BlueSci Issue 50 - Lent 2021

Lent 2021 Issue 50 www.bluesci.co.uk

Cambridge University science magazine

FOCUS

The Chicken or the Egg?

CRISPR . The Game of Life Stress . Music of Black Holes

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Contents

Cambridge University science magazine

Regulars

Features 6

On The Cover News Reviews

Stressful Stuff: Is Psychological Stress More Damaging Than We Realise?

Eleanor Sherlock investigates the hidden connection between psychological stress and immune-related illnesses 8

FOCUS

Mesenchymal Stem Cells and Osteoarthritis Minji Ai discusses the strides being made in the development of new therapies for osteoarthritis

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Cutting Edge: CRISPR/Cas9’s Molecular Scissors

Hazel Walker explores the Nobel Prize-winning innovation of CRISPR/Cas9 gene editing 12

The Electrifying World of Energy Harvesting

Liam Ives explores how we can harness the wasted energy from everyday processes

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50th Issue Special Feature

A look back at 50 issues of BlueSci and 50 years of scientific innovations 28

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THE CHICKEN OR THE EGG? FIRST CAME A CHICKEN VIRUS

Benedetta Spadaro and Harry Bickerstaffe

The Music of Black Holes

Owain Salter Fitz-Gibbon discusses how sound waves from a violin resemble gravitational waves emitted from black holes

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John Conway’s Game of Life

Maria Julia Maristany takes a look inside the marvelous and magical mind of John Horton Conway

Improved with Crystals

Evelyna Wang discusses the intricacies of crystal formation and their many uses

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

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Making an Internet From Scratch

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A Sprinkling of Gold Dust

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Weird and Wonderful

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Charles Jameson explores the mechanisms that make the Internet work

William Hotham discusses the many unexpected uses of gold

Illuminating the Northern Lights Stepped-drum Calculators to Math Grenades Why Position Matters

President: Leia Judge �������������������������������������������������������������������������������������� Judge �������������������������������������������������������������������������������������� president@bluesci.co.uk Managing Editor: Sarah Lindsay..................................................

Lindsay........................................................managing-editor@bluesci.co.uk ......managing-editor@bluesci.co.uk Secretary: Tanvi Acharya.......................................... �������������������������������������� Acharya.......................................... ��������������������������������������enquiries@bluesci.co.uk enquiries@bluesci.co.uk Finance Officers: Juliana Cudini & Kate O’Flaherty.....................................finance@bluesci.co.uk Film Editors: Tanjakin Fu, Roxy Francombe �������������������������������������������������������� Francombe �������������������������������������������������������� film@bluesci.co.uk Podcast Editors: Ruby Coates & Simone Eizagirre.....................................podcast@bluesci.co.uk News Editors: Zak Lakota-Baldwin & Adiyant Lamba ������������������������������������ Lamba ������������������������������������news@bluesci.co.uk news@bluesci.co.uk Webmaster: Clifford Sia.............................................................................webmaster@bluesci.co.uk Communications Officer: Emma Soh........................

Soh........................... ....................communications@bluesci.co.uk .................communications@bluesci.co.uk Art Editor: Pauline Kerekes.........................................................................art-editor@bluesci.co.uk

Contents

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Issue 50: Lent 2021 Issue Editor: Dean Ashley Managing Editor: Sarah Lindsay First Editors: Mirlinda Ademi, Laura Chilver, Catherine Dabrowska, Hollie French, Luisa Deragon Garcia, Lucy Hart, Debbie Ho, Ernestine Hui, Lizzie Knight, Savanna Leboff, Miriam Lisci, Sruthi Ranganathan, Francesca Seymour, Holly Smith, Anna Townley,Yan-Yi Second editors: Mirlinda Ademi, Laura Chilver, Jessica Corry, Catherine Dabrowska, Hollie French, Luisa Deragon Garcia, Lucy Hart, Debbie Ho, Ernestine Hui, Lizzie Knight, Savanna Leboff, Miriam Lisci, Sruthi Ranganathan, Francesca Seymour, Holly Smith, Anna Townley,Yan-Yi Art Editor: Pauline Kerekes News Team: Adiyant Lamba, Clifford Sia, Zak Lakota-Baldwin Reviews: Debbie Ho, Kate Howlett, Dean Ashley Feature Writers: Eleanor Sherlock, Minji Ai, Hazel Walker, Liam Ives, Owain Salter FitzGibbon, Maria Julia Maristany, Evelyna Wang, Charles Jameson,William Hotham Focus Team: Benedetta Spadaro and Harry Bickerstaffe Weird and Wonderful: Lucy Hart, Kathryn Bowers, Oakem Kyne Production Team: Leia Judge, Sarah Lindsay, Dean Ashley Caption Writers: Leia Judge and Dean Ashley Copy Editors: Juliana Cudini, Sarah Lindsay, Hazel Walker Illustrators: Marzia Munafo, Nataliia Kuksa, Biliana Tchavdarova Todorova, Biliana Tchavdarova Todorova, Eva Pillai, Mariadaria Ianni-Ravn, Debbie Ho, Jocelyn Tang, Zuzanna Stawicka, Josh Langfield Cover Image: Mariadaria Ianni-Ravn

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.

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Editorial

The Magic of Mechanisms A multidisciplinary approach to research is becoming ever more important in furthering our understanding of both our universe and those around us. This year collaboration between individuals, countries, and scientists alike will be integral to not only scientific progression, but also the return to societal normality. In this 50th edition of BlueSci, authors and artists highlight the interconnectivity of scientific mechanisms, alongside the depth and breadth of knowledge available here at the University of Cambridge.

Arguably one of the biggest changes to our lives recently, accompanying the change in circumstances, is the increased stress it can bring. Eleanor Sherlock discusses how increased levels of stress are linked to tangible increases in disease occurrence and progression, reminding us all to take note of our psychology for the sake of our physiology. Evidently, understanding mechanisms can both increase our understanding of diseases whilst also offering avenues for alleviative approaches. Minji Ai discusses osteoarthritis, mesenchymal stem cells, and how our mechanistic understanding of them both is bringing us closer to a therapeutic solution currently just out of reach. The translation of our mechanistic understanding into therapeutic interventions is embodied

by CRISPR/Cas9 gene editing. In Hazel Walker’s article we discover the story of CRISPR, its ability to edit genomes, and why it warrants Nobel Prize-winning status. Of course, mechanistic understanding underpins all scientific disciplines. We see this articulately presented in Liam Ives’ Feature article, which details energy harvesting from everyday mechanisms, ‘recycling our energy’, and how combining these breakthrough technologies may be key in minimising our impact on the planet.

From Earth to space, collaborating between fields not only makes complex theories and mechanisms easier to understand but also more memorable. Owain Salter Fitz-Gibbon’s Feature comparing sound waves to the gravitational waves of black holes demonstrates this perfectly; making an often unapproachable topic impressively relatable. Black holes also begin our journey through the ‘Brief History Through Scientific Time’, which celebrates scientific progress across multiple disciplines over the last 50 years. The poster is combined with our own trip down memory lane, with interviews from previous BlueSci contributors that helped us reach this momentous 50th issue. We look at where they have been, where they are now, and some of the many exciting careers and possibilities within the sciences.

Benedetta Spadaro and Harry Bickerstaffe continue our celebratory dive into scientific progress over the past 50 years in this issue’s FOCUS piece. We explore the giant leaps made in the field of cancer genetics, therapeutics, and mechanistic understanding that enable us to better address the once untouchable disease that is cancer. Not only is it our 50th edition, but it is also John Conway’s Game of Life’s 50th birthday too. Maria Julia Maristany outlines how John Conway united the fields of computer science, physics, cell biology, and mathematics, plus many more, through a game that requires no players but asks big questions. In a similar fashion, Evelyna Wang answers all the big questions in the world of crystals, what they are, how they form, how they make our world a better place, and a whole lot more. Just like the atoms of a crystal, the world is a very connected place and one great contributor to this interconnectedness is The Internet. Charles Jameson discusses how this is possible and the various mechanisms we take for granted whilst searching for our favourite BlueSci articles. One thing hard to argue is overlooked is gold. However, in William Hotham’s Feature we learn how a little gold can go a long way; from catalytic converters to drug delivery. We finish the issue on a high, quite literally, with Lucy Hart’s Weird & Wonderful article surrounding the northern lights. Oakem Kyne takes us into the world of stereoisomers, and we learn of the development of a humble yet herculean invention, the calculator, with Kathryn Bowers.

The magic of mechanisms is the foundation of all sciences and I urge you, in these times of uncertainty, to appreciate as many of these as you can. Whether that be discovering them by diving back in time through previous BlueSci issues or understanding, in greater detail, the world outside your window. You will be surprised at just how interconnected everything is

Dean Ashley Issue Editor #50

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On the Cover John conway (the man behind The Game of Life) and Francis Rous (the pathologist who discovered the chicken sarcoma virus) sit atop a monumental chicken, its sarcoma tumour shining. A stream of light connects Conway’s hand to the chicken’s tumour, carrying a crystal, a gold particle, and a CRISPR/Cas9 complex, framed by musical notes and mathematical symbols. The last century of science has seen huge leaps in understanding, which would have sounded like a fairytale in the not-so-distant past. I wanted to convey this with a touch of child-like wonder in my illustration

Mariadaria Ianni-Ravn Cover Artist

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On the Cover

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News

Check out www.bluesci.co.uk, our Facebook page, or @BlueSci on Twitter for regular science news and updates

AI: Thinking in Three Dimensions

A Stomach-Churning Discovery

A classical problem in structural biology is the ‘protein folding problem’ — that is, figuring out what final 3D conformation a protein takes. The 3D shape of a protein is important as it is closely linked to its function, but there are many theoretical ways that one protein could fold into its final shape. Biologists have traditionally resorted to expensive and laborious techniques for solving the problem, such as nuclear magnetic resonance and x-ray crystallography. However, DeepMind’s revolutionary artificial intelligence (AI), AlphaFold, could provide a much more accessible solution.

British AI company DeepMind, co-founded by Cambridge alumnus Demis Hassabis, specialises in designing neural network systems: each is a series of computer algorithms that collectively act like a human brain, in that they can extract and learn underlying relationships in a dataset and apply this to new data, albeit much more powerfully. Learning from past examples, AlphaFold is able to take the sequence of amino acids that make a protein — its building blocks — and predict the final 3D structure with incredible accuracy: better than all other teams that entered the CASP14 protein folding contest and very close to the experimentally determined structures.

Although experimental data still remains the gold standard for determining protein structure, AlphaFold’s immediate impact will be to reduce the amount of data needed to reliably predict a protein’s 3D shape, empowering research that was simply not feasible beforehand. AL

Our impulse to look away from disgusting images is triggered by changes in the electrical rhythm of our stomach, according to new research from the MRC Cognition and Brain Sciences Unit at the University of Cambridge. The study, published in Current Biology, showed that domperidone, an anti-nausea medicine which acts on this stomach rhythm, was able to significantly reduce the time volunteers spent looking away from a series of disgusting images.

The effect of domperidone is to stabilise the rhythm of electrical signals in the stomach muscles — signals which can cause involuntary vomiting if strongly disrupted by powerful feelings of revulsion. In the study, some volunteers were given domperidone while others received a placebo, and they were then shown a selection of disgusting and neutral images. At a certain point in the study, the volunteers were given a monetary incentive for spending longer looking at the disgusting images. The researchers found that, in the round of testing after the incentive was applied, volunteers who had been given domperidone spent significantly longer than the placebo group looking at the disgusting images.

‘We’ve shown that by calming the rhythms of our stomach muscles using anti-nausea drugs, we can help reduce our instinct to look away from a disgusting image’, explained Professor Tim Dalgleish, one of the researchers from the MRC Unit, ‘but just using the drug itself isn’t enough: overcoming disgust avoidance requires us to be motivated or incentivised.

This could provide us with clues on how we can help people overcome pathological disgust clinically, which occurs in a number of mental health conditions and can be disabling.’

