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FOCUS
The Fight against Cancer
Fat-Busting Immunity . Urban Birdsong . Ebola Biomusic . Suggestive Memory
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Easter 2015 Issue 33
Contents Features 6
Regulars
Running Away from Unwanted Inflammation Kimberly Wiggins explores the anti-inflammatory effects of exercise
8
Defeating Ebola Miha Pipan reviews the current Ebola outbreak and discusses treatment options
10
How Reliable is Your Memory? Ann (Chen) Hascalovitz discusses the authenticity of memories
12
What’s in a Name? Sophie Protheroe explores the life of the famous taxonomist Carl Linnaeus
14
On The Cover News Reviews History
22
Abigail Wood investigates the human impact of leprosy
Science and Art
24
Laura-Nadine Schuhmacher explores the emerging field of biomusic
Behind the Science
26
Jenny Westoby describes the life and career of the physicist and chemist Marie Curie
How Does Nature Deal with Humans?
Pavilion
Ornela De Gasperin explores how animals adapt to cope with human activities
BlueSci celebrates the 25th birthday of the Hubble Space Telescope
FOCUS
3 4 5
Technology
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30
Nathan Smith explores vehicle adaptations for extremely cold environments
The Fight against Cancer BlueSci looks deeper into what causes cancer and how we can beat it
Weird and Wonderful
BlueSci was established in 2004 to provide a student forum for science communication. As the longest running science magazine in Cambridge, BlueSci publishes the best science writing from across the University each term. We combine high quality writing with stunning images to provide fascinating yet accessible science to everyone. But BlueSci does not stop there. At www.bluesci.co.uk, we have extra articles, regular news stories, podcasts and science films to inform and entertain between print issues. Produced entirely by members of the University, the diversity of expertise and talent combine to produce a unique science experience.
President: Abigail Wood .....................................president@bluesci.co.uk Managing Editor: Zaria Gorvett ............... managing-editor@bluesci.co.uk Art Editor: Eliza Wolfson......................................art-editor@bluesci.co.uk Secretary: Robin Lamboll ................................... enquiries@bluesci.co.uk Treasurer: Chris Wan..................................... membership@bluesci.co.uk Film Editor: Shayan Ali ................................................film@bluesci.co.uk Radio: Hinal Tanna and Ann (Chen) Hascalovitz ......... radio@bluesci.co.uk News Editor: Joanna-Marie Howes ..........................news@bluesci.co.uk Web Editor: Nathan Smith ................................web-editor@bluesci.co.uk
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Contents
Issue 33: Easter 2015 Editor: Hilda Mujcic Managing Editor: Zaria Gorvett Second Editors: Ornela Gasperin, Abigail Wood, Joy Thompson, Sarah Smith, Caroline Steel , Amy Danson, Verena Brucklacher-Waldert, Laura Schuhmacher, Samantha Flint, Kimberley Wiggins, Sophie Protheroe, Ana Leitao-Fernandes-Duarte, Chiu Chai Hao, Robin Lamboll, Samiha Shaikh, Camice Revier, Laura NunezMulder, Josh Shutter, Emma Evans, Kirsten Dundas, Felicity Bedford, Sufia Rahman, Suyi Zhang, Shirin Ashraf, Jennifer Harris Copy Editor: Hilda Mujcic News Editor: Joanna-Marie Howes Reviews: Laura Nunez-Mulder, Abigail Wood, Robin Lamboll, Focus Team: Patrick Short, Abigail Wood, Hilda Mujcic, Robin Lamboll, Nathan Smith Weird and Wonderful: Ann Hascalovitz, Nathan Smith, Arporn Wangwiwatsin Production Team: Hilda Mujcic, Robin Lamboll, Eliza Wolfson, Laura Schuhmacher, Sheralyn Loh, Aneesh Aggarwal, Abigail Wood, Jessica Mchugh, Amy Danson, Joanna-Marie Howes, Camilla d’Angelo, Joy Thompson Art Editor: Eliza Wolfson Illustrators: Eliza Wolfson, Angela Ibler, Jessica Mchugh, Alex Hahn Cover Image: Gavin Rutledge
ISSN 1748-6920
Science Is a Battlefield THE AVERAGE LIFE EXPECTANCY has risen sharply in the past 100 years. If you were born in the 1900s, you were not expected to live past the age of 50. Nowadays, newborns could expect to live just over 80 years in the UK. This dramatic increase in life expectancy in the 20th century was accompanied by a shift in the leading causes of death, with infectious diseases being responsible for the vast majority of deaths at the start of the century, whilst heart disease and cancer are now leading the way in westernised countries. In 1971 US President Nixon declared the ‘War on Cancer’ by signing the National Cancer Act, an initiative to boost national cancer research. Extensive progress has been made towards battling cancer in these last few decades. In this issue’s Focus article we zoom into the fight against cancer. We review current treatment options, their limitations, and the future of cancer treatments. Many of the infectious diseases that were once considered a death sentence have been completely eliminated in certain parts of the world or have become easily treatable. However, a few of these are notoriously hard to prevent and control. This is best exemplified by the recent Ebola virus outbreak in West Africa, the most deadly so far. There are currently no proven treatments or vaccines that provide protection against the Ebola virus. In this issue we report on some of the most promising experimental Ebola treatments and vaccines. We also take a closer look at two other infectious diseases that continue to cause a great deal of human suffering: leprosy and malaria. But it’s not all doom and gloom! This BlueSci issue includes articles that cover some highly fascinating and colourful science. We celebrate the 25th birthday of the Hubble Space Telescope with a double-page spread of a breath-taking image taken by the HST. In our Arts and Science section we explore the emerging field of biomusic. We also take a look at how urban noise has influenced animal communication. This and much more! As usual, this BlueSci issue is the result of a joint effort of many writers, editors and other people with a passion for science communication. If you share this passion and would like to contribute to future issues, do not hesitate to get in touch!
Hilda Mujcic Issue 33 Editor THIS WORK is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (unless marked by a ©, in which case the copyright remains with the original rights holder). To view a copy of this license, visit http://creativecommons. org/licenses/by-nc-nd/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA.
2 Editorial
Easter 2015
On the Cover Gavin Rutledge discusses how gene networks can help us understand malaria disease
Easter 2015
clusters, one in the top right and one in the bottom left. Not surprisingly, most of the mouse genes shown in the network are genes related to the immune system. However, the type of genes present in the two clusters is different, with genes involved in innate immunity and T-cell mediated immunity located in the lower cluster. These are genes that are expressed in the early stages of an infection, with innate immunity genes being non-specific defence mechanisms, whilst the T-cells recognise the pathogen and activate the downstream B-cell response. B-cell mediated immunity genes, which are expressed at late stages of infection, after activation by T-cells, are found in the upper cluster of the network. B-cells target the pathogens in a very specific manner, thereby being more effective. The network is therefore giving us a snapshot of the infection, with different parts of the network corresponding to different periods of the infection. Studying gene networks such as this one provides an overview of how a large system like our body changes during the infection. It also provides a framework for conducting further experiments. Using this gene network we can investigate specific interactions between genes, which may elucidate novel host-parasite interactions crucial to disease progression.
KEN DOERR
Around half a million people die from malaria each year
EVERY YEAR, AROUND half a million people die from malaria. Malaria infections range from mild to lethal and can last between a few days to many years depending on the person being infected. Yet, little is known about what underlies this variation. Deepening our understanding of how malaria parasites manage to subvert our immune system may enhance the discovery of new treatments or vaccines. The interactions between the human host and the malaria parasite are likely to be central to the disease outcome and duration. It has been shown that genes involved in host-parasite interactions can be identified by their correlated gene expression. Thus, some genes in the host are only expressed when certain genes from the parasite are expressed at the same time. So, if certain genes are used at the same time in both the host and in the parasite, then those genes (or the proteins that they code for) are likely to be interacting directly or indirectly with one another. Applying this knowledge to malaria disease may enable us to better understand the interactions between the malaria parasite and its host. Members from the Pathogen Genomics group at the local Wellcome Trust Sanger Institute and collaborators from the Infectious Diseases group at the Francis Crick Institute set out to study the relationship between the genes expressed in hosts and parasites in a laboratory setting. Firstly, they grew a malaria parasite inside mice. They then extracted and quantified messenger ribonucleic acid (mRNA) molecules from both the mice and the parasite for 5-12 days post-infection. mRNA molecules are produced when genes are expressed, and because every gene produces a slightly different mRNA molecule, it is possible to identify which genes are being expressed, and at what time. Using this pattern of gene expression changes over the time course of an infection, the researchers were able to statistically determine which genes in the host and the parasite were connected. In order to visualise these genetic associations, they generated a gene network, which is pictured on the cover. This network was created using a network visualisation software that plots objects, in this case genes, as dots and visualises potential genetic interactions through lines connecting the dots. The red dots represent genes from the parasite, whilst the blue dots are genes from the mouse. Genes that are positioned closer to each other in the network are more strongly correlated than genes further away from one another. The image shows how the genes expressed in the parasite and in the mouse are interconnected. From the picture, it is clear that the genes fall into two large
Gavin Rutledge is a PhD student at the Wellcome Trust Sanger Institute The image by Gavin Rutledge was submitted for the 2015 Graduate School of Life Sciences’ Poster and Image competition. The competition was sponsored by Linguamatics and Science Magazine.
On the Cover 3
WIKIPEDIA
News
Check out www.bluesci.org or @BlueSci on Twitter for regular science news and updates
A closer look at earthquakes
Exercise-mimicking hormone
NEW MICROSCOPIC MEASUREMENTS of earthquake behaviour are now possible thanks to researchers at the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory. Most earthquakes occur when tectonic friction builds up in rocks along active faults and is suddenly released in the form of seismic waves. Minerals are deformed by these tectonic forces and so measuring the degree of elastic deformation can provide information on how much strain the minerals are under during an earthquake. Until now, our understanding of these stresses has been based on macroscopic measurements, large enough to be seen by eye. The new approach employs microscopic analysis of rock samples taken from the San Andreas Fault. The technique uses Laue X-ray microdiffraction to look at the strength of the rock in the fault. Co-author Martin Kunz reports the surprising findings that whilst some areas within individual quartz fragments showed no deformation, others were subjected to enormous stresses in excess of 200 million pascals. These stresses are much higher than reported by macroscopic measurements, suggesting that “there are different processes at work at the microscopic and macroscopic scales. Understanding the stress fields under which different types of rock fail will help us better understand what triggers earthquakes”, says Kunz.
