for university scientists in the race to publish. But it is a practical way to translate knowledge out of the academic ivory tower into real world products with beneficial application. Less a profit driven grasp for commercial success, and more a decision for development and protection, it is undoubtedly a choice worth considering. With University help and numerous information sources available, the decision can be made with an understanding of what is involved. And whether it’s a cure for cancer or something far less revolutionary, every invention deserves its chance to change the world. Alistair Moore is a PhD student in the Department of Biochemistry
Robots: the Next Generation? Anna Lacey goes in search of artificial life The Terminator, C-3PO and HAL: Hollywood’s robot stars. Scientists and engineers have spent years attempting to turn this science fiction into reality, but have we really come any closer to creating an artificially intelligent being? Amateur scientist and self-proclaimed “nerd with a mission”, Steve Grand has come closer than some. Close enough, in fact, for Richard Dawkins to label him “the creator of what I think is the nearest approach to artificial life so far”. Grand’s aim is to create a machine ‘brain’; a machine capable of self-organising into a series of more specialised machines, with only sensory information as a guide. Lucy the orang-utan is the first step on his mammoth quest.
Lucy the orang-utan is the first step on his mammoth quest
Lucy (pictured on the right) comes fully equipped with binaural hearing, monocular vision, virtual muscles, touch and temperature sensors, and even a voice. Information from the environment is detected by these sense devices and passed to her brain. The brain itself consists of over 50, 000 virtual neurons, which work together to form an array of neural circuits. Grand aims to show that these circuits can interact to produce outcomes that are unpredictable. In other words, that complexity can arise from apparently simple beginnings.With this intellectual toolbox behind her, Lucy can distinguish a banana from an apple, a simple feat for a human, but impressive for a robotic orangutan. How does she do this? The answer lies in the building of Lucy’s virtual brain. Grand used conventional computer programmes to simulate different brain structures.This included a model of the superior colliculus, the part of the brain that receives visual information and stimulates motor responses.The visual part of Lucy’s ‘brain’ enables her to differentiate between apples and bananas, while the motor part allows her to move her eyes and arms to a visual point in space. But why would Lucy want to point at a banana rather than an apple? It is certainly not due to Lucy having a penchant for tropical fruit. Instead, Grand has had to build a preference for bananas into her program, as the reasoning behind why organisms choose one option over another is far beyond our current understanding.The programming integrates to allow Lucy to distinguish boundaries, recognise two fruit shapes, realise her intrinsic preference for the long, yellow fruit and final-
ly point at the banana. Joining together these fairly simple components makes Lucy special: separate areas of her ‘brain’ are programmed with individual functions, and yet together they interact to combine visual sensation with movement. In many ways this does not seem like ground-breaking robotics. After all, there are many pre-programmed house robots that can sense the environment and respond accordingly. Even Grand admits that Lucy only points at bananas because this is what she was wired up to do. Despite
Lucy’s true importance lies in her giving us a tantalising glimpse of how we think
this, Grand’s virtual orang-utan still deserves a place in history. Although Lucy was given pre-programmed machinery, she didn’t actually know anything about apples and bananas, and so had to work it out for herself. Grand argues that this shows neural circuits organising themselves into something more complex, and is thus an example of development and learning.
The difficulty arises in knowing exactly what it is ‘to learn’. Definitions and mechanisms of learning and intelligence have long been debated by philosophers and scientists. Without understanding what it means to say ‘I learn’ on a descriptive or mechanical level, it is impossible to judge whether Lucy has learnt or not. Lucy’s true importance lies in her giving us a tantalising glimpse of how we think. If simple circuits can allow a robot to recognise a banana and point at it, then there is no reason to think that our own brain cells cannot create more complicated networks and outcomes. So should the Cambridge applicants of the future worry about competing for places with robots? Grand thinks not. If a real breakthrough in artificial intelligence is to be made, scientists must work out the processes behind learning, intelligence and creativity. “Until then, there’s the small matter of making Lucy smart enough to pick up the application form!” says Grand. Understanding the brain through experimenting with circuits seems a worthwhile course for now.After all, evolution did not get the wiring perfect first time. Perhaps one day an amateur in a shed will strike lucky and get it right. Anna Lacey is a third year Natural Scientist specialising in Zoology
The Genetic Origins of Humanity Andrew Lin explains how small genetic changes go a long way towards making us human Even setting aside the knotty philosophical problem of what makes us human, there is still a biological puzzle: how did we acquire the features that set us apart from our nearest relatives, the chimpanzees? Humans and chimps share 98.5% of their genetic material, more than many other sibling species pairs. That number increases to 99.4% if you consider only the stretches of DNA containing the information to synthesise proteins. How could this tiny remaining difference account for all the peculiarities of Homo sapiens: walking upright, brain size, intelligence, language and complex society? A general answer lies in the way genes build organisms. The development of an organism is controlled by the intricate dance of genes turning on and off in exactly the right place and time. A very subtle change in this dance, a gene expressed slightly longer or over a slightly
Humans and chimps share 98.5% of the same genetic material
small cerebellum and caudate nucleus, as seen by brain imaging. Perhaps FOXP2 helps to direct the development of this brain circuitry, and the unique human version subtly alters the development so that we can make the specialised mouth and tongue movements required for speech. Nimble tongue muscles are only one requirement of speech, and there is no evidence to suggest that FOXP2 is the only ‘language gene’. In any case, we still need to understand the genes that FOXP2 regulates before we know how these differences arise. Meanwhile, researchers have also been pursuing genes that might be responsible for the difference between our outlandishly large brains and those of other primates. For example, an international team of scientists led by Geoffrey Woods at Leeds University found that a mutation in a gene called ASPM makes the brain abnormally small, indicating that it regulates brain size. Like FOXP2, this gene has also undergone intense selection in human evolution, with several ‘sweeps’ of new versions through early human populations every few hundred thousand years, the last sweep being 200,000 to 500,000 years ago. ASPM was also under selection pressure before humans split off from chimpanzees, suggesting that it increased brain size in the great apes as well. Biologists hypothesise that ASPM may control brain size by regulating cell division in the developing brain. ive rch yA rsit Va
smaller area, can have profound changes in the end result. Until a few years ago, this general answer was all we had, but now, with full genome sequencing capabilities and modern molecular biology techniques, we are starting to get fresh insights into the fascinating question of what makes us unique. One of the most intriguing of these answers concerns a gene named FOXP2. This gene appears to be involved in human language ability, as demonstrated by a recurring mutation that causes inherited language impairments. Furthermore, the normal human FOXP2 protein differs from the version that other primates have by only
two amino acids (protein building blocks). By statistically analysing the traces of evolutionary change in modern human genomes, scientists have estimated that the human population underwent intense natural selection in favour of our unique version about 100,000 years ago, the time that many anthropologists believe language developed. FOXP2 encodes a transcription factor, a protein that promotes the expression of other genes. In other words, FOXP2 is a ‘master switch’ that directs part of the developmental dance of genes. In human foetuses, FOXP2 is expressed in areas of the brain that will become important for fine motor control, such as the cerebellum and the caudate nucleus in the basal ganglia. Indeed, people with defective FOXP2 have an abnormally
protein muscle found in nonhuman primate jaw muscles, is missing in humans. It was probably knocked out approximately two million years ago, about the time when our brains
H oweve r, evolution takes place within constraints, and the brain can only grow as big as the skull cavity. One critical step in allowing the extraordinary brain expansion in human evolution was to weaken our jaw muscles. Powerful jaw muscles exert strain on the skull, inducing thick bone that constrains brain growth. Human jaws are more delicate than those of our ape cousins, suggesting that weakening our jaws allowed our brains to get bigger. Hansell Stedman and colleagues at the University of Pennsylvania have recently found that MYH16, a critical
tical comparison between the human and chimpanzee genomes has revealed hundreds of other genes that have undergone selective pressure in human evolution. These have diverse functions from hearing and smell to bone development and metabolism. With this word of caution in mind, these case studies demonstrate that a few subtle tweaks to the genome can wreak dramatic changes. So the next time
Human jaws are more delicate than those of our ape cousins, suggesting that weakening our jaws allowed our brains to get bigger
started to grow. These studies have revealed for the first time a few specific genes that give humans some of our uniqueness. Still, we should hesitate before focusing on them as the genes that make us human. In fact, a statis-
you see a chimpanzee, marvel at how similar, and yet so different, you are. Andrew Lin is an MPhil student in the Department of Anatomy
Charley Barber explores the remedies for the morning after You probably know the feeling. Your alarm clock is ringing and it’s time to face the morning. Suddenly, memories of the previous night come flooding back, along with a pounding headache and raging thirst. You struggle to lectures with wobbly limbs and waves of nausea, making that tired old vow, “Never again. Never again.” Despite our many scientific advances, there has never been a scientifically based, experimentally verified hangover cure. It simply isn’t in our best interests to find one. The hangover is our body’s way of telling us that we have poisoned ourselves. Through understanding the science behind hangovers, how can we make them disappear?