ZLB

Making a Map of the Universe

The Gaia mission was launched in 2013 and aims to help us map the universe, as there is still a great deal of uncertainty in the distances of the stars and galaxies around us. Knowing the distances to nearby stars may help calculate brightness of the stars and model stellar evolution. From this rudimentary interstellar ruler, it is possible to measure the distances and brightness of nearby galaxies, and even those distant enough that individual stars cannot be observed. Recently, the European Space Agency has released a new round of preliminary data from the Gaia mission, featuring an additional 34 months’ worth of observational data including new types of analysis on a much bigger scale than before.

The most accurate way of measuring interstellar distances — short of travelling to the stars themselves — is to measure the infinitesimal shifts, or parallax, of these pinpoints of light over the course of half a year as the Earth moves from one side of its solar orbit to the other. Gaia is well suited to measure these parallaxes with greater precision than ground-based telescopes, which must contend with the distortion of incoming starlight by ripples in the atmosphere. The new information will ultimately help in determining the distribution of mass in the universe, and the high precision to which objects can now be localised in the sky will also be useful in other areas of physics, such as the detection of exoplanets or multiple-star systems. This astounding new data is only part of the full dataset which is scheduled for release in the middle of next year. CS

Artwork by Josh Langfield

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News

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Reviews A Life on Our Planet Narrated by Sir David Attenborough Natural historian Sir David Attenborough’s latest documentary ‘A Life on Our Planet’ is his witness statement.

He warns that, without intervention, the global ecological decline which occurred throughout his lifetime will only be exacerbated by following generations.

Presented as a monologue, Sir Attenborough takes you on a journey through his life’s work, drawing on his previous documentaries as reference points. As expected of his documentaries, awe-inspiring images of wildlife instil wonderment in the audience. However, unlike his previous work, this documentary places emphasis on the interconnectivity between the decline of the natural world and the growth of our species and its unsustainable habits. There is an obvious ultimatum — we can continue our destruction of ecosystems across land and sea, or we can change. It concludes, more cheerfully, with small changes that have already had beneficial effects for ecosystems and ways in which societies have adopted these new attitudes. Although the negative impact of our species on the natural world is familiar to us, by laying it bare before the audience, Sir Attenborough’s statement is an emotive call to action for all. DA

Winter Birds, Lars Jonsson

Hope Beyond Hype, EuroStemCell

Lars Jonsson’s Winter Birds is a book for those who want more from birding than simply ticking a species off a list.

Jonsson explores over 50 species in exquisite and charming detail, all of which he can watch during the winter months from the window of his studio on the Swedish island of Gotland.

However, this book is much more than a basic field guide.

Jonsson accompanies each entry with beautiful watercolour drawings — to be expected since he is, after all, known first and foremost as an ornithological illustrator. The book is full of personal anecdotes from Jonsson’s time spent observing the birds’ behaviour and is littered with the perspective of an artist trying to capture every detail and hue of plumage. It makes for a beautiful read, effortlessly intertwining cultural snippets of etymology and history with ecological information. But it’s hard to know quite how to classify the book; it functions as an exceptionally beautiful field guide, a coffee-table book for dipping in and out of, and simply as a work of art. Jonsson’s refusal to write a book that fits into a conventional box just adds to its novelty and charm. KH

Hope Beyond Hype is a short comic which offers general readers a glimpse into the world of stem cell biomedical research. This comic captivates its audience by introducing novel treatments for patients with severe skin conditions or corneal blindness. While these new therapies have inspired an explosion of research, a refreshing twist in the plot explains that new treatments need to pass through meticulous testing and approval processes before they are rolled out.

The authors realistically showcase the vigorous stages of laboratory research, where years of diligent optimisation precede moments of great discovery. While novel scientific breakthroughs are hard-earned achievements worthy of celebration, one must acknowledge that it often takes years to bring clinical innovations from bench to bedside. Innovative treatments have to undergo multiple stages of clinical trials under strict regulations to ensure that patients receive a safe and effective cure.

Unfortunately, rogue clinics which sell ineffective or unsafe stem cell products also operate across the globe. Furthermore, misinformation and overhyping can mislead the general public. To address these problems, this story highlights the importance of dialogue between patient communities, scientists, and policymakers to debunk myths and take hold of true hope.

To continue this dialogue, readers are encouraged to visit EuroStemCell’s website, where European Union-funded scientists give independent expert-reviewed information on stem cells. DH

Artwork by Eva Pillai and Jocelyn Tang Lent 2021

Reviews

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Stressful Stuff: Is Psychological Stress More Damaging Than We Realise?

Eleanor Sherlock investigates the hidden connection between psychological stress and immune-related illnesses Stress is an unavoidable part of life. For something so draining, most people never imagine that those days of exam cramming or worrying about family might lead to long-lasting health consequences. At most, you might have noticed the pimples that seem to come up before that tight deadline, or the colds you come down with just after.

Recently, however, the scientific world has begun to realise that, as abstract as psychological stress may be, it can have a very concrete influence on our physiology and the illnesses we may be at risk from. In particular, stress is thought to reprogram the immune system, increasing susceptibility to immune-related illnesses.

What chemical changes accompany those unpleasant feelings of psychological stress? Stressful environmental triggers will activate a variety of brain centres that then mount a hormonal stress response, during which stress hormones are released from the adrenal glands.

This process occurs in two stages. In the first stage,

noradrenaline and adrenaline are released, hormones that mediate the ‘fight-or-flight’ symptoms of stress, such as an increased heart rate. In the second, cortisol is released, a hormone that ensures the continued maintenance of the stress response.

Noradrenaline, adrenaline, and cortisol exert their effects by binding their respective receptors on nearly all cells of the body. Binding leads to changes within the cell that prepares the body for a ‘fight-or-flight’ situation.

Within the immune system, this leads to the activation and redistribution of immune cells from the lymph nodes into the bloodstream and to vulnerable areas such as the skin. This process is known as inflammation and helps prepare the body to fight potential infections, which may accompany the stressful environmental trigger.

More specifically, noradrenaline and adrenaline stimulate inflammation, while cortisol has a more regulatory effect, helping to keep this inflammation from getting out of control and becoming damaging.

This acute change in the immune system in response to stress is generally useful, protecting the body against infection in potentially dangerous situations. The issue arises when this stress response is chronically activated, as it is in certain stress-related conditions such as generalised anxiety disorder, or in long-term suffering.

It is hypothesised that chronically elevated cortisol levels can lead to cortisol resistance — where the same level of cortisol no longer exerts an effective regulatory response.

Subsequently, chronic inflammation ensues, where the pro-inflammatory effects of elevated noradrenaline and adrenaline are no longer controlled.

Chronic Inflammation Can Only Be Bad News | Chronic inflammation underlies a range of seemingly unrelated illnesses. The ability of psychological stress to induce and exacerbate this condition means that it is a serious health risk which is only beginning to be taken seriously. For example, chronic psychological stress has been observed to increase susceptibility to certain infections. Initial work has suggested that infection rates of the common cold were higher in individuals exposed to higher levels of psychological stress. Recent work has also indicated that individuals with stress-related disorders such as anxiety or PTSD are at a higher risk of contracting life-threatening infections. This association was mainly observed for infections which involve some kind of overreaction of the immune system, indicating that chronic inflammation could be the underlying

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Stressful Stuff

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The mounting of a hormonal stress response following stressful environmental triggers

connection between the two factors. This is extremely applicable to the ongoing COVID-19 pandemic, where researchers are looking for reasons why some patients experience severe immune overreaction in response to the virus, leading to serious disease. Early work on COVID-19 has already observed strong associations between stress-related mental illness and COVID-19 severity.

Chronic stress has also been associated with incidence of autoimmune disorders. A 2018 study concluded that having a clinical diagnosis of a stress-related disorder significantly increases the risk of autoimmune disease in later life. This is consistent with previous work that has associated chronic stress with flare-ups and incidence of rheumatoid arthritis, multiple sclerosis, Crohn’s disease, type I diabetes, and several other autoimmune diseases.

Mechanisms behind this link are still unclear but initial studies in chronically stressed children indicate proinflammatory responses to self-proteins, consistent with cortisol insensitivity. Chronic inflammation induced by chronic stress is therefore a probable explanation, although more complicated imbalances in immune cell profiles are likely to be involved in this complex process.

This is also likely to underlie the association between chronic stress and other immune disorders. Maternal stress during pregnancy, for example, has been observed to increase rates of asthma and dermatitis, both allergic conditions caused by hyperinflammation. Links have even been established between stress, chronic inflammation, and Alzheimer’s disease, which is recently beginning to be considered an immune disorder.

Stress-induced chronic inflammation is also thought to be a predisposing factor for mental health disorders.

Stress-induced neuroinflammation in glial cells, which Lent 2021

surround and support neurons in the brain, can disturb the production of neurotransmitters such as serotonin, melatonin, or glutamate. The imbalance of these key hormones can predispose the individual to mental health disorders. This effect has been observed in the manifestation of anxiety, depression, PTSD, and schizophrenia. It has also been supported by studies where chronic inflammation induced by chronic stress in rats correlated with an increase in depressive and anxious behaviour. It is commonly accepted that periods of stress and personal suffering can often lead to mental health issues such as depression or anxiety; by looking at the link between chronic stress and the immune system, concrete mechanisms for why exactly this occurs are beginning to emerge.

Why Does Any of This Matter? | Psychological stress has largely been ignored in the quest for new therapeutics; more traditionally physiologically important processes such as heart function or cell cycle regulation tend to take priority in medical research. The abundance of new evidence connecting chronic stress to immunerelated illness now begs to differ — psychological stress must be taken just as seriously. With the advancement in knowledge of how stress drives disease, we can create drugs to reduce the risk of those with mental health issues developing life-threatening illnesses, or to mitigate the suffering of people with stress-induced disorders.

Of course, there are still many barriers preventing true progress in this field. Stress is often accompanied by physiologically damaging behaviours such as smoking, worsening sleep patterns, or increased drug use. It is often difficult to separate the effects of these behaviours from those of stress itself. Scientifically robust experiments are also difficult to conduct, as stress is very personal, and is defined differently for each individual. The immune system is also vastly complicated, and the true interaction between chronic stress and immune dysregulation is far more complex than the simple mechanisms described here. This complexity will take a large amount of time to be unravelled.

Despite this, the connection between psychological stress and the immune system is undoubtedly an exciting avenue for future research. The conditions mentioned here only skim the surface of diseases that may be connected to stress via inflammation — obesity, ageing, and cancer are also known to be involved, to name just a few. Perhaps the lesson here is to respect stress just that little bit more. Next time you notice that stress pimple or cold, stop and rest, just like you would with any other illness - it may be doing more damage than you realise!

Eleanor Sherlock is a 3rd year Natural Sciences Undergraduate at Magdelene College. Artwork by Biliana Tchavdarova Todorova.

Stressful Stuff

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Mesenchymal Stem Cells: Vanquisher Or Accomplice Of Osteoarthritis?

Minji Ai discusses osteoarthritis, mesenchymal stem cells, and and how our mechanistic understanding of them both is bringing us closer to a therapy currently just out of reach

Osteoarthritis | Is there an old lady living next door to you who complains about joint pain every winter as the temperature drops? If so, she may have arthritis.

Osteoarthritis is the most common form of arthritis affecting over 250 million people worldwide, particularly the elderly. In the UK, one in three adults aged 45 and over have reported osteoarthritis symptoms, 60% of which are in the knee joint. Primary osteoarthritis symptoms include chronic pain and stiffness in joints, which hugely impair one’s mobility and quality of life.

How does osteoarthritis become established in joints? To answer this, we need to first understand how a healthy joint functions. A joint is a connective structure where two bones meet. A typical moving joint, such as the knee joint, consists of bones, articular cartilage covering bone ends, a synovial capsule forming the joint cavity, and connective tissue linking the two bone ends.

Similar to the renewal of our red blood cells, joint tissues also renew, albeit at a much slower pace. It takes nearly 25 years for proteoglycan, a main component of cartilage, and 10 years for bone to renew in adults. Underlying this slow 8

Mesenchymal Stem Cells

self-renewal process is the constant breaking down and regrowth of tissue components, termed as turnover, which is regulated by tightly controlled biological mechanisms.

This renewal process can be easily disrupted, leading to diseases such as osteoarthritis. Osteoarthritis arises from abnormal joint tissue turnover, which can be triggered by various factors such as ageing, obesity, joint injury, or overuse of joints. These skew the renewal balance in cartilage and bone, leading to typical osteoarthritis-like features such as cartilage loss and abnormal bone growing in the joints. Such features progress slowly over time as highly differentiated cartilage and bone cells have a limited capacity to stop or reverse this skewed turnover.

Treatments For Osteoarthritis | Sadly, there is currently no cure for osteoarthritis. There are treatments available for symptom relief and joint function improval. Physical therapy and pain relief medication are usually prescribed to patients with moderate osteoarthritis. Invasive surgical methods such as joint replacement surgery are recommended to patients with advanced osteoarthritis. However, these treatments Lent 2021

have limitations. Long-term use of pain relief medication comes with the risk of addiction or cardiovascular disease development, while surgeries may come with complications.

Recently, cell therapies have shown promise in treating osteoarthritis.

The high death rate of cartilage cells, termed chondrocytes, in osteoarthritic joints is a key process underlying cartilage loss. Thus, injecting chondrocytes directly into damaged joints can be beneficial. Autologous Chondrocyte Implantation (ACI), which uses laboratorygrown chondrocytes derived from the patients themselves, is now a common cellular therapy for osteoarthritis. Despite promising outcomes, this technique is not perfect. As these chondrocytes originate from the osteoarthritic joint, they do not function as well as healthy chondrocytes and thus fail to produce the high-quality cartilage needed. Further, only a small percentage of injected cells (<22%) survived and these cells do not readily multiply, which leaves the ultimate goal of replenishing the chondrocytes hard to achieve.

MSCs Stopping Osteoarthritis Progression | Rather than chondrocytes, mesenchymal stem cells (MSCs) have gained popularity as a new cellular therapy for osteoarthritis.

MSCs are cells which can make copies of themselves and become specialised tissue cells such as fat cells, cartilage cells, or bone forming cells under the right stimuli. They are most commonly found in adult bone marrow and fat tissues.

Researchers have shown that injecting MSCs into osteoarthritic joints can relieve pain and improve joint function with very few side effects. It is thought that MSCs slow osteoarthritis progression through two main mechanisms. First, MSCs can turn into chondrocytes to compensate for chondrocyte loss. However, similar to the injection of chondrocytes, only a small proportion of injected MSCs survive and remain in the joints, and an even smaller percentage of these MSCs turn into chondrocytes, which means this mechanism contributes very little to stop disease progression. Therefore, most of the research in the past decade has focused on the second mechanism: the ability of MSCs to regulate immune response through secreted molecules.

In osteoarthritis, cartilage debris triggers the body's innate immune response and recruits immune cells into the joint to ‘clean up’ cartilage debris. These cells also secrete inflammatory mediators, such as cytokines and chemokines, to further aid the ‘cleaning’ process. However, these mediators sensitise chondrocytes to secrete more cartilage-degrading enzymes, which in turn enhance cartilage breaking down. This establishes a negative feedback loop within the joint, whereby losing cartilage leads to more cartilage breakdown and worsens disease severity. MSCs can break this loop through immunomodulation. Through secreted molecules or direct binding with immune cells, MSCs can reduce the secretion of inflammatory molecules and enhance the production of anti-inflammatory ones in those cells. In this way, MSCs reduce inflammation in the osteoarthritic joint and minimise cartilage loss and disease progression.

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Resident MSCs In Osteoarthritis | MSCs can be found in both joint tissues and bone marrow, which can all be recruited to the joint cavity following joint injury. This raises the question of why native MSCs did not heroically stop the development of osteoarthritis in the first place. They may have tried but often become the accomplice of osteoarthritis!

Compared to MSCs from healthy joints, MSCs in arthritic joints grow slower and are less likely to turn into chondrocytes. Researchers at the University of Leeds found that MSCs from patients with severe osteoarthritis have a higher expression of genes responsible for new bone formation, which means these MSCs tend to become boneforming cells. This means that native MSCs may facilitate osteophyte formation, a bony structure typically found in osteoarthritic joints. Osteophytes worsen the disease through narrowing the joint space and creating misalignment of bones.

You may wonder what determines the type of cells MSCs turn into. This largely depends on the chemical environment that MSCs are situated in. Key molecules such as vitamin C can trigger a series of downstream chemical reactions inside cells through switches on the cell surface. These reactions are termed signalling pathways. Studying these pathways may identify ways to manipulate MSC differentiation in arthritic joints.

Modified MSCs For Slowing Osteoarthritis Progression | Scientists at John Hopkins University spotted a strong relationship between osteoarthritis development and a signalling factor named transforming growth factor beta (TGF- ) in MSCs. The activation of TGF- signalling along with bone-forming signalling transforms MSCs into osteoblasts. In a mouse model of osteoarthritis, abnormal bone formation closely correlates with increased TGFsignalling in MSCs. A further study showed that blocking the binding site of TGF- on the surface of MSCs led to a reduction in osteoarthritis symptoms in mice. In the future, it may be therapeutically useful to inject MSCs which lack TGF- receptors, as these are more likely to differentiate into chondrocytes and advance cartilage healing.

The duality of MSCs in either slowing or contributing to osteoarthritis means that clinicians need to carefully use them for therapy. By acquiring a deeper understanding of the disease and MSCs at a molecular level, researchers can make the most optimal treatment for millions of patients just like the old lady who lives next door with osteoarthritis Minji Ai is a 2nd year PhD student in Biological Science at Darwin College. Artwork by Biliana Tchavdarova Todorova.

Mesenchymal Stem Cells

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Cutting Edge: CRISPR/Cas9’s Molecular Scissors Hazel Walker explores the Nobel Prize-winning innovation of CRISPR/Cas9 gene editing On the 7th October 2020, the news broke that the Nobel Prize in Chemistry had been awarded to Professors Emmanuelle Charpentier and Jennifer Doudna for the ‘development of a method for genome editing’. Only eight years after their discovery that the CRISPR/Cas9 system can be used to edit genes, it is hailed as one of the most impactful scientific breakthroughs of the 21st century.

Notably, this was the first time the prize had been awarded solely to two women with Charpentier telling the Nobel Prize Committee, ‘My wish is that this will provide a positive message to the young girls who would like to follow the path of science, and to show them that women in science can also have an impact through the research that they are performing’.

Like many scientific breakthroughs, the story of this genome-editing discovery started with an unexpected observation. In 1993, Francisco Mojica, a doctoral student based in the University of Alicante, noticed a curious repetitive sequence of DNA in the genome of the bacteria he was studying. Upon realising that these repetitive sequences of DNA were present across many strains of bacteria, and had first been reported in 1987, Mojica and other scientists set to work on understanding their purpose. They concluded that the stretches of DNA, which they named Clustered Regularly Interspaced Short Palindromic Repeats or ‘CRISPR’, were part of a defence system to protect micro-organisms such as bacteria and archaea from viral infection.

Like us, bacteria are susceptible to viruses, called bacteriophages. When a bacteriophage infects a bacterial cell, some of the foreign bacteriophage DNA is integrated amongst the repetitive CRISPR sequences. This forms a sort of ‘immune memory’, similar to how the human immune system can remember a prior infection and more effectively defend against it a second time. The stored bacteriophage DNA is transcribed to a messenger molecule called RNA, which can then recognise and bind to its complementary sequence, should this particular bacteriophage attempt to invade the bacteria again. The CRISPR RNA also brings with it a CRISPR-associated protein, ‘Cas9’. Cas9 acts as a pair of scissors, chopping up the incoming foreign DNA and stopping the infection in its tracks. This step forward in the understanding of bacterial defence was exciting in itself, as it was the first time that immune memory had been demonstrated in bacteria. However, CRISPR/Cas9’s potential as a revolutionary genome editing tool was yet to be realised.

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Cutting Edge

In 2011, Emmanuelle Charpentier, an Associate Professor at Umeå University in Sweden, added another piece to the puzzle. She found that a second type of RNA, ‘transactivating RNA’ or ‘tracrRNA’, was required for CRISPR RNA to take its mature form. Shortly after this, Charpentier started a lifechanging collaboration with University of California, Berkeley biochemist Jennifer Doudna. Charpentier and Doudna hypothesised that, if they tweaked the sequence of CRISPR RNA to match a target of their choice, they would be able to cut DNA at selected sites. They were right, publishing their ground-breaking work in Science in 2012.

The breaks in DNA that the Cas9 scissors introduce are key to the system’s potential as a genome editing tool. When DNA is cut, it must be repaired. Fortunately for those hoping to edit genes, the DNA repair mechanisms employed by cells are error prone. This means that the resulting repaired DNA sequence is often incorrect. If there are too many mistakes in the genomic DNA, the resultant protein will be nonfunctional, essentially causing it to be switched off. Genes can also be edited by introducing extra DNA to the cut site, allowing for precise modification of the DNA sequence within the gene.

The possibility to have such precise control over genetic sequences expanded the existing genome editing toolkit and quickly became a widely used method in research laboratories due to its efficiency and low cost compared to previous methods. Researchers can even buy pre-designed CRISPR RNAs or use simple software to design their own, drastically speeding up the genome editing process.

With a tool that can permanently switch off a chosen gene, researchers can study the effect that its loss has on biological processes in model organisms, unpicking the role of the gene in health and disease. Furthermore, researchers can use CRISPR/Cas9 to tag proteins of interest with geneticallyencoded fluorescent probes which, when viewed under a microscope, can reveal information about the expression pattern and function of that protein.

Perhaps the biggest impact CRISPR/Cas9 could have is the treatment of genetic diseases. Shortly after the landmark Science paper, the CRISPR/Cas9 system was used to successfully edit mammalian and even human cells. The power of this technology for editing the human genome was evident and the moral and ethical implications of this were worrying.

In 2015, many prominent researchers called for a global

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"The power of this technology for editing the human genome was evident and the moral and ethical implications of this were worrying"

moratorium on the use of the technology to edit human germline cells (eggs, sperm, and viable embryos) in which potentially unknown side effects could be inherited by future generations. While this moratorium from respected scientists proved a deterrent for most, CRISPR hit the headlines in 2018 when Chinese researcher, He Jiankui, announced the birth of the world’s first CRISPR edited babies. Jiankui had convinced a couple undergoing in vitro fertilisation (IVF) that their embryos could be edited to be immune to HIV, sparking widespread controversy, outrage, and condemnation from both the scientific community and the public. Whether the babies are actually immune to HIV and do not suffer from side effects still remains to be seen.

Currently, the safety and efficacy of CRISPR/Cas9 genome editing is being tested in tightly regulated human clinical trials, targeting non-germline cells to treat diseases such as cancer, blood disorders and blindness. In most cases, a patient’s cells are removed from their body, edited, and then re-introduced — which is likely to be safer than injecting the CRISPR components straight into the body. A 2019 trial involving three cancer patients confirmed for the first time that a treatment of this kind was safe and feasible in humans, although it did not improve the patients’ cancer prognoses. In March 2020, researchers moved one step further, injecting the CRISPR components directly into patients for the first time in order to treat hereditary blindness. Administered via

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the eye, this treatment aims to rectify the mutation that causes a condition called Leber Congenital Amaurosis 10.

The trial is expected to conclude in 2024.

CRISPR also has the potential to be an important tool for agriculture. CRISPR-induced changes can accelerate the traditional process of selective breeding. As the world’s population increases, crops edited to withstand extreme climate conditions could prove key for global food security. Researchers are also working to generate more nutritious crops or those that lack common allergens such as the protein responsible for gluten intolerance and coeliac disease. UK company Topic Bioscience has even developed decaffeinated coffee beans, cutting out the lengthy and expensive process required to decaffeinate normal coffee beans.

In their quest to understand bacterial immunity, researcher’s curiosity and creativity brought us a powerful new technology. A mere eight years after the development of CRISPR/Cas9-mediated genome editing, the possibility of drought-resistant crops and cures for disease are closer than ever. Only time will tell what impact this exciting technology will have on the future but, if its first few years are anything to go by, it looks like it will be world-changing Hazel Walker is a 4th year PhD student in Immunology at Fitzwilliam College. Artwork by Eva Pillai.

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The Electrifying World of Energy Harvesting Liam Ives explores how we can harness the wasted energy from everyday processes Imagine the climax of a superhero film. The villain plans to drain the planet of all of its energy to fuel their terrible scheme, and society as we know it collapses. At least, that is what it might sound like when someone hears the term ‘energy harvesting’ for the first time. Actually, energy harvesting is the extraction of small amounts of untapped energy from every day processes that would otherwise be lost, and is done by an array of new technologies. This energy is then stored and used in low-power applications.

This can help to replace bulky, wasteful batteries while still powering our lives. As it turns out, not only is energy harvesting currently used over a much smaller scale than an evil plot, it may actually benefit the planet. Here, I will uncover the hidden world of energy harvesting through the unusual mechanisms of piezoelectricity, triboelectricity, and thermoelectricity.

Piezoelectricity: power beneath your feet | Piezoelectric materials generate a charge in response to mechanical stress, whether this is from a vibration in a building, stamping with your shoes or just bending small fibres. The reverse also works — applying a voltage can deform a piezoelectric material.

Piezoelectricity was first demonstrated in 1880 by Jacques and Pierre Curie, who used crystals, such as quartz, tourmaline and topaz. It was later discovered that this piezoelectric effect arises from asymmetry within the crystal structure resulting from pressure.

As a result, positive and negative ions in the material separate in response to the applied force, creating an overall charge.

Piezoelectric materials are used in a range of applications, such as in sensors, the ignition in electric cigarette lighters, as a time reference in quartz watches, and high-resolution microscopy. Currently, these are small-scale uses, but research is being done to adapt these materials for much larger scale applications.

Two graduate students from MIT’s Department of Architecture proposed the Crowd Farm, a project that incorporates piezoelectric elements into a network of floor tiles such that human steps can power lights in public places. One step can power two 60 W light bulbs for one second; around 30,000 steps can power a train for one second, and 84 million steps can theoretically power the launch of a space shuttle.

With the average person in the UK taking 3,000 to 4,000 steps per day, this is a huge untapped resource.

Another example is the Shibuya train station in Tokyo, Japan, where the floor tiles of the station have 12

The Electrifying World of Energy Harvesting

incorporated piezoelectric elements. Every time a person steps on one of these tiles, a message lights up on the station wall, and an LED board updates how much power has been generated that day. There are two main challenges these applications face: energy transfer must be efficient because steps are taken quickly, and the actual power generated by each step can be quite low, at just 0.1 W. However, with an estimated 2.4 million people passing through the station every day, a large amount of energy can be generated. Therefore, while piezoelectric materials are traditionally used for low-power energy harvesting, these devices can be scaled up to solve much larger problems.

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Triboelectricity: giving your electronics a jump(er) start | Most people have done the trick of rubbing a balloon on their jumpers to stick it to the ceiling, or to make their hair stand on end. To many, the static electricity that builds up from rubbing certain materials together is a fun, but unimportant physical phenomenon. This phenomenon is called the triboelectric effect, and much research has been done into taking advantage of it.

‘The triboelectric effect is a combination of contact electrification and electrostatic induction occurring when two surfaces touch and separate.’ explains Tommaso Busolo, PhD student at the Department of Materials Science at the University of Cambridge, who is working on developing novel triboelectric materials. While the mechanism has been exploited for many purposes, it is still not yet clear what causes it. ‘Contact electrification is poorly understood despite being known about since the ancient Greeks.

The key unanswered questions are: what type of charge is being transferred (electrons, ions or molecules) and what is the timescale of this process (i.e. there is evidence that contact electrification happens at different timescales from seconds to hours)’.

Small devices that use the triboelectric effect to generate electricity are called triboelectric nanogenerators, and these are being incorporated into a variety of different applications. Fortunately, many of our clothes are made from triboelectric materials such as nylon, cotton, and silk, which means that we could use our own clothes to generate useful electricity. ‘My yarn is able to transform body movement into electricity and thus power small wearable biosensors.’ says Tommaso, who is making triboelectric textiles ‘durable, washable, and with scalable manufacturing methods’. Tommaso is excited to work on tailoring the fabrication process to achieve industry standard levels of energy output and durability. The electricity obtained from these devices could then be transmitted wirelessly into devices such as pacemakers or cochlear implants, therefore removing the need for surgery to replace batteries.

Thermoelectricity: a hot new energy source | Heat is something that we let go to waste in our homes, our cars, or even in our bodies. Interestingly, a class

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of materials known as thermoelectric substances can make use of that ‘heat waste’ and convert it into electricity. Harvesting energy from a thermal gradient relies on the Seebeck effect: when two dissimilar materials are connected and one is heated up, the electrons flow towards the colder material, resulting in an electric current.

Thermoelectric generators have been used since the 1950s. Large thermoelectric generators are used in the Mars rover, Curiosity, and the Voyager 2 space probe.

However, these generators only operate efficiently at high temperatures and use toxic components.

Current research is focusing on developing this technology into much more portable and humanfriendly applications. For example, small generators are being developed to harness human body heat to power electronics attached to the skin. In the future, the temperature of your hand or wrist may mean you never have to charge your phone or watch again.

Thermoelectric materials have the potential to make use out of a lot of wasted heat in transport, such as that produced by combustion engines in cars. The tyre company Goodyear has even invested in research looking into the possibility of utilising thermoelectric materials for their tyres. As the car moves, friction between the tyre and the road produces a lot of heat.

In addition, piezoelectric materials can take advantage of the tyre deformation and convert this into electricity, which could be fed back into the vehicle to lessen its environmental impact.

For decades, it has become more and more important to recycle our waste materials, but modern technology has given us the ability to start recycling energy itself using unconventional energy sources.

While the materials discussed in this article are not the solution to our energy crisis, they can help to alleviate the burden. In a few years, they may become more widespread and replace traditional, environmentally-harmful power sources for lowpower applications. Importantly, electricity can be harvested from places you might not have previously considered Liam Ives is a 2nd year PhD student in Material Sciences at Selwyn College. Artwork by Marzia Munafo and Mariadaria Ianni-Ravn.

The Electrifying World of Energy Harvesting

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The Music of Black Holes Owain Salter Fitz-Gibbon discusses how sound waves from a violin resemble gravitational waves emitted from black holes P icture a violin string . When it is plucked, it vibrates and disturbs the air around it, causing sound waves to travel to your ears. The result may be a rich and pleasant sound, maybe even the start of your favourite symphony.

The story of how a few vibrating strings can lead to such a rich diversity of phenomena as Bachâ&#x20AC;&#x2122;s violin concertos and how this is connected to the modern science of gravitational waves is a long one, going back at least as far as the ancient Greeks.

The Pythagoreans discovered that there was a simple mathematical relationship between the length of the string that was plucked and the pitch (or frequency) of the note that is produced. This can be visualised in physical terms.

The violin string vibrates in a smooth, regular wave. Since both ends of the string are fixed in place, a half-integer number of wavelengths must fit into the length of the string, so the longest wavelength possible is the length of the string itself. Frequency is inversely proportional to wavelength, so the lowest, or fundamental, frequency is inversely proportional to the length of the string. The string can also vibrate at higher frequencies, corresponding to two, three or more wavelengths fitting into the length of the string. These are called the pure tones of the string.

It took many centuries, from the Pythagoreans to the Napoleonic Wars, for the next chapter in this story. In 1801 Joseph Fourier started to attack the problem of the conduction of heat in a solid. This work culminated in 1822 with the publication of The Analytical Theory of Heat.

Although the subject of the book is the study of heat, it also introduces Fourier Analysis. The central assertion of Fourier Analysis is that essentially any mathematical function can be decomposed as a sum of sinusoidal waves. Although the functions that Fourier was

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The Music of Black Holes

interested in represented the heat of a metal rod, the theory applies to the function representing the displacement of our violin string. Interpreted in this context, Fourier says that any vibration of the violin string can be understood as a superposition of pure tones; all of the varied complexity of notes produced by a violin can be understood in terms of this discrete family of pure tones.

If we plucked our violin string in a vacuum chamber, with no friction or air resistance, then the resulting waves would carry on indefinitely, neither increasing nor decreasing in amplitude. Each pure tone is described by a single number, the frequency of oscillation, which is called the normal frequency. The corresponding mathematical function representing the pure tone is called a normal mode. Of course, this situation is very theoretical.

In reality, there will always be some friction which will cause the oscillations to lose energy, causing the amplitudes to decay exponentially in time. Each pure tone has a specific rate of decay associated with it. In this case, the fundamental mathematical objects are called quasi-normal modes. Quasi-normal modes are described by two numbers, the frequency of oscillation and the rate of exponential decay. These two numbers describe a single complex number called the quasi-normal frequency.

Moving forwards in history again by another hundred years, we reach Einsteinâ&#x20AC;&#x2122;s discovery of the general theory of relativity. General relativity was formulated by Einstein and his contemporaries as an attempt to resolve conflicts between the earlier special theory of relativity and Newtonâ&#x20AC;&#x2122;s theory of universal gravitation. The end result was the hypothesis that four dimensional space-time is curved by the presence of matter. The curvature of space-time in turn affects the motion of

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matter. It is this interplay which explains the force of gravity.

General relativity accounted for some hitherto unexplained astronomical observations, most notably in the orbit of Mercury. However, the most profound and unexpected prediction of the theory was the existence of black holes: regions of space-time which are so warped that nothing, not even light, can escape. The first indication of black holes in general relativity came from Karl Schwarzschild in 1915, months after Einstein published his theory.

For many years, black holes were a purely theoretical prediction, and many experts, notably Cambridge astronomer Arthur Eddington, refused to believe that they were anything other than a mathematical oddity. As such, black holes were neglected by physicists for decades.

However, a renaissance began in the 1960s with a flurry of exciting work from the likes of John Archibald Wheeler (who first coined the term black hole), Roger Penrose, and many others. In particular, Penrose provided the first convincing evidence of the physical existence of black holes by showing mathematically that, under very general conditions, black holes would form as the result of gravitational collapse. It was for this work that Penrose won the 2020 Nobel Prize in Physics. Observational evidence of black holes had to wait until 1971, when astronomers Louise Webster and Paul Murdin at the Royal Observatory in Greenwich and Charles Thomas Bolton in Toronto found a binary system consisting of a star and a black hole orbiting each other in our galaxy.

Whenever a black hole is formed, whether by gravitational collapse, or by the merger of two other black holes, the final result will always be either perfectly spherical, or spheroidal if the black hole is spinning.

However, in the early stages of formation, the black hole takes on a different shape. As the differences from the final state die down, the black hole

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will emit gravitational waves, akin to ripples in space-time itself. Although the existence of gravitational waves had been predicted by Einstein, it was not until the renaissance of the 1960s that serious effort was put into understanding how to observe them.

In the early 1970s, Zerilli derived the equations which govern black hole perturbations. There is a very strong mathematical analogy with the equations which govern the vibrations of a string. Thus it was discovered that black holes also emit gravitational waves at certain pure tones, oscillating at one of a discrete family of frequencies which depends only on the final state, completely independent of the process by which the black hole is formed. Although there is no friction or air resistance to damp gravitational waves, the presence of the black hole, into which energy can fall never to return, causes the same exponentially decaying behaviour that we saw with the violin string.

Astronomers began their first serious attempts to understand how to detect gravitational waves in the 1960s.

However, due to technological difficulties and shortage of government funding, it wasnâ&#x20AC;&#x2122;t until 1994 that the construction of the Laser Interferometer GravitationalWave Observatory (LIGO) began. The first observations from LIGO between 2002 and 2010 made no discoveries, but after 2010, upgrades led to an advanced LIGO in 2015. On 11th February 2016, LIGO made the first direct detection of gravitational waves. This was a striking confirmation of the theory which Einstein had first proposed almost exactly a hundred years earlier, one which fundamentally changed the way we understand the universe. In the process, humanity heard the beautiful orchestra of black holes for the very first time. This symphony is one that astronomers will enjoy for years to come Owain Salter Fitz-Gibbon is a 4th year PhD student in Mathematics at St. Johns College. Artwork by Debbie Ho.

The Music of Black Holes

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A Brief History of Leia Judge speaks to past Bluesci contributors about where their careers have taken them and what they have learned along the way Jon Heras

Micheal Marshall

Then | Pictures editor and President (2008–09) Now | Founder and Science Animator at Equinox Graphics

Then | News editor and President (2005–07) Now | Author of The Genesis Quest “I think in a funny way the most lasting thing I did [while at Bluesci] was to change the name of the society. It was originally called Cambridge University Science Productions, but the BlueSci magazine had swiftly become its best-known product, and the difference was confusing, so I went for consistent branding and had the society’s name changed to BlueSci. Start writing or editing now. Student journalism is great experience, particularly if you do it regularly and systematically. Don’t just write the odd thing: write regularly, hit your word counts and your deadlines, and don’t worry if some of the pieces are crap along the way. Don’t take any facts for granted: double-check everything!

Newton never had an annus mirabilis, the dinosaur extinction wasn’t 65 million years ago, and dinosaurs aren’t entirely extinct.”

“I decided to try to make my hobby into a job, and though there’s been ups and downs, it’s been creative and rewarding. I have my own business, with employees and really varied and interesting clients, from satellite manufacturers like Airbus, academics in cutting edge science, and commercial science companies like Microsoft Research and pharmaceutical companies. I’m always learning new science, and never bored! I know a little about everything from quantum physics to synthetic biology to space missions.

It’s not possible to go from zero to full-time freelance. You’ll need time to learn skills, develop your own style, and create a portfolio that reflects this. Each project, I over delivered and could then use this to fish for better clients. Or better yet, get a job somewhere you can learn best practices, which will save you a lot of headaches and get you where you want to be faster.”

Ian Fyfe

Nick Crumpton

Then | Issue editor (Issue 17) and President (2010) Now | Senior Editor on Nature Reviews Neurology

Then | Writer (2010) and film editor (2011–12) Now | Zoologist and children’s author

“My highlight was definitely being Issue Editor — I put my heart and soul into making the issue the best it could be, and holding it in my hand at the end of the process was super-rewarding!

I definitely wouldn’t be where I am now without BlueSci. At the time, it helped me decide that a career in publishing was what I wanted.

And the experience was also crucial for securing my jobs.

Make the most of the opportunities that BlueSci (or similar student publications) provide to get experience of publishing. Even if you’re interested in editorial, try getting involved in the layout and production because it’s really valuable to know how all the processes fit together. All experience of publishing will be really valuable when you come to apply for jobs.”

2004 First issue published

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A Brief History of Bluesci

“I was awarded a British science association fellowship at the BBC News website pretty much thanks to my work with Bluesci. This then led directly on to some time working for the BBC Natural History Unit which helped me get a role as a science communicator at the Natural History Museum, London and now — after a jaunt through a couple of postdocs and a position at the Royal Society — I write non-fiction books for children. My career’s been a twisty ride, but one that can be traced back almost directly to my time at BlueSci. Don’t compare yourself to other people working in similar fields, try to write with your own voice, stay open to opportunities you might not have previously considered, and don’t be frightened to pitch your heart out.”

2007 Bluesci Film started

2011 Bluesci Radio established

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Jonathan Lawson Then | Web editor (2011) and President (2012) Now | Head of Content at Owlstone Medical “BlueSci was one of my biggest commitments and helped me to develop many of the skills I’ve used on a daily basis in my career since. Being part of the committee also helped me to start exploring the management and leadership skills that are so useful for career progression.

Science communication is an enthusiastic, supportive, and diverse community. Make the most of the opportunities that come to you and explore a wide range of different skills and activities to find what you love doing. Be proud of your choices and the direction you’ve chosen.”

Anand Jagatia Then | Bluesci radio producer and presenter (2011–13) Now | BBC CrowdScience Presenter and Video Producer at The Royal Institution “I presented and produced [Bluesci Radio] for two years with some really passionate and creative people, and had an absolute blast. I interviewed academics, students, chocolatiers, and even got to meet an astronaut.

The best piece of advice I’ve heard on this is from American radio producer Ira Glass: just make stuff. It doesn’t matter if it’s not as good as you’d hoped — the only way to get better is to keep on making stuff. So go on!”

Eva Higganbotham

Then | News contributor and podcast host and producer (2018–20) Now | Producer for The Naked Scientists Podcast “I now work as a producer for The Naked Scientists. We make accessible science radio shows for a range of outlets, including the BBC. My job involves researching interesting stories, interviewing lots of scientists, designing and producing shows, lots of audio editing and mixing, and presenting on live radio.

Get involved in an organisation that gives you practice talking — out loud, in public — about complex ideas in straightforward language.

Don’t let perfectionism get in the way of practice!”

2012 25th issue published

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Tim Middleton

Then | News editor and President (2011–12) Now | PhD student in ecotheology and communications editor at the William Temple Foundation

“I started out as News Editor, but I made the mistake of posting a story on the website on Christmas Eve. The President at the time quickly realised that I’d be mad enough to consider running the show, and I ended up as President from 2011 to 2012!

BlueSci cultivated my love of writing, which has been so helpful as I’ve moved over into the humanities. It also equipped me with editorial and managerial skills that are proving invaluable in my other roles. Try and stay patient: it can sometimes take a long time to get to where you hope to be!”

Elsa Loissel Then | Issue and managing editor and President (2016–18) Now | Associate Features Editor at eLife “I showed copies of the BlueSci issues I worked on during my interview at eLife, and I’m pretty sure this landed me the job.

Get a portfolio; gather some knowledge of social media and multimedia tools; and keep your mind open as to the many different jobs you can do where you get to write about science — it’s not just about being a science journalist.

You don’t necessarily need a PhD to do scicomms; and join newsletters such as Science Writing News Roundup or PSCI-COMS — great places to find that elusive first job.”

2018 Bluesci Podcast began

A Brief History of Bluesci

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Puzzles Can you find the answers to these questions, based on BlueSci FOCUS articles from the past 50 Issues, in the wordsearch?

1. A group of whales.

2. Prof Tim Crow was the first to link changes in brain structure to which mental health disease.

3. Joesph Muray pioneered the transplantation of which organ in 1954?

4. Other than the primate family, which animal is known to have fingerprints?

5. The Wechsler scale is designed to measure _____.

6. The type of clouds responsible for storms.

7. A well-known infectious disease that is caused by plasmodium parasite.

8. The Higgs Boson was discovered with this machine.

9. Lieutenant James Cook’s first expedition to Australia and New Zealand was aboard this ship. HMS ______.

10. The study of tree rings is known as _______.

11. The term given to a large compound formed from many repeating units.

12. Charles _____ invented the first computer.

13. What is made of colonial polyps which secrete calcium carbonate?

14. Organisms that thrive in extreme environments such as high pressures and temperatures.

15. Jennifer Doudna and Emmanuelle Charpentier won a Nobel prize for this discovery. ____/Cas9.

16. Sub-microscopic objects can be held using a laser beam with _______ tweezers.

17. Brian Cox presents this podcast making science accessible to the public. The Infinite ____ Cage.

18. The property of a stem cell if it is able to self-renew and differentiate into any other cell in the adult human body.

19. The theory of the atomic bomb was discovered by Otto Hahn. Which element did he prove could be split by a

Match the invention/discovery/event to the scientist Valentina Tereshkova

Cinema

Frederick Banting and Charles Best

Dynamite

Lumière Brothers

First woman in space

Anna Connelly

Synthetic insulin

Alfred Noble

Fire escape

How many words can you make from DEOXYRIBONUCLEIC ACID

Let us know on social media @BlueSci #BlueSci50

ANSWERS. No peaking unless you are sure you want to know. Wordsearch 1. Pod 2. Schizophrenia 3. Kidney 4. Koala 5. Intelligence 6. Cumulonimbus 7. Malaria 8. Large hadron collider 9. Endeavour 10. Dendrochronology 11. Polymer 12. Babbage 13. Coral reef 14.

Extremophiles 15. CRISPR 16. Optical 17. Monkey 18. Pluripotent 19. Uranium 20. Hubble space telescope. Match with the scientist 1.Valentina Tereshkova.The first woman in space 2. Frederick Banting and Charles Best Synthetic insulin for diabetics 3. Lumière Brothers Cinema 4. Anna Connelly Fire escape 5. Alfred Noble Dynamite.

20

Puzzles

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Take a break and colour in the conical flask Has been shown to reduce stress and anxiety

Promotes creativity, which can increase our ability to problem-solve

Engages both hemispheres of the brain

Allows us to draw our attention into the present moment

The semi-mediative state can provide relief by reducing the activity of the amygdala â&#x20AC;&#x201C; the part of our brain that controls emotion

Avoiding screens before going to bed improves sleep

Show us your creations on Facebook, Twitter, or Instagram @BlueSci #BlueSci50

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Puzzles

21

"All events inside the cell are finely regulated in a perfectly orchestrated symphony. Sometimes, however, a player (the oncogene, here represented as a violinist) may go out of tune as a result of a mutation. The new melody played by the oncogene can have devastating consequences, such as driving malignant cell proliferation and eventually tumour formation."

- Marzia Munafo, Artist

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FOCUS

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The Chicken or the Egg? First Came a Chicken Virus: Celebrating 50 Years of Oncogenes Research Benedetta Spadaro and Harry Bickerstaffe delve into the discovery of oncogenes and the development in our understanding of cancer genetics and the therapeutics available C ells can be seen as machines driven by biological components and cogs, which work in harmony to allow for cell survival, growth, and death. In cancer, these finely-tuned and elegantly orchestrated processes are disrupted by one or more broken cogs. The result? Cells proliferate carelessly, invade healthy body parts, and ultimately cause irreparable damage. It comes as no surprise that precisely these mechanisms by which cells disobey programmed cell fate and turn into ever-replicating cancer cells have been the protagonists of countless research projects and scientists’ investigations. 50 years ago, in 1970, G.S. Martin and colleagues at the University of California Berkeley revealed a crucial mechanism by which specific genes termed oncogenes can be responsible for the onset of cancer. They were the first to identify some of the broken cogs that cause cells to lose track of their normal function. V-SRC was the first ever confirmed oncogene and it came from a chicken retrovirus causing sarcomas. This discovery represented an incredible stepping stone for cancer treatment by offering new druggable targets and diagnostic markers. 50 years later, our understanding of oncogenes and their role in cancer has dramatically progressed, enabling more targeted and efficacious therapies. We celebrate this 50-yearold discovery by retracing its history and the impact it has had on our understanding of the mechanisms behind cancer onset.

A chicken virus can transform healthy cells into cancer cells | The history of the first oncogene is rooted in observations made at the start of the 20th century when P. Rous, a scientist at the Rockefeller Institute in New York, was presented with a hen bearing a large tumour. He found that the hen’s cancer could be transplanted and propagated in chickens. Rous went further and showed that the tumour could be transmitted using cell-free filtrates.

He concluded there was a ‘filtrable agent’ later called Rous Sarcoma virus (RSV) that caused tumour onset

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in chickens. His discovery was met by the scientific community with skepticism. Most experts thought that transmissible cancers pertained only to animals and held no value in human cancer research. Rous even reported being told ‘My dear fellow, don’t you see, this can’t be cancer because you know its cause’. With time, more light was shed on viruses and their properties, such as the fact they carry genetic information in the form of RNA or DNA and use information encoded in their genes to infect and replicate. Viral genomes became a hot topic of research and various experiments were designed to help disentangle and identify the function of various viral genes. These settings primed the field for the discovery of the first oncogene.

In fact, Rous’s discovery never fell into oblivion as labs continued researching the RSV virus. Some found that certain tumours induced by RSV did not appear to produce more viral particles once infected.

This observation allowed scientists to isolate strains of virus that could infect cells and transform them into cancer cells, but lacked the ability to cause viral replication: these strains were called replicationdefective. A few years later, other RSV strains that had opposite characteristics were identified.

These strains caused viral replication, but infected cells were not transformed into cancer cells. Taken together, these findings showed that replication and transforming abilities were genetically different and separable characteristics carried by the RSV genome.

Finding the first oncogene, V-SRC | Researchers worked ceaselessly to separate replication-defective strains from transformation-defective strains. At the same time, other scientists identified RSV variants that induced different phenotypes in the cells they transformed. These mutant variants induced the formation of spindle-shaped cells, while infection with common RSV caused cells to round up. The characterisation of RSV strains that

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induced different morphologies in transformed cells suggested that the phenotype of the cancer cell is controlled by the genetic information carried by the viral genome. H. Temin, the scientist who published this result concluded: ‘Mutational differences in the virus determine the various morphologies of the infected cells, thus the virus becomes equivalent to a cellular gene controlling cell morphology’ moving a step closer to the identification of the gene behind the transformation into cancer. The year 1970 marks a turning point in the first oncogene history. In that year, G.S. Martin at UC Berkeley isolated a temperature sensitive strain that at the nonpermissive temperature failed to transform cells but continued to replicate. Moreover, when cells transformed by this mutant strain were shifted to the nonpermissive temperature, they reverted to their normal appearance losing the cancer-like phenotype, indicating that the mutant function was needed to maintain the transformed cancer-like state. This unequivocally indicated the existence of a viral gene that is necessary for cell transformation but dispensable for replication. Shortly after, the incredible work by two other scientists led to the physical identification of the gene. P.H. Duesberg and P.K. Vogt isolated the genome of nontransforming strains and of transforming strains.

The latter always contained a slightly bigger RNA subunit called ‘a’ while non-transforming strains contained a shorter subunit ‘b’. They concluded that the genetic material missing from the b subunit was the gene responsible for transformation of cells i.e. an oncogene. Hence, the first oncogene V-SRC was physically identified.

From viruses to humans, C-SRC is the first human proto-oncogene | The following step in the history of V-SRC had a disruptive effect in the fields of tumour virology and cancer genetics. M. Bishop and H. Varmus at UC San Francisco were surprised that RSV didn’t need V-SRC for replication and wondered why the virus would carry a seemingly unnecessary gene. Could it be that it was acquired from cells? Using viral genetic material as a template, Bishop and Varmus made a probe to see if it would bind and recognise similar genetic sequences in the DNA of birds. This was indeed the case and it was found that several species contained sequences closely related to V-SRC. The animal version of the gene was called C-SRC. It became clear that viruses could acquire this gene during their replication cycle. Free from careful cellular regulation, the V-SRC gene becomes a broken cog constitutively expressing active protein and driving the cell in continuous growth and division.

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It was found that whenever overexpressed or mutated, C-SRC caused cells to transform in a cancer-like state in a similar fashion to the RSVmediated cell transformation. The term ‘protooncogene’ was coined to describe genes that were not intrinsically oncogenic but could become so if mutated or over-expressed. Bishop and Varmus’ landmark discovery of C-SRC stimulated a burst of research into proto-oncogenes. Spearheading this new approach to cancer research, Vogt and Duesberg studied other viruses that cause avian blood cancers and identified other proto-oncogenes, additional cogs that could be broken or modified leading to the transformation of healthy cells into cancer cells.

These novel oncogenes were later also shown to be derived from cellular oncogenes known today as some of the most important drivers of human cancer.

MYC, RAS, ERBB: the trio that consolidated the view of cancer as genetic disease | One of the first oncogenes to be identified was ERBB. This oncogene of avian retroviruses can induce an acute form of erythroid leukemia called erythroblastosis and biochemistry studies revealed that the viral protein ERBB protein was closely related to an important family of human proteins. In 1984, J. Downward and colleagues reported its sequence similarity to a human gene EGFR setting the scene for several studies involving the human ERBB/EFGR gene and its role in cancer. Various studies proved that EGFR can function as an oncogenic ‘driver’ of cancer in diverse human tumours. For instance, mutations that mechanistically resemble those seen in the viral oncogene occur in the EGFR of glioblastoma multiforme and non-small cell lung cancer. Genetic studies then showed that the human genome contains three additional genes that are closely related to EGFR: HER2, HER3, and HER4. HER2 is frequently expressed at high levels in breast cancer and its oncogenic potential became clear when DNA from tumours containing amplified HER2 was shown to turn healthy cells into cancer cells.

MYC was another one of the first oncogenes that emerged after SRC. The function of the MYC protein was then investigated and a fundamental insight was offered by the observation that MYC would localise in the nucleus of cells. The immediate reaction was to think it could regulate DNA expression, though investigating the protein’s role was easier said than done. It took substantial effort to find that MYC proteins must couple to MAX proteins in order to bind DNA. Following this realisation, scientists revealed a myriad of cellular pathways affected by the activity of MYC. Indeed,

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cellular levels of MYC are tightly regulated, and when MYC is overexpressed cells can undergo either uncontrolled replication or apoptosis, depending on a multitude of factors that are still not completely elucidated. Recent studies have shown that in cells overexpressing MYC, the MYC protein can bind to more than 7,000 genomic locations (in jargon, loci) demonstrating MYCâ&#x20AC;&#x2122;S potential for disruptive regulation of cellular activities. Furthermore, it has become clear the role of MYC goes beyond a protooncogene that can drive cancer formation. In fact, MYC can also affect resistance to cancer treatments and can cause regression in certain types of cancers driven by other mutated oncogenes.

One such gene is RAS, which also emerged from research on viruses. A series of pivotal experiments linked RAS directly to human cancer. Initially, transfer of DNA from human cancer cells was found to transform mouse cells. The eureka moment came with the discovery that the transforming DNA derived from human cancer cells was homologous to the RAS oncogene isolated from Harvey sarcoma virus and Kirsten sarcoma virus. Within two years, 1982 to 1984, the findings of c-MYC in Burkitt lymphoma, N-MYC in neuroblastoma and oncogenic RAS in diverse human cancers, linked these oncogenes to human tumours. The discoveries with MYC, RAS, and ERBB have special historical significance, because they consolidated the view of cancer as a genetic disease. The significance of identifying oncogenes in viruses was at first exclusively theoretical and experimental, but it then showed that normal vertebrate cells could be transformed into cancer cells by the action of a single gene. This was the revolutionary insight offered by all the scientists who dedicated their lives to the very early stages of cancer genetics research.

Oncogene addiction and targeted therapy | We now know that MYC is involved in several cancer types including breast, colorectal, pancreatic, gastric, and uterine cancers. The ERBB/EGFR gene family also represents an important proto-oncogene group: EGFR overexpression is often associated with many cancers such as gliomas and non-small-cell lung carcinoma, while ERBB-2 overexpression can occur in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other cancer types.

Mutations in the RAS family of proto-oncogenes are very common, occurring in an estimated 20% to 30% of all human tumours. Research on the trio of human cancer (RAS, MYC, and ERBB) fostered further research into human oncogenes. If we define an oncogene as a replication-promoting gene whose

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product is overly active in cancer, then the number of oncogenes we now know is probably in excess of a thousand and growing. The arsenal of oncogenic genetic alterations would not be complete without the multitude of mutations that cause the loss of function of genes that act as tumour suppressors and the role of microRNAs, which are small non-coding RNA molecules that can have anti- or pro-oncogenic activity. However, this complex picture fades in importance when some cancers show a striking dependency on one single oncogene. The growth and survival of oncogene-dependent cancers can often be impaired by the inactivation of a single oncogene.

This so-called oncogene addiction represents the ideal basis for creating targeted therapies against cancer.

Finding what oncogene cancers are addicted to is equivalent to finding Achillesâ&#x20AC;&#x2122; heel. If a drug is then used to target the right oncogene or switch it off, cancers succumb. For instance, switching on the C-MYC oncogene in blood cells leads to the development of leukemias in a transgenic mouse model. When this gene was switched off, the leukemia cells stopped proliferating and several died. Evidence supporting the concept of oncogene addiction is strong and has guided important advancements in our therapeutic approaches to cancer. For example, antibodies have been designed to target specific oncogenes in human cancers and their efficacy probably represents some of the most convincing evidence for the importance of oncogene addiction. One of the earliest examples is the antibody trastuzumab (Herceptin), which targets the receptor protein HER-2/NEU in breast cancer.

Herceptin was approved at the end of the 90s in the US and arrived in the EU in the year 2000. Its efficacy looked so promising from the very first trials that the drug was fast-tracked by regulators (FDA) so that it could promptly reach the clinic. It is now on the World Health Organization's List of Essential Medicines, a list reserved to the medications considered to be most effective and safe to meet the most important needs in a health system. Other success stories of targeted therapy are provided by drugs such as imatinib, which targets the BCR-ABL oncogene product in chronic myeloid leukemia and gefitinib and erlotinib, which target EGFR in nonsmall cell lung carcinoma, pancreatic cancer, and glioblastoma.

Although our understanding of oncogene addiction has led to disruptive results in cancer treatment and scientific evidence does indeed show that cancers can depend on a single oncogene at

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certain points in time, it is apparent from mouse models and clinical experience with targeted drugs that cancers can ‘evade’ oncogene addiction. This can be due to mutations in other genes and cellular pathways that ensure survival and uncontrolled growth, thus escaping targeted therapy aimed at hitting the cancer in its Achilles’ heel. For this reason, treatment resistance can arise and it is unlikely that the use of a single targeted therapy will achieve long-lasting remissions or cures in human cancers. This is especially true for late-stage cancers which often present high mutational loads and heterogeneity, giving the cancer many ways to escape from one specific type of oncogene addiction.

Thus, combining different types of therapy becomes necessary: this approach is called combination therapy.

Combination therapy: biochemistry & physics cocktails | Clinical studies have indicated that targeted therapy can be enhanced by combination with cytotoxic agents which act by inhibiting and interfering with DNA or chromosomal replication.

The design of combination therapies has also gone beyond a mere biochemical approach of pairing two or more drugs by leveraging technologies such as radiotherapy in combination with pharmaceutical agents. Radiotherapy uses X-rays and gammarays, (high-energy radiation in the electromagnetic spectrum), to ionise atoms, causing the loss of an electron and leaving a positively charged ion. Ionised atoms, crucially, can disrupt the functions of various biological molecules in cells and ultimately cause cell death. Beams of radiation are produced by machines called linear accelerators that cause high-speed electrons (other particles may be used) to collide with a metal target, releasing photons. The radiation waves in the form of photon beams can then be targeted to the patient’s cancer. At the cellular level, radiotherapy mainly causes indirect DNA damage.

Radiation causes the formation of free radicals which are toxic to cells and cause breaks in the cell’s DNA. As DNA damage accumulates, the cancer cells are overwhelmed with mutations and dysfunctional DNA leading to cell death.

The history of radiotherapy ran parallel to the efforts in understanding the molecular and genetic basis of cancer until combination therapy showed how combining medical physics with pharmacology could yield better results. Radiotherapy finds its origins in the 1890s when, shortly after the discovery of X-rays, radiation was used to treat some cancer patients successfully. In the first half of the

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1900s, progress was made in defining radiation dosage and treatment regimen, and cobalt therapy machines were adopted between 1950 and the early 1980s. These machines emit gamma rays, which allow the treatment of deeper cancers. Subsequently, linear particle accelerators replaced cobalt units as they can produce higher energy beams without the need for a radioactive source inside them. Starting in the 1970s, radiotherapy saw the advent of more sophisticated techniques that included computerised tomography and integrated computerised image therapy that increased accuracy and efficacy thanks to three dimensional modelling of the tumour mass.

Radiotherapy is often combined with chemotherapy, together with certain types of the afore-mentioned targeted therapies. In preclinical settings, several of these agents have been demonstrated to enhance the effect of radiotherapy making cells more susceptible to radiation damage. However, the safety profile of combination therapy is still unknown for many of these agents.

An alternative approach to combining radiotherapy and targeted therapy was offered by gold nanoparticle (AuNP)-based therapeutics. Gold nanoparticles boast several chemical and physical properties that make them suitable for cancer treatment. Among the physical properties of AuNPs, localised surface plasmon resonance, radioactivity and high X-ray absorption coefficient allow AuNPs to absorb incident photons and convert them to heat to destroy cancer cells (photothermal therapy). On the chemistry front, AuNPs can form stable chemical bonds with sulphur and nitrogen-containing groups, which allows AuNPs to bind to a variety of biological molecules and drugs. Taken together these properties allow AuNPs to be targeted to the cancer by coupling them to antibodies that recognise proteins, often oncogene products, on the surface of cancer cells. However, there are still limitations to their application in the clinic. For instance, phototherapy utilises light to excite the AuNPs, but it is strongly limited by the fact that light cannot reach more than a few centimeters under the skin surface, making some cancers unreachable. Using deeper-penetrating radiation such as gamma-rays could be a solution: gamma rays would excite core electrons near the atomic nucleus of gold and electrons may be released by a so-called Auger deexcitation process, which would then cause DNA damage and cell death. However, the optimal size of AuNPs to achieve this effect is still subject to debate.

Further research in the field of medical physics holds promises in leveraging new technologies coupled with current knowledge of cancer biology, oncogene

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addiction and targeting to yield more efficacious treatments.

Whatâ&#x20AC;&#x2122;s next? To AI and beyond | Having explored and celebrated the discovery of oncogenes and the terrific knock-down effects that this discovery has had in the field of cancer treatments, it is now time to project into the future. What will oncogene research and related scientific efforts reveal? The initial oncogene findings were fundamental in revealing cancer as a genetic disease. They also appeared to explain cancer in simple terms with changes in one, or at most a few genes, to yield novel and specific therapeutic targets. However, careful cancer genome analyses, as part of the cancer genome project, have uncovered an unexpected multitude of genetic changes in all cancers, revealing complex mutational landscapes.

Increasing complexity can also be found in our investigation of the role of oncogenic genesâ&#x20AC;&#x2122; products. All these proteins show multiple activities, giving rise to diverse and specific cancer phenotypes. A complete molecular understanding of how these activities cause and maintain cancer remains a challenge, but striving to characterise cancers and go beyond an initial level of understanding oncogenes can lead to better diagnoses and treatments. Future revelations in the field of oncogene research may come from Big Data science and Artificial Intelligence (AI) which hold promise in addressing some of the challenges and questions that keep haunting oncologists and researchers.

Characterising cancers often remains a challenge, especially when fast sequencing of the whole cancer genome is not quickly available and extracting knowledge that can guide treatment is difficult.

Oncogenes can be detected and combined with a more holistic range of cancer prognosticators, with AI bringing the data together for faster and more accurate treatment decisions. Recently, a convolutional neural

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network demonstrated efficacy in interpreting cancer biopsy slides by measuring not only the appearance of cancer cells but going beyond human vision to predict the driver mutations and wider transcriptomic changes. The algorithm was able to identify patterns and correlations between mutations and histological appearance, namely the aspect of the cancer tissue under the microscope. More than 17,000 slide images from 28 cancer types were analysed and correlated to the matched genomic, transcriptomic, and survival data of the patients who suffered from those cancers.

While the researchers admitted that the number of associations between histopathology and molecular traits is remarkable, this AI approach is still lacking the same accuracy of genetic and transcriptomics testing.

However, better algorithms hold promises for future diagnostics and for pointing out correlations between genetics, transcriptomics and cancer behaviour that can be used as a starting point for further experiments.

Such experiments may reveal new mechanisms behind certain cancer features, in the same unexpected way a chicken virus ended up revealing one of the key principles of cancer biology. Ultimately, the fuller-picture AI can help establish may lead to faster and more accurate diagnosis and more personalised management options.

Therapeutic development may then evolve to a multiomic approach, targeting the full cancer signature rather than a single gene, so what started from oncogenes may become a system-wide treatment Benedetta Spadaro and Harry Bickerstaffe are Therapeutic Sciences MPhil students at St John's and Homerton colleges, respectively. Artwork by Marzia Munafo and Nataliia Kuksa. Photographs are from https://commons.wikimedia.org.

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A Mathematician, a Monster, and a Game with No Players Maria Julia Maristany takes a look inside the marvelous and magical mind of John Horton Conway The year of 1970 was unusually sunny in the UK, albeit quite tumultuous around the world. The Beatles had just announced their separation, the Brazilian football team won their third World Cup, and bicycles were finally permitted across San Francisco's Golden Gate bridge. Also, the US invaded Cambodia, expanding the reach of the Vietnam War, the Apollo 13 mission had failed, and episodes of political violence were increasing in Northern Ireland. But in a place that oftentimes seems to be far away from the rest of the world, in a remarkably untidy office in the middle of the calm city of Cambridge, John Horton Conway was fiddling with a GO board and a computer. He would ultimately invent the rules of what is perhaps his most famous invention: the Game of Life.

This year, the Game of Life, one of the most well known mathematical games of the century, turns 50 years old. It seems only fitting, during this 50 year special edition of BlueSci, to then celebrate the magnum opus of one of Britain’s most eminent mathematicians. Although, in all honesty, I have the feeling that if Professor Conway heard me call the Game of Life his ‘magnum opus’, he would throw a book at my head. And he would be absolutely right.

Through numerical games, mathematical teasers, and the unabridged curiosity of an insatiable mind, Conway proved and disproved a myriad of mathematical claims and theorems. Peeking into his achievements is similar to following the white rabbit into the proverbial hole in the ground. Among his contributions to mathematics, we find many mathematical games of great relevance in the fields of combinatorial game theory, number theory, and recreational mathematics. He invented sprouts, an addictive game where each player takes turns connecting dots by lines that 28

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never cross each other. The game ends when it becomes impossible to draw a line that will not cross another. He also created phutball, short for philosophers football — as a matter of fact, he came up with dozens of games, which can be found in his book Winning Ways for your Mathematical Plays. He discovered a new category of numbers, the surreals, a set of numbers that includes all that are infinitely big, and infinitely small. He designed a new notation, useful to write down particularly big numbers. He created a whole new algebraic structure — a group — that carries his name. Down the rabbit hole, we are greeted by a Doomsday algorithm, and we find a curious zoo of mathematical creatures, such as quaternions, octonions, and even a huge monster (The monster group, a very special algebraic structure, was Conway’s favourite pet).

It was however the Game of Life that, despite Conway’s eye rolling and fist clenching, catapulted him to fame, making him well known by people outside of his field of expertise. It all started with a column written by a friend of Conway’s, Martin Garden, for the magazine Scientific American. Before the internet was even a thing, Conway and Life went viral — it is speculated that there was a time in the 1970s when the game was played in a quarter of the world’s computers, making it the most coded game in history.

The rules of Life are hauntingly simple. Starting with a two dimensional grid, where each space may harbor a living cell at a time, the game evolves as follows: if the cell has less than two neighbours, it dies of loneliness. If it has more than four, it dies of overcrowdedness.

Otherwise, it survives to live happily to the next round of the game. Finally, a cell may be born in an empty space, if that space has exactly three living neighbours.

Each round of the game is called a generation. The rules are applied in all spaces simultaneously, and cells survive, die, and are reborn following Conway’s four commandments. The algorithm runs again and again. In this game with no players, all you have to do is set the initial configuration, and then sit down and watch it unfold. Some patterns eventually completely disappear, leaving behind a cold, lifeless, grill-shaped universe. Others are random or repeat themselves for all eternity.

Beyond the beautifully hypnotic patterns, its playful nature, and the simplicity of its rules, Life has a remarkably complex outcome.

To begin with, the game has a property known as undecidability: there is no way to predict if an arbitrary configuration of cells will live on, or if they are eventually doomed to extinction. It is also a universal model of computation, meaning it is a very powerful data analysis tool. Perhaps more importantly, it also means that with enough cells and a big enough grid the game can actually simulate, and it is therefore equivalent to, any computer. Any results, mathematical curiosities, theorems, and postulates that can be proven true in the Game of Life can potentially be extended to results that hold true for entire areas of study in computer science.

The game also fuels a discussion that roots in very fundamental aspects of physics, ignited by a deceptively silly question: is Life alive?

What kind of complex patterns could potentially emerge if we had an infinitely large grid, and no time limits? And what does that tell us about free will and our own reality? Many years after he created Life, Conway together with Canadian mathematician Simon Kochen postulated the so-called free-will theorem, where it is stipulated that if we, as observers of reality, have free will — meaning that our actions are not determined by a past configuration — then, under certain assumptions, elementary particles must have free will too.

Life is an example of a larger class of mathematical models called cellular automatons. While these models were proposed initially during the 1940s, Conway was the one who, through Life, popularised them among mathematicians, computer scientists, physicists, biologists, academics, and non-academics alike. The field of research involving cellular automatons exploded, and applications were found aplenty. These automatons can be developed to simulate and predict physical, biological, chemical, ecological, social, political, computational, and medical phenomena, to name a few. They have even been used to create art and music.

It is very hard to quantify the impact Life has had, and continues to have, both inside and outside the academic community. Being a particularly simple case of the larger group of cellular automatons, Life provides a great toy model on which to test different hypotheses.

In arXiv, the biggest online repository of academic pre-prints, hardly a week goes by without a new article being posted analyzing the countless facets of the game. Outside of the secluded world of academia, Life sparked a somewhat cult following: there is even an entire wiki, LifeWiki, devoted to the game.

Conway was a great mathematician. Beyond his contributions to the field, he had the rare and admirable ability of being able to burst the bubble of academia and reach out to the public. He did this by illustrating complex mathematical concepts via games and word plays. He did not particularly like the attention that Life received, and he definitely did not consider it his biggest achievement. In Conway’s opinion, Life didn't have any interesting consequences, and he presumably gave it very little thought in his later years. When asked during an interview what he would like to know before he died, Life did not cross his mind. He answered: ‘I’d like to know why does the monster exist’. He passed away in April 2020, three days after contracting COVID-19. He never found out why the monster exists — or if he did, he never told us. But that is a story for another time Maria Julia Maristany is a 1st year PhD student in Physics at Robinson College. ­Artwork by Eva Pillai.

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Improved With Crystals Evelyna Wang explores the intricacies of crystal formation and their many uses From beautiful gemstones in underground caverns to saltencrusted rocks by the ocean, crystal structures are found throughout the material world. Not only are they beautiful but they are also highly functional. By understanding how crystals grow, we developed exciting technologies of the Digital Age, paved the way for safer planes, and even explained the magic of snowflakes.

What makes up a crystal? | We start at the atomic level.

Although the term ‘crystals’ brings to mind colourful, faceted gems often used in jewellery, many solids actually form crystalline structures. A crystal structure simply refers to the ordered and periodic arrangement of atoms (or molecules) within a material.

Imagine, for instance, a cube with an atom placed at each corner. By repeating this cube in three dimensional space (x, y, and z directions), a crystal is formed. If instead of a cube, the atoms arrange into a rectangular prism or a hexagonal prism, a different crystal structure with different symmetries and physical properties will form.

Another type of crystal structure is a cube with atoms on the corners and one in the center of each cube face. Many metallic elements, gold and silver for example, are crystalline solids that follow this particular cubic atomic arrangement. In fact, you can see this by probing gold at the atomic scale, possible today due to advances in electron microscopy!

These atomic positionings are determined by the conditions that lead to crystallization.

How are crystals formed? | Examples of crystal formation are all around us. A simple one is cooling molten metal into a crystalline solid state: in the liquid state, the metal atoms have plenty of kinetic energy to move around and the probability of atoms forming a cluster is very low — imagine energetic children running around in a classroom. As the temperature decreases, the atoms lose their kinetic energy, becoming increasingly likely to cluster. When the temperature drops below the freezing point, a solid crystalline state becomes more favorable than the liquid state — now imagine tired children who would rather sit at their desks arranged in neat rows. Any cluster of atoms that forms then has the potential to arrange into a tiny crystal called a nucleus. If the surface area (total energy cost of nucleation) to volume (total energy gained) ratio is less than a certain value, the nucleus can be stabilized. The atoms at the edges provide a specific orientation for neighbouring atoms in the liquid phase to align and attach, thus growing the crystal.

Another example is the formation of salt crystals from solution. As the water evaporates, the concentration of

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dissolved salt ions increases, until the saturation point is reached. Beyond this, the solid crystalline state is energetically more favorable than remaining in solution, and clusters of salt ions have the potential to nucleate. Salt crystals form cubic arrangements of atoms, and close examination of any crusty rock at the beach will usually reveal small white crystal cubes! Similarly, stalactites and stalagmites are formed in caverns when limestone crystallizes from drops of concentrated solution.

Atmospheric water freezing into snowflakes also follows the nucleation-and-growth theory. Below a certain temperature, the saturation limit of water vapour in air is exceeded, and the preferred state of water is a solid, meaning that ice crystals can nucleate and grow. Due to the arrangement of water molecules into a hexagonal array, beautiful six-sided snowflakes are formed.

Furthermore, the same material can form different crystal structures depending on the crystallisation conditions. These differences in atomic positionings lead to different physical properties. In steel, one crystal structure causes it to become extremely hard and brittle, while another arrangement of the same atoms results in a more pliable steel. The reason Japanese samurai swords were so incredible is because the blade edge was made of brittle crystalline steel for cutting, while the body had atoms arranged in the more flexible crystal structures to absorb shock. In order to achieve this, swordsmiths apply a different cooling rate to the edge compared to the spine of the sword.

As we can see, crystallization dictates the atomic positionings which in turn dictates the material properties. Specific crystals with specific electronic, thermal, or physical behaviours can be synthesized and used to improve our lives.

What are crystals used for? | Without crystals, we would not have computers, planes, electric cars, many pharmaceutical drugs, or even vaccines. It doesn’t take a crystal ball (which are sometimes just glass balls) to see that our lives would be drastically different without understanding and harnessing the magic of crystals.

Silicon single crystals serve as a semiconducting substrate onto which microelectronic devices are fabricated, such as the transistors that make up a computer chip. Since polycrystalline silicon have poor electronic properties, developing methods to grow single crystal silicon efficiently and economically was a major factor in launching the world into the Digital Age (also known as the Silicon Age). Other single crystal semiconductors with precise electronic properties are also produced at large scales for the LED lights, solar panels, and sensors that are ubiquitous today.

Lithium-ion batteries that power most of our portable

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Crystallization can even occur in molecules that assemble into devices and electric vehicles are also reliant on the crystalline materials. The energy provided by a battery comes from lithium periodic arrays. Biological materials such as proteins and DNA can pack into ordered layers that form crystals up to hundreds ions entering a crystalline host structure. Changes in the crystal structure can affect the amount of energy delivered and the ease of micrometres in size. The double helix structure of DNA and many important protein structures were discovered by analysing of charging or discharging the battery, ultimately affecting how their crystals. long your battery can last.

Ongoing research in crystals is found across all disciplines.

Another class of interesting crystals are piezoelectric materials.

In chemistry, understanding and controlling the crystal These materials demonstrate a change in electrical conductivity structures in battery materials can lead to better performance when the crystal structure is elongated or compressed in a in phones, laptops, and electric vehicles. While in biology and particular direction. Ultrasound transducers, used for nonpharmacology, research in protein crystallisation is important invasive medical imaging like pregnancy monitoring, employ for the development of novel vaccines and drugs. A recent piezoelectric crystals to detect the returning ultrasound echos. example of this was the rush to solve coronavirus protein The soundwaves cause a slight deformation in the detectorâ&#x20AC;&#x2122;s structures. crystal structure resulting in electrical signals that are converted Our world consists of and is built upon crystal structures. to an image.

Many natural wonders as well as many of our technological Thermal properties can be improved by crystals too. Single advances are a direct result of crystal magic. Who knows crystals of nickel alloys are grown and used as jet-engine what weird and wonderful crystals we will discover or turbine blades because their thermal stability and mechanical strength exceeds that of steel, which is prone to cracking during formulate in the future... operation. Without these single crystals, catastrophic failure of turbine engines would make planes very unsafe!

Evelyna Wang is a 3rd year PhD student in Chemistry at Girton College.

Artwork by Jocelyn Tang.

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Making an Internet From Scratch Charles Jameson explores the remarkable levels of complexity underlying something we all take for granted — The Internet Computer scientists are remarkably good at not telling anyone what they are doing.

Even when their inventions are changing the fabric of our society, you probably will not hear about it. For instance, imagine picking up your phone and searching for an image on Google. This is an incredible power that we have forged for ourselves. But how does this actually happen? Where is that picture stored? How does our phone know where to find it?

To make things worse, the internet is constantly changing.

There are many twists and turns coming up in this story which will profoundly change how the whole world stays connected, but what chance will anyone have to understand them if we don’t know what we already have?

So, in this spirit, take this article as a ‘Last week on…’ catchup of sorts in the TV show that is The Internet. And get ready for the rest of the season, because it’s coming thick and fast.

Wi-Fi | Our journey starts by pressing ‘Search’ on a phone to look up a picture. The goal is to reach Google with a request for the picture. But first, that request has to get off the phone.

Wi-Fi is a system developed by Australian radio-astronomers in the 1990s. Every modern phone contains a small antenna which can send and receive messages across a certain range of frequencies. Our phones are constantly ‘listening’ for announcements, also known as ‘broadcasts’, from a Wireless Access Point (WAP) to let them know that there is a way to access the internet. The WAP listens for replies from phones and talks to each of them over different radio frequencies.

IP Packets | It begs the question, what do these ‘messages’ look like? To operate properly, all of these devices need to agree on what order to send information, bit by bit, so that the recipient knows what they are looking at. The exact layout of this information is called the ‘protocol’, and a single

chunk of this information is called a ‘packet’. For example, one of the first things that is sent in a packet is its intended destination, known as the ‘IP address’. 13 servers scattered across the globe, known collectively as the ‘DNS root zone’, control how domain names like ‘google.com’ get turned into IP addresses.

Internet Service Providers | Our message then makes its way out to an ‘Internet Service Provider’ (ISP). These companies create sprawling infrastructure networks across entire countries, with the sole task of receiving packets and getting them where they need to go. The inner workings of each ISP are well-kept secrets, but in general, they calculate efficient routes to get packets across their network. Each ISP will also form business relationships with other ISPs to share packets. These relationships are critical to the internet’s success, as otherwise every ISP’s users would be cut off from the rest of the world. It also prevents ISPs from attracting users with ‘exclusive websites’, since all data is shared across all ISPs. Data Centres | Once our message has found its way to an ISP, it hops from country to country to make its way towards a Google data centre. Data centres are huge warehouses full of millions of computers (‘servers’), each handling different requests. These data centres, now more commonly known as ‘the cloud’, store data, process search requests, show you your photos, and more.

Data centres across the world are a grand exercise in engineering, networking, and computation. They handle billions of users, trillions of requests, and quadrillions of pieces of data, and require enormous teams of engineers to manage them properly.

There And Back Again | Once Google has processed our request for a photo, how does it reply? It retraces the initial packet’s steps! ISPs remember where your packet came from so immediately know where to send the reply. Once this connection is established, Google can finally send the photo to your phone, packet by packet.

Of course, there is a lot of complexity being omitted here.

How is this conversation kept private? How are all of the packets, which assemble to make up the picture, sent in the right order? There is a more important question...

How Did We Get Here? | The most remarkable mechanism here is not any one invention — it is the nature of the endeavour itself. The internal structure of computers provides engineers with extraordinary permission to place blind faith in each other in the pursuit of ever-larger and ever-faster systems.

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Making An Internet From Scratch

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This hyper-collaborative structure is a result of careful planning during the creation of ARPANET, a predecessor to the Internet. Connecting two computers through an ‘inter-network’ would require enormous amounts of planning, code and infrastructure. But with so many developers attempting to contribute to this new field, how could there possibly be any agreement? A seminal paper from Vint Cerf and Bob Kahn in 1973 provided a solution by imposing deep structure into the way the internet functions. It split the internet into ‘layers’, each with a distinct role, and outlined how each layer would communicate with the next. For instance, one layer was responsible for controlling the order of 1s and 0s being sent down copper cables. Another was responsible for handling errors in unreliable networks.

Cerf and Kahn recognised that these divisions were necessary to ensure that development of the internet was structured and sustainable, even if it restricted the choices available to engineers working in each layer.

Communicating in ARPANET prior to this was like addressing your post to ‘the red house near the station’ — Cerf and Kahn had just invented street numbers, street names, and a whole postal service.

Cerf and Kahn chose not to specify how each layer should be implemented. These gaps have since become battlegrounds between companies, fighting to create the fastest systems for each layer.

It also ensured that the advancements made within every layer would be felt across the entire internet. For instance, a researcher testing improvements to Wi-Fi and a developer working on Google’s search algorithm will almost certainly never collaborate during their careers.

However, if the Google developer takes a year off and Wi-Fi continues to be refined, the developer may return to find that their product appears faster to users without having moved a muscle simply because phones connect to Wi-Fi faster! Cerf and Kahn’s proposal demands complete faith between engineers and it intertwines their fates, since every success and failure can be felt by billions of people.

security risks.

The Internet might seem like your favourite TV show, but seasons of character development can sometimes be thrown away in a single moment.

Will The Internet’s next season be even more exciting than the last? It certainly has the foundations for it. But never take it for granted — it could very well be headed for early cancellation Charles Jameson is a 3rd year Computer Scientist studying at Queens' College. Artwork by Zuzanna Stawicka.

"These structures that have been placed on the internet form the basis for a competitive market. However, this organism is at risk."

Next time on… The Internet | These structures that have been placed on the internet form the basis for a competitive market. However, this organism is at risk. ISPs have lobbied for the end of ‘net neutrality’, which requires all packets over the internet to be treated equally. Without it, tech giants like Google and Netflix could dominate even further by paying for higher bandwidths and faster connections. Governments are also requesting backdoors into encrypted communications over the Internet, which introduces new privacy and

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Making An Internet From Scratch

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A Sprinkling of Gold Dust: Fairytale or Modern Science?

William Hotham discusses the many uses of gold, from drug delivery to renewable energy

"when we use very small quantities of gold such as nanoparticles, we discover new, magical properties that make it valuable"

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When we think of gold, many of us will see a gold ring, or perhaps an expensive item of jewellery. But what if we think about gold in a scientific way? A-Level chemistry tells us that gold has an atomic number of 79 and occurs naturally in a pure state. It is soft, malleable, and inert, which makes it resistant to corrosion. This is probably why we never used it in our chemistry experiments (nothing to do with budgeting!). However, when we use very small quantities of gold such as nanoparticles, we discover new, magical properties that make it valuable in applications from environmental science to medicine.

complementary charge interactions, and UV radiation is used to reverse the charge on the gold nanoparticle, releasing the DNA. This has been used for targeted gene delivery as once the DNA is removed, the gold nanoparticle will have no hazardous side effects within the body and is naturally excreted.

These studies highlight the versatility of gold nanoparticles and how binding molecules to the surface can allow drug delivery via gold. If we go further, to nanoparticles as small as 30 nm, we can begin to manipulate the electron properties of gold.

Gold Catalytic Converters? | If we look at the structure of gold at the nanometer scale, the properties of gold can be manipulated. This was initially discovered

by Dr Haruta of the Osaka Government Industrial Research Institute, who showed that smaller gold nanoparticles supported by metal oxides can exhibit a catalytic activity and facilitate the conversion of carbon monoxide to carbon dioxide.

Before Dr Haruta, this catalytic activity had been reported but at low levels. By using smaller gold nanoparticles, Haruta displayed a greater efficiency of catalytic activity. This discovery revealed how nanoparticle size can affect the functional properties of gold.

Surface Plasmon Resonance â&#x20AC;&#x201D; The Science | The use of gold nanoparticles relates to their basic photophysical responses that do not exist in nonmetallic particles. When gold is exposed to light (an oscillating electromagnetