Bang! Science Magazine Issue 11 by The Oxford Scientist

Bang!

The Vision Issue Oxford Science Magazine 11th Edition Trinity Term 2012

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In This Issue:

3. Editorial 4. News 5. Manufacturing the Weather 6. Facing the Facts 8. Emotional Logic 9. The End is Nigh 10. Making Man Immortal 12. Robert MacLaren Vision 14. Building a Bionic Eye Section 16. Resolving the Rainbow 18. Seeing Stars 20. Is Seeing Believing? 21. Chemistry with a Bang! 22. Popping the Pill 23. It’s Hip to be Square 24. The New Ancients 26. Life in Old Bones 27. Transmissable Tasmanian Tumors 27. Killer Conus Snails 28. Bang! is online Editor-in-Chief — Anna Pouncey Deputy Editors — Hugh Lindsey, Laura Soul & Isobel Steer Sub Editors — Philip Bennett, Jack Binysh, William Brandler, Christian Camm, Lauren Passby, Jack Sennett & Jessica Smith Creative Director — Sofia Hauck Layout Editors — Natasha Chetina & Joey Faulkner Assitant Creative Team — Ilse Lee & Iona Richards Artists — Natalia Davies, Maria Demidova, Aparna Ghosh, Inez Januszczak, Natasha Lewis, Clementine McAteer, India Stephenson, Hanna-Liisa Vilu & Rachel Zacharia Website — Jai Juneja & Paul Tsui Publicity & Distribution — Sian Evans & Rosalind Gealy Business — Miranda Kent & Paulin Shek

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Editorial

Try these illusions to test your skewed perceptions: The red lines are perfectly parallel.

literature and philosophy, ‘vision’ is synonymous with knowledge, understanding and insight into the future. This seems reasonable, as sight is our main tool for understanding the nature and location of the objects around us. The human eye is so sensitive that it can respond to a single photon of light, and processing the visual world is one of the most complex tasks that the brain performs. It involves nearly half of the cerebral cortex. However, there are limits to this sensory apparatus. Firstly, the photosensitive cells in the human eye are only responsive to a restricted range of the wavelengths in the electromagnetic spectrum. We only see between 400-700nm, while bees can see ultraviolet and snakes infrared. Moreover, what we perceive may not actually be the truth that exists in the world around us, but instead is a product of our cognitive processing. A good example of this is when we recognise an object as 3D even though we only see its facing surface, a process known as amodal perception. Furthermore an image is recognizable even when interrupted, for example looking at a dog through a picket fence. This use of preconceptions and hypothesis in cognitive processing is essential in optimising our understanding of visual information when we have minimal cues. However, the drawback is that we can miss the obvious or jump to false conclusions, as occurs in optical illusions. If this is taken into account, then the phrase “seeing is believing” is a rather spurious one. Similarly, if the words of philosopher Arthur Schopenhauer were true, that “every man takes the limits of his own field of vision for the limits of the world”, then our understanding of the world would be a rather narrow, incomplete one. While this perspective can extended to all aspects of life, it is particularly important in science. The scientific method offers a seductive promise; that through the use of disciplined and testable methods we can deduce the laws of the world around us. With ever-increasing technology and the wave of advances and discoveries in the last century or so, it can be tempting to think that man is gaining a measure of the Universe. But for this to progress further, an awareness of the fallibility of our current conclusions and an open mind to what might be, are essential to ensure we don’t miss the obvious.

Focus on the red dot and move the magazine back and forth.

So, readers of Bang!, we hope you advance as visionaries. Perhaps one day you will change our insight into the workings of the world.

Anna Pouncey Editor

Keep an eye out on pages 12-19 for our special vision section.

News

Electricity Goes Viral

Analysing Ash

ll of us can remember the eruption of an Icelandic volcano that plunged Europe into transport chaos. But this cloud turned out to have a silver lining. Two years down the line it seems that the event provided a great natural laboratory, from which we have learned a great deal. Several Spanish research groups have recently published work explaining how aerosols (fine particles) released during the Icelandic eruption were intensely tracked and studied like none had been before. Measurement devices and precise models were tested and rapidly improved. Aerosols have been frustrating climate scientists for years. They are a vitally important factor to understand if we want to attempt to model and forecast our planet’s future climate. Research suggests that they affect everything from sea surface temperatures and the state of the arctic ice sheets, to the strength of a monsoon. The data and models that have just been released will not only aid in climate modelling but will help reduce the economic impact and risk to human health from any future events of this kind, allowing us to be prepared.

One Protein to Rule Them All

single protein may be the key to unlocking the secrets of signal transmission in the brain. A team led by Dr. Timothy Ryan at Weill Cornell Medical College, New York, have shown that the protein α2δ acts like a tap on the end of nerve cells. Discovering how to turn this tap on and off could be vitally important in understanding how the brain works, and how to treat neurological disorders. The researchers have shown that α2δ controls the number and position of calcium channels at the tip of a nerve cell. Calcium released from these channels triggers release of neurotransmitters, which allow a nerve impulse to jump the gap from one cell to the next. When the protein adds more channels, the tap gets turned on, and nerve impulses can be transmitted rapidly and effectively across the gap. When it removes channels the tap is turned off, blocking any signal. Certain pain medication seems to utilise this effect by ‘breaking’ α2δ molecules, which prevents the formation of new calcium channels, thereby blocking off pain signals in the brain. What is interesting is that only α2δ seems to have this role. “We are amazed that any single protein has such power,” said Dr. Ryan. This has important implications. If we can learn how to control this one protein there is potential for advances in treatments for pain, as well as treatments for neurotransmitter diseases such as Parkinson’s. News by Laura Soul, Art by Ilse Lee.

ortable charging devices have the potential to revolutionise our use of technology. Researchers at California’s Lawrence Berkeley National Laboratory have taken the first steps towards creating such a device by designing a tiny electricity generator that never needs to be plugged in. The team, led by Seung-Wuk Lee, used a virus called the M13 bacteriophage to make a prototype that produces enough energy to flash up numbers on a screen with just a tap. The key feature of the virus is that it is piezoelectric; it converts mechanical energy to electricity. Lee and his co-workers genetically engineered M13 to enhance this ability to produce electricity, and then stacked up 20 one centimetre square layers to further enhance the effect. The virus itself has ideal properties for this application: it only attacks bacteria and so is completely harmless to people; it replicates itself millions of times over every hour, effectively providing an endless supply; it can easily be genetically engineered to enhance its electricity generating skills; and finally it naturally aligns itself with all of its neighbours due to its rod shape, i.e. it self assembles. “Piezoelectric materials based on viruses could offer a simple route to novel microelectronics in the future.” says Lee. The team is now working on ways to turn this demonstration into useable technology. Perhaps the day when we can charge our mobile phones from a paper thin device on our shoe, just by walking, is not so far away.

Manufacturing the Weather Is climate intervention the solution?

he slow pace of negotiations in international politics has left many sceptical that we will ever reach a meaningful agreement on CO2 emissions reduction. Could there be a better alternative to tackle climate change? For some, the solution lies in the concept of geo-engineering.

elsewhere in the atmosphere and causing warming. Promising results from the Met Office’s latest climate model suggest that only a 2.1 increase in the percentage of reflected sunlight would be enough to offset a doubling of atmospheric CO2 .

Geo-engineering is the deliberate large-scale manipulation of the environment to counteract anthropogenic climate change, this covers a range of techniques, all of which act to combat the greenhouse effect.