The hangover is our body’s way of telling us that we have poisoned ourselves
The first ‘cure’ is the most obvious: pure and simple water. One of the main problems with alcohol is that it causes dehydration. Ethanol is a diuretic. It acts on the brain’s pituitary gland and blocks production of anti-diuretic hormone (ADH). Normally, ADH acts on the kidney to reabsorb water that otherwise ends up in the bladder. When this hormonal hydrostat is disabled, we start needing the toilet a lot more than usual. We end up expelling more water than we drink. To deal with this drought, the body borrows water from other parts, such as the brain, causing it to shrink temporarily. The brain is not able to sense pain, but it is
thought that dehydration shrivels the thin membrane, the dura, which covers it. As the dura shrivels, it causes tension in pain sensitive fibres that attach it to the skull. This is why it feels like your brain might burst out of your head. Whilst it is a good idea to down a couple of pints of water before retiring to bed, plain water is often not enough for the most vicious hangovers. Frequent visits to the toilet cause not only dehydration, but also loss of vital ions from the body. Ions such as potassium and sodium are key to the way nerves and muscles work, and slight imbalances could explain some symptoms such as headaches, fatigue and nausea. At the same time, alcohol depletes our reserves of sugar.
While alcohol is being metabolised, the production of new glucose is inhibited and glycogen, the sugar storage in the liver, is depleted.Acute alcohol consumption, especially in combination with sugar, augments insulin secretion and causes temporary hypoglycaemia. This can explain the weak and wobbly feeling of the morning after the night before. Given the loss of ions and glucose, it might be a good idea to drink an isotonic sports drink rather than plain water before going to bed.These drinks are full of vital ions and sugar, and could go some way to correcting the balance before it’s too late.
Many ‘hangover cures’ have been marketed over recent years, but for most of them one can only rely on manufacturers’ claims regarding their effectiveness. Many are simply vitamin supplements, which purport to speed up the body’s clean-up operation.Alcohol causes depletion of some vitamins, so it won’t do any harm to take a multivitamin tablet before bed, but you can’t rely on it to work miracles. Some remedies make use of the filtering properties of carbon to reduce the number of impurities the body has to process. Alcoholic drinks contain natural by-products of the fermentation process as well as ethanol. These contaminants include methanol, aldehydes, acetone, histamine, tannins, iron, lead, cobalt and sulphites, with darker coloured drinks such as whisky and red wine having more than clear drinks. Charcoal based remedies claim to remove some impurities to reduce their impact on the body while you sleep. One supplement that is claimed to aid the prevention of hangovers is N-acetylcysteine (NAC). This is an amino acid supplement sold in health food shops. NAC is supposed to work by boosting the body’s ability to mop up harmful chemicals called free radicals, which build up in the liver as it breaks down ethanol. Normally, free radicals are removed by glutathionine, but after a heavy night’s drinking the reserves of glutathionine run low. NAC is useful because it is formed from cysteine, an amino acid that forms the core of glutathionine. With the extra cysteine available from NAC, glutathionine remains plentiful, and can carry out its clean-up operation for longer.This could also explain the use of old remedies, such as an English fried breakfast or raw eggs, as eggs are naturally rich in cysteine. As a bonus, fried breakfast also boosts blood
sugar levels.Wash it down with fruit juice, and you’re well on your way.That’s if you can stomach it of course. Taking painkillers is one of the most obvious, and often necessary cures, but it isn’t always a good idea to rely on them as some are more effective at relieving hangovers than others. Combinations of paracetamol and caffeine can be effective because the caffeine acts as a vasoconstrictor, reducing the size of the pounding blood vessels. However, doctors warn against using paracetamol as it may amplify alcohol’s damaging effect on the liver. Like alcohol, caffeine is also a diuretic, so it will add to the problem of dehydration.As an alternative, aspirins are in a class of anti-inflammatory drugs called prostaglandin inhibitors. These might help reduce inflammation in order to ease the headache in the morning. The final and perhaps most dubious cure is the ‘hair of the dog’. Many people believe that a small amount of alcohol the morning after will get rid of the hangover and allow you to face the day. Perhaps not the best tactic for Saturday morning lecture-goers, but there is science behind the idea. Research has shown that some hangovers kick in long after ethanol has been cleared from the body. Here the culprit tends to be methanol. In dealing with toxins, the liver cleans out in a strict order, starting with ethanol. When it eventually reaches methanol, this is broken down into formic acid, which is believed to be the cause of some more severe hangover symptoms. The logic behind the ‘hair of the dog’ is that another dose of alcohol switches the liver back to breaking down ethanol, preventing the build up of more formic acid. However, be warned, the relief is only temporary; eventually the liver will return to breaking down the methanol. Clearly, none of these cures are perfect, but a combination of them all might be a good idea. In the end, only time will allow your body to detoxify itself.
Charley Barber is a third year Natural Scientist specialising in Zoology
Nine Things You Should Know About Alcohol 1. Britain’s binge drinking culture is costing the country £20 billion a year The long term effect of heavy drinking is serious and the NHS estimates it spends £164m a year treating alcoholrelated conditions. 2. Binge drinking is defined as drinking more than 10 units of alcohol in a single session for men and 7 units for women One unit is equivalent to 8 g of ethanol, which is about half a pint of beer. The current recommendation for alcohol consumption in men and women is 21 and 14 units per week respectively. Minimal effects may occur at a blood alcohol concentration (BAC) of about 45 mg per 100 ml and 10 times this can cause death. 3. Alcohol is absorbed mostly through the stomach and small intestine When you have a drink, about 20% of the alcohol is absorbed directly through the upper gastrointestinal tract, mostly the stomach, and the rest through the small intestine.About 5% is excreted by the kidneys and 5% by the lungs as vapour, which is the basis of the breathalyser test. 4.Alcohol is mainly broken down in the liver by alcohol dehydrogenase This enzyme converts ethanol to acetaldehyde, which in turn is broken down by aldehyde dehydrogenase to acetic acid (a component of vinegar).
reduce circulating levels of anti-diuretic hormone (ADH). When ADH levels drop, the collecting ducts of the kidneys do not reabsorb as much water, resulting in an increase in urine production (diuresis) and dehydration. In fact, the hangover headache is caused by water loss from the brain due to excessive alcohol consumption. 7.The human body can adapt to continued exposure to alcohol The body’s increased tolerance to alcohol involves an elevated level of alcohol dehydrogenase and aldehyde dehydrogenase, as well as an augmented brain activity. As the body becomes more efficient at eliminating the high levels of alcohol in the blood, you need to drink more to experience the same effects as before. This can contribute to addiction. These adaptations are accompanied by behavioural changes. 8. Long-term heavy alcohol cosumption can affect the liver, heart and brain The most common form of disease associated with alcohol abuse is liver cirrhosis, which is the scarring of the liver associated with destruction of its normal architecture. Atrophy of grey and white matter in the brain and increased risk of stroke can also result. Alcohol is also thought to lower levels of aldosterone and increase levels of corticosterone in the blood vessels and increase the vasoconstrictor response
In the end, only time will allow your body to detoxify itself
5.Alcohol affects both higher and lower centres of the brain Alcohol enhances the action of GABA, an inhibitory neurotransmitter, and disturbs the processing of sensory information, resulting in unconsciousness and amnesia. In the cerebral cortex, alcohol depresses the behavioural inhibitory centres, so you become more talkative, more self-confident, and less socially inhibited. It also slows down the processing of information from the five senses, and can inhibit thought processes. As alcohol affects the limbic system, you may experience excessive anger, aggressiveness, withdrawal, and memory loss. Finally, alcohol affects the cerebellum, leading to uncoordinated muscle movements and loss of balance. 6.Alcohol causes dehydration Alcohol acts on the pituitary gland to
to noradrenaline. This leads to high blood pressure, which further increases the chances of stroke and heart failure. 9. Moderate alcohol consumption is thought to be beneficial to health The French are known to consume foods high in saturated fats and cholesterol, yet they have a low mortality rate from coronary heart disease. Several red wine components show promise for their possible cardioprotective effects, for example polyphenolic components such as bioflavonoids and proanthocyanidins. Components of grape skin, such as resveratrol and nitric oxide, are also important, as the latter has a relaxing effect on the endothelium of arteries. Ryan Patel is a third year Natural Scitentist specialising in Pharmacology
Mobile Medicine Katherine Borthwick finds out how just a simple text message helps the medicine go down Mobile phones have revolutionised our lives in many ways. They are invaluable when you miss your train or when your car breaks down. For a small group of people in two very different parts of the world they are turning out to be, quite literally, a life-saver. A major problem facing health services worldwide is that a considerable number of patients don’t take their medication as prescribed.This means that serious illnesses are not treated as effectively as they might be.A worrying example of this is the persistently high level of tuberculosis (TB) in South Africa.An extremely effective TB treatment exists, but it relies on patients taking medication consistently for six months. The trouble is that a significant proportion of patients don’t complete enough of their course of drugs to cure them, keeping levels of TB unnecessarily high. In an effort to alleviate this problem the World Health Organisation recommends that a doctor observes patients taking their medicine each day. Unfortunately, this means daily trips to a health care centre, which are inconvenient for patients, and a burden on already stretched health resources. Frustrated with this conventional and time-consuming approach, Dr David Green, a GP from Cape Town, pioneered an innovative solution to the problem. He investigated the reasons why people were not taking their medication, and discovered that in many cases they simply forgot. He thought up the idea of sending his
patients text messages each day, reminding them to take their medication, in this case the TB drug Rifafol. Initially he used the simple message, “Take your Rifafol now,” but after feedback from his patients, progressed to messages that combined the medication reminder with disease information, lifestyle tips, general knowledge and even the occasional joke. The scheme was a tremendous success. The 32 patients initially enrolled have reached the end of their six month course of medication. All completed the full course and all but one are free from TB. A further 70 patients are taking part in the study and are showing equally promising results. When I asked Dr Green why he believed that the scheme was so successful, he said: “It is based on good science with respect to why people don’t take their medicines. It is very simple, low cost and uses a device [the mobile phone] that is popular and readily available. All that and hard work and passion!” Encouraged by his success, Dr Green has gone on to provide a similar service for patients suffering from HIV, high blood pressure, arthritis, and diabetes. Forgetting to take medication regularly is also a significant problem here in the UK. As well as being detrimental to the patient, it is enormously costly to health care providers. According to some figures, the NHS spends a staggering 4% of its budget on medication that is effectively wasted by not being taken as prescribed. Dr
Ron Neville, a GP from Dundee, has taken advantage of the fact that text messages are particularly popular amongst young people to pilot a scheme to help teenagers manage their asthma, a disease which affects 15% of under 18s and can be controlled reasonably well with regular medication through an inhaler. Dr Neville decided to use a virtual friend called Max to remind patients via daily text messages to use their inhaler. Thirty teenagers took part in the study,
patients don’t complete enough of their course of drugs to cure them
receiving reminders such as,“Bonjour, c’est Max. Hav U taken Ur inhaler yet?” Like the Cape Town study, they could also receive lifestyle messages about sport, celebrity gossip and horoscopes, as well as health advice on dealing with asthma.The study, reported in the British Medical Journal, showed very positive results, with inhaler use improving considerably. As Dr Neville explains,“We tried to make the disease and its treatment comply with the patient, not the other way around.” Both studies have attracted considerable interest from groups worldwide. Indeed, groups in Spain and Korea have recently published results of trials using text messages for the management of diabetes and as reminders to attend hepatitis vaccination sessions. However, as Dr Green warns, “A substantial effort is needed in setting up and maintaining such schemes.” His company, On-Cue, have tried supplying reminders to other countries, but found that they were disappointingly unsuccessful, probably due to the lack of personal attention and drive required to keep the system going. As Dr Green recalls,there were times at the beginning when the system would crash and he became the system, sitting at his desk sending the messages manually every half hour, day and night! Despite the teething problems, it does seem that text message medication reminders could prove an innovative and successful way for health services to improve patient compliance. So next time you hear that familiar beep beep of a text message, spare a thought for those for whom that message could mean much more than you might imagine.
This article was entered into The Daily Telegraph BASF Awards and is reproduced here with kind permission of The Daily Telegraph
Katherine Borthwick was a PhD student and postdoc in the Cambridge Institute for Medical Research, and has recently taken up a postdoc position at Manchester University
We want your science writing! This year the MAYS editors are welcoming submissions for poetry, prose and graphic literature. We hope to publish a broad range of writing, both creative and non-fiction. For twelve years the MAYS has published the best student writing from Oxford and Cambridge. It is sold across the country and distributed to literary agents and industry professionals. Deadline for submissions: 30 January 2005
We are also seeking an arresting cover design and innovative ideas about the bookâ€™s overall presentation. Application deadline for publication designer: 24 January 2005
MAYS 13 email@example.com www.varsity.co.uk
Nature’s Motor: Putting a Spanner in the Works
the enzyme is reminiscent of manmade motors … analogous to a waterwheel
Nature’s Motor: ATP Synthase
ATP synthase uses rotation of its parts to produce ATP. Rotation is not a favourite motion in living organisms: there is no animal with wheels, no bird with a propeller and no fish with a screw! Remarkably, atomic level pictures show how the enzyme is reminiscent of manmade motors, and strong evidence supports a mechanism analogous to a waterwheel, which harnesses the energy of flowing water to drive a shaft.
Although ATP synthase normally resides in the mitochondria, it is becoming increasingly evident that this enzyme can be found elsewhere within cells, playing quite a different role. Recently, ATP synthase has been identified on the surface of cells that form blood vessels. It has been suggested that it assists in energy production, enabling these cells to grow and proliferate creating new blood vessels.The formation of new blood vessels,
with fatal consequences. How might this be related to ATP synthase? Without oxygen, respiration cannot occur in the mitochondria.Therefore, once tissues are oxygen starved, the imbalance of protons collapses and the production of ATP ceases. Worse still, ATP synthase starts to run backwards, breaking down ATP. Most cells typically have no more than
In each and every one of the billions of cells in the body there are thousands of copies of a biological motor 200,000 times smaller than a pinhead, an enzyme complex called ATP synthase. This motor rotates surprisingly fast (approximately 6,000 revolutions per minute!) and is essential for life. However, research at Professor Sir John Walker’s laboratory suggests that disrupting this tiny machine might be a way to kill cancer cells, lower cholesterol levels and reduce the damage caused by heart attacks and strokes. ATP synthase is normally found within cellular compartments known as mitochondria, which burn molecules derived from carbohydrates and fats in food using the oxygen we breathe. This process, known as molecular respiration, releases energy, which is used to create an imbalance of protons (positively charged hydrogen atoms, H+) across the mitochondrial membrane in which ATP synthase is embedded.This is analogous to the imbalance of water across a dam. ATP synthase uses the downhill flow of protons from one side of the membrane to make the energy currency of biology, a small molecule called adenosine triphosphate (ATP). ATP is then distributed throughout the cell and used to drive the many fundamental processes that define life.The production of ATP by ATP synthase is the most prevalent chemical reaction in the biological world and this motor is one of the most abundant proteins on earth, found in almost all organisms from bacteria to plants and mammals.