discovered
JH
the adverse effects of obesity has been discovered by researchers at the University of Southern California, UCLA and National Institutes of Health. A high-fat diet often results in obesity-related diabetes where cells become insulin resistant. This means that they no longer respond to insulin’s instructions to take in glucose and fatty acids and so these remain in high concentrations in the blood causing adverse health effects. When injected into mice on a high fat-diet, the newly-discovered hormone, MOTS-c, suppressed obesity and acted primarily on muscle tissue, where it restored insulin sensitivity and normalized the cells’ metabolism. MOTS-c is slightly unusual because its DNA comes from mitochondria, not the nucleus like other hormones. As lead author Changhan Lee states, “This discovery sheds new light on mitochondria and positions them as active regulators of metabolism.” Although the team have so far only worked on mice, the same molecular pathways also exist in all mammals, meaning that it could potentially be used to tackle human obesity and diabetes. The preliminary MOTS-c data currently belongs to a biotechnology company that hopes to begin human clinical trials within the next three years. JH
A HORMONE THAT FIGHTS
Life possible on Titan – but not as we know it A NEW FORM of methane-based life has been
NASA
proffered by researchers at Cornell University. The oxygen-free life form has a metabolism and is capable of reproducing in a manner similar to organisms here on Earth. Conditions on Saturn’s moon Titan are harsh, with liquid methane instead of water and a temperature of −179.5°C. Forming a template for a life from that could live under such conditions required imaginative chemical engineering to succeed. “We’re not biologists, and we’re not astronomers, but we had the right tools,” says lead researcher Pauline Clancy. Clancy, a molecular dynamics expert, is an interdisciplinary scientist on the Cassini-Huygens mission that discovered methane-ethane seas on
4 News
Titan. Together with Jonathan Lugine, Director of Radiophysics and Space Research at Cornell, they devised the life form’s structure. They propose a cell membrane made of small organic nitrogen compounds that can still function in ultra-low temperatures. Similar structures make the cell membranes here on Earth, and while small vesicles made from these are called liposomes, Clancy and Lugine named their membranes ‘azotosomes’, after ‘azote’, the French word for nitrogen. The next step is to demonstrate how these cells would survive in their ‘native’ environment and the scientists someday hope to test these ideas on Titan itself. JH
Easter 2015
Reviews The Book of Trees: Visualising Branches of Knowledge - Manuel Lima
MICROBE WORLD
MANUEL LIMA TAKES us on a quirky and visually unique tour through 800 years of human
Princeton Architectural Press, 2014
history in this carefully collated testimonial to humanity’s obsession with the tree diagram. Touching on such diverse topics as the Yggdrasil tree, an immense ash tree venerated in Norse mythology; the original drawings of the tree of life: Charles Darwin’s map of the Origin of the Species; through to the visualisation of the content of Barack Obama’s rhetoric, this book draws out some of the most beautiful examples of organised information. In many ways this book is a design folio but it is one that has a lot to offer to the scientific reader: the thoughtful examples of how best to systematically organise and present data are crucial reading for any scientist hoping to communicate their work to a wider audience. Biology features more heavily than the physical sciences, although there are nods to nuclear physics through the stark depiction of the organisational structures of the Manhattan Project. The chapters are divided not by subject, but by the different forms of tree, all the way from the simple linear tree to the complex and intricate hyperbolic and sunburst trees. This book describes the veneration of trees as ‘dendrolatry’. After reading this beautifully crafted, treasure trove of a work, you can consider me a convert. AW
The Science Magpie - Simon Flynn
Icon Books, 2013
THE SCIENCE MAGPIE is a collection of science miscellany made up of a plethora of anecdotes, poems and facts about science. Although it is sure to delight any 10-year-old or non-scientist, most of the people picking it up will be adults who already like popular science, and for them the delight will be spread a little thinner. A lot of the trivia and bad jokes are already as well known as they deserve to be amongst this audience. If you don’t know that Tom Lehrer wrote a song called ‘The Elements’, then run out and buy this book immediately. But you should also listen to the song on YouTube, rather than just reading the lyrics. Whilst there are some great facts obscure enough for all to enjoy, the disjointed nature of the book means that subjects aren’t explored in much depth. Perhaps the most unusual feature of the book is the set of literary references and poems from scientists throughout the ages, which are interesting to discover even if many of them aren’t well written. If you love science trivia enough, you’ll find it worth the effort of sorting through for new bits, and it’s a good introduction for newcomers to science pop culture. However, for long-term fans looking for shiny new science, it’s a bit of a lucky dip. RL
Human – The Definitive Guide To Our Species - Nigel Ritchie & Robert Winston EIGHT CHAPTERS, COMPILED by a team of expert writers and consultants, encompass
Dorling & Kindersley, 2004
what it means to be human, from the biology of the eyeball to the variety of funeral traditions around the world. Beginning with Origins, the book explains our evolutionary roots and all that has happened since - although details are somewhat sparse as millennia are compacted into several pages. The two biological chapters, Body and Mind, are accompanied by wonderful photography and illustrations that bring trickier concepts to life. Unlike similar books that attempt to give a comprehensive overview of human biology, Human strikes the balance between scientific depth and clarity in way that does not alienate those with little prior knowledge. The remaining chapters look at our species through the lens of sociology and anthropology: Life Cycle explores universal rites of passage - birth, coming of age, birthdays, funerals; whilst Society, Culture and Peoples compares and contrasts how humans live around the globe. For a cover-to-cover reader, these latter chapters can quickly become repetitive, despite our world’s diversity. The final, relatively small chapter is a refreshing contrast; Future looks at the progress yet to come, both in biological and anthropological terms. This encyclopaedic work will certainly capture your interest somewhere within its pages. LNM
Easter 2015
Reviews 5
Running Away from Unwanted Inflammation Kimberley Wiggins explores the anti-inflammatory effects of exercise
The benefits of exercise stretch far beyond that initial endorphin high to include powerful antiinflammatory effects
INFLAMMATION - IT CAN save your life, or it can kill you. The process is necessary for the body’s response to injury and infection, where it helps to repair damaged tissue and fight off invading microbes. The problems start when levels of inflammatory mediators rise throughout the body in the absence of infections or tissue damage. This is known as ‘chronic low-grade systemic inflammation’, and has been implicated in many diseases, including cardiovascular disease, type 2 diabetes and even colon and breast cancers. What can we do to stop it? Surely we need some sort of anti-inflammatory drug or medical intervention? Perhaps not. We might be able to help ourselves more than we think by getting fit! It has long been known that exercise is good for the mind: it stimulates the release of endorphins, which give the athlete an allround feeling of positivity. However, it now seems that the benefits of exercise stretch far beyond that initial endorphin high, to include powerful anti-inflammatory effects. For example, studies have linked regular exercise with a reduction in circulating levels of C-reactive protein, a key marker of inflammation, within the blood. To unlock the secret of how exercise fights inflammation, we have to go right down to the molecular level and think about cell signalling. In this process, proteins sequentially activate or inactivate each other to allow cells to communicate with their neighbours - as a person might pass a note to their friend - and to respond to changes in their environment with great precision. Cell signalling is the molecular mechanics of how we function, and when it goes wrong, we get ill. Tiny messenger proteins called cytokines are key players in these delicately balanced,
6 Running Away from Unwanted Infammation
intricate biological networks. There are proinflammatory cytokines, such as tumour necrosis factor alpha (TNFα), which activate immune cells, promote cell death and induce fever. There are also anti-inflammatory cytokines, for example interleukin 10 (IL-10), which suppress inflammation by switching off pro-inflammatory molecules. When fatty tissue is laid down in the body, it also triggers the release of pro-inflammatory cytokines. This means that simply burning off fat through exercise can lower the level of these inflammatory mediators in the tissue. To make things even more complicated, some cytokines can be either proinflammatory or anti-inflammatory, depending on their context. One such cytokine is interleukin-6 (IL-6), which appears to provide the missing link between exercise and inflammation. In an inflammatory environment, such as during an infection, immune cells produce large amounts of proinflammatory cytokines. These then stimulate the production of other cytokines, including IL-6, to recruit more immune cells and drive the rest of the inflammatory response. During exercise, however, IL-6 is the first cytokine released in huge quantities directly from the working muscle cells. The amount of IL-6
KYLE CASSIDY
ELIZA WOLFSON
Easter 2015
During exercise, IL-6 is the first cytokine to be released in huge quantities
RAMIN HERATI
produced is proportional to the intensity and duration of the workout, and is higher in older people than younger people. (So it really is never too late to get fit!) Remarkably, the IL-6 released by exercising muscle cells does not promote the huge inflammatory response that the immune cell-cytokines evoke. Instead, it increases anti-inflammatory cytokine production, and even inhibits the king of the inflammatory cytokines, TNFα. This was demonstrated in a 2003 study, in which Bente Pedersen and colleagues simulated low levels of inflammation by injecting healthy volunteers with a toxin from the bacterium E. coli. They found that those who had been resting prior to injection experienced a 3-fold increase in TNFα levels in their blood. By contrast, those who had been exercising before toxin injection had no increase in the inflammatory mind? It looks like it can. For instance, a study cytokine, which suggests that exercise was able of patients suffering from coronary heart to quench the inflammatory response. disease showed that exercise led to a decrease However, IL-6 isn’t the only mechanism in mortality. Other trials have found that that can take credit for the anti-inflammatory more physical activity protects people with response to exercise. Both the motor sensors in impaired glucose tolerance from developing the brain that detect physical movement and type 2 diabetes, to which they are predisposed. the IL-6 produced by muscle cells stimulate For those who have already developed the the adrenal glands to release the hormone disease, exercise is used as a treatment (in cortisol into the bloodstream. Cortisol inhibits combination with dietary changes and the production of pro-inflammatory cytokines medication), where it lowers the risk of by immune cells and thereby prevents the complications. inflammatory response. Before you are tempted to fly off into In addition, exercise doesn’t just change workout mode, hitting the gym for four hours which signalling molecules immune cells a day in the hope that this will protect you produce; it also alters their movement from ever suffering from disease, it’s important and abundance in the blood. The lowto remember that the key is balance. Firstly, it grade chronic inflammation observed in is possible to do too much: excessive exercise fatty tissue is largely due to immune cells can pushes the anti-inflammatory response called macrophages. These cells are guided so far that it can lead to immunosuppression. to the fat by a trail of signalling proteins That is why elite athletes who endure lengthy known as chemokines. It is thought that intense training are more susceptible to upperexercise promotes the general production of respiratory tract infections than people who chemokines from multiple locations, which do absolutely no exercise. Secondly, exercising makes the trail ‘fuzzy’ and more difficult for doesn’t guarantee you a disease-free life. It’s the macrophages to follow. just one of those little steps that you can take Finally, exercise also alters the proportions to increase your overall health and reduce your of different types of immune cells within risk of disease. So jump on that treadmill or the blood. It reduces the number of prointo the pool, take the time to re-connect with inflammatory cells, such as macrophages, and your favourite activity or sport, and keep your increases the number of regulatory T-cells, mind and body happy and healthy. which keep the macrophages in check by suppressing their activity. So how important is this anti-inflammatory Kimberly Wiggins is a PhD student in the Institute of Metabolic Science response? Would exercise make a difference to diseases where inflammation is involved in onset and development? Can it really be used as a medicine for the body and not just the Easter 2015
Running Away from Unwanted Inflammation 7
ELIZA WOLFSON
Defeating Ebola Miha Pipan reviews the current Ebola outbreak and discusses treatment options DESPITE RECENT COVERAGE, the first Ebola virus outbreak dates back to 1967, when World Health Organisation (WHO) officials first identified Ebola in Sudan. In subsequent decades many more outbreaks followed, affecting small rural communities throughout Central Africa. The disease carries an astonishingly high mortality rate, along with the non-existence of useful therapeutics; this has made Ebola a popular topic in speculative fiction, literature and film. Ebola epidemics were confined only to the entertainment industry – until the outbreak in West Africa in 2014. This current outbreak, mainly limited to Guinea, Liberia and Sierra Leone, represents the first known case of Ebola in urban communities. Past outbreaks occured in regions whose size, location and isolation inherently limited the spread of Ebola virus. Whilst in the past isolation as a form of infection control has proved key in preventing the disease from spreading, this strategy is impossible to implement in a crowded urban environment. Both local and global health communities found themselves inadequately prepared to respond to Ebola virus taking over hubs like Freetown and Monrovia. As a result, the global community is experiencing the largest Ebola outbreak in known history, having claimed thousands of lives it continues to cause fear and chaos in affected areas. However, whilst traditional outbreak control strategies have proven inefficient, we now live in a time of rapid technological advances. Advances in Ebola research, coupled with a globally coordinated response, and drug development are for the first time enabling us
PUBLIC PUBLIC DOMAIN
Isolation as a form of infection control is difficult to implement in urban communities
8 Defeating Ebola
to fight Ebola virus directly. Over the past year many novel and repurposed therapeutic candidates, ranging from small molecule inhibitors to biologicals, have been created and tested in pharmaceutical pipelines around the world. The most promising candidates amongst them are the vaccines. Ebola vaccines hold the potential to stop current and prevent future Ebola outbreaks. Vaccines are useful in two ways: they can grant long-lasting immunity, thus acting as a preventative measure, and they have the potential to generate a ‘herd immunity’ effect. ‘Herd immunity’ is a term used to describe the condition when a large enough proportion of the population is rendered immune to infection, in turn reducing the pool of potential candidates for the virus to infect to a level where the virus is then incapable of causing a widespread epidemic. The combination of these key effects of vaccines can ultimately result in Ebola virus eradication. There are several different ways to design a vaccine. All current efforts have focused on generating so called ‘subunit vaccines’, where using genetic engineering subunits of the target pathogen, that can still generate an immune response, are placed into a second less virulent viral vector. There are two main advantages in developing a ‘subunit Ebola vaccine’ as apposed to other vaccine types. Firstly, relatively little is known about Ebola virus biology and its pathogenesis, therefore, using a less pathogenic, attenuated version of the virus would be a too dangerous proposition, as we cannot properly assess the risks involved. Secondly, working directly on Ebola virus requires the highest level of security clearance and complicated containment facilities, both of which are limited in supply and expensive to maintain. Two different vectors are being used by the most promising vaccine candidates. Both use the Ebola virus surface glycoprotein as their immunogenic subunit component. GlaxoSmithKline (GSK) and Johnson & Johnson based their respective vaccines on adenovirus vectors, whereas Merck’s vaccine relies on a recombinant vesicular stomatitis virus. Both vectors are innocuous to humans, well characterised, and provide an ideal platform for engineering the vaccine. The hype generated by the West African outbreak has fast-tracked development of the three main vaccine Easter 2015
WIKICOMMONS
This world map shows areas affected by the 2014 Ebola outbreak
candidates. Late 2014 saw wide media reporting of promising results from early animal studies. All three vaccines managed to grant long-lasting immunity to tested non-human primates.With most trials reporting 100 per cent success rates in preventing mortality in tested animals upon Ebola challenges. Accompanied by unanimous agreement from WHO and Ebola specialists around the world, human phase I medical trials started taking place towards the end of 2014. Results from those phase I and phase II trials are now coming in. Successful trials have allowed GSK and Merck, in collaboration with the National Institutes of Health, to progress to phase III field medical trials in Liberia. Over 30,000 individuals are to be vaccinated with the hope of rapidly approving these vaccines for general release. The promising efficiency of vaccines in treating Ebola can be increased by designing combination treatments. This month saw American Emergent BioSolutions produce a booster vaccine to enhance the protective effects of GSK and Merck vaccines. With the international community having secured financial support for vaccine manufacturing and distribution, we can hopefully expect this outbreak to quickly be brought to a close. However, in light of this positive news it is still important to note vaccines are only effective as a preventative measure against Ebola infection. Once an individual is infected, vaccines have little or no treatment potential. Fortunately, a plethora of therapeutics capable of treating ongoing Ebola infections are being developed and tested around the world. Examples include small interfering RNA-based techniques, recombinant protein and interferon therapies. Additionally, a highly favoured current approach uses antibodies to treat Ebola. These molecules bind to Ebola virus particles, tagging them in the process and aiding the host’s immune system in killing the virus. One of the most promising candidates is ZMapp, an antibody cocktail developed by the San Francisco biotech Mapp Biopharmaceuticals. Animal studies and emergency aid worker experimental treatments have demonstrated Zmapp to be one of the most effective strategies in combating ongoing Ebola Easter 2015
infections. A similar therapeutic strategy involves Ebola survivor serum transfusions. After successfully beating the infection, a survivor’s blood is swarming with Ebola antibodies. The serum acts in a way homologous to ZMapp. Therapeutics represent the key to ending this outbreak and helping to prevent future ones. However, radical changes beyond vaccine introduction are also required to complement this plan of action and contain viral spread. A large proportion of Ebola outbreaks occur due to lack of education on how the virus is contracted and spread. Consumption of bushmeat (especially fruit bats), inadequate safety precautions in caring for the diseased, and traditional burial practices have been determined to represent the main factors mediating Ebola outbreaks. Additionally, restructuring of local healthcare systems is required to tailor for quicker and more efficient responses in the future. Basic supportive care such as fluid rehydration has been shown to dramatically increase a patient’s survival prospects. Personnel training, easy-to-use diagnostic kits and strategically placed intervention wards are required to limit the size of outbreaks. These reforms require significant international support, much of which must be financial. Several financing models have been proposed to ensure all countries at risk are able to afford subsidised therapeutics, including vaccines. Looking forward, a collaborative approach from local and global communities is required to shape policies which will ensure a faster and more efficient response should another outbreak of this magnitude occur. Now we must wait. With the latest WHO reports showing that the 2014 West African outbreak is slowing down, all eyes are fixed on vaccine medical trials. Should the vaccines be proven to work, we will have a fighting chance against this otherwise often terminal disease. Miha Pipan is a 3rd year undergraduate student in the Department of Biochemistry
Defeating Ebola 9
Finding your keys uses a critical brain function: memory
10 Memories
Ann (Chen) Hascalovitz discusses the authenticity of memories and the implications for the justice system
IT’S MONDAY MORNING; you’re all ready to go when you suddenly realise that you can’t find your keys. You try to think back: what did you have in your hands when you entered the house last night? Aha! There they are, on the side of the kitchen counter next to the fridge. You grab them, run out the door, hop on your bike, and make it to class just in time. You’re asked the first question, so what’s the answer? You focus as hard as you can. Right! You remember it, you finish the test and when the class is over, you’re ready to chat about the fun party you went to at the weekend Everything you did, from finding your keys to riding your bike, to passing your tests, required your brain to use a critical function: memory. Psychologists use the term ‘memory’ to describe how the brain processes, stores and retrieves information. The formation of memory begins with its perception. When the brain holds onto the perceived sensory information for less than a second, it is called sensory memory. The sensation is then stored in short-term memory. This allows you to recall around seven items, without rehearsal, for several seconds to a minute. Finally, long-term memory permits us to retain information indefinitely. Memory can be very convincing, but it is not always accurate. In fact, when it comes to episodic memory, perspective, past and present experiences, biases, imagination and suggestion, can all turn memory into a mistress of deception. Just like memory can change your experience, your experience can also change your memory. You’ve heard the adage: “There are two sides to every story, and then there’s the truth.” It’s not necessarily because both sides are lying, but because people can perceive the exact same event differently. Sometimes the experience is so different that their memories of the event become distorted. And it’s not just relationships that are at risk here. False memories
have put innocent lives in prison. Eyewitness testimonies were considered for a long time the best way to identify a criminal, until extensive research from the 1970s showed that it was one of the most inaccurate ways to identify a criminal due to faulty memory. Since then, proper conviction has been put into question. The ‘Innocence Project’ is a group in the United States founded in 1992 dedicated to protecting innocent people from being sentenced to jail. They have already helped over 300 falsely convicted felons who were proven innocent after DNA testing. Moreover, over 25 per cent of the ‘felons’ had been accused of committing murder. After analysing the 300 case studies, the researchers confirmed that three-quarters of the false accusations were due to faulty memory, such as incorrect eyewitness testimony. Counter-intuitively, the more confident someone is about a memory, the less accurate they may be, since authentic memory is riddled with blind spots, even when it comes to your own experience. In a separate study conducted by Julia Shaw at the University of Bedfordshire in the UK, and Stephen Porter at the University of British Columbia in Canada, it took only a few hours to get innocent participants believing they had perpetrated serious
SERGEI S SCUR-
ANGELA IBLER
How Reliable Is Your Memory?
Easter 2015
JESSICA MCHUGH
Memory describes how the brain processes, stores and retrieves information
crimes in their teenage years, such as assaults with weapons. In this experiment university students were brought to the lab for three 40-minute friendly interviews, each done one week apart from the previous one. In the first interview they told the students about two events that they experienced as a teenager, only one of which had really happened. For some, the false memory was related to a crime, but for others the memory was emotional in nature, such as an injury or a loss of a valuable item. The false stories included true details about the student’s life, as previously told by their caregiver. Participants were asked to explain what happened in each of the two events. If they had difficulty remembering the false event, the interviewer suggested them to try and remember anyway. In the second and third interviews they asked participants again to remember as much as possible about both memories, they also asked them to include how vivid their memories were and how confident they were about them. Of the 30 participants who were told they had committed a crime, 71 per cent had developed some type of false memory of the crime, and 11 had even elaborated the details of dealing with the police. In a stressful situation, such as a police interrogation, the result could be even worse. The question remains: are you innocent until proven guilty, or innocent until you or someone else believes you’re guilty? Memory is a constructive and reconstructive process; influenced by others and by
Easter 2015
yourself, and it can change. Cases of patients going into therapy with one problem and leaving with another, accompanied by strange memories and no physical evidence, has been another dispute that had scientists question the validity of memory recall. Moreover, false memories can be intense enough to have a lasting effect on a person’s behaviour. Most memory studies seem to successfully implant memories in between 15 to 80 per cent of their participants. Researchers have wondered if certain types of people are more susceptible to false memories than others. However, so far, there has been no conclusive evidence suggesting that certain types of people are more prone to false memories. Even those who have highly superior autobiographical memory (HSAM) can still have false memories thrust upon them. At the end of the day, however, real memories are reported better than false ones. In the case of the justice system, the restriction of suggestion, poor interviewing techniques, and a heavy reliance on witness-testimony can all contribute to unjust outcomes. So don’t take your memory for granted, and the next time you’re arguing about some past event with a friend, you may want to be more open to their side of the story: memories can be deceiving at times, after all. Ann (Chen) Hascalovitz is an MPhil student in the Department of Physiology, Development and Neuroscience.
Memories 11
WELLCOME IMAGES
What’s in a Name? Sophie Protheroe explores the life of the famous taxonomist Carl Linnaeus
The walls of Linnaeus’ house was lined with botanical drawings
12 What’s in a Name?
THERE MAY BE 100 million species on our planet, so the classification and naming of them is a formidable task. Taxonomy is the science of classifying organisms by sorting them into groups and then naming these groups; to date, scientists have classified approximately 1.5 million. An 18th century Swedish botanist named Carl Linnaeus is regarded as the father of modern taxonomy. Linnaeus was a unique character, blooming with eccentric ideas and elaborate schemes. Taxonomy has come a long way since Linnaeus’ time, but his basic classification system is still used today, providing scientists across the globe with a definitive method for cataloguing species. Perhaps surprisingly, given its reputation today, botany stems from a history of pioneering expeditions and scandalous tales. Botany only became an academic discipline less than 200 years ago. Historically, the study of plants was considered an activity for ladies and gentlemen of leisure, pottering around their gardens. This image was set to change as a result of voyages of discovery that were sent out to explore and colonise foreign lands, and also to bring back exotic curiosities, including new species of flora and fauna. However, taxonomy in early modern Europe was very problematic, with no uniform methods for the identification or naming of species. Without a centralised scheme, virtually every collector had his own system and species names were often convoluted and uninformative so it was almost impossible to tell if two botanists were talking about the same species. Linnaeus’ legacy to botany was his classification system. He divided organisms into a five-tiered hierarchy of categories and gave them two part names. For example, Linnaeus introduced the term ‘Homo sapiens’, meaning ‘wise man’ for human beings. As a result of Linnaeus’ work, the 18th century is often described as the ‘Age of Classification’. Linnaeus’ scheme for classification was controversial at first, categorising plants by reference to their sexual characteristics. The fact that plants reproduce sexually was only recognised at the end of the 17th century and uptight British botanists were shocked by the crudity of Linnaeus’ system. Botany became highly eroticised in the literature and poetry of the
era, to the extent that it was thought inappropriate as a pastime for young ladies. Linnaeus was a pastor and his terminology reflected his Christian morals. He described plants with unequal numbers of male and female parts in terms of ‘two husbands in one marriage’ and so on. This also reflected the chauvinism of 18th century Europe; Linnaeus’ system gave priority to male characteristics and referred only secondarily to female characteristics.