Experimental projects to test the feasibility of SRM geo-engineering are currently in preparation. The Cambridge University SPICE project (Stratospheric Particle Injection for Climate Engineering) plans to build an injection method for stratospheric

One approach to geo-engineering is use of carbon removal methods (CRMs). CRMs tackle the greenhouse problem by actively removing CO2 from the atmosphere. Techniques range from direct carbon capture out of the air, through to schemes that increase the ability of the ocean to absorb carbon from the atmosphere. Unfortunately, as current CO2 emissions are 8.5 Gigatonnes per year, CRMs would have to be implemented on a huge scale to offset this, and would need to be in place for at least several decades to make significant impacts on longterm atmospheric concentrations.

aerosols using a 20 km high tethered balloon based aerosol source. This would technically be the tallest manmade structure in history!

could allow us to bypass the political turmoil “I t of conferences like Copenhagen”

An alternative to CRMs is solar radiation management (SRM). Unlike CRMs, solar radiation management methods do not attempt to alter the atmospheric CO2 concentrations. Instead they attempt to offset the warming effect of the gas by altering the amount of solar radiation absorbed by the Earth. Currently, the most favoured method of SRM is the injection of specific aerosols into the stratosphere. These aerosols would reflect sunlight away from the Earth, preventing it from being absorbed

The attraction of geo-engineering is that it may allow management of global warming without having to negotiate a legally binding emissions reduction treaty. It could allow us to bypass the political turmoil of conferences like Copenhagen and Durban. Furthermore, modelling data suggests that schemes like SRM will be able to reduce global temperatures within a couple of years, making the

One solution involves tethering a 20km high balloon to a boat and using it to inject aerosols into the atmosphere.

technique especially useful as a method of last resort, used to avoid crossing a “tipping point” beyond which the climate system’s normal state is fundamentally changed. However, the scale of any intervention could still be a source of conflict. Different nations, attempting to optimise the climate for their geographical location, may push for different levels of climate adjustment. The exact effects of geo-engineering are far from clear. Industrialisation led us to release greenhouse gases into the atmosphere without understanding the effects they might have on the climate. Many scientists are worried about repeating past mistakes by trying to fight global warming with more changes to the climate that they cannot fully predict. As our understanding of the climate improves, and if negotiations over emissions continue to fail, interest in geo-engineering will inevitably grow. It would undoubtedly be a useful tool in humanity’s quest to control its own destiny, but unless properly understood and implemented, it has the potential to make the global climate situation much worse. Geo-engineering might not be the perfect solution, but it may end up as humanity’s only option.

Richard Millar is a 4th year at Merton College, studying Physics Art by Sofia Hauck

Bang! You

Facing the Facts The truth about social networks

FACTS 50% of Facebook users will log in on any given day On average, each user will have a total of 229 friends More than 125 billion friend connections exist There are 30 million Facebook users in the UK More than 10 million photos are uploaded each day 80% of Facebook friend requests are accepted Women average 21 status updates per month, while men average 6

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If you’re reading this, there is a good chance that you’re one of the 800 million Facebook users, 30 million of whom reside in the UK. Half of those users have logged in today, and the ones at university will spend half an hour updating statuses, liking wall posts and peeping at friends’ photos. You’re not the only one looking. Academia has cottoned on to the usefulness of social networking sites. Researchers the world over, from fields as diverse as evolutionary anthropology, communication and computer science are looking to sites like Facebook for the very social data we spend hours uploading. In just the past few years, scientists have discovered why checking Facebook feels addictive, a connection between the bits of your brain involved in social interaction and your friend count, and even what your profile really reveals about you.

playing chess, writing poems… and checking facebook? Between replying to wall posts and tagging friends, hours can be spent on Facebook. Sure, social networking sites help people to communicate efficiently, but why do we really spend so many hours on them? Well, because it feels good. A 2011 article in Cyberpsychology, Behavior, and Social Networking reveals that using Facebook puts us in a “core flow state”. This is a psycho-physiological condition that combines the high mental stimulation of stress with the positive feelings of relaxation, leaving us feeling happy and excited. It acts as a feel-good signal that promotes repetition and practice. “Findings from a wide range of domains, including chess playing, writing, sports, and visual arts, show a positive correlation between flow

state measures and…performance,” the authors say. We like it, so we do it a lot, and that repetition makes us even better at it. But why might our bodies encourage us to dedicate so much time to Facebook? There is an evolutionary reason why some things feel good. Back before food shops, we evolved tastes for fat and sugar because they contain enough calories to see us through lean times. In the case of social indulgence, it feels good to be well liked. Emotionally and practically, friends are a major source of support; that support is every bit as important to survival as getting enough calories.

bigger friend count, bigger brain According to recent animal studies, more friends may actually result in bigger brains, and savvier social skills. Researchers found a correlation between the volume of the parts of the brain dominant during social interaction–the amygdala, amongst others–and the number of companions an individual was housed with. Human testing too has long shown that people with more friends and better social skills have enlarged amygdalas. As yet though, there have been no long-term studies

on humans and social networking sites that indicate whether having Facebook friends grows grey matter, or if it is this expanded social brain that leads to a high friend count in the first place. Extrapolating from the relationship between primate brain sizes and community sizes, Oxford evolutionary psychologist Robin Dunbar estimates that our social networks (those people we would feel comfortable sitting with if we saw them at a café) are limited to about 150 people. This might explain why, despite the

relative ease of clicking the “Add friend” button, the median user has around 100 Facebook friends. But maybe that’s a good thing. Astronomical friend counts send bad signals. In a recent study, university students viewed the same Facebook profile, but experimenters varied the friend count to 100, 300, 500, 700 and 900. Results showed that none were keen to call the 100-friender cool, but the big surprise was that the further north of 300 someone’s friend count went, the closer their coolness scores got to that of the 100-friender.

How many facebook friends do we keep in contact with?

out of 50

out of 150

out of 500

39 9 4 47 2 7 26 17 10 16 19 22 2 7 11 1 57 910 1 46 34 maintained relationship one-way communiaction mutual communication

female

your profile, your self People checking out your profile notice a lot more than your friend count. Everyone’s own profile is easily manipulated. This led some American researchers to predict that people would pay more attention to “othergenerated information”, posts from friends and the like, that cannot be doctored by the profile owner.

male

In areas where users are prone to lie, other-generated information is rated much more highly–anyone who has tried Internet dating knows physical attractiveness tops that list. The most important source of this information is photographs. More than friend counts and comments, photos make big impacts. In fact, having hot friends makes people think you’re hotter yourself.

log out

In Facebook-land, personal appearances are so important that unless your own profile picture is somehow revelatory of something negative, people ignore the text and mine all their information from photos alone. Undergraduates who viewed a profile picture of a classmate having a good time rated her as extroverted, even if her “About Me” section said she preferred quiet nights alone by a fire. As for us here at Bang!, whether we are trending on twitter or adding friends on Facebook, we love to be connected. Don’t worry, we will add you even if your friends aren’t that good looking.

Jaimie Arona Krems is studying Cognitive and Evolutionary Anthropology at Kellogg college.

Graphic by Iona Richards

Emotional Logic Is it an oxymoron?

nger, revenge, forgiveness—most think these emotions have little to do with cold, hard rationality. We regularly describe people as ‘mad with rage’, but rarely as reacting ‘completely logically with anger’. However, recent research suggests that our emotions may be more rational than we think. In the last two decades, researchers in evolutionary psychology have been uncovering how our emotions can drive us to better behaviour—better, that is, in the Darwinian sense. They suggest that the neural pathways behind emotions such as anger and forgiveness might have evolved to solve recurrent problems faced by our ancestors.

Anger

According to Dr. Aaron Sell of Griffith University in Australia, anger has an entirely rational purpose.

orgiveness and revenge are “F just as much logical strategies as they are emotional reactions”

All people have Welfare Trade-off Ratios (WTRs): internal calculators of the extent they’re willing to gain benefits by imposing costs on someone else and the extent to which they’re willing to tolerate someone else imposing costs on them. Of course, everyone has different WTRs for different people.We see this in action whenever you let your friend (but not a stranger) jump ahead of you in the cinema queue, or when you let your father have the final bit of cake you would fight a sibling for. Everyone places more importance on some people’s welfare than others, and when it comes to how much other people value your own welfare, anger can be a tool.

Forgiveness

Anger isn’t the only emotion ruled by rationality. Ignoring your hunger-fuelled ire, your brother stuffs the cake in his mouth. Do you forgive and forget, or fly across the table? University of Miami evolutionary psychologist Mike McCullough thinks you’d actually react pretty rationally. Like anger, research reveals that forgiveness and revenge are just as much logical strategies as they are emotional reactions.

Anger can incentivise someone to place more weight on your happiness than they did at first, if you can back it up. For example, as you glare at your brother over that bit of cake, he is forced to think about the costs you could inflict on him (kicking his arse once the parents are out of earshot) or the benefits you could withhold (not lending him any of your belongings).

Forgiveness is necessary for survival in a world where social ties mediate access to food, shelter and sexual partners—it makes sense that there is a strong conciliatory tendency, starting in infancy, that can be seen across cultures. So is revenge, which functions as a primitive form of social justice.

Dr. Sell found that men with greater upper body strength (i.e. those who could inflict higher physical costs) were quicker to anger, and it worked most of the time. Even though stronger males were likelier to come to blows than weaker ones, often just flexing their angry biceps was enough to prevail.

According to McCullough, both are also the computational output of our evolved mental machinery. He asked 1,300 undergraduates how close they felt to their current romantic partners and had each rate what they’d do if their partner borrowed something of theirs, ruined it and didn’t apologise. Analysis revealed, perhaps unsurprisingly, that likelihood of forgiveness was correlated with how much the person meant to them and how likely the victims thought they were to get hurt again.

This result suggests that anger is more about logic and negotiation than we would assume.

These unconscious calculations are the result of natural selection, shaping our minds into complex machines that use our seemingly irrational emotions in logical ways—to repair relationships, ward off exploitation, and occasionally get our hands on some cake.

Jaimie Krems studies Cognitive and Evolutionary Anthropology at Kellogg college

Art by Hanna-Liisa Vilu

The End is Nigh... Or is it? Should we be dreading doomsday?

ecember 2012 will bring the apocalypse, doomsday and Armageddon, at least according to numerous theories. So, should we expect the arrival of the four horsemen, followed by earthquakes, floods and locusts? Should we empty our bank accounts and spend the money whilst we can? Probably not, says NASA’s page of FAQs dedicated to quelling people’s fears and preventing mass hysteria. Yet despite efforts to quash rumours about our impending demise, the Internet is crawling with disaster websites and false prophets preaching that the end is almost upon us. One of the most popular predictions is that of the ‘Nibiru collision’. According to this myth, a small planet popularly known as Nibiru, or Planet X, will crash into or pass closely by the Earth, causing a polar shift that will end all life. Polar shifts are changes in the location of the poles of the Earth, which could cause floods and tsunamis. Don’t start choosing your hat for Judgement Day just yet though, since Nancy Leider proposed the idea of the ‘Nibiru collision’ in 1995, claiming to be receiving messages from aliens via an implant in her brain. She initially foretold that this doomsday was

than Pluto that is on the outskirts of our solar system. But again, NASA refutes this notion: “The closest it can come to Earth is about 4 billion miles.” Another ‘apocalypse 2012’ theory comes from the notion that the Mayan calendar ends in 2012. Some believe that the ancient civilisation

has a dedicated page of FAQs for quelling “NASApeople’s fears and preventing mass hysteria” supposed to occur in 2003, but when nothing happened the date was conveniently pushed back to 2012. Numerous scientists have debunked this myth, stating that there is absolutely no evidence to support the existence of a Planet X. “If Nibiru or Planet X were real and headed for an encounter with the Earth in 2012, astronomers would have been tracking it for at least the past decade, and it would be visible by now to the naked eye,” declared NASA. Some apocalyptic theorists, faced with a lack of evidence for Planet X, claim that Eris will cause the collision, a dwarf-planet larger

of Maya, famed for their iconic art and architecture as well as their astronomical systems, predicted the end of the world to be in 2012. So were the Mayans: a) prophetic, b) pessimistic or c) too lazy to continue the calendar? The answer is none of the above. The Mayan calendar works using a series of cycles, both long and short, with one of the longer cycles ending in 2012. The Mayans never actually predicted the end of the world; rather another long cycle of the calendar begins in 2012.

But what about the threat of giant solar storms? Scientists have stated that there will be increased solar activity in the next couple of years. Naturally, some disaster theorists took this a few steps further and have claimed that the Sun will turn against us, producing deadly eruptions and bursts. Solar activity does flare up on an approximately eleven-year cycle and so we are due to experience solar flares - some have even occurred already. If the charged particles are sufficiently energetic to disrupt our satellite or radio systems, they could disable power stations and our GPS and communication systems. While this may be detrimental to our civilisation, it is not quite apocalyptic. So the only truth we have to face is that people are willing to exploit these predictions for their own gain. However, if you are still concerned, smart phone users can now download an app that will give a warning 30 minutes prior to doomsday. Mahnoor Naeem is a 1st year at Keble College, studying Chemistry

Art by Aparna Ghosh

Making Man Immortal

When will we celebrate the first 1001st birthday? he prospect of immortality is a tantalising one. What once would have been dismissed as science fiction is increasingly being debated as a serious, attainable goal for humanity. Some argue it will be with us sooner than we think...

“Utterly unrealistic, optimistic and nonsensical” Oxford recently played host to a fierce debate between Professor of Neuroscience Colin Blakemore, and Aubrey de Grey, a famous advocate of the Immortality Institute. In between sniping about the perils of pension schemes for thousand year old retirees, the two men argued over the nature of ageing itself. De Grey laid out “7 categories of molecular change” which cause agerelated decline, and claimed that his Strategies for Engineered Negligible Senescence foundation will soon have the “regenerative medicine” to halt the ageing process in humans. In the words of Colin Blakemore, the solutions to the seven causes

of aging are “utterly unrealistic, optimistic, and nonsensical”. But each of these proposals has one not-so-wacky fact in common: they are already technically feasible. Even the most radical, WILT (Whole-

“I

increase in lifespan. De Grey insists that their combined effects will be substantial, saying “I do not recall Henry Ford alerting potential customers that the components of a car—in isolation—remain obstinately

do not recall Henry Ford alerting potential customers that the components of a car remain obstinately stationary when burning petrol is poured on them”

Body Interdiction of Lengthening of Telomeres), has been shown to work on rat blood and stomach tissues, in a 2005 paper by de Grey. One major criticism however, is that each of these treatments has not yet individually caused substantial

Don’t let them eat cake However, such radical solutions are years – twenty five according to de Grey - away from practical applications in humans, even if fully funded. In the meantime there is a DIY solution, but it’s not exactly a palatable one (literally). It is called, in a fairly self-explanatory manner, Calorific Restriction, and has been shown to increase lifespan o mice by 40%. When food is plentiful, our bodies increase insulin production, as well as related hormones and proteins that cause cell growth. Insulin, our sugar-sweet friend, is actually cellular poison. It inhibits DAF genes, and these are the ones that control ageing. By drastically reducing our calorie intake, we may be able to avoid this production of insulin. However, most consider human calorie restriction unviable, since it requires a degree of starvation that would lead to infertility.

stationary when burning petrol is poured on them”. Rather, he claims that such research is currently well on the way to doubling rodent lifespan within the next 10 years.

TOR on tour Research on the link between diet and ageing has found a key nutrient sensor called TOR (Target of Rapamycin). When an abundance of nutrients is entering the body, TOR reacts by prompting cell growth and division and simultaneously instructs cells to reduce intracellular recycling (autophagy). When food is scarce TOR becomes inactive, meaning cells focus on self-preservation instead of replication. Meanwhile, autophagy increases to provide the raw materials for cellular repair and energy generation. After an organism reaches maturity, TOR’s continued activity can lead to excessive protein synthesis, forming destructive protein aggregates. It can also result in unwanted proliferation of certain types of cells (such as smooth muscle, which contributes to narrowing of arteries and heart disease). In addition it can cause decline in various cell functions (such as reduced insulin sensitivity) and promotes cellular senescence (when cells stop dividing but grow abnormally large and become toxic). TOR activity also suppresses autophagy, allowing damaged cellular material to accumulate in cells. Inhibition of TOR interferes with these effects and is thought to slow ageing. Such inhibitors can be chemical (Rapamycin) or physical (calorific restriction). However, at the moment such strategies come laden with side effects such as toxicity and immunosuppression. With de Grey’s solution to aging a long way off it seems that if you want to live to 1001, you can have your cake but you can’t eat it. Isobel Steer is a 2nd year Biological Sciences student at St. Hilda’s College

The Seven Challenges of Ageing EXTRACELLULAR JUNK The white blood cells of our immune system could be stimulated by vaccination to eat it along with bacteria. CELL LOSS This can be combated by growth factors and exercise. (The steroidsand-treadmill approach.)

INTRACELLULAR JUNK This could be spring cleaned by the 3. Extracellular junk The white blood EXTRACELLULAR introduction of –enzymes cells from of our immune system could be CROSS LINKS other species. stimulated by vaccination to eat it along These links, which cause with bacteria. tissue to lose elasticity, can be broken by the right drugs.

CELL AGING This can be erased by simply laser-zapping any ageing cells before they turn toxic.

CANCER Age related cancers are caused by elongation of telomeres (the caps on the ends of our DNA), which allows continued mutation. WholeBody Interdiction of Lengthening of Telomeres (WILT) would regulate the genes needed for telomere elongation.

Art by Natasha Lewis and Sofia Hauck

MITOCHONDRIAL MUTATION Mitochondria are the engines of our cells but their genes quickly become damaged as we age. The suggested solution is to transfer these genes to the more protected cell nucleus to slow their mutation rate.

Bang! talks to... R

Robert MacLaren

obert MacLaren is Professor of Ophthalmology at the University of Oxford, Consultant Ophthalmologist at the Oxford Eye Hospital, and Bodley Fellow of Merton College. He specialises in diseases of the retina and developing new treatments for blindness using gene therapy or stem cells. His clinical focus is on the genetics of retinal diseases and new techniques in retinal surgery.

So Robert, what exactly do you do? I’m an eye surgeon, but I am an academic as well, so I do research in the lab. I am interested in finding out how we can develop new treatments for blindness. Most of the common and untreatable causes of blindness are due to diseases of the retina. This includes age-related macular degeneration in the elderly (the most common cause of sight loss in the developed world), and retinitis pigmentosa in younger people (an inherited genetic condition). I have observed that is that it is possible to treat and cure many of these diseases in laboratory models. However, there appears to be a bottleneck in getting laboratory work translated into clinical trials. So, one area that I am interested in is converting laboratory work into viable clinical trials, which could help many of the patients I see. How did you come to choose the very specialized field of ophthalmology (the science of the eyes)? I am quite keen on surgery and I realised that eye surgery was a very satisfying form of operation. It is technological - we use lasers, ultrasound and all sorts of gadgets. It is also quite challenging, which makes it more interesting. Saying that, it’s very civilized; you perform the operations sitting down and they are short, so it isn’t too tiring! Most importantly, the patients are generally very happy with what you do. It is a great thing to help someone see the world clearly again.

Why is the study of genetics particularly important in ophthalmology? The photoreceptor is the lightsensing cell in the retina, and it is arguably the most complex cell in the body, involving hundreds, maybe thousands of different proteins working together. The failure of any one of those proteins can lead to photoreceptor degeneration. This is why the photoreceptor is so susceptible to gene defects- an

that you will get the disease. With risk associated genes there is a probability that you might correct that disease, but it is not guaranteed 100%. What are the most exciting projects that you are working on at the moment? We have a gene therapy trial, the first of its type in the world, to try and treat an inherited retinal disease known as chorioderemia (an X linked, recessive, vision degenerating

is technological - we use lasers, “I t ultrasound and all sorts of gadgets.” estimate is that 1/3 of all genetic diseases lead to blindness in the retina. In the study of retinal diseases we are quite privileged in knowing that genetics plays a large role in most diseases that we treat directly. If you go blind because of a condition in which you are missing a single gene, it means that when we can replace the gene, we can correct the disease at its most basic defining level. Therefore, you won’t go blind.

Lens

In many other diseases we are Cornea unraveling a polygenetic role; Iris where there are several genes that confer risk and there is a random probability

disease). We inject a virus into the eye, and the virus carries the DNA of the missing gene (inserting it into the cells DNA). It has been shown in the laboratory that this technique will in fact stop or slow the degeneration of sight. Through the trial our patients have had full restoration of their sight. This means that the use of gene therapy to prevent sight loss is something that in the future should be very achievable. Research is still

Retina Retinal blood vessels

Macula

ongoing, so it is too early to say whether the treatment has been truly effective, but the initial results have been very promising. We are also working on an international trial of an electronic retinal implant developed by Professor Eberhart Zrenner. We have treated one patient in Oxford. His eye had no light perception for

- take for example a pacemaker. If we could develop stem cells so that they could be injected into the eye and regenerate the retina without being rejected, that would be very exciting. But, work on this is a long way off and I have to keep reassuring people that all the talk about stem cells is the talk of the future. I may see it done in my lifetime, possibly. The electronic retina and gene therapy is something

his is an absolutely amazing concept; “T to take someone who has been blind and enable him to see again.” about ten years, but now, when the electric retinal implant is switched on, he can see basic shapes, objects and outlines. This is an absolutely amazing concept; to take someone who has been blind - in total darkness - and enable him to see again. The technology is very early, and this is the first clinical trial, so we didn’t know whether restoring sight in this manner was really possible until now. I understand that this restored vision is in black and white. Do you think that in the future it will be possible to restore colour sight too? The current electronic device consists of 1500 diodes that are just on or off. You could in theory have a device in which the diodes had different colours and responded differently, but then the brain would have to learn which diode corresponded to which colour all over again. It would not be impossible, because the electronic retina would stimulate the next layer of cells beneath the degraded photoreceptors. In your opinion which is the most promising area of research - robotic devices, gene vectors or use of stem cells? I have to be honest with you and say that I think that a biological approach is probably the most promising. Saying that, there are artificial electronic devices that are used in medical treatment that work very well

that can potentially be used now, so it is important to focus on developing that. So, where do you see things being in the next 20 years time? In 20 years time we will probably be using gene therapy as a routine procedure, to prevent sight loss in patients with a variety of retinal diseases. That is how I would like it to be; that we will cure pretty much most inherited retinal diseases. Macular degeneration affects around 1 in 4 people over the age of 75, and in our ageing population the cost of repeated injection treatment of the disease is phenomenal, so to develop a one off treatment of genetic therapy would be ideal. When we achieve that I will probably retire! Which do you prefer: ocular surgery or the study of genetics? I like the study of genetics, but I wouldn’t give up the operating, because that is the patient contact. So, if I were to do one or the other I would choose clinical work, but I would read genetics books on the quiet when no one was looking.

You are a tutor at Merton College and do quite a bit of teaching. What motivates you to do this? I like to keep my mind fresh, and a good way of doing that is to teach subjects, because when you teach something, you need to think about it clearly in your own mind. I think that teaching is a very good discipline to make sure that you keep up to date with things, and I am of the strong opinion that it is something that helps research and doesn’t detract from it.

Interview by Anna Pouncey Art by Iona Richards

Subretinal Implant

Retina Lens

Building a Bi

Using robotics to b

he subretinal implant is designed photoreceptors in their eye due t into the space where the photorec function of the degenerated photore to light.

Optic Nerve

Vitreous Humour

Sclera

1mm

Microphotodiode Array Photodiode

Although each human retina has r only 106 nerve axons. This data understanding what we see begins i the signals it transmits still pass thr

How does the

The implant is designed by Professo sensitive microphotodiodes in a silic electric current. This is then amplifie This triggers signals in the retina, w

Laye

Electrode Contact Hole The chip is being tested in an international clinical trial. The UK branch is led by Professor Robert MacLaren (see pages 12-13) and Mr Tim Jackson, in Oxford.

To the Brain Muller Cell Ganglion Cell

What can users of the chip see? The chip gives 1600 pixels of resolution. The human eye has been estimated to have at least 576 megapixels. The brain recieves flashes of light rather than normal vision. Images are seen in black and white. It can provide the user with a 12 degree angle of useful vision. (About the width of a CD case held at arms length.) Users of the chip are able to distinguish objects on a table and even to read large letters (height 5-8cm).

Amacrine Cell Bipolar Cell Horizontal Cell Photosensitive Cell Layer Rod Cell Cone Cell Retinal Pigment Epithelium

Bionic Eye

The Retinal Players

bring sight to the blind...

d to restore sight to people who have lost the light-sensitive to disease. The retina has many layers and the chip is inserted ceptors would normally lie. The implant aims to replace the eceptors, point by point, by stimulating the retina in response

roughly 108 photoreceptors, output to the brain occurs via compression shows us that processing of visual input and in the eye itself. The subretinal implant has the advantage that rough this information processing system.

subretinal chip work?

or Eberhart Zrenner in T端bingen. It has an array of 1500 light con chip. Light falling onto each microphotodiode generates an ed and passed through an electrode to stimulate bipolar cells. which travel through the optic nerve to the brain.

ers of the retina

Light

Light-sensitive retinal ganglion cells contain a

photopigment, melaopsin. These cells are non-image forming, but are important in control of your natural body clock and of pupil restriction.

Ganglion cells transmit signals from the retina to the brain.

Cone cells are used in daylight and colour vision. (See pages 16-17.)

Rod cells are found all over the

retina. They do not discriminate colour and are 100 times more sensitive to light than cones and so used for dim light vision.