termed angiogenesis, is a vital part of wound healing, but it is also required for tumour growth.All cells, including cancer cells, require a supply of blood vessels for oxygen and nourishment. Without this supply network, a tumour cannot grow beyond a certain size and is unable to migrate to other locations around the body to create secondary tumours. Disrupting this enzyme on the surface of these cells could conceivably slow or even halt tumour growth. Meanwhile, problems can still arise in the mitochondria. Strokes and heart attacks may be caused by a lack of blood flow to the brain and heart respectively, which starves parts of these organs of oxygen, leading to irreversible damage. As a result, brain and heart cells die, often
Jonathan Gledhill reports on why we may want to interfere with ATP synthase, the motor producing our cellular energy
drugs targeting ATP synthase might bring surprising benefits
two minutes supply of ATP and so this breakdown must be prevented, a role performed by its natural inhibitor protein IF1. IF1 is a protein that acts as a ‘spanner in the works’, preventing rotation and breakdown of ATP.This protein, therefore, helps to limit the loss of valuable ATP when tissues are deprived of oxygen. Perhaps other molecules can be designed to specifically prevent this breakdown of ATP, and also to help slow tumour growth in cancers. ATP synthase has also been found on the surface of liver cells, where it is believed to facilitate the uptake of cholesterol by breaking down ATP. Cholesterol that is taken up by the liver is broken down and excreted, and ATP synthase appears to play a role in maintaining normal cholesterol levels in the blood. Excessive intake of fatty foods is wellknown to lead to elevated cholesterol levels and subsequently, a greater risk of heart disease. Stimulating this enzyme in the liver, perhaps using enhancer molecules, may help to maintain lower cholesterol levels. In another interesting development, this molecular motor has been used to power nanomechanical devices and also forced to rotate using external magnets. In addition, a switch has been successfully engineered into an ATP synthase from bacteria, allowing chemical control of the motor.These critical steps are bringing us closer to the realisation of biomolecular motor powered structures. The intricate workings of this incredible machine need to be unravelled before any biotechnological applications can be implemented. Jonathan Gledhill is a PhD student in the MRC-Dunn Human Nutrition Unit
What Children Leave Behind Joanna Maldonado-Saldivia investigates the long lasting effects of pregnancy
male DNA was present in six of the women, including one who had her last child, a boy, 27 years before the test
Nelson examined female patients with scleroderma, a disease characterised by chronic inflammation of the skin that advances to attack the internal organs. The symptoms of scleroderma resemble those of graft-versus-host disease, a complication arising after bone marrow transplants, in which the immune cells from the donor attack the recipient’s organs. Scleroderma most commonly affects women after their childbearing years, and Nelson discovered that the patients carried up to 30 times as many foetal cells in their blood as healthy
women.This suggested that scleroderma could in fact arise from an immune reaction to the foetal cells. The term microchimaerism, after the mythical Greek creature chimaera (consisting of the head of a lion, the body of a goat and the tail of a serpent), has been adopted to refer to the persistence of foreign cells in the body. Microchimaerism is closely involved with several auto-immune diseases such as scleroderma. Auto-immune diseases related to microchimaerism can occur in the child as well as in the mother, albeit to a lesser extent. In all cases, there is a strong
a mother suffering from hepatitis C was found to be carrying male foetal cells in her recovering liver
correlation between the severity of the auto-immune disease and the number of foreign cells the patient is carrying. How these cells succeed in escaping detection and elimination by the immune system is a more complicated question. Our body recognises ‘self ’ from ‘nonself ’ via a combination of genes known collectively as the major histocompatibility complex (MHC). Each individual carries two versions of each gene, creating a great diversity among individuals, rather like an immune fingerprint. When cells from the immune system come across others with a different MHC, they tag the invading cells for destruction. However, in scleroderma patients, the foetal and maternal cells are compatible at the level of one gene, DRB1, thus the foetal cells are not efficiently recognised and may remain in the circulation for a prolonged period. It is not known whether microchimaerism is a direct cause or a by-product of auto-immune diseases. Bianchi, now a professor at Tufts University School of Medicine in Boston, is focusing on the healing potential of foetal cells. Her team examined female mice which were past their breeding age and had suffered from
severe liver injury. The relative level of male foetal cells in the liver increased dramatically after injury, suggesting that the invading cells had been ‘recruited’ to help with the healing process. This correlates with an observation made in humans, where a mother suffering from hepatitis C was found to be carrying male foetal cells in her recovering liver. Bianchi’s team is now seeking to demonstrate that the increased presence of foetal cells in injured organs responds to a need for new cells to repair the damaged tissues. Rather than disease causing agents, she suggests that the foetal cells may act as stem cells. Whether foetal cells cause the mother more harm than benefit is not yet clear, nor do we know if they play an active role in women’s health or are simply innocent bystanders. Perhaps, by uncovering the mechanisms of action of these long lasting cells, scientists can shift the balance in favour of women’s well-being. This article was entered into The Daily Telegraph BASF awards and is reproduced here with kind permission of The Daily Telegraph
Joanna Maldonado-Saldivia recently finished her PhD in the Gurdon Institute of Cancer and Developmental Biology
In 1995 Dr Diana Bianchi was trying to develop new non-invasive methods of prenatal diagnosis. She and her colleagues at the Children’s Hospital in Boston examined blood samples from 32 pregnant women and tested for the presence of cells with a Y chromosome, a good indicator that the women were carrying a male foetus. Bianchi found male cells in 17 of the patients, but when she compared her results with those of the amniocenteses, she noticed that only 13 of the women were actually pregnant with boys. The other four women carrying cells with a Y chromosome had all been pregnant before: two of them had given birth to sons and the other two had had terminations. Bianchi then went on to analyse blood samples from eight non-pregnant mothers with sons.To her surprise, male DNA was present in six of the women, including one who had her last child, a boy, 27 years before the test. Although the presence of foetal cells in the maternal circulation during pregnancy is a phenomenon documented as far back as 1969, the persistence of these foetal cells years, even decades, after pregnancy was a relatively novel concept. Soon after the publication of Bianchi’s findings, Dr Lee Nelson from the Fred Hutchinson Cancer Research Center in Seattle published a report on the association between enduring foetal cells and the incidence of certain auto-immune diseases in the mother. It had long been known that women are more susceptible to this type of disease than men, and these new findings offered a possible explanation for this phenomenon.
On the Cover
All in the Mind The three hundred occupants of the Babraham Institute conduct their biomedical research in surroundings that are a little out of the ordinary: a 19th century stately home in a small village just to the south of Cambridge. There I met Paul Cuddon, a final year PhD student who is completing his studies under Dr Martin Bootman at the worldrenowned Laboratory of Molecular Signalling. With the help of Dr Simon Walker, the group’s imaging specialist, Cuddon has taken photographs of neurons at the extraordinary level of detail seen on the front cover. These images allowed him to visualise the fine level of interaction between two of the principal cell types of the brain, the neuron and the astrocyte.
Calcium is essential for the normal function of a wealth of bodily processes
As Cuddon explained to me, the photograph featured on the front cover shows neurons in green, and their nuclei – just 10 micrometres in diameter – in blue. The neurons communicate with each other both via tiny fibres called neurites and larger, one micrometre diameter axons that lead away from the cell nucleus. The red wool-like structures seen in the photograph are astrocytes, supportive cells that provide neurons with vital nutrients and oversee the formation of neuron-neuron connections. Cuddon has been examining the role of calcium ions in the development of hippocampal neurons, which are necessary for learning and memory consolidation in the brain. Calcium is essential for the normal function of a wealth of bodily processes, including muscle contraction, bone structure, fertilisation, and cell
communication. It is not surprising then, that these ions also play a critical part in neuronal development by controlling the physical growth of embryonic cells. However, measuring ionic fluctuations in intact brains is not easy. So instead, Cuddon cultured neurons on glass coverslips at low and high densities, both with and without the supporting astrocytes. Such models of the brain then allowed him to compare the development of neuronal networks with neurons grown in isolation. Mature high density cultures best represent the brain cells’ native environment, and after two weeks, the cultured cells begin to exhibit synchronised oscillations of intracellular calcium. Cuddon monitored these changes by applying a calcium sensitive dye, which makes changes in intracellular calcium visible under a microscope. So how were his impressive photographs created? Cuddon explains that neurons and astrocytes were labelled with different primary antibodies, via a technique known as immunofluorescence. Each antibody binds only to a specific protein expressed by a given type of cell, or part of a cell, such as the
Side view of a neuron and its nucleus (blue)
nucleus. The neurons are then washed with different fluorescently tagged, secondary antibodies that bind uniquely to each primary antibody. Finally, the cells were illuminated with three different colours from a laser. Since each secondary antibody only emits light at a distinct wavelength, one is able to image a specific type of cell, or part of a cell, with each of the three laser colours. A state-of-the-art computer combines the separate red, green and blue images to produce a photograph of the astrocytes, neurons and nuclei, which appear in red, green and blue respectively. It is even possible to focus the lasers at different depths through the cells, letting Cuddon and Walker build up threedimensional movies of the neurons.
Paul Cuddon of the Babraham Institute tells Jonathan Zwart about the neurons pictured on the cover
Paul Cuddon at work
Cuddon’s photographs allow him to determine the exact densities of neurons and astrocytes on each glass coverslip.This has led to a number of important discoveries. Most significantly, the longer the high density neurons were kept in culture, the more advanced their calcium signalling pathways became. Although the lower density neurons survived damaging prolonged stimulation better than their high density counterparts of the same age, they did not develop the same normal intracellular signalling machinery. This means that a high density is essential for a new neuron to develop correctly. The red wool is also important: the astrocytes helped the low density neurons to live longer and maintained the health of the adult neurons. Once Cuddon’s work is published, he will leave the Babraham to move to the Cambridge Institute for Medical Research, where he hopes to carry out more clinical research into therapies for neurodegenerative diseases, such as Alzheimer’s, Huntington’s and Parkinson’s. It is in this that Cuddon’s current research into the role of calcium ions in the development of hippocampal neurons may prove vital. Perhaps, by manipulating neuronal development, treatment for these so far incurable diseases may even become possible! www.babraham.ac.uk Jonathan Zwart is a PhD student in the Cavendish Laboratory
A D ay I n t h e L i f e o f . . .
A Forensic Scientist Nerissa Hannink talks to Helen Butler about her work with the Forensic Science Service
What initially interested you in becoming a forensic scientist? During my O-levels, my dad fitted the phone system in a FSS lab, and brought me home their leaflet because I was interested in biology and chemistry. I went on to do a Natural Sciences degree at Girton College, but wasn’t accepted for my first FSS application. Instead, I worked as a research assistant in molecular biology, investigating water contamination for 18 months.Then, the London (FSS) lab advertised for positions, I applied and began my career with the service. Was that the traditional entry route? Yes, although some come into the service with just A-levels, and many people do the forensic science degree at the University of East Anglia. Most people have chemistry or biology degrees, and some have PhDs. A degree is required to become a reporting officer (RO). How many people work directly with you in the Huntingdon lab? There are 60 assistants in the Evidence Recovery Unit (literally, gathering evidence), and 40-50 reporting officers, who are usually the only people who present findings of evidence collection in court.We are split into four teams of recovery and reporting units. We always work with the same team of reporting officers, and the teams have a mix of specialists in the various evidence types, mine being fibres analysis and blood work. Do you have a typical day? No, it depends on the caseload. For example, a few days ago I received a couple of case files, so first I spent some time getting it clear in my mind what the RO wanted me to look for. I then collected the items of evidence from our store.The first case was an armed robbery during which two people had tried to rob a pizzeria. A balaclava had been found nearby, so I had to search it for hairs, blood and saliva. I checked for saliva with a test that reacts with amylase (an enzyme) to give a colour
The Forensic Science Service (FSS) aims to contribute to crime detection, conviction of criminals and exoneration of the innocent. In 2003, the FSS dealt with 140,000 cases and continued to run a research facility responsible for many forensic science breakthroughs and innovations, particularly in the field of DNA technology. Helen Butler works as an assistant forensic scientist at their Huntingdon lab, one of seven laboratories across England. marker.We had a reaction, so I extracted the cellular material and sent it off for DNA analysis.The second case was evidence from a fight between two males, and I had to look for blood on the knives found, but I haven’t had the results yet. ROs will sometimes tell you about the findings, but mostly we don’t get much feedback on the results of our tests.When you work on a big case though, you may hear the outcome from the press. Are there any particular skills that you think are definitely needed for a career in forensic science, like patience or attention to detail? For fibres you certainly need a lot of patience. If you think about how many fibres and debris you could get off a car seat, you can spend days searching them with a low power microscope. How are you trained? We are trained in house. With fibres for example, I trained for six to eight weeks.We have mock cases, and we don’t do any work on real cases until we have proved we are competent. Even then, we have five to 10 cases that are mentored. Is it stressful because you know that your work will go to court? I like to think there is purpose to my work. I find it a plus to have cases where you might find the evidence to place someone at a crime scene. When you see case details, how do you cope with what has happened to that person? I don’t think you’d come into this job if you couldn’t step back from it. There are some people who just deal with chemistry cases and don’t think they can cope with the blood or sexual assault cases. You do have to switch off a bit. What would you say the biggest benefits and downsides of your job are? Benefits are that it has a meaning to me; it’s why I wanted to do the job. I like that it’s hands on, I like the chemistry side of it and I have the patience to do the fibres as I enjoy the challenge. Downsides are that many people here are on shift work, so we
can get more people into the lab space. They work one weekend in four, and nineand-a-quarter hour days, which is a long time to be concentrating. But I work part time now, so it’s not as bad for me. Are you or anyone in your lab involved in researching new techniques? We don’t tend to do research here,but we sometimes have students for a few months. One was looking at scratching and how long evidence remains under fingernails, while another worked on fibres remaining in hair after contact. That is the kind of thing presented at forensic science conferences. Who decides which cases you work on? The cases go to the ROs and it depends whether it’s a reporting officer in my team, and whether I have the specialist training to work on some or all the aspects of the case. Who goes to a crime scene? It depends how serious the crime is. Usually it is dealt with by the police’s own scene of crime officers.They respond to the majority of cases: taping fibres, point of entry, footprints. Then if the police want some more specialist knowledge they will call in a RO. Sometimes a RO will take an assistant if it’s a big scene. Do you think forensic science TV shows increase interest in your career? It’s always been popular.When I applied in London there weren’t many programmes around, and I think there were 800 applicants for 12 jobs. It is one of those jobs that people think,“Oh wow!” but it is perhaps a little more routine than people expect and there is as much paperwork as anywhere else. It’s certainly not like Amanda Burton! If you would like to find out more about working for the Forensic Science Service, visit the careers section of the FFS website at www.forensic.gov.uk Nerissa Hannink is a postdoc in the Department of Plant Sciences
Away from the Bench
At Home With the Ashaninka It had been one of those days; 6am start and straight to the lab after breakfast. I had hardly moved since, just identified and recorded frogs found the night before. It wasn’t the usual Cambridge lab, all white coats and humming computers. My bench was bamboo lashed together with vines, and a nearby tree provided hooks for my equipment. Oh, and the nearest phone, computer or power socket was a day’s journey away. The lower montane forest of central Peru is not the kind of place you expect regular mail, so I was surprised when a letter arrived from the community a few hours away. It was from Mago, a frog specialist, who had worked with us for several weeks in the field before returning with our samples to Lima’s Natural History Museum. One species interested her particularly, a cadaverous looking tree frog as big as your palm, found on one of our late night sojourns up the river. This species was found perched on an overhanging branch, calling to find a mate. Although
the nearest phone, computer or power socket was a day’s journey away
Arriving at the Ashaninka community of Coriteni Tarso
ic species and isolated populations might be expected. Its tortuous terrain has protected it from much human impact, and allowed the native Ashaninka people to live undisturbed. But, the last 25 years have seen many changes to the region, including an influx of settlers, cocaine growing and terrorist activity.Thousands of Ashaninka lost their lives at the hands of Sendero Luminoso, the Shining Path terrorist organisation. Now, thanks to the help of the Asociacion para la Conservacion del Patrimonio del Cutivireni (ACPC), an organisation dedicated to the development and aid of the Ashaninka, much of the violence is over. However, a range of problems still remain. Ranking high amongst these is how the Ashaninka should develop their forest.To pay for the improvements people want, such as primary education, basic health care and electricity, they have few options.They can log their forests or grow drugs. However,ACPC want them to consider a third way.The rugged forest, and the Ashaninka communities themselves, provide a truly unique location for any naturalist or adventure traveller. Ecotourism could provide a more sustainable income for these people. Our expedition planned to collect the first biological data of any kind from the area, concentrating on potential ecotourism sites which would feel the brunt of any development. We collected information about the frog populations, as frogs,
similar to a relatively common species, Mago told us that on closer inspection she believed that this was an entirely different genus, and most likely a new species to science! This was, without a doubt, one of the highlights of the expedition I took part in last summer. Like many biology students, I have always held a secret desire to discover a new species, so to be part of that team was a dream realised. However, our expedition was by no means a glory hunt for new species. We were working in the Cordillera de Vilcabamba, a remote mountain range jutting out from the Andes into the upper Amazon basin. The 5000 m peaks form a distinct island habitat where many endem-
Michael FitzPatrick shares his memories from an expedition in Peru
ecotourism could provide a more sustainable income
The expedition was the most challenging and rewarding experience I have ever had.We organised the expedition through CUEX, the Cambridge University Expeditions Society, from whom we received much valuable advice. I now realise that you don’t have to be Steve Irwin or Ray Mears, or run marathons before breakfast to carry out such a trip, just be willing to give it a go and not give up when your plans have to change, as they surely will! Tropical rainforests and their people, like the Ashaninka, are under threat. Students can make a real difference, carrying out real scientific work themselves, that no one else will do. I would like to thank our patrons and supporters, without whose help this project would not have been possible. For more information about the project, or links to sites about the Ashaninka people, visit www.srcf.ucam.org/ashaninka
A tree frog of the genus Osteocephalus – a new species?
with their obligate aquatic development and porous skin, have been shown to be sensitive to small environmental changes. One great part of the project was the opportunity to live and work amongst the Ashaninka people. We got to know our guides well, to understand their deep knowledge of the forest, and to appreciate their amazing practical skills with machetes and natural materials. Yet, most have had only very basic schooling, and have little knowledge of the world outside Peru.They were fascinated by our pictures of family and friends, and by the postcards of Cambridge colleges, but particularly the fact that the forests of England do not have monkeys! We also spent a couple of enjoyable days teaching some basic biology in the community schools and showing the children the frogs we had found.
Michael FitzPatrick is a third year Natural Scientist specialising in Zoology
I n i t i at i ve s
The Virtual Department
Tom Walters, Paul Cuddon, Jonathan Zwart
Mark Woodbridge discusses how computational biology is inspiring a new era of collaboration
The recent establishment of a ‘virtual department’ at Cambridge University, uniting researchers in biology, medicine, physics and engineering, is recognition of an emerging discipline. The Cambridge Computational Biology Institute (CCBI) is co-ordinating efforts across almost all scientific departments, with the involvement of no fewer than 16 professors representing an impressively wide spectrum of knowledge and experience. This is cooperation on an unprecedented scale, but what is the motivation for such initiatives, and can they help to counter overspecialisation in scientific research? There are countless examples emphasizing the importance of cross-discipline collaboration for scientific progress. Any description of Watson and Crick’s discovery of the structure of DNA should include the fact that neither Nobel Prize winner was a qualified crystallographer. In practice, their
Establishing the human genome has required considerable computational resources
respective backgrounds in zoology and physics no doubt provided important inspiration in making their breakthrough. In the 50 years since this revolutionary insight, biology, and especially genetics, has attracted researchers from hugely varied backgrounds. Recent challenges have led to the involvement of individuals from independent and sometimes unexpected fields. Hence, the arrival of statisticians,
computer scientists, and even physicists in traditionally ‘wet-lab’ dominated environments. In reality, if specialists are to work in unison they need to be co-ordinated: this takes vision and a broad knowledge base. Sydney Brenner, another Nobel Prize winner in genetics, raised some relevant issues during the recent Cambridge-MIT Institute Distinguished Lecture. Whilst apparently bemoaning the dominance of research valuation by journal publication, which can result in overspecialisation, he was optimistic about computational biology. Brenner’s view that all biologists will have to conduct computer simulated experiments in the future, was accompanied by advice to all aspiring bioinformaticians to “go and work in a lab”.This stressed the advantages of being a generalist and embracing varied approaches to research. So are there any examples of such collaboration and generalisation? The most obvious example in biology is that of genome analysis, including the much heralded endeavours of the Human Genome Project. Establishing the complete human genomic DNA sequence has required considerable computational resources, even though the sequence itself, at about three gigabytes, is not huge by modern standards. However, decoding the sequence to discover exactly what it represents is a much more complicated task. Fortunately, help is at hand through a variety of computational approaches. The location of genes can be roughly established using statistical methods. Cross-referencing of experimental results with the wealth of existing literature can be performed using techniques from computational linguistics. Further examples are easy to find, but the prevalent theme is that we have more analytical techniques and resulting experimental data than we can manually interpret and organise. Vital as this experimental data
obviously is, recognising patterns and trends appears to be highly significant in deciphering the genomic code, therefore, the involvement of computational specialists is essential. The CCBI has been active since the start of this academic year with funding from the four science schools of the University.The
individuals will increasingly need to turn to experts in other disciplines in order to face challenges in their own fields
institute is committed to encouraging and facilitating new cross-Cambridge research projects, bringing together individuals from wide-ranging fields of expertise.The CCBI has a mandate to develop relevant academic courses, promote industrial liaisons and organise workshops to advance the exchange of ideas between departments. The institute is running a new MPhil in computational biology, an 11-month course providing suitable preparation for a PhD or a career in industry, and modules in computational biology are now being offered to undergraduate engineers. The success of these initiatives will take time to quantify, but if Brenner is correct then individuals will increasingly need to turn to experts in other disciplines in order to face challenges in their own fields. Hopefully, thanks to the CCBI and similar ventures, this may prove less of a novelty for those in biology than in many other disciplines. www.ccbi.cam.ac.uk Mark Woodbridge is a software developer in the Department of Genetics
Einstein’s Miraculous Year Born in Ulm, Germany on 14 March 1879, Einstein was fascinated by the mysteries of nature from a young age. However, he resented the rote learning that dominated his school curriculum, preferring instead to construct and solve his own simple algebraic problems from scratch. Despite his disdain for formalised schooling, his aptitude for mathematics was quickly recognised by his teachers and in 1896 won him a place at the prestigious Swiss Federal Polytechnic Institute in Zürich to study physics. He was not particularly diligent when it came to attending lectures, leading one of his tutors to describe him as “a lazy dog…[who] never bothered about mathematics at all.” Unfortunately, this assessment of the young Einstein was shared by other members of the university staff and meant that when he graduated in 1900, he was unable to secure a job at the Institute as he had intended. Einstein spent several years teaching physics and maths here and there, before landing a position at the Swiss Patent Office in Bern after some string-pulling by a former school friend.The job was perfect for Einstein: not being that much of a challenge for him, it provided ample time to think about physics! It was here at the patent office that he was to develop and publish some of his most famous ideas.
I have no special talents. I am only passionately curious. - Albert Einstein
Einstein’s annus mirabilis arrived in 1905 when, at the age of just 26 and still with only an undergraduate degree in physics to his name, he published a series of papers that would revolutionise the field of physics. He would later say of this time that it was as if “a storm broke loose in my mind.” Certainly, Einstein’s activities this year were characterised by a furious productivity: the three key papers which were to make this young scientist’s name were all published within just fifteen weeks.
Emily Tweed takes a look at the ideas that made Albert Einstein an international icon
The first of these papers gave a new account of the nature of light, an account able to explain a tricky physical puzzle, called the photoelectric effect, that had been troubling physicists for years. In this paper, Einstein proposed that light was not a wave as traditionally thought, but instead consisted of tiny, discrete packets of energy called photons.This paper was to form the basis of the modern discipline of quantum mechanics and to win Einstein the Nobel Prize for physics in 1921. The second publication detailed Einstein’s explanation of the phenomenon known as Brownian motion: the random and jerky movement of smoke particles in air, or pollen grains in water. Einstein showed that this motion was due to the particles being constantly bombarded from all sides by other moving particles, and in doing so convinced many scientists of the existence of atoms and molecules. While the atomic theory of matter is something we take for granted nowadays, before Einstein’s paper this theory lacked experimental evidence and was doubted by a significant section of the scientific community. The third paper produced by Einstein in 1905 was perhaps the most revolutionary of all, containing the theory of special relativity. So what was so special about special relativity? Relativity as a concept originated with Galileo, who recognised that all motion is relative and cannot be detected without reference to an outside point. For example, if you
were travelling on an aeroplane you would not be able to tell whether or not the aeroplane was moving without looking outside. Einstein built on these ideas to show that the laws of physics and the speed of light are universal constants, and thus that space and time are not absolute as previously thought. This innocuous-seeming theory has some radical and far-fetched implications. For instance, the faster you travel relative to the speed of light, the more time slows down! However, as Einstein himself once said, “If at first an idea is not absurd, then there is no hope for it.” Special relativity was also to provide the foundation for another of the ground-breaking breakthroughs that Einstein made this year: the theory of mass-energy equivalence, better known as E=mc2. For an explanation of the significance of this legendary formula, see Andy Hodge’s article, E = mc2, on the next page.
The most incomprehensible fact about the universe is that it is comprehensible - Albert Einstein
What is especially amazing about Einstein’s work in 1905 is that all these discoveries were made while he was working alone at the patent office, isolated from other physicists and from the
What Does it All Mean?
But as his friend, the philosopher Bertrand Russell, once said, “Everyone knows that Einstein did something astounding, but very few people know exactly what it was he did.” In celebration of Einstein Year, we look at Einstein’s life and legacy, as well as the physics behind his famous equation, E = mc2.
collaborative experience that underlies most scientific breakthroughs. Some have even suggested that this detachment from any kind of scientific community was necessary for Einstein to be able to conceive and develop such unorthodox theories. One thing is for sure: Einstein went on to become one of the most famous scientists who has ever lived, pioneering the general theory of relativity and beginning the quest for a ‘unifying theory’ to integrate all of physics, a quest that physicists are still pursuing today. Moreover, as an active campaigner for social justice and nuclear disarmament, his impact extended far beyond physics. Adorning a million posters, T-shirts and coffee mugs, he captured the public imagination in a way few other icons have; he embodied (and perhaps still does) the popular perception of what it means to be a genius. But it was in that miraculous year of 1905 that the seeds for Einstein’s extraordinary legacy were sown with three revolutionary papers overturning contemporary assumptions about the way in which the universe works, making the rest of the world sit up and take notice of this brilliant young patent clerk. For more information on Einstein and Einstein Year 2005 go to www.einsteinyear.org Emily Tweed is a second year Natural Scientist
A Universal Speed Limit One important result of the special theory of relativity is that the faster you move relative to a stationary observer, the more mass you acquire. For example, if you and a friend weighed the same at rest on the surface of the Earth and then one of you went running across that surface, he or she would weigh more than the person standing still! The ‘m’ in the equation represents the mass you have whilst travelling at a particular speed relative to the observer.The application of this principle has some interesting implications.As an object approaches the speed of light, its mass increases at a faster and faster rate so that if it were to reach the speed of light, its mass would be infinite. Since force is directly proportional to mass, the force needed to accelerate it would have to be infinite too. This explains why it is impossible for an object to reach the speed of light: infinite forces are a bit hard to come by!
Mass-Energy Equivalence What the equation tells us is that energy and mass are equivalent.This raises the intriguing possibility that energy could be converted into mass and vice versa. As it turns out, a very modest mass can be converted into a huge amount of energy.This is the science behind the process of nuclear fission, in which atoms are split under controlled conditions in order to generate energy.The source of this energy is the mass difference between the heavier raw materials and the lighter products of decay.
Einstein and the Bomb More famous, however, is the splitting of atoms under uncontrolled conditions: the reaction responsible for the devastating effects of the atomic bomb.The use of the bomb on Hiroshima and Nagasaki marked the end of World War II, resulting in huge loss of life and changing the face of modern warfare forever. Einstein subsequently declared himself a pacifist, remarking poignantly:“If I’d have known they were going to do this, I would have become a shoemaker.”
Andy Hodges reveals all you need to know about the mysterious E=mc2
The unkempt white hair, the bushy moustache, the slightly otherworldly expression: even 50 years after his death, Albert Einstein is an instantly recognisable figure around the world. And with 2005 designated Einstein Year to commemorate the centenary of his annus mirabilis in which he published three of his most influential papers, Einstein and his achievements are back in the public eye once more.
E=mc2: Einstein first published the equation in a 1905 paper entitled Does the Inertia of a Body Depend Upon Its Energy Content? The ‘E’ stands for energy, the ‘m’ for mass and the ‘c’ for the speed of light in a vacuum, the fastest speed in the universe at which particles can travel. Einstein developed the equation from the theory of special relativity that he had devised earlier that year.
The Cutting Edge Particle accelerators, some of the most important tools of modern physics, also make use of the principle of mass-energy equivalence that E=mc2 embodies.Within these huge machines, subatomic particles are crashed together at tremendous speeds, often of the order of half the speed of light. Relativistic effects come into play here, as particles travelling at this speed have more mass than when they are travelling at low speed, so when they collide with other particles they impact with more energy. One extreme example of this is the collision of such particles with their ‘anti-particle’: when this occurs, all of the mass-energy in the particles is converted into heat and light energy! Such an efficient mode of energy production may power our cities in the future – if we are able to procure an anti-matter source.
The Sky at Night E=mc2 has not only influenced how we think about abstract scientific concepts like mass, energy, space and time, but also provides a physical explanation for the beauty of a starlit night or sunny summer’s day. Inside the centre of stars, a process called nuclear fusion occurs in which the nuclei of several hydrogen atoms fuse together to make heavier helium atoms. Each helium atom formed has a lower mass than all of the hydrogen atoms from which it is formed put together.This difference in mass is converted into highly energetic photons (light particles), explaining why stars, including our sun, shine as they do.
Andy Hodges is a third year Natural Scientist specialising in History and Philosophy of Science
Edited by B. Jack Copeland (Oxford University Press, 2004, £14.99). Reviewed by Tom Walters The Essential Turing is a collection of the key writings of Alan Turing and his correspondence with contemporaries, covering computing, logic, philosophy, artificial intelligence and code breaking. Spanning the whole of Turing’s life, the book is broadly chronological, but is interspersed with essays by Copeland. These essays, Artificial Intelligence, Artificial Life, Enigma and Computable Numbers: A Guide, provide a lucid preparation for the writings that follow. This is not a popular science book; the first of Turing’s writings to appear is On Computable Numbers, with an Application to the Entscheidungsproblem, in which he develops what came to be known as the Turing Machine. This paper, like many of those that follow, is heavy on maths, formal logic and number theory. However, there are some less mathematical gems interspersed. History of Hut 8 to December 1941 by Patrick Mahon, a contemporary of Turing’s at Bletchley Park, was declassified only in 1996 and provides a first-hand account of Hut 8’s breaking of naval codes. The rest of the Enigma section is filled with similar primary sources, which would make fasci-
Oxford Univeristy Press
Arts & Reviews
The Essential Turing
nating further reading for anyone gripped by recent popular accounts of the wartime code breaking at Bletchley, including a letter from Turing and his compatriots to Churchill. The final sections, on artificial life and intelligence, deal with Turing’s fascina-
tions during the latter years of his life. The essay, Computing Machinery and Intelligence, expounds the ‘Turing Test’, a game Turing controversially suggested might be the criterion on which machine intelligence should be judged. This book gives any reader with a reasonably strong mathematical background the opportunity to study logic, artificial inelligence and the very fundamentals of computer science in the words of the man who developed them, and to see in action the processes that led to the development of these ideas. However, the more mathematical elements should not frighten off the casual reader, and anyone with an interest in the life of Turing would not be disappointed by the wealth of information surrounding the maths and science that Copeland has woven in. On dipping into a particular section, the reader is likely to be gripped, and to emerge several pages later even more amazed at the man who produced such a wide range of innovative fundamental ideas in such a short life. Tom Walters is a Research Assistant in the Department of Physiology
Big Bang Simon Singh’s book is a history of the evolution of the Big Bang theory, from the earliest mythological attempts to understand the structure of the universe to the model in place by the 1990s. As a biologist with a limited knowledge of physics and cosmology, the topic always seemed rather inaccessible to me. However, following Simon Singh’s clear, concise and intriguing presentation style at the Cambridge Union in November, I was tempted to learn more. Everyone has heard of the Big Bang theory (ironically, a term coined by supporters of the rival Steady State theory, and intended as a criticism), yet most are unclear about where the theory stands with cosmologists today. The book addresses this without avoiding technical detail, managing to make the material accessible to all, including those with little background in science. Each of the five comprehensive chapters is helpfully summarised in an amusing comic style, but do not be tempted to skip the detail if you want to gain a greater understanding. The depth of
By Simon Singh (Fourth Estate, 2004, £20). Reviewed by Rachel Mundy
explanation accompanying the various ideas is perhaps laboured at times, but for those to whom this topic is new, the repetitive style, more commonly used in verbal presentations, helps to consolidate the message. Those familiar with the physics may find the oversimplified detail superfluous. However, the history surrounding the science is in itself fascinating. What’s more, this is a down-to-earth humanistic portrayal of science, the char-
acters involved and the rivalries present in the pursuit of knowledge and discovery. Ultimately, Simon Singh’s book is a clear, but perhaps rather long-winded attempt to present the scientific method in action: how a new theory is suggested, refuted and tested, before being discarded or accepted, and all the drama that this can possess. Rachel Mundy is a second year Natural Scientist
A r t s & R ev i ew s
Soft Machines: Nanotechnology and Life Oxford Univeristy Press
By Richard A. L. Jones (Oxford University Press, 2004, £16.99). Reviewed by Joe Piper
Nanotechnology: what exactly is going on behind the hype? This book successfully outlines the current research on matter from one to 100 nanometres in size (one nanometre is a millionth of a millimetre). It provides a much needed injection of realism into the ‘grey goo’ debate. The author points out how scientists are laughably far from creating evil nanobots, while admitting that they have raised expectations in the competitive search for funding. The main focus of the book is to provide a visualisation of the nanoworld and
the current efforts to understand it.There is a clear introduction to the microscopy needed to observe this world, including an extraordinary image of a motor protein walking along a track. The author describes how soft, random and sticky the surroundings are, with some interesting examples, such as how the viscosity of air limits the smallest flying creature to a tenth of a millimetre. The book also describes the journey from the first ever photograph to the printing of silicon chips, and to the possible future of molecular electronics and cell signalling. There is a great photograph of the world’s smallest silicon guitar, at 12 microns, with fully playable strings that generate radio waves. Fabrication, from control of individual atoms to self-assembly and protein folding, is discussed before moving on to the
construction of nanomotors. The author himself runs a group in Sheffield researching a pH sensitive gel, which swells and contracts to the rhythm of an oscillating pH reaction, for use as a possible motor. The writing is clear, anecdotal and highly readable in a manner reminiscent of Richard Feynman. Although aimed at a general audience, the concepts described are best visualised with some scientific background, and there are several moments when the text cries out for a diagram.The book’s central message is that nanotechnology relies more on biology than conventional engineering. It dwells briefly on the potential dangers of this research, but explains how unlikely nanotechnology is to surpass evolution. Joe Piper is a PhD student in the Department of Chemistry
MSc in Science Communication MSc in Science Media Production These courses are designed to help science and engineering graduates develop the necessary skills and knowledge to switch to media careers. The Science Communication Course is a general preparation while the Science Media Production programme is designed for those who specifically want to go into televsion or radio. Both courses are available full-time over 12 months, and Science Communication can be undertaken part-time over 24 months. For more information contact Paul Wynn Abbott, Science Communication Group Administrator, Room, 313C, Mech. Eng. Building, Imperial College, London, SW7 2AZ. Tel: 020 7594 8753 Fax: 020 7594 8763, email: firstname.lastname@example.org web: www.imperial.ac.uk/sciencecommunication Closing Date: 25 February 2005 Valuing diversity and committed to equality of opportunity
Dr Hypothesis Dr Hypothesis needs your problems! If you have any worries (purely of a scientific nature, obviously) that you would like Dr Hypothesis to answer, then please email him at email@example.com He will award the author of the most intriguing question a £10 book voucher. Unfortunately, Dr Hypothesis cannot promise to publish an answer to every question, but he will do his very best to see that the most fascinating are discussed in the next edition of BlueSci. Dear Dr Hypothesis, Over Christmas I decided to avoid my annoying family, and spent the whole two weeks watching films in my room. Several of these films contained scenes of beheading. The time it took the beheaded person to die seemed to vary considerably, depending on the ego of the actor involved. Could you please tell me how long it actually takes a human to die, following decapitation? Headless Henry DR HYPOTHESIS SAYS: It’s not really known exactly how long it takes brain activity to cease following beheading, because – to my knowledge – no scientifically controlled experiments have been carried out. Anecdotal evidence from executions during the French Revolution suggests that a head could respond up to thirty seconds after being removed from the body. However, this is nothing compared to cockroaches: they are known to survive for up to a week after beheading, ultimately dying from dehydration as they obviously have no way of drinking! http://huah.net/scixf/xbetts.html
Dear Dr Hypothesis, My name is Duncan and I’m an alcoholic. There, I’ve said it. Phew! However, a friend of mine recently told me that red wine could actually be good for you and so, if I were to give up drinking, I could continue drinking only red wine.Why is red wine good for health, and why is it better than white wine? Drunken Duncan DR HYPOTHESIS SAYS: Recent work has shown that wine contains a number of different antioxidative compounds that can help to slow damaging oxidative processes in cells. These compounds are naturally found in grape skin, seeds and stems.There is a higher concentration of antioxidants in red wine because the wine is incubated with the skins for longer during the manufacturing stages. However, it is important to remember that these benefits only occur if wine is consumed at a moderate level, as higher consumption will increase the damage to the liver and brain, outweighing any potential positive effects. If you believe that you already have a problem, Duncan, it would probably be safer for you to stop consuming alcohol altogether and to seek some professional help. www.sanluisobispo.com/mld/sanluisobispotribune/news/special_packages/homefront/7781178.htm www.alcoholics-anonymous.org.uk Dear Dr Hypothesis, I live directly under the flight path of Stansted airport and have recently become concerned about the possibility of my house being hit by a plane as this would cause me considerable distress. What is the scientific basis for the ability of a plane to fly, and are there any situations under which this could fail? Flight Path Fiona DR HYPOTHESIS SAYS: Fiona, Fiona, there’s no need to worry! There is a long-established answer as to why aircraft fly, which is based on the structure of the wing. Air particles moving over the upper surface of a wing or airfoil travel faster than those under it, and it was then discovered by Daniel Bernoulli in the 18th century that this meant there would be an area of lower pressure above the wing.Therefore, there is a net force under the wing to push it upwards. This difference in velocity is generated either by the shape of the wing or by the angle to its movement. While I cannot guarantee that a plane won’t fall on your house, I feel reasonably certain that it would not be due to a failure of the laws of physics. www.grc.nasa.gov/WWW/K12/airplane/wrong1.html
Dear Dr Hypothesis, I have recently been suffering from insomnia brought on, I believe, by the stress of an impending court case – but that’s by the by. As I spend the sleepless nights looking up at the stars (or, more frequently, the clouds), I have often pondered what life would be like without nights and how much more I could get done – if I wasn’t so tired all the time! Could you tell me why the Earth spins in the first place? Sleepless Simon DR HYPOTHESIS SAYS: There are several theories as to why the Earth spins, but it is hard to prove these ideas because of the difficulty of testing them with experiments. My personal favourite is that it is a consequence of the way the Earth was formed. It has been proposed that the solar system arose from a cloud of gas and dust collapsing in on itself but, as it collapsed, it began to swirl in eddies similar to those sometimes observed when water goes down a drain.As one of these swirls gathered matter to itself and formed the Earth, it continued to spin and has continued to this day, as there are no forces in space to stop it. The speed at which the Earth spins at the equator has been calculated to be about 1,000 thousand miles per hour. www.madsci.org
Think you know better than Dr Hypothesis? He challenges you to solve this problem: Can men park cars better than women, and if so, why? Please e-mail him with answers, the best of which will be printed in the next edition.
Closing date for internship applications is 18th February. Apply now!