IVICA LETUNIC
Carl Linnaeus
Despite the scandalous associations between botany and sex, Linnaeus’ system of classification gained recognition. The British Museum was one of the first institutions to implement the Linnaean system and by the second half of the 18th century it had become very fashionable. Linnaeus was an intriguing individual, passionate about plants from an early age. As a baby, Linnaeus is said to have frequently slept in the grass with a flower placed in his hand by his father, who decorated his son’s cradle with flowers. As a child, he collected and sketched plants. His interests in plants were both Easter 2015
Easter 2015
ELIZA WOLFSON
scientific and economic; he dreamt of growing exotic commodities such as tea, rice and coconuts in Sweden so that his country might become self-sufficient. As a result of this wild notion, he successfully grew the first banana tree in Europe. Linnaeus was an excellent self-publicist. He is said to have regarded himself as a second Adam, naming the species of creation. A colleague remarked, “God created and Linnaeus organised.” Linnaeus planned the botanical gardens of Uppsala University to resemble the Garden of Eden. He lived just outside these gardens in a house designed as a museum for God’s creations; the walls were lined with botanical drawings, shells hung from the ceilings, and birds, monkeys and racoons scampered freely amongst the geological specimens. Linnaeus commissioned portraits to commemorate his travels, in which he was dressed in supposedly traditional Sami clothes, as if he had just returned from the Arctic. In reality, he had put together this costume for travelling through Europe, and his outfit unwittingly comprised a motley selection of male and female, summer and winter, clothing. At the pinnacle of his career, Linnaeus established and controlled a global scientific empire. From this, he sent out his best students, whom he called his ‘disciples’, to spread the knowledge of his classification system and to collect new specimens. Over 250 years later, taxonomy relies on the Linnaean system of classification. Biologists classify species using his five-tiered categories; class, order, genera, species and variety, with every species having its own Latin two-part name. The aim is to provide a name that distinguishes a species from others and gives some information about it. When a species is named for the first time, the scientist who discovers it provides the name, along with a description, to serve as the formal reference for future identification. For example, Linnaeus was very fond of a modest looking plant with white flowers, which he believed could be a Swedish alternative to Chinese white tea, and he named his beloved plant Linnaea borealis. The first part of the name denotes the genus; Linnaeus named this after himself. The second part denotes the species and in this case it means ‘from the north’. Scientists now also provide a type specimen - this is a preserved individual of the species, or an illustration or photograph if the organism is rare. This wasn’t required in Linnaeus’ day but is a twist that he would have loved. Linnaeus himself is now recognised as the type specimen of Homo sapiens. The naming of species is relatively straightforward, however, the grouping of organisms is a more contentious issue. Originally, species were distinguished on the basis of physical characteristics. However, problems arise when different species
Linnaeus divided organisms into a hierarchy of categories
appear very similar, or when members of the same species appear very different. In response, behaviour, especially reproductive habits, was used to give further clues about the natural groupings of organisms. The biological species concept, proposed by Ernst Mayr, states that a species consists of a population of organisms that can reproduce with one another and cannot reproduce with other populations. This has been largely accepted by the scientific community and is used in contemporary classification. Recent advances in biotechnology have allowed scientists to use new techniques such as DNA sequencing to produce quantitative comparisons of organisms and to propose evolutionary relationships. The use of DNA sequencing relies on the principle that the level of difference between DNA sequences implies the degree of divergence from a common ancestor. Using these methods, we can define thresholds between species in terms of numerical values. So it seems that there is much in a name. The field of taxonomy is crucial in allowing us to categorise and make sense of the diversity of the living world. We owe much to Carl Linnaeus, the eccentric Swedish pastor, seen smiling from his portraits, wearing ladies clothing and clutching his precious Linnaea borealis. We might find different ways to classify this brilliant and bizarre man, but he will be forever remembered as the father of taxonomy. Sophie Protheroe is a student at Murray Edwards College
What’s in a Name? 13
ANGELA IBLER
How Does Nature Deal with Humans? Ornela De Gasperin explores how animals adapt to cope with human activities
WELCOME TO THE ANTHROPOCENE: a new
geological epoch that scientists are proposing to describe the time span on which human activities have had a significant ecological impact. Human activity has changed the Earth so rapidly that new rocks have been observed to form out of plastic, and the amount of plastic on the oceans is estimated to be around 269,000 tonnes. Moreover, during the last 500 years, at least 322 animal species have gone extinct as a direct result of human activity. In general, animals living near human settlements have smaller home ranges compared with non-urban areas, and behavioural changes of all sorts have been documented as a result of human presence. As worrying as this is, many animal species are adapting their behaviour to cope with this dominating human influence.
PUBLIC DOMAIN
A man-made landscape
As urban areas, airports and highways spread across the land, noise pollution has become ubiquitous and most species are exposed to it. Many animals use noises, songs and/or calls to communicate. Therefore, scientists have begun to investigate how urban noise influences communication in dierent animal species. Birds use songs and calls in a variety of social contexts: to attract potential mates, to advertise and 14 Urban Animals
defend their territories from rivals, to locate their chicks, and as alarm calls when predators are nearby. Urban noise can interfere with all of these social processes; however, birds still remain living in cities and urban areas. Has this noise interfered with their social interactions and how have they managed to cope with it? In 2003, a study developed by Hans Slabbekoorn and Margriet Peet at Leiden University in the Netherlands, asked exactly this question by studying the calls of 32 male great tits across the Netherlands. Their results showed that males living in very noisy locations sing at a higher frequency (pitch) to prevent their songs from being masked by urban noise, as opposed to the singing pitch of tits living far away from cities. Noises in cities tend to have a low frequency; therefore, by singing at a higher frequency their songs can still be heard by individuals of the same species. Similar studies have shown that other bird species, like song sparrows, the Northern cardinal and blackbirds do this as well. Besides changing the frequency of their song, birds can also change their singing schedules to avoid urban noise contamination. Robins, for instance, start singing earlier than dawn, presumably because at this time of the day there is less noise from the city. This phenomenon is not restricted to avian species; frogs and squirrels have been shown to increase or decrease the frequency of their songs or the number of vocalisations as a response to human noise. Sometimes these changes only occur during the noisiest part of the day and the animals maintain their normal habits outside these hours. A similar study was conducted on orca whales. Whales live in social groups and they use sound to communicate between one another. Researchers from the University of Durham, UK, wondered whether or not whale-watchers influence their subjects’ communication. The researchers compared the vocal communication of orcas in the Easter 2015
initiated the flight. Presumably, the sooner a bird flies away from an approaching car, the less likely it is from being hit by it, but if the bird flies away too soon too often, it may not manage to get enough food. What they found was remarkable: birds adjusted their flying distance from cars according to the speed limit of the highway - they flew away from the approaching car sooner on roads with higher speed limits. Interestingly, the actual speed of the vehicle did not affect their flying distance. Animals have also changed their behaviours to incorporate human-made materials. For example, many birds build nests that they use to lay their eggs. Parasites develop in these nests too, which can be detrimental for the chicks. Parent birds change the composition of their nests to reduce parasite loads, for instance, by bringing into the nest plants with volatile components that reduce parasitic growth. Recently, birds have started to bring cigarettes butts into their nests, and an experimental study performed by Montserrat Suarez and collaborators in Mexico City showed that smoked butts act as an insect repellent. Unfortunately, while there are short-term benefits of bringing smoked cigarettes into a nest, there are also costs. Birds exposed Easter 2015
JERRY KIRKHART
Insects and birds incorporate humanmade materials such as plastic into their nests
to more butts from smoked cigarettes had higher levels of genotoxicity in their blood, so the positive effect may be counterbalanced by long-term costs. Bees are also starting to use human-made materials to build their nests. Bees live in complex societies within large colonies. A queen lays her eggs, which are tended by worker bees. Worker bees then construct the chambers where the eggs develop and pupate. These chambers, called brood cells, are hexagonal and are usually made out of organic matter. However, two species of bees in Ontario, Canada have been observed to collect pieces of plastic bags, which were then used to construct and close brood cells. These cells were used by the queen, and the eggs and larvae fully developed and successfully emerged as adults. These types of behavioural changes may be what animals need to do in a world where humans have become omnipresent. So, although humans are having major impacts on wildlife, at least some animals are adapting themselves to our presence and learning how to cope with us.
Birds follow the speed limit of streets and highways
Animals adapting to the urban envronment
JESSICA MCHUGH
DEFACTO - WIKICOMMONS
presence and absence of whale-watchers in the US State of Washington. Surprisingly, they found that these whales produced longer calls while whale-watchers were present, which suggests that whales also change their behaviour according to humans’ presence. Perhaps more surprisingly, birds have learnt the speed limit of streets and highways, and they have adjusted their behaviour accordingly in order to avoid danger. This startling result was found by Pierre Legagneux from the University of Quebec and Simon Ducatez from the University of McGill in Canada. They performed an experiment in France by driving on roads that had different speed limits (20, 50, 90 and 110 km/h). They also varied their own speed from the posted speed limit and registered how long it took the birds on the street to fly away from the car. They recorded the time from the moment the bird started to fly until the car reached the spot where the bird had been, and they calculated the distance at which the bird
Ornela De Gasperin is a PhD student in the Department of Zoology
Urban Animals 15
The Fight against Cancer
MARKUS SCHOBER AND ELAINE FUCHS
FOCUS
OUR UNDERSTANDING OF CANCER has vastly
BlueSci looks deeper into what causes cancer and how we can beat it
improved over the last few decades, fuelled by technological advances in fields like molecular and genome biology. Likewise, we have seen major advances in cancer diagnosis and treatment. This progress is depicted in the latest statistics from Cancer Research UK, showing that cancer survival rates have doubled in the last 40 years, and half of people diagnosed with cancer now survive their disease for at least 10 years. Yet, despite these optimistic numbers, cancer is still the cause of more than one in four of all deaths in the UK. Cancer is not a singular disease. Instead, cancer is a collective name for more than 200 different types of malignant growths. However, there are a few characteristics that all cancers have in common. Cancer researchers Hanahan and Weinberg described at least six traits or ‘hallmarks’ shared by all cancers, which include uncontrolled growth of abnormal cells in the body and the ability of these cells to invade surrounding tissues and spread to other organs - a process also referred to as metastasis. Whether cancer is curable is highly dependent on the stage of the disease. Many tumour types that are confined to one area of the body can be successfully treated by local treatments, usually surgery and/or radiotherapy. However, most cancer are considered incurable after they have spread to other organs or tissues. Local treatments are inadequate for patients with metastatic disease and therefore systemic therapies - drugs that will circulate throughout the body - are administered instead. Systemic therapies include chemotherapy, hormonal therapy and immunotherapy. Chemotherapy is the treatment of cancer with cytotoxic (cell-killing) drugs and it is the most common form of systemic therapy. Chemotherapeutic drugs function by killing dividing cells in the body. Since cancer cells generally divide more frequently than normal cells, they are more likely to be damaged or killed. However, normal cells that are in the process of dividing are also affected. This high level toxicity to normal tissues often limits the dose of chemotherapeutic drugs that can be administered, thereby reducing their anti-tumour activity. The choice of treatment is primarily dependent on the site of origin and the clinical stage of the tumour. Therefore, most patients with a specific cancer type and stage will receive a standard treatment plan. However, treatment response is known to vary greatly among patients, and even two patients with the same type of cancer can respond differently to therapy. In the past decade, advances in cancer genomics technologies and drug development have sparked the emergence of a novel treatment paradigm for cancer: personalised cancer medicine. This form of medicine aims to tailor
The uncontrolled growth of cells in squamous cell carcinoma, the second most common form of skin cancer
Focus 17
Normal human chromosomes have regular appearances
18 Focus
treatment to individual patients using molecular characteristics that are specific to the patient’s cancer. Cancer is as genetic disease, caused by changes or mutations in the DNA of a cell. For cancer to develop, an accumulation of multiple mutations in several genes is required. Personalised cancer medicine is based on the identification and specific targeting of faulty genes that are responsible for the development and growth of cancers. Until very recently, the discovery of cancer-causing genes has been a slow process, limited by the availability of experimental approaches to study more than one candidate gene at a time. However, this changed with the development of novel biotechnologies such as whole genome sequencing technologies, which allowed large-scale and systematic screens for cancer genes through sequencing of cancer genomes. Several large-scale cancer genome sequencing projects have been launched over the past two decades, including the Cancer Genome Project (CGP) at the local Wellcome Trust Sanger Institute in Cambridge, and The Cancer Genome Atlas (TCGA). In 2006, The Cancer Genome Atlas (TCGA) began in the United States as a pilot project, aimed at the comprehensive characterisation of the genetic and molecular profile of two cancer types: ovarian cancer and a specific type of brain cancer. Soon, the project blossomed to include many more cancer types. As of March 2015, the programme has sequenced more than 11,000 tumours in 33 different cancer types. Nearly all of these tumours have now been exome-sequenced (covering only the protein-coding regions of the genome) and whole genome sequence has been completed for 1,000 of the tumours. Projects like the TCGA have provided researchers with a tremendous amount of publicly available data, catalysing the discovery of hundreds of cancer-causing genes. Many of these targets have spurred the development of new therapeutics. Over 100 targeted cancer drugs have now been approved for patient use. One of the earliest and most successful examples of targeted therapy is imatinib mesylate (marketed as Glivec or Gleevec), which is the main treatment for most patients with a rare type of blood cancer called chronic myeloid leukaemia (CML). Over 90 per cent of CML cases are characterised by the presence of a chromosomal abnormality that results in the formation of the fusion gene BCR-ABL. Imatinib mesylate targets the product of this gene, an oncoprotein that disrupts normal regulation of haematopoiesis. Whilst targeted therapies show great promise, these advances face difficulties on both biological and economic fronts. Biologically, researchers face the constant reality that cancers are not static; as tumours grow, additional mutations may give rise to groups of
THOMAS RIED
FOCUS
cells within a single tumour that have different genetic and molecular characteristics from other cancer cells that make up the tumour. Researchers also refer to this phenomenon as ‘tumour heterogeneity’. The existence of such biological diversity within single tumours poses a major challenge in developing effective targeted therapies for the treatment of solid tumours. Also, tumour heterogeneity is regarded as one of the main limiting factors to the success of any targeted therapeutic approach, as resistant subclones of cancer cells most likely pre-exist in the cancer cell population prior to treatment. One way to overcome this issue is through drug combination treatments, which are a major topic of study at the moment. The use of more than one cancer drug will allow the targeting of several different signalling pathways at once, eliminating more subpopulations. Economically, splintering common cancers into increasingly specific subtypes will necessitate the development of ever more specialised therapies, which, whilst great for patient outlook, can be a challenge for existing healthcare and pharmaceutical business models. The growing burden of diagnostic testing can likewise be costly if tests are applied inefficiently. Personalised medicine comes with its share of difficulties, both economic and biological, but ultimately holds great promise for advances in cancer care. Another very active area of cancer research is the use of immunotherapy to treat cancer. The goal of immunotherapy is to boost the body’s natural immune system to help fight cancer. Whilst the human immune system is naturally able to prevent the development of many cancers, often tumour cells are not recognised by the immune system as being dangerous. In addition, cancer cells use multiple mechanisms to actively evade detection by the immune system. Sometimes the immune system recognises the cancer cells, but the response might not be strong enough to destroy the Easter 2015
THOMAS RIED
FOCUS
cancer, for example because cancer cells themselves give off substances that weaken the immune system. There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies and cancer vaccines. Antibodies are large Y-shaped proteins that are naturally produced by the human body. They bind to specific markers, also known as antigens, on the surface of cells that are recognised as foreign by the immune system. Once bound to their corresponding antigen, antibodies can recruit other parts of the immune system to destroy the foreign cells displaying the antigen. Antibodies used in cancer therapy are artificially generated to recognise antigens that are found on cancer cells only. Because therapeutic antibodies are produced in a genetically identical population of immune cells, they are said to be ‘monoclonal’. There are currently different groups of monoclonal antibodies (mAbs) used in the treatment of cancer. Some of these mAbs are designed to specifically increase the host immune response against the cancer cells, whilst others function to prevent the growth of cancer cells by binding to different growth factor receptors found on the surface of cancer cells. Trastuzumab (Herceptin) is a well known example of this group of mAbs and it is used to treat breast and stomach cancer patients whose cancers produce large amount of the HER-2 growth factor receptor. Finally, some mAbs are bound to chemotherapy drugs or particles that give off radiation (conjugated mAbs) and thus are used to deliver these substances directly to cancer cells. Non-specific immunotherapies involve triggering a strong, all-round immune response using cytokines. Cytokines regulate normal cell function, mediate immune responses and can stimulate or control cell growth. Some therapeutic cytokines have proven to be effective in targeting tumours and are regularly used in clinical therapy. However, a lot of the mechanistic Easter 2015
detail as to why these cytokines are effective in patients is still yet to be elucidated, and due to the many different forms of cancer, some may not have been tested in the disease state for which they are most effective. Cancer vaccines have been a subject of study for several decades, but progress in this field has been slower than for other forms of immunotherapy. Therapeutic anti-cancer vaccination is a seductive idea for exploiting the host’s immune system, given the efficacy of vaccines in preventing infectious disease. Could this be a realistic strategy in cancer treatment? Possibly, although there is a difference between preventative (prophylactic) vaccines and therapeutic vaccines, which are used to treat cancers that have already developed. Whilst important preventative cancer vaccines have been developed and shown to be effective, these all target infectious agents associated with the disease, hepatitis B virus and human papillomavirus (HPV). At this time, no therapeutic vaccines have been approved yet in the UK. However, in the US, sipuleucel-T (Provenge) is approved for treatment in some men with metastatic prostate cancer. The vaccine has been shown to extend life expectancy by several months and to cause less side effects than chemotherapy and radiation. The limited number of currently available cancer vaccines highlights the need for more research into the biological mechanisms of cancer development. Given the fact that cancer arises as a result of genetic changes leading to uncontrolled cell proliferation, it might seem rather surprising at first sight that there is significant geographical variation in cancer distribution. To show the extent of difference, Denmark has an average cancer incidence rate of 338 cases per 100,000 people, whereas Niger has an average rate of only 63 cases per 100,000 people, a fivefold difference. This is the result of both environmental and cultural differences between populations. One of the earliest studies of environmental factors causing cancer was conducted by Dunn in 1975. This study compared the rates of stomach and colorectal cancer among Japanese and white Californian individuals. The incidence of stomach cancer was found to be eight times higher in the Japanese compared to white Californians. The study also found that the cancer occurred at a younger age in the Japanese population. Stomach cancer is associated with gastritis caused by the bacterium Helicobacter pylori, and indeed, Japanese individuals are found to have much more severe gastritis and at an earlier age when compared to patients from the UK. Conversely, the study found that white Californians had a fivefold higher risk of colorectal cancer compared to Japanese individuals. Colorectal cancer is more prevalent in countries with a high-income economy,
Chromosomes from cancer cells show hallmark abnormalities
Focus 19
FOCUS
and risk factors for developing this type of cancer include red meat consumption, physical inactivity, obesity, smoking and alcohol consumption. In keeping with this, in the decades since the study, incidence of colorectal cancer has increased vastly in Japan as it has made the transition towards a high-income country. Importantly, Dunn’s study showed that the variation in cancer incidence rates between the Japanese and Californians was largely the result of environmental factors and not differences in genetic makeup between the two populations. As it happens, the study also included Japanese immigrants and US-born Japanese Americans. For stomach cancer, a stepwise reduction in incidence was seen, with high rates in Japan, intermediate rates among first-generation Japanese immigrants, and low rates for American-born Japanese progeny. Colon cancer rates were shown to be increased about equally in both generations of Japanese and were nearly identical to those for white Californians as the American lifestyle was adopted. As countries become richer, their cancer patterns are likely to change. In several sub-Saharan African countries, breast cancer has now become the most frequently diagnosed cancer in women. In previous decades, cervical cancer was more common due to a high prevalence of human papillomavirus (HPV) infection, the cause for nearly all cervical cancers, and a lack of screening services. This shift in cancer patterns is believed to be due to increased economic development and westernisation, resulting in the increase in incidence of associated risk factors. These include earlier onset of menstruation, having fewer children and later in life, and obesity. However, a common misconception is that cancer is a rather novel disease that has emerged as a result of our modern society. In fact, the oldest descriptions of cancer date back as far as 3000 BC and were discovered in the ancient Egyptian civilisation. Given the fact that age is the biggest risk factor for developing cancer, it is not surprising that cancer is a much more common disease today that it was several centuries or even
BRYAN LEDGARD
Cancer Research UK’s Race for Life event, Sheffield
20 Focus
decades ago, when life expectancy was significantly lower. For normal cells to become cancerous, they need to acquire multiple mutations in several key genes. Hence, the longer people live, the more time there is for these genetic changes to occur. Nevertheless, certain cancers are linked to modern-day lifestyle factors, for example lung cancer and smoking. Some people might argue that too much money is being spent on cancer research compared to other areas of research, especially since certain cancers are preventable. In developed nations, cancer research is funded by both the government and by charities more than any other medical condition, absorbing a third of the UK government’s medical research expenditure. However this still equates to only about £4.30 per person per year. The next largest expenditure, heart disease, only gets about £1.30 from the government, in spite of causing approximately the same number of fatalities each year. Contributions from charities roughly match these numbers, doubling the disparity. But is this entirely irrational? One factor to consider is that cancerous deaths tend to be more protracted. Whilst the unpleasantness this causes the sufferer and family is difficult to quantify, the economic burden of the disease can be estimated. Estimates from a US study by Hartunian et al. show that cancer is the most costly disease of all the major killers. This applies both to cost of treatment and lost years of productivity. However, it is far from the most costly killer overall; dementia, killing few but requiring long periods of care, costs the economy almost double. UK estimates from Dr Jose Leal in Oxford suggest that cancers may cost us £200 per year each, compared to £130 for heart disease and £380 for dementia. There are similar oddities between different types of cancer when it comes to available research funding. In Europe, breast cancer is the second most prevalent cancer type and only the third most common cause of death from cancer, but receives by far the most funding. Lung cancer is by far the most deadly, responsible for 22 per cent of all cancer-related deaths, followed by bowel cancer with 10 per cent and only then breast cancer (7 per cent). However, lung cancer remains significantly underfunded compared to other major cancers. In 2012, breast cancer received £41 million in research funding, bowel cancer received £35 million, whereas lung cancer was given only £14.6 million. Again, there are possible explanations: breast cancer has marginally higher rates of incidence than other kinds of cancer in the UK, even if it tends to be more survivable. There is also the factor of lifestyle choice. All of these cancers are influenced by behaviour, but approximately 85 per cent of lung cancers can be attributed to smoking. According to Easter 2015
FOCUS
NATIONAL CANCER INSTITUTE
Cancer Research UK estimates, smoking is the largest single cause of cancer in the UK, responsible for an estimated 19 per cent of cancer cases in the UK each year. Similarly, about another 18 per cent of all cancer cases in the UK are linked to poor diet choices (too little fruit, vegetables and fibre; too much red and processed meat and salt), obesity and alcohol use. Whilst a fair proportion of breast cancers are also preventable, the lifestyle choices needed to do so are more various. Factors like obesity, heavy drinking, reproductive history, hormone replacement therapy and a lack of time spent breastfeeding are all associated with a few per cent higher risk, but there is no single large contribution. This leads to the suggestion that cancer funding is influenced by the degree of blame placed on the suerer. The second best funded type of cancer research is leukaemia in spite of being responsible for only 2.8 per cent of all cancers. It is, however, the most common type of cancer in children, whose lifestyle cannot be blamed for their condition. Given this lack of funding for preventable cancers, it may be surprising that less than four per cent of cancer research funding is directed towards prevention. Over the past decades researchers have learned that tumours are biologically much more complex than initially believed. We now know that a vast genetic variety exists not only between tumours of the same type but also within individual tumours. It is therefore unlikely that there will ever be one magical cure for all cancers. However, as our understanding about the molecular mechanisms that drive cancer development and progression increases, our abilities to pursue novel and more eective therapeutic strategies to battle cancer also improves.
Hilda Mujcic is a postdoctoral researcher at the Department of Medical Genetics Patrick Short is a PhD student at the Department of Applied Mathematics and Theoretical Physics Abigail Wood is an undergraduate student in the Department of Biochemistry Nathan Smith is an undergraduate student in the Department of Plant Sciences
Close up: a picture of a breast cancer cell taken by an electron microscope
Robin Lamboll is a PhD student at the Department of Physics
Easter 2015
Focus 21
Leprosy: A History of Stigma Abigail Wood investigates the human impact of this ancient disease LEPROSY IS AN INFECTIOUS disease that has been depicted in human culture for over 4000 years, yet it still persists in human populations to this day. It is a truly global problem with a wide geographical and historical distribution, moving from the Asian subcontinent to mainland Europe, before spreading to South America. The disease is still endemic in modern-day India, Brazil and Indonesia. The word ‘leprosy’ derives from the Ancient Greek ‘λέπρα’ (lepra) meaning ‘scales’, but the exact definition of leprosy has changed over time. Prior to the discovery of its causative agents, many skin diseases were lumped together under this definition making tracking the true spread of leprosy a particular challenge when studying the disease’s history. Scientists currently understand that leprosy is a chronic disease that is caused by an intracellular infection with Mycobacterium leprae, a bacterium closely related to the species that causes tuberculosis. Its ability to infect new hosts varies over time, but aside from humans the only known natural reservoir of M. leprae is the armadillo, which acts as a good host due to its low body temperature (30–35°C). Whilst the disease can be transmitted between infected humans, leprosy has a strong genetic component, with only five per cent of people being susceptible to infection in studied populations. Research into new treatments for leprosy is limited, as M. leprae features the longest doubling time of any known bacterium, at 13 days. This makes it difficult to generate the large quantities of bacteria required for experimentation.
STEVE HOPSON
The armadillo is the only non-human host for leprosy causing bacteria
22 History
Patients with leprosy initially experience numbness before skin lesions being to appear. First to be lost is the sensation of temperature change as nerve damage removes the extremes of hot and cold. Next is the loss of light touch, followed by loss of pain and deep pressure. The lesions progress and can cause deformities - nasal damage, loss of eyebrows and eyelashes, and distortion to the face and body. This disfigurement can result in profound mental health consequences, with social ostracisation applying another burden of suffering to those afflicted. Our earliest archaeological evidence for leprosy is a 4000-yearold skeleton, discovered in India during 2009. In terms of written descriptions, the earliest definitive example can be found in the Indian medical treatise, Sushruta Samhita (600 BC). A Chinese text entitled Nei Ching by Huang Ti also includes an authentic account of leprosy. However, the date of these writings is disputed, with estimates ranging between 230 and 2005 BC. From this we can conclude that leprosy has existed on the Indian subcontinent from around 2000 BC onwards, with later records indicating spread in South Asia, Africa and the Middle East. The most common written accounts of leprosy arise from the best-selling book of all time: the Bible. This document has proved to be a source of misinformation regarding leprosy for several centuries. Words traditionally interpreted as ‘leprosy’ arise in both the Hebrew Old Testament and the Greek New Testament; however, it is now thought that these are inaccurate translations. The Hebrew word ‘Tsara’ath’ probably refers to lesions that are associated with ritual impurity and not a specific disease. Whilst this could include leprosy, it also covers stains appearing on cloth, leather and houses along with other skin afflictions. However, that early conception of leprosy as a religious synonym for sin or uncleanliness has subsequently been taken by some Christian societies to show that those with leprosy are set apart and may either be cursed or blessed. European accounts of leprosy begin with the return of Alexander the Great from India (326 BC), and in Roman history with the return of Pompeii’s soldiers from Asia Minor. It failed to
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take hold across Europe until the 11th century, when it is thought that Crusaders returning from the Middle East carried the disease to the continent – although as a result, it was initially viewed as an upper-class disease and sufferers were treated well. The medieval belief that the disease was highly infectious led to the establishment of leper houses. According to the monk Matthew Paris, there were 19,000 such institutions across Europe by the
mid-12th century. Some thought that lepers were experiencing purgatory on earth; others suggested that they existed between life and death as sacred knights or ‘Nazarites’. By the 13th century, certain monks alleged that community leaders were declaring sufferers legally dead in order to confiscate their property and goods – although spouses were expected to honour their marital bond and support the leper until their death. In the later Middle Ages, the leper houses (or leprosariums as they came to be known) were made mandatory for all those with the disease. Sufferers were expected to carry a loud bell or clapper to announce their presence to others, and were often expected to walk on a particular side of the road, dependent on wind direction. Lepers were increasingly reviled, with church doctrine leading to the popular theory that God inflicted leprosy as a punishment. An end to widespread leprosy in Europe came with the Black Death that killed a large percentage of the population; lepers were especially vulnerable to this secondary infection as they were already immunocompromised. By the end of the 17th century, Norway and Iceland were the only countries in Western Europe with large leper populations. In 1840s Norway, the leper population increased after visitors from India arrived with the disease. Scientific research was established, and in 1873 Gerhard Henrik Armauer Hansen made an important breakthrough: using a microscope, he identified the disease-causing leprosy bacterium and demonstrated that it was contagious. Hansen
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was punished for deliberately attempting to infect a 33-year-old woman with leprosy in order to test his theories about the disease, but he was later honoured at the first International Leprosy Conference held in Berlin, 1987. Treatment of leprosy has developed slowly over time. Prior to the 20th century remedies have included arsenic, creosote and elephants’ teeth. The use of poisonous mercury was also common as it was already available for the treatment of syphilis. From the early 1900s onwards, doctors administered repeated injections of chaulmoogra nut oil. Whilst the treatment appeared to work in some cases, it was often too painful for use in patients. The first leprosy drug was introduced in 1941 and was used to treat patients in the US although it required several unpleasant injections. A new compound was discovered in the 1950s, but the leprosy bacilli quickly developed resistance to the treatment. Eventually, drug trials in the 1970s produced a cocktail of the three most effective drugs, christened multi-drug therapy (MDT). Despite the fact that leprosy is now completely curable, it still haunts humanity. The World Health Organisation (WHO) declared official elimination of leprosy to less than 1 case per 10,000 people in 1991. However, hundreds of thousands of sufferers remain worldwide, with 180,618 cases reported in the first quarter of 2014. Detection and early treatment is crucial for preventing disfigurement, but poverty reduces access to medical care, particularly in rural areas. Women are disproportionately likely to present later with more damage from the infection, as their families may deny them the expense of medical treatment and a timely diagnosis. The resultant social abandonment of leprosy sufferers makes treating these neglected populations much harder. Thus, despite the development of affordable and effective treatment, the social stigma of leprosy still causes suffering across the world – and will continue to do so in the 21st century. We will only be free from this ancient disease after we undermine this prejudice and provide accessible treatment for all.
Clappers carried by leprosy sufferers in the Middle ages
Abigail Wood is an undergraduate student in the Department of Biochemistry
History 23
(Bio) Music to Our Ears Laura-Nadine Schuhmacher explores the emerging field of biomusic, a new way of enjoying, understanding and engaging with biology MUSIC IS ALL AROUND US, and everybody seems to
have an innate appreciation for it. Without learning an instrument or understanding how to read a score, we can immediately differentiate between a harmonious chord and an off note that doesn’t fit in. Music can create strong emotions in the listener, and due to its repetitive elements it is easy to memorise; so easy in fact that we often can’t get rid of a melody that is stuck in our head. A new way of creating music has emerged over the past few decades, called biomusic. This is any kind of sound that originates from nature and that can be perceived as music to our ears. Originally, the term was used to describe musical animal sounds such as bird and whale song, but more recently this definition has expanded to include music that has been created through the translation of biological information into sounds, for example by appointing musical notes to letters of genetic code or sonification (representing data as non-speech sounds) of a physiological parameter such as heartbeat. In the 1980s, scientists first began to create algorithms that would transcribe the building blocks of life, DNA and amino acid sequences, directly into sounds. The pioneers of this art used palindromic or short repeat sequences, because they most closely resembled the repetitive structure of musical compositions. They were searching for a new form of creative input to their music, as well as trying to make science more appealing to the general public. One difficulty biomusicians face is the capacity of the code itself to translate into musical melodies;
WIKIPEDIA
The structure of a protein can be interpreted as music
24
Science and Art
DNA for example only consists of four different nucleotides. To circumvent this problem, Takahashi, Miller and Klionsky devised a system in which they assigned chords to each of the amino acids and used the underlying DNA codons (up to four different combinations for each amino acid) to encode the length of the chord, thereby creating a rhythm (Takahashi et al. 2012). In their publication ‘SNARE Dance’, they created an audible representation of SNARE family proteins, functioning in the process of macroautophagy, where waste products of a cell are enclosed in vesicles and subsequently digested. The amino acid sequence of the proteins involved in this process in yeast cells, Atg9 and three SNARE proteins, were transformed into a musical score and each protein was assigned to a different musical instrument. The piece was then arranged based on biological interactions of the proteins, creating an additional layer of information to a conventional visual representation. Going one step further from protein sequences, how about using a whole organism as the template? Eduardo Miranda, Professor for computer music at Plymouth University and a driving figure in the field of ‘Unconventional Computing’, has found an unlikely duet partner in the slime mould Physarumplycephalum. In its plasmodium state (a gooey collection of many cell nuclei in one large cell), the slime mould can be used as a biological substrate to perform computational tasks, such as finding the fastest connection between food sources. In one extraordinary experiment, food pellets were arranged to represent Tokyo and the surrounding 36 cities, and the brainless slime mould was able to build a network strikingly similar to the existing train network between the points, using the most effective routes to connect them. When Professor Miranda makes them grow on a network of electrodes, the movements and physiological state of the slime mould create electrical impulses that can be transformed into sound. At this year’s 10th Peninsula Arts Contemporary Music Festival, Miranda performed a duet for piano and slime mould for the first time, using the electrical stimuli from the slime mould to vibrate the strings of a grand piano, thereby creating a completely new, eerie kind of music. The sonification of biological electrical stimuli is Easter 2015
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not just a tool to find new ways of creating music; it also has an important clinical application. In a recent study, Professor Miranda used a technique called Brain-Computer Music Interfacing (BCMI) to enable patients with severe physical disability to express themselves creatively by making music. This way patients who retain cognitive ability, such as with locked-in syndrome, can experience recreational or therapeutic music sessions. An electroencephalogram (EEG) consisting of electrodes placed on the scalp, can record the overall electrical activity of millions of neurones. The patient can evoke EEG activity by imagining the process of movement (for example thinking about lifting an arm) or, in patients with healthy vision, by eye movement. In the pilot study, a patient faced a screen with icons that represent sounds, and was able to play them like a piano just by staring intently at them. The bravest and most emotional story about the use of biomusic came from a study led by Stefanie Blaine-Moraes at the University of Michigan. In this study, she tried to improve the personal bond between patients with multiple disabilities, who have completely lost the cognitive and physical ability to communicate, and their parents and caregivers. The study looked at three patients and their group of parents and caregivers, who were interviewed before and after experiencing the patient’s music to establish the effect that biomusic had on their interaction. Music was created from physiological states of the otherwise completely unresponsive patients: ectodermal activity created the melody, fingertip skin temperature served as the key, pulse defined the tempo and respiration was translated into phrasing. Real-time music was created during daily routines. Almost all participants, especially the parents, described the
Features
experience as very positive, because they could now hear changes in physiology in direct response to their actions. One parent reported that the music intensified when they came closer to their child, and it made them feel like their presence was acknowledged, giving them a sense of meaningful interaction. This is a powerful example of the use of science and music to create an emotional connection, something that these families hadn’t been able to experience in years.
Slime moulds use electrical impulses that can be translated into music
The field of biomusic has undergone an expansion from the simple recording of birdsong to the creation of music from electrical activity of neurones, protein sequences, heartbeat or breathing rhythm. The possibilities seem endless, and this platform of interaction for scientist and artists is sure to contribute to both fields: it gives artists a new instrument to play with and creative input. A project along these lines to look out for is the new album of the band OK Go, who are planning to encode their album in DNA. For scientists, it is a chance to present data in new dimensions and make it more accessible. Laura-Nadine Schuhmacher is a PhD student in the Department of Pharmacology
References:
Running Away From Inflammation: Gleeson, 2011, Nature Reviews Immunology; Pedersen, 2006, Essays Biochem. Defeating Ebola: WHO Ebola reports, http://www.who.int/csr/don/30-december-2014-ebola/en/ How Reliable is your Memory?: The Innocence Project, http://www.innocenceproject.org/cases-false-imprisonment How does Nature Deal with Humans?: MacIvor and Moore, 2013, Ecosphere; Foote, 2004, Nature Comms
Focus CRUK cancer stats: http://www.cancerresearchuk.org/cancer-info/cancerstats/; Tursz, 2015, Molecular Oncology;
Regulars
History of Leprosy: http://www.britannica.com/EBchecked/topic/336868/leprosy/248485/History BioMusic: Blain-Moraes, 2013, Augmentation and Alternative Communication; Miranda 2007, Medicine and Music Behind the Science: https://www.mariecurie.org.uk/who/our-history/marie-curie-the-scientist
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Science and Art 25
Jenny Westoby describes the life and career of the physicist and chemist Marie Curie
THINK OF A FAMOUS female scientist. For many
Marie Sklodowska Curie (1867-1934) was the first woman to win a Nobel Prize
26 Behind the Science
people, Marie Curie is the first name that comes to mind. Not only did she win the Nobel Prize in Physics for her work on radiation, but she also won the Nobel Prize in Chemistry for discovering two new chemical elements. She was the first woman to win a Nobel Prize and the only person ever to receive a Nobel Prize in both Chemistry and Physics. Whilst Marie is rightly remembered for her impressive scientific achievements, less is known about the woman behind them. Marie Curie was born in 1867 in the Russian partition of Poland. Her father worked as a science teacher at a time when teaching experimental science was banned in Poland. After use of laboratory equipment was banned in schools, he brought the equipment home and taught his children how to use it. Despite excelling at school, Marie was unable to attend university in Poland because it was illegal for women to study at Polish universities. So, Marie and her older sister Bronya made a pact: Marie would stay in Poland and work as a governess to pay for Bronya to go to medical school in Paris. In return, after graduating, Bronya would support Marie through university in Paris. Initially, she struggled at the University of Paris, both with the language and her lack of previous experimental training, but she overcame these struggles and graduated first in her year in chemistry and second in physics. Whilst searching for lab space to perform research on the magnetic properties of steel, she was introduced to Pierre Curie, who was to become her husband in 1895. In early 1896, Henri Becquerel reported that uranium and uranium compounds emitted ‘rays’ that discoloured photographic plates. These ‘rays’ were dubbed ‘uranium rays’, and were to become the focus of Marie Curie’s doctorate. By measuring the electric current in the air around pieces of uranium, she was able to confirm Becquerel’s observation that the intensity of the electric current produced by uranium rays was proportional to the amount of uranium present, and was unaffected by the form of the uranium (solid, liquid or gas). She
also created a hypothesis that would revolutionise our understanding of the atom; she postulated that uranium rays were an intrinsic property of uranium atoms. If this hypothesis was true, then atoms must be divisible as they were able to emit rays and particles. This went against the commonly held belief at the time that atoms are indivisible. Marie demonstrated that another chemical element, thorium, also emitted radiation, and she invented the word ‘radioactivity’ to describe this phenomenon. During her research, Marie discovered that two uranium ores called pitchblende and chalcolite were much more radioactive than uranium. From this, Marie deduced that the ores must contain undiscovered elements that were more radioactive than uranium. Her husband Pierre became interested in her work and the two of them set about trying to extract the new elements. After several years of hard work, they finally managed to identify two new
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EMMA L DAVIS
Marie Curie
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Uranium is a chemical element with atomic number 92 (the number of protons found in the nucleus of that element)
WIKICOMMONS
elements, polonium and radium. It took them three years to extract 0.1 grams of radium from the ores. They were unsuccessful at extracting polonium due to its very short half-life. In 1903, the Curies were jointly awarded the Nobel Prize in Physics for their work on radiation alongside Henri Becquerel. Marie Curie was not originally nominated for the prize, which would have been solely awarded to Pierre Curie and Henri Becquerel had it not been for Pierre’s insistence that she receive the recognition she deserved. She was not allowed to give a lecture at the prize-giving ceremony because of her gender. Marie Curie was to win a second Nobel Prize in 1911, this time in Chemistry for the discovery of radium and polonium. Unfortunately, this time she would be unable to share it with Pierre, who died in 1906 after being run down by a horse-drawn wagon. Between winning her first and second Nobel Prize, Marie Curie endured a turbulent ride with the French press. She was portrayed as a heroic wife and mother until 1910, when she offered herself as a candidate for a seat in the French Academy of Science. Her main rival was Eduoard Branly, a French scientist who had made contributions to wireless telegraphy. French patriots felt strongly that the seat should go to a Frenchman, and French Catholics were keen for Branly to win the seat because he had been singled out for honour by the Pope. The right wing press attacked Marie and spread false rumours that she was Jewish. One academy member said, “Women cannot be a part of the Institute of France.” Marie Curie lost the seat by two votes, possibly in part because of negative press. But worse was yet to come. Rumours that she was having an affair with one of Pierre’s former students began circulating. Paul Langevin was married but separated from his wife and had four children. In late 1911 the French press claimed to have found love letters sent between the two of them, starting a media storm. Some newspapers described Marie as a Jewish homewrecker, whilst others claimed she had started the affair before Pierre’s death, driving Pierre to commit suicide. Marie returned home from a science conference to find an angry mob outside her door and had to rescue her daughters from the house. Amid the media chaos, she received a telegraph saying she had been nominated for a second Nobel Prize. History tends to remember Marie Curie for her Nobel Prizes, but Marie’s life was far from over after 1911. The First World War broke out in 1914, and Marie realised that X-rays could help doctors save lives at the battlefront. She set up the first military radiography centres in France, becoming Director of the Red Cross Radiology Service. She not only
taught herself how to use X-ray equipment and how to drive a car, but also learnt human anatomy and went with doctors to the battlefront to treat injured soldiers. Her eldest daughter Irène became Marie’s first radiological assistant. Irène was awarded a military medal for her hospital work. However, Marie received no recognition for her work, possibly because of her recent scandals in the press. After the war, Marie ran a successful fundraising campaign in the US to enable her laboratory to buy more radium. During her campaign she attracted the attention of the US President Warren G Harding who presented her with the radium himself. Marie became Director of the Radium Institute in Paris, which published 483 works between 1919 and her death in 1934. Marie died of aplastic pernicious anaemia, almost certainly due to her lifetime of exposure to radiation. It is right that Marie Curie is remembered for her scientific achievements, but it should also be remembered how much prejudice she had to overcome. She faced xenophobia and sexism at almost every stage of her career. Although she received recognition for some of her scientific achievements, she was given very little recognition for her wartime efforts, and many of the things she achieved after her second Nobel Prize have been largely forgotten. Marie Curie’s successes should be remembered in context of the obstacles she had to overcome to achieve them, making her one of the most inspiring scientists of her time. Jenny Westoby is a student at Sidney Sussex College
Behind the Science 27
NASA, ESA ADN THE HUBBLE HERITAGE
4 News
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Happy Birthday Hubble! 25 YEARS AFTER being launched into orbit, the Hubble Space Telescope continues to produce astonishingly high-quality images of the skies. Here it combines visible light with infrared light that can penetrate dust clouds to show the red stars as they are being formed in the Westerlund 2 star cluster. RL
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Reviews 5
Extreme Engineering Nathan Smith explores vehicle adaptations for extremely cold environments IT IS NOT UNUSUAL for the UK transport network to grind to a halt over extreme fluctuations in the weather. Snow, wind and rain have all been culprits of innumerable delays. So how is mechanised transport adapted to a place that is the coldest on earth and covered by snow throughout the year? Antarctica is one of the most inhospitable places on earth – at least for mammals – and is a good example of an extreme climate. Whilst there is no permanent human population on the continent, numerous researchers travel and live there each year to accomplish tasks ranging from as broad as monitoring and surveying, to as niche as analysing algal populations. All of these workers require transport. Traditionally, dogs have been used for transport in Antarctica; from being the force that powered Amundsen to the South Pole in 1911, right through to the end of the 1970s. However, Annex II to the Protocol on Environmental Protection to the Antarctic Treaty banished dogs from Antarctica in 1994. The ban was introduced due to concerns about the possible transfer of diseases, such as canine distemper, from dogs to native seal populations with potentially devastating ecological consequences.
Additionally, there were fears that some dogs could escape and disturb or even attack the native species of Antarctica. Finally, it was considered contradictory to have strict controls on the introduction of non-native species in Antarctica, whilst maintaining a breeding population of sled dogs. However, the ban had little eect on transport in the Antarctic as by the end of the 1970s, after a period of mechanisation of Antarctic transport, the dogs were principally kept at research stations for recreational purposes and to raise morale. Indeed, only 14 dogs were left when they were finally all removed in February 1994. Vehicles from temperate climates are unsuitable for use in Antarctica and require numerous modifications in order to be used reliably. The adaptations can be simple or more complex, intending to improve both motility and safety for the driver. On the simple level, vehicles are brightly painted. Whilst this may seem a trivial adaptation, it allows for easy visibility during snow storms. The same cannot be said for collections of UK cars in varying shades of grey. Additionally, many vehicles are equipped with electric heaters to ensure the engine stays warm. When the vehicle is not active,
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Sled racing is popular around the Arctic but banned in the Antarctic
30 Technology
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the heaters are plugged in. This allows the use of many ‘normal’ cars and as a result, many of the vehicles in Antarctica are very similar to the ones found driving around the rest of the world. Indeed, the first ever production vehicle to be used in Antarctica was a Volkswagen Beetle with only a few adaptations to make it suitable for the use in Antarctica. Its modification included an insulated battery, an aluminium cover for air intake (as part of the air cooling system that pulls air past the hot engine avoiding the problem of frozen cooling fluid) and strengthening bars to the front and rear. Indeed, apart from the ‘Antarctica 1’ plates given to the car, the modifications were all standard adaptations to VW vehicles destined for northern Europe. However, this isn’t to say that specially adapted vehicles don’t exist. Hägglunds are dual-cab tracked vehicles with a variety of impressive modifications that allow them to operate in extremely cold climates. Perhaps most surprisingly, they float. One might initially question the need for a floating vehicle in the land of ice and snow, but this is an important feature. In uncharted areas of sea ice, the thickness of the ice is unknown and, should it break, the Hägglund’s buoyancy will prevent the vehicle (and crew) from going straight to the bottom of the ocean. Its tracks are another highly useful feature. The tracks reduce the risk of ice break-ups by increasing the area over which the vehicle’s weight is applied, thereby decreasing the pressure placed on the ice. Furthermore, the tracks of both cabs are powered, providing the track equivalent of a
four-wheel drive and enhanced traction. Extreme conditions require extreme fuels. The pour point of diesel (the point at which it becomes gel-like in consistency and unable to be pumped) ranges from about -6°C to -18°C and, in a place where the monthly mean winter temperature at coastal stations is between −10°C and −30°C, this provides an obstacle to vehicle operation. As such, the vehicle fuel used in Antarctica is ‘Special Antarctic Blend’, a very highgrade diesel free from additives that freeze at higher temperatures. Petrol, with a freezing point of between -40°C and -60°C, is less susceptible to freezing and tends to be used by smaller vehicles. Furthermore, there is now the development of zero-emission cars that are able to function in the Antarctic climate. Capable of withstanding temperatures as low as -50°C, the vehicle ‘Venturi Antarctica’ is able to recharge itself through both wind and solar power. With a range of only 20 kilometres, it still needs further development. However, it certainly seems that electric vehicles will become an increasingly important part of travel in the Antarctic.
Tracked vehicles called Hägglunds can float
The Venturi Antarctica is a green vehicle built to be used in Antarctica. It is a zero-emission vehicle capable of functioning under extreme weather
The Antarctic will continue to be an important area for scientific research and these extreme vehicles are going to accelerate the process of discovery. The vehicles themselves are unique to the icy deserts of both the Antarctic and the Arctic region, and represent fantastic feats of engineering. Further improvements will continue to be introduced and it may not be long before we even see a Polar Express. Nathan Smith is an undergraduate student in the Department of Plant Sciences
Technology 31
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Weird and Wonderful A selection of the wackiest research in the world of science.
ALEX HAHN
IT’S LATE SUNDAY MORNING and you’re making breakfast. You’re boiling some eggs when, next thing you know, you’re craving an omelette. Is it too late? Fear not! Scientists at the University of California, Irvine, have discovered how to un-boil an egg; and not only could this save your breakfast, it could also save your life! The trick is in the folding, unfolding and refolding of proteins. As the cell’s best workers, proteins are responsible for catalyzing metabolic reactions, transporting molecules and replicating DNA. The proteins in a boiled egg are tangled and disordered, or ‘denatured’, from being heated. The key to un-boiling an egg is to administer the reverse effect and untangle the proteins, snapping them back into their natural shape. Pharmaceutical companies are interested in this process because it provides scope for more efficient methods of drug manufacturing. Cancer antibodies, for example, are made from hamster ovary cells because they are less likely to become denatured in the first place. Unfortunately, these cells are very expensive. If scientists could use cheaper cells in conjunction with the ‘un-boiling’ method to keep proteins in their desired formation, cancer treatments would become much more affordable. One caveat though, this process requires the use of ‘urea’, the main component of urine - so you may want to skip the technique for breakfast after all. AH
Parasite Puppeteers there are twisted tales of mind-controlling parasites. Usually, this is because the parasite requires two different host organisms to complete its life cycle and therefore needs to ensure transmission from one host to another. To do this, the parasite manipulates the behaviour of its first host to increase its likelihood of being eaten by its second host. An example of this is the tapeworm tongue-twistedly named Schistocephalus solidus. These tapeworms begin life inside tiny aquatic crustaceans called copepods, but complete their development in fish. Being a mind-controlling master, it makes the copepod host more active and thereby more likely to be spotted and eaten by a fish. Conversely, if the tapeworm is still too young
IN THE ANIMAL KINGDOM
ALEX HAHN
32 Weird and Wonderful
to move hosts, it decreases the copepod’s activity. But what if the tapeworms are forced to share their host? Interestingly, two mature tapeworms work as a team to make their copepod more active than if it was infected with only one. However, when an old and a young tapeworm inhabit the same copepod, the older tapeworm takes control and masks the effect of the younger tapeworm completely. What makes the younger tapeworms give way, or are they sabotaged? The question still remains. AW
Head in the (Mushroom) Clouds
ALEX HAHN
Which came first: the cancer cure or the un-boiled egg?
“LET US TURN ours into a country of mushrooms by making mushroom cultivation scientific, intensive and industrialized!” This is one of 310 slogans recently released by North Korea. It may seem a rather peculiar statement to rally a country behind, but is there a point to it? The expansion of North Korea’s mushroom industry is a favoured project for Kim Jong-un, the Supreme Leader who ensures his people never starve. In 2013 he announced plans for mass production of mushrooms. His reasons may be linked to his grandfather Kim Il-Sung, the Eternal President of the Republic, who hoped to turn North Korea into a leading mushroom producer. His ambition gathered pace in 2014, with the alleged development of a new mushroom-based sports drink for athletic prowess, though no further details have since been released. North Korea already has a well established mushroom industry. Whilst statistics are few for the hermit kingdom, it is an important exporter of the expensive matsutake mushrooms, which once accounted for up to 30 per cent of the Japanese market, where they are particularly prized. In 2006 the Japanese government banned them, following testing of the nuclear bomb. North Korea’s fungal fantasy is still rather restrained by wider policy. The question is: is there mushroom for change? NS
Illustrations by www.alexhahnillustrator.com
Easter 2015
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Moreover, house was lined population 15 to 80 per cent to a with g a teenager, is still used today, to spread of committin reproduce was related is over, you’re ready accused ‘disciples’, memories in between s have wondered if certain s new specimens. some, and cannot method for cataloguin false memory botanical drawings theanother to collect researcher nature, by the ‘felons’ had been his case studies, one the and with a definitive largelyinaccepted emotional on system wasbeen on the For 300 went to at the weekendfrom finding your keys to ly, given its reputation participants. Researcher susceptible to false memories s. This has rary the memory taxonomys relies The population After analysing the classificati in contempo did, later,accusation Perhaps surprising item. the false more of pioneering but for others is used 250ofyears valuable Everything you Overters from a history Biologists classify been no a loss oftya and tests, required your types of people are communi injury or scientific confirmed that three-quar such student’s as an so far, there has of classification. to passing your today, botany stems as incorrect Botany only ; class, order,such details about the have allowed memory, others. However, Linnaean system riding your bike, true on. scandalous tales. than faulty memory. certain types of categories and to more s years ts that included due the classificati 200 function: logy were expedition his five-tiered suggesting false stories usingntuitively, in biotechno caregiver. Participan species having Counter-i discipline less than species brain to use a critical term ‘memory’ to describe by their advances conclusive evidence to false memories. Even those Recent told the of DNA the less with every is to provide the eyewitness testimony. and variety, became an academic study of plants was considered each as in such life, as previously prone techniques a memory, newhappened genera, Psychologists use is aboutspecies the ns of to use The aim what people are more phical memory and retrieves someone is name. explain scientists compariso e stores to leisure, the of autobiogra ago. Historically, memory confident two-part ing asked and others were authentic remember and gentlemen highly superior its own ps. sinceLatin upon to produce be, to how the brain processes, difficultyquantitativ es atospecies your from sequencin of memory begins and who have If theyghad memories thrust an activity for ladies gardens. 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In the case Shaw much to serve own experience. named for thebyfirst as sequences between DNA sensory informatio remember anyway. and colonise foreign better than false conducted Juliaalong with a description, level of difference ts again to remember theparticipan suggestion, a common ancestor.are reported sent out to explore , including new the perceivedcalled sensory memory. The sensation from In a separate study UK, and Stephen identification. For the restriction of they asked thename, provides they also asked exotic curiosities of divergence it is ire inthe degreeboth This allows memories, thresholds theabout the justice system, a heavy reliance taxonomy in second, also to bring back reference forinfuture a modest looking and we can definewere University of Bedfordsh in short-term memory. techniques, and as possible as theofformal British Columbia and fauna. However, these methods, their memories values. ic, with nois then stored to unjust was very fond of without rehearsal, poor interviewing species of flora be to Using of numerical Linnaeus couldthem include how vivid Porter at the University can all contribute in termsthem. was very problemat to get innocent example,hours field Of thea30 around seven items, of The on which he believed long-term between species witness-testimony in name. only a fewwith for granted, were about early modern Europe the identification or naming you to recall white flowers, is much a d serious there had tea, and hehow confidentitthey to a minute. Finally, indefinitely. Canada, it took plant take your memory for committed So seems that theyin they had perpetrateto Chinese white past n us to categorise for several seconds virtually every uniform methods outcomes. So don’t allowing ts who wereistold false world. of living arguing about some crucial some participants believing a Swedish alternative us to retain informatio it is not borealis. The first type a centralised scheme, names were you’re participan permits time Linnaea taxonomy Without of next the plant of memory developed more open species. species g, but and the cent had the diversity Linnaeus named may want to be named his beloved own system and sense of 11 crime, 71 permake can be very convincin had even elaborated the eccentric event with a friend, you to episodic denotes the genus; collector had his tive so it was almost Memory species and can be deceiving crime, and of the to Carl Linnaeus, part of the name fact, when it comes d and uninforma a stressful part denotes the memoryWe In s, owe muchwith portraits, to their side of the story: memories second his police. talking aboutalways accurate. In The the experience from often convolute were of dealing seen smilingon, the result this after himself. if two botanists your keys uses e, past and present the north’. precious the isdetails Swedish pastor, it means ‘from impossible to tell interrogati memory, perspectiv Finding , can all turn and clutching his at times, after all. a police clothing specimen - this and in this case such asladies n and suggestion function: on situation,wearing different ways to also provide a type the same species. in his classificati a critical Just like biases, imaginatio was brain an illustration be even worse. We might find untilbut he will be s between botany Scientists now to botany of deception. z is an MPhil student and memory s associationexperience could Linnaea borealis.are you innocent of the species, or into a mistress Linnaeus’ legacy a five-tiered the scandalou bizarre man, else . Ann (Chen) Hascalovit memoryDespite , your gained remains: a preserved individualorganism is rare. This wasn’t The question organisms into , Development this brilliant andyou or someone your experience of classification change can system. He divided father of taxonomy the Department of Physiology h if the them two part would classifyor innocent ed until Linnaeus’ system the of the first he memory gave as sex, one that and photograp and was or twist memory. ve and day but is a forever remember proven change your hierarchy of categoriesLinnaeus introduced the term can also the guilty, n. The British Museum system and two sides to Memory is a constructi are Linnaean Neuroscience. recognitio required in Linnaeus’ himself is now recognised as “Theret the adage: believes you’re guilty? influenced by others and by for human implemen names. For example, heard the s to It’s not it had become th century institution have loved. Linnaeus sapiens. truth.” meaning ‘wise man’ the 18th centuryYou’ve the 18 there’s of the Murray Edwards thenhalf reconstructive process; ‘Homo sapiens’, of Homo second is a student at every story, by theand straightforward, type specimen of Linnaeus’ work, are lying, but because Sophie Protheroe species is relatively a more e. sides . beings. As a result the ‘Age of Classification’. because both , passionate differently The naming of necessarily very fashionabl is event as individual ial same organisms exact described of College controvers intriguing the was is often perceivewas an theirLinnaeus is Linnaeus were a baby, people can for classification however, the grouping age. Asthat so different to their Originally, species Linnaeus’ scheme from anis early experience nota flower s the plants with Easter 2015 about grassit’s contentious issue. basis of physical characteristics. Sometime g plants by reference in the And distorted. becomeslept at first, categorisin The fact that plants reproduce frequently on the haveevent to the 13 decorated his th memories said of distinguished Easter whomemories 2015 when different species stics. here. False What’s in a Name? his father, at risk arise are by sexual characteri end of the 17 hand that he collected and placed inpshis However, problems recognised at the just relationshi flowers. As a child, were both sexually was only British botanists were shocked son’s cradle with plants His interests in Botany became century and uptight sketched plants. Linnaeus’ system. Easter 2015 10 Memories by the crudity of and poetry of the in the literature highly eroticised Easter 2015 JESSICA MCHUGH
IVICA LETUNIC
ELIZA WOLFSON
ANGELA IBLER
Memories 11
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