Muller glial cells act like fibre

optic cables, channelling light to photoreceptors. They also help to refract blue light to bring it into focus on the retina at the same point as red.

Bipolar cells transfer information

from rods and cones to ganglion cells. ON cells depolarise in response to light and are responsible for signalling bright parts of an image. OFF cells hyperpolarise in response to light and signal the darker parts of an image.

Direction of signals sent through the Retina

Horizontal Cells have many

connections with each other and so respond to light over a larger area of the retina. They are important in lateral inhibition which increases our perception of contrast at borders.

Electrode Light Sensitive Microphotodiode Amplifier

Amacrine cells are implicated

in detection of motion and also in surround inhibition. This is a process which helps to increase perception of contrast.

Subretinal Implant Anna Pouncey is a 5th year Medicine student at Merton College

Resolving the Rainbow What gives us an eye for colour?

olour perception is a creation of the brain. It is the system we use to identify the different wavelengths of light to which we are exposed. This enables us to distinguish boundaries between areas, which are equally bright but reflect light differently. This perception is the result of a chain of neural events beginning with specialised photoreceptors in the eye, finishing with high level cognitive processes. So, how does this process unfold?

An Eye for Detail

outer segment of cell containing photosensitive chemicals

The origins of colour detection lie at the fovea; a small area of the retinaonly 1.5mm in diameter- found at the back of the eye. There are three types of photoreceptors (cone cells) used to recognise colour, each of which is most sensitive to a different wavelength of light. The receptors are often labelled as blue, green and red. This discrepancy in wavelength sensitivity is due to the different types of photopigment (cone opsin) within the cone cells. Cone opsins are molecules that change their shape in response to light. This change is used to convert the light energy to a signal in the cone cell. The fit between the wavelength of light and the binding site on different photopigments determines sensitivity of the cone cell to different colours (wavelengths) of light.

nucleus

Blue Genes

con es

ro ds

d con re

gre en

retinal response

75%

es on

Fig. 1: Cone cell (blue) and rod cell (red.)

100%

blue c

However, the different types of cone cell do not respond to mutually exclusive wavelength ranges; instead there is overlap between them. Why is this overlap necessary, and why do we need three different colour receptors? The answer lies in the existence of another variable – light intensity – which also affects the extent to which colour receptors respond to incoming light. A green colour receptor may respond similarly to bright yellow light as to dim green light; thus, a greater light intensity can compensate for a receptor’s poor absorbance of that wavelength.

50%

25%

visible spectrum

Fig. 2: The photopigments found in rod and cone cells are most responsive to different wavelengths in the visible spectrum.

In order to remove this ambiguity in colour perception, our brain compares the relative activation of the three different colour receptors to specify the light’s wavelength. For example, if the green colour receptor is strongly activated in addition to the red colour receptor, our brain interprets this as a bright yellow light. Approximately 8% of men and 0.5% of women have some form of colour blindness. This discrepancy between sexes is because the genes for both the red and green photopigments are located on the X chromosome. Men carry only one X chromosome whereas women carry two. Any mutation that disrupts the function of one these photopigment genes will result in colour blindness in a man, but not in a woman, as long as their other X chromosome photopigment genes function.

See What I Mean?

However, the importance of higher-level brain functions in colour perception cannot be overlooked. Imagine a world where different wavelengths were seen not as distinct colours but as different shades of grey – this is the experience of those affected by achromotopsia. The condition is caused not by faulty photoreceptors – but by damage to an area of the brain called V4. This is a part of the brain’s visual pathway, which is critical to our conscious experience of colour. Activity in V4 can be demonstrated by carrying out a simple task. Draw a dot in the middle of a blank page and large green, red, blue, and yellow circles surrounding it.

no r

“A

Fig. 3: Experience colour after-effects by staring at the left black dot for 20 seconds and then the space on the right.

pproximately 8% of men and 0.5% of women have some form of colour blindness”

al m

vision

red-blindness ‘protanopia’

blue-blindness ‘tritanopia’

green-blindness ‘deuteranopia’

Stare at the dot for 20 seconds before looking at a completely blank piece of paper. You should see colour after-effects: colours where none actually exist.

is clear that colour perception relies upon a chain of events extending from cone cell responses in the eye through to higherlevel brain processing. Disruption anywhere in this pathway can affect the entire system. However, perception of colour is not the only aspect of vision. Colour, form, movement and depth perception are analysed in parallel production lines in the brain. What scientists have yet to answer is exactly how and where these separate streams of information are re-integrated to form the consciousness we experience daily. Nonetheless, it is clear that the process of colour perception is not so black and white.

Fig. 4: Simulations of how individuals with three types of colour-blindnesses might view a colour wheel. Robert Blakey is a 1st year undergraduate at St Catherine’s College, studying Experimental Psychology Art and graphics by Iona Richards

Seeing Stars Adventures of the Hubble Telescope

very 97 minutes, at an altitude of 353 miles, the Hubble Space Telescope completes an orbit around the Earth. It is constantly in contact, sending us new photos of distant galaxies, and helping us to understand the structure of the Universe. Operating in space, Hubble is unique in avoiding atmospheric distortion, the major problem faced by ground-based telescopes. Shifting air pockets in the Earth’s atmosphere act like small lenses, bending light in different directions, and so images appear blurred. For the same reason our eyes observe stars twinkling. Situated above the atmosphere, Hubble can capture images of distant galaxies with a clarity that groundbased telescopes simply cannot achieve.

A Look Back in Time One of Hubble’s aims was to address the difficult problem of determining the age of the Universe. Before the telescope was launched, the best estimates were between 10 and 20 billion years old. A margin of 10 billion years isn’t exactly the most precise result but thanks to Hubble’s position above the atmosphere, it

But this isn’t all Hubble did for us. In December 1995, over a period of 10 successive days, astronomers turned Hubble towards a seemingly blank piece of sky and allowed it to capture as much light as it could. The result was the Hubble Deep Field, a remarkable and quite unexpected

thousand galaxies of different “T hree shapes, sizes and colours.”

was able to observe galaxies more distant than we had ever seen before. In a definitive study of 31 Cepheid variable stars (see box), astronomers were able to determine how far away these galaxies are. These distance measurements enabled the estimates to be refined and the age of the Universe to be narrowed down to approximately 13.7 billion years.

image. Looking back through time at 3,000 galaxies of different shapes, sizes and colours, at all stages of their development and including some of the oldest and most distant objects we know of, the Hubble Deep Field allowed cosmologists to follow the development of the Universe.

Quasars and Black holes Quasars, one of Hubble’s most notable discoveries, are among the brightest objects known in the Universe. They occupy the centres of young, active and very distant galaxies. They were first detected as single points of extremely bright light, initially thought to be stars, but Hubble helped reveal their encompassing galaxies. What’s more, the observations from the telescope helped to conclude that these dazzling galactic nuclei are powered by supermassive black holes. The black hole attracts a disk of swirling matter and, as some of this material falls into the black hole, the nearby region heats up and emits incredible amounts of energy and light: this is the quasar.

It must be noted, however, that Hubble has unearthed as many new puzzles as it has solved - none more confounding than dark energy. Every object in the Universe exerts a gravitational force on every other object; the larger and closer the objects are, the stronger the force. The net result of all these gravitational forces should be a drag, slowing down the expansion of the Universe, something astronomers turned to measure in the late 1990s using supernovae. Supernovae are stellar explosions which give out tremendous amounts of light and radiation and are the key to measuring long distances in space. Studying a supernova is very difficult as they only last a few weeks, so, astronomers turned to Hubble - the only telescope capable of studying the supernovae in detail in such a short time. The results, however, were not as expected. The supernovae were dimmer and, therefore, further away than theory predicted, suggesting that the expansion of the Universe was actually speeding up. Gravity, an attractive force, could not be causing this. Some unknown type of repulsive force must be responsible for this acceleration in the Universe’s expansion. Theories began to circulate of an undetectable ‘dark energy’ behind this force and supported by Hubble’s observations - they are now widely accepted.

absolute brightness

Dark Energy 13.25 13.50 13.75 14.00 14.25 14.50 2

time (days)

Cepheid Variables Determining distances in space is a difficult problem. How do you distinguish between a bright object far away and a dim one nearby? Without knowing the true brightness (absolute luminosity) of a star it is impossible to tell the two cases apart. Edwin Hubble, American astronomer of the early 20th century who gave his name to the Hubble Space Telescope, solved this problem using a type of star called a Cepheid variable.

distances is now easy, “Measuring just find a Cepheid variable.” Cepheids have the very special property that their absolute luminosity varies with an incredibly regular period (see graph) as the star’s size oscillates about an equilibrium size. In 1908, Henrietta Leavitt found a relationship between pulsation period and the average absolute luminosity of the star. In 1924, Edwin Hubble established the distance to the Andromeda Galaxy and since then Cepheid variables have played the vital role of being a “ruler” through space. Measuring distances is now easy: find a Cepheid variable and measure the period of its pulsation, thus determining its absolute luminosity; compare this to the brightness we see in the sky and you can calculate how far away the star is. — James Wills

A Lasting Legacy These are merely a few of Hubble’s contributions and achievements. Since its launch in 1990, Hubble has been our eyes into the infinite depths of the Universe. Its far-reaching gaze has helped to uncover many of the great mysteries of the cosmos. Hubble has been witness to the births and deaths of many stars, observed comet crashes and found extra-solar planets. Its adventures are sure to continue but eventually Hubble’s time will end. Its legacy, however, will remain.

Mahnoor Naeem is a 1st year at Keble College, studying Chemistry Art and Graphics by Iona Richards

Is Seeing Believing? M

The curious case of blindsight

ost of us are familiar with the visual sensations we obtain from the surrounding environment; on waking up we see a world of shape, colour, depth, and movement. But how necessary are these sensations? How much of the world are we able to ‘know about’ without consciously perceiving it? Broadly speaking, vision is a function of the cortex: the outer layer of the brain associated with more complex abilities. The ‘visual cortex’ is situated at the back of the brain and is divided into different areas, which correspond to different aspects of the visual experience. However, of particular importance is the primary visual cortex, or V1, which receives the information captured by the eyes and projects it to other areas of the brain. V1 is well suited to the job of vision. In 1982, Roger Tootell, of Harvard University, demonstrated ‘retinotopy’, a direct link between the visual scene and activity in the cortex. One-to-one correspondence between points in the visual field to parts of the brain effectively maps what we see onto the cortex. However, what is more interesting is what happens when V1 is removed.

Figure 1. Each area of the target seen by the eye is respresented in a specific area of the visual cortex.

Perhaps unsurprisingly, when someone’s visual cortex is removed; they report they can’t see. However, psychologists have been able to show that many people suffering from ‘cortical blindness’ can still process and respond to a range of visual information – a phenomenon known as ‘blindsight’. The first demonstration of blindsight was in 1974. By removing the visual cortex of an adult monkey, Professor

be the case. The condition suggests that there is a separation between ‘conscious’ and ‘unconscious’ vision. If all these abilities can operate without conscious vision, does awareness of what you see add anything useful? Sufferers of blindsight have no trouble using the visual information subconsciously. Professor Anthony Marcel showed that blindsight is not limited to dots and colours, instead,

the patients think they are guessing, “W hile their performance suggests otherwise” Humphrey of Cambridge University observed that the monkey, ‘Helen’, was still able to navigate obstacles and detect features as small as raisins (though she could not distinguish these from small patches of duct tape). This was despite the absence of V1. Similar observations have been made in humans whose V1 was destroyed by accident or by stroke. In 1987, British psychologist Larry Weiskrantz showed that a blindsight patient was able to spot the presence of a light projected into his ‘blind field’. While later work showed that patients with blindsight are capable of more sophisticated discriminations, such as detecting changes in colour. Usually these abilities are not detected from subjective testimony, as the patients themselves report seeing nothing at all. Instead researchers use the ‘forced choice’ technique. A range of choices are presented and the patient must pick a response. While the patients think they are guessing, their performance is statistically too good for this to

words or pictures could activate the same mental representations of these concepts. Perhaps conscious awareness of vision evolved to help guide behaviour. Other patterns of brain damage can lead to more specific sensory deficits. These include achromotopsia, in which the perception of colour is lost, and akineotopsia, where sufferers are unable to perceive motion. However, knowledge of motion and colour are important for survival: the critical difference in blindsight is that this information is still there, just not available to conscious inspection. Blindsight demonstrates that despite this ongoing stream of visual consciousness, what actually guides our actions might be completely unconscious. Exactly what, however, is a complete mystery. Daniel Yon is a 2nd year at Somerville College, studying Experimental Psychology Art by Iona Richards

Chemistry with a Bang!

The science of explosions

sk a ten year-old what chemists do and their first answer will probably be “make explosions”. As explosions can be inconvenient, most chemists try to avoid them - except high-energy materials chemists, who spend their days devising new and improved explosives. An explosion is caused by the very rapid expansion or release of gas, such as in chemical explosives or the intense heat of a nuclear weapon. The power of explosives is due to their chemical structures. The earliest explosive was gunpowder, first discovered by Chinese alchemists over a thousand years ago. It consists of a mixture of three chemicals: charcoal is the fuel, potassium nitrate contains oxygen that facilitates combustion, and sulphur is the catalyst. The key to making effective gunpowder is to grind the mixture into a fine powder, maximising contact between components and speeding up the reaction; and the faster the reaction, the bigger the bang. Any chemical reaction that is sped up sufficiently can become explosive – even burning flour. The first reported bakery explosion was in Turin in 1785. Flour itself is not very flammable, but it does contain carbohydrates that can be used as fuel. When the flour is dispersed in a dust cloud, it has an enormous surface area and the reaction speeds up, causing an explosion. The chemical revolution in the middle of the 19th century produced nitroglycerine, a more powerful and sensitive explosive than gunpowder. It was so dangerous that the British government banned it completely in the 1860s. Their concern was well founded. Alfred Nobel lost his brother to a nitroglycerine explosion in his factory. Perhaps it was this loss that drove him to create ‘dynamite’, the first stable explosive. The personal wealth that followed from this discovery provided the funds for his eponymous prizes.

Other explosives soon followed nitroglycerine, and many of these were safer, such as TNT. These new explosives have one chemical feature in common – the nitro ‘functional group’ - consisting of a nitrogen atom bonded to two oxygen atoms. The nitrogen-nitrogen bond in gaseous N2 is one of the strongest bonds known; therefore its formation in explosions gives out a lot of energy. The two oxygen atoms are key, as they can combine with carbons and hydrogens in the rest of the explosive to form CO or H2O, producing even more energy. Current research aims to synthesise safer and more powerful explosives, through careful design of chemical structure. To increase safety, molecules are engineered to bond to each other more strongly. This raises their melting point and so prevents them spontaneously detonating. One way to increase the stability of a substance is to increas the size of the molecules. To increase the power of the resulting explosion, extra nitro groups can be added. Earlier this year a molecule was made that had 10 contiguous nitrogen atoms. Another way to increase the power of an explosion is to add tension to the molecular structure. Octanitrocubane, an extremely powerful explosive, has eight carbon atoms tightly bonded at its core, but the bonds are forced into a rigid (and unstable) cube. The strain induced by this unnatural bond angle causes the cube to spring open and release the stored energy when detonated. It is inevitable as more ingenious techniques are devised that ever more unlikely-looking molecules will be crafted. However, this frontier of chemistry will probably remain the preserve of specialists, as even hardened chemists shy away from a reaction for which you need to wear body armour. High Energy Materials Chemists – we salute you. At a safe distance.

600 Discovery of gunpowder in China 1425 Gunpowder is granulated for the first time, increasing its power 1627 Explosives used in Hungary as a blasting agent for mining 1785 First known dust explosion in Turin bakery

1846 Nitroglycerine discovered 1863 TNT discovered as a yellow dye 1888 The British military replace gunpodwer with Pitric acid 1902 The German military make use of TNT in their shells 1930 Britain starts looking into RDX, the most widely used military explosive 1999 Octa- and Heptanitrocubane synthesised for the first time in Chigago

Matthew Cliffe is a graduate at Merton College, studying for a DPHil in Inorganic Chemistry Art by Inez Januszczak

Popping the Pill

to tell you a terrific story about oral contraception. “I want I asked this girl to sleep with me and she said ‘No.’” - Woody Allen

he Oral Contraceptive Pill (OCP) is, without question, one of the most prolific inventions of the past century. It has contributed to enormous social changes, redefining the roles of gender within society. At present, the ‘Pill’ is taken by over 2 million women in the UK and over 100 million worldwide. The ‘Pill’ refers to both the combined (oestrogen and progesterone) pill, developed in the 1950s, and progesterone-only pills that followed later. The hormonal nature of the treatments, and their common use, has resulted in a range of health scares; but what solid evidence do we have that the benefits out-weigh the problems with the Pill?

Effects on Health

Since their inception, a plethora of information on the various effects of OCPs has been reported; the struggle has been to rationalise this information and draw significant conclusions. It has been shown that use of the combined pill can lead to an increased risk of blood clots. However, this effect and others must be taken in context: in most 20-49 year old women the baseline rate of

Beyond Women

Some of the most interesting recent developments have been in the effects of OCPs on the wider community. Concerns have been raised relating to the levels of oestrogen-like hormones released into the watercourses of developed countries. With over two million women regularly making use of the pill, it is not surprising that the uptake of oestrogen by men

levels of oestrogen uptake has been shown “Higher to result in feminisation of fish population” thrombosis is negligible and therefore the absolute increase in risk is tiny. More seriously, studies suggest a slight increase in rates of breast and cervical cancer with combined pill use, but a large drop in the incidence of ovarian cancer. The effects of the progesterone-only pill are less well defined but studies have shown the results to be less significant. Overall, taking either type of pill has been shown to give a slight decrease in mortality.

and various fauna has increased dramatically. Higher levels of oestrogen uptake has been shown to result in the feminisation of fish populations, giving rise to poorly developed reproductive systems. Furthermore, recent research from a Canadian group suggests a link between prostate cancer and environmental oestrogens. More research will be required before the link can be confirmed, but these outcomes add a degree of complexity to our consideration of the pill’s population-wide effects.

More Subtle Effects:

The development of the OCP has been seen as liberating women in many ways. However, the use of OCPs often comes at the expense of barrier

contraceptives such as condoms. With no protection from sexually transmitted diseases (STDs) provided by the pill, rates of transmission of many STDs including chlamydia have continued to rise. It is difficult to ascribe this trend directly to OCP use, but it highlights the difficulty in fully assessing the effects of such a medication.

Conclusions

Science has developed powerful methods of monitoring the adverse effects of particular medicines such as the Pill. This allows us to define certain aspects of the safety of a medicine; but the effects of medicines extend beyond simple calculations. The myriad of psychological and social effects associated with the pill perhaps make defining such a ubiquitous medication as good or bad an insurmountable challenge. Whatever the conclusion, it is clear that oral contraceptives are here to stay and may even expand to both genders. Recent Israeli research has suggested calcium channels as a potential target for a male oral contraceptive and stage III trials are underway to test the efficacy of testosterone analogue injections. These advancements promises to make the question posed a whole lot more complex.

Thomas Mortimer is a 2nd year at Somerville College, studying Biochemistry Art by Natalia Davies

It’s Hip to be Square T

The dramatic life of Évariste Galois

o many, mathematics is seen as incomprehensible and boring, and mathematicians are viewed in a similar light. To fight this misconception I would like to outline the turbulent life and tragic death of one of the most inspirational minds in history: 19th century French mathematician Évariste Galois. In his teenage years Galois solved a long-standing problem regarding

But Galois’ world was far from confined to mathematics. He was politically active during a time of turmoil in nineteenth century France. Having written a letter criticizing the director of the École Normale, Galois was expelled from the institution. Before the formal expulsion took effect, he quit the school and joined Republican artillery unit of the National Guard. Soon afterwards, the unit was disbanded out of fear that

this frantically scrawled message he included the “I n outline of his most important mathematical ideas” solutions to polynomial equations. This first realization of Galois’s talent proved to be just the tip of an iceberg of mathematical brilliancy that was to follow. Budding mathematician that he was, he applied to the most renowned mathematical school of the time: the École Polytechnique. However, due to Galois’ lack of formal mathematical education, he was found to be too unclear – he did not know the terminology and notation used by professional mathematicians. As a result, his application was rejected. Instead he entered the École Normale, an inferior institution, and continued his research. It was here at the École Normale that he laid the foundations to modern group theory – an extremely important branch of mathematics which was still embryonic at the time. Galois was, in fact, the first to use the term ‘group’ in a meaning close to its modern technical understanding. Whilst at the École Normale he also worked on what is now known as “Galois theory”. These insights were vital for solving the ancient geometrical question of the possibility for some compass and straight edge constructions - like the famous problem of squaring the circle. Despite this, the Academy of Sciences still refused to publish his papers due to their lack of clarity.

they might destabilize the government and 19 officers were imprisoned. After several months, the arrested officers were acquitted and a banquet was held in their honour. Here, Galois proposed a toast to King Louis-Philippe with a dagger above his cup; this was considered a threat against the king. He was detained the following day, but released shortly afterwards. During Bastille Day Galois was at the head of the protest, wearing the uniform of the disbanded artillery, and came heavily armed. He was arrested again and imprisoned for six months. He continued his research both in prison and after his release, but his work remained unrecognised by the mathematical community. Galois’ life was brought to a premature end in 1832, when he was just 20. He died in a duel, the reasons for which remain unclear. It is strongly suggested that the reason was a broken love affair, indicated by a letter written the night before the fatal duel. In this frantically scrawled message he also included the outline of his most important mathematical ideas. It was to become his mathematical testimony and a legacy that continues to fuel mathematicians. Hermann Weyl, a mathematician, said of this testament;

“this letter, if judged by the novelty and profundity of ideas it contains, is perhaps the most substantial piece of writing in the whole literature of mankind.” Galois was a political firebrand, an unfulfilled lover, and a mathematical genius at the same time. Remarkable though his work was, it was not recognized by his contemporaries. It took years before he was fully appreciated, but his ideas still strike generations of mathematicians with their beauty, neatness and power. Some of the problems stemming from Galois’ considerations still have yet to find their tamer. One can only ponder how mathematics and the world would look like if that fatal duel had never taken place. Przemyslaw Pobrotyn is 2nd year at Lady Margaret Hall, studying Mathematics Art by Hanna-Liisa Vilu

The New Ancients Are you under the dino-delusion?

a glimpse into the past, dinosaurs offer a view of how different our world might have been if history (and a certain meteor) had taken a different course. The fossil record is notoriously incomplete, and palaeontologists must describe a creature sometimes based on no more than a single bone. Despite this, research continues and is as fastpaced today as ever. If the last dinosaur fact you discovered was at primary school, you might be surprised at how much your favourite childhood creatures have changed in your absence. Here is some of what you may have missed.

Oviraptor Oviraptor has a bad reputation. After all its name means “egg thief ”, and artists’ impressions often show them gingerly holding the stolen goods in their short arms while making a swift getaway.

arental care “P observed in birds today

No longer a thief, but a doting parent

This image could hardly be further from the truth. Fossils that show Oviraptor lain over eggs were originally used as evidence that they may have begun were scavengers, but have now been with their scalier interpreted in a very different way. ancestors” New discoveries of Oviraptor, and its close relative Citipati, demonstrate that the fossils are in fact the remains of a parent sitting on a nest of its own creation, much like today’s brooding birds. Modern birds are descended from dinosaurs and this discovery suggests that the intense parental care observed in birds today might actually have begun in their scalier ancestors.

Microraptor The evolution of flight in birds is still somewhat of a mystery. The most famous flighted ‘dinosaur’, Archaeopteryx, was about the size of a raven, but had broader wings and a large tail. Its feathers are remarkably similar to those seen in modern birds, despite its 150 million years of age. For decades it was touted as the missing link between avian and reptilian dinosaurs. In fact - despite features like teeth and a boned tailed - it is classified as a true bird. Although the discovery of Archaeopteryx gave us our first insight into the evolutionary icroraptor origin of birds, there remained a large gap in our was knowledge of the dinosaur-tovery small and bird transition. probably weighed

“M

about a kilogram”

Fortunately several new finds have begun to close that gap. One of these is Microraptor, which had feathers on all four limbs effectively making it four-winged. As the name implies, Microraptor was very small and probably weighed about a kilogram; perhaps the smallest dinosaur of its time. Its feet and claws suggest that it lived mostly in trees, supporting the idea that powered flight appeared as the next step in the evolution of species that could already glide by jumping off high platforms such as trees.

Four wings in one tiny bird ancestor

Anchiornis An old fossil may still yield new information if approached with a new tool. In 2010 researchers used a technique known as “Scanning Electron Microscopy” on the fossils of a small dinosaur called Anchiornis. It became the first dinosaur for which the colours in the artists’ impression were based on evidence, not speculation. Melanosomes cells that produce pigment - were found in the fossilised feathers and became their density the first and shape were dinosaur for which compared to colours were based melanosomes in a on evidence” variety of existing birds.

“It

A dinosaur with a colourful past

The surprise: Anchiornis had a red crown and speckles on its cheeks, black wings with white details, and a grey body. This is much tamer than the rainbow-coloured feathers seen in many artists’ impressions, but still a loud display for a small prey animal. Its feathers were unsuitable for flight, so this colouration is most likely an early form of the sexual displays that we see in colourful male birds today.

Tyrannosaurus Supposedly a ferocious predator, new evidence about the life of Tyrannosaurus rex should help us lay our childhood fears to rest. T. rex appears to have had trouble with locomotion, and was unable to run at all. The most recent simulations are based on data collected for animals around today. They show that for a T. rex to break 25mph, over 80% of its body mass would have to have been dedicated to its leg muscles, and that ew evidence only for straight sprints!

“N about T. rex

The king may have been the court jester

should help us lay our Turning around, still a struggle for childhood fears to rest” some modern reptiles, may have taken several seconds. Furthermore, any fall could be fatal as a T. rex ’s momentum would not be broken by its arms during a crash. In fact, there is considerable controversy over whether this king of dinosaurs was a predator at all; many palaeobiologists believe it to have been a pure scavenger.

inosaurs live on in our imaginations as large ferocious scaly beasts, but the more we learn about them, the more familiar they seem: they too were doting parents, put on strange colours to attract others’ attentions and sometimes had to eat leftovers. It seems that even after 100 million years, some things in life never change.

Sofia Hauck is studying Biological Sciences at St. Hugh’s College Art by Clementine McAteer

Life in Old Bones

Will woolly mammoths walk again?

ichael Crichton’s 1990 science fiction book Jurassic Park imagines a theme park where dinosaurs are brought back from the dead using DNA preserved in mosquitoes that fed on them and were subsequently trapped in amber for millions of years. Could such a theme park be possible? In 1994, scientists published a paper in the prestigious journal Science suggesting they were able to extract DNA from 80 million year old bone fragments. However, further analyses revealed that these dinosaurs were more closely related to humans than birds or crocodiles. Clearly this had to be a case of contamination. Thankfully paleogenetics did not go the way of the dinosaurs. Recently there has been a renaissance in paleogenetics as increasingly sophisticated techniques have become available. In 2008 a draft of the woolly mammoth genome was published, followed two years later by around half of the Neanderthal genome. Ancient DNA sequenced from extinct human cousins has changed our view of human evolution. The Neanderthal genome suggests that the

small population of modern humans that first left Africa, mixed genetically with Neanderthals. If you are of Eurasian descent between 1-4% of your genome traces back to our Neanderthal relatives. Neanderthals weren’t the only archaic humans we bred with. Bones found in a cave in Denisova in Siberia have also had their genomes sequenced to an even higher coverage than the Neanderthals. The analyses determined these Denisovans were

But paleogenetics is inevitably entwined in controversy. In 2010, genetic fingerprinting was applied to ‘the boy king’ Tutankhamun. The technique used is the same as that featured in episodes of Jeremy Kyle to resolve paternity and involves determination of the number of repeats of specific DNA sequences; these are conserved within families and differ between unrelated individuals. The pharaoh Akhenaten, who tried unsuccessfully to transform the religion of ancient Egypt, was shown

of Eurasian descent 1-4% of your “I f you aregenome traces back to Neanderthal relatives” a distinct species from Neanderthals that bred with the ancestors of modern day Australian Aborigines and Melanesians, such that up to 6% of their genomes are Denisovan. It is likely that we are a mosaic of extinct archaic humans who live on today through us. In 1991 two hikers discovered a 5,300 year old frozen corpse of a man in the Otztal Alps in Italy. Otzi, as he came to be known, had his genome sequenced just over 20 years later. Otzi had brown eyes, was blood group 0 and got gas when he ate cheese. Had he not sadly met a brutal end somewhere near the Tisenjoch pass, he would have had to watch his diet; Otzi carried a mutation associated with cholesterol build up on artery walls and CT scans showed this was indeed the case.

to have fathered Tutankhamun with one of his sisters. (It really is just like Jeremy Kyle!) The study also identified malaria parasite DNA in several mummies, including Tutankhamun’s. However, the study was vociferously criticised, as many questioned whether DNA could survive 3,300 years in the heat of Luxor. DNA degrades over time: it is thought that after 10,000 years too much damage will have occurred for reliable sequence information to be derived. However, this can be extended by exceptional preservation conditions, particularly in permafrost deep-freeze. Despite this limitation paleogenetics can provide fascinating insight into the lives of extinct species and the origins of extant ones. Two years ago a partially synthetic organism was created at the J. Craig Venter Institute; might paleogenetics someday give us the ability to resurrect Neanderthals, woolly mammoths and more?

Charlie Gilbert is a 3rd year student at Brasenose, studying Biochemistry Art by Maria Demidova

Transmissible Tasmanian Tumors

% of us will get cancer at some point in our lifetime. This terrifying figure could be even higher if cancer was a directly transmissible disease. Worryingly, in the Tasmanian devil a contagious facial tumour has evolved that is able to do just that and now threatens them with extinction. In 1996 the first case of devil facial tumour disease was recorded; and it has since devastated the devil population by 60%. The cancerous cells spread between individuals during fighting or through shared food. Once lodged on the face or mouth of another devil the cells divide and form tumours, causing death within a few months. The tumours share genes that are different from the devils themselves, making some researchers study it as more of a parasite than a cancer.

There are only two other recorded contagious cancers: one is sexually transmitted in dogs, the other transmitted by mosquitoes in Syrian hamsters. The dog and devil tumours have similar chromosome abnormalities, but the devil’s disease is much deadlier. The devil genome and that of the tumours were sequenced earlier this year, revealing mutations in several immune system genes that may allow the disease to evade immunological defences. A series of mutations in a single cell (probably a type of nerve cell called a Schwann cell) allowed it to become cancerous not only in the original host, but also in other devils.

disease ever emerged closer to home. The prospect is horrifying but unlikely; we are less inbred than the devils, have better immune systems, and (usually) tend not to bite each other over a chocolate bar. Isobel Steer is a 2nd year Biological Sciences student at St. Hilda’s College Art by Maria Demidova

Understanding the genetic basis of the disease will not only help us protect the Tasmanian devil, but might one day be of paramount importance if a similar

Killer Conus Snails

he genus Conus is a group of over 600 different species of venomous snail that are found in tropical seas and oceans worldwide. Historically they have been known for the exquisite patterning of their shells and have been highly sought after by collectors. In 1796 a specimen of ‘the matchless cone’, Conus cedonulli was sold at an auction for 273 guilders, while, at the same auction, Vermeer’s masterpiece ‘Woman in blue reading a letter’ fetched only 43 guilders.

Today, ‘cone snails’ are valued not for their beauty, but instead for their venom. All Conus species are carnivorous predators. The snails harpoon their victims, firing from a mobile proboscis a hollow tooth through which they inject paralysing toxins. These toxins are potent in humans too, Conus geographicus is colloquially known as the cigarette snail, as sting victims are supposed to have only time to smoke a cigarette before death. The toxins consist of small peptides which inhibit the normal function of cells - specifically, they block the action of ion channels. Ion channels are required for the transmission of nerve impulses and are essential for stimulating muscle contraction. Ion channels are involved in numerous

physiological and pathological processes, so ‘conotoxins’ represent a fantastic resource for pharmaceutical development. Each species is believed to produce between 50-200 distinct conotoxins, so there are in theory up to 50 000 distinct neuropharmalogical activities. Indeed a potent analgesic, ziconotide, derived from Conus magus ω -conotoxin, has already been approved for use in humans as an alternative to morphine. Conotoxins are not only useful as pharmaceuticals, but important research tools. Many other conotoxins are currently being tested, some already in clinical trials, for their ability to treat pain, epilepsy and depression. Their Beauty may only be skin deep, but the true ingenuity of these creatures lies not in the intricacy of their shells but in their skill as apothecaries. Charlie Gilbert is a 3rd year student at Brasenose, studying Biochemistry. Art by Maria Demidova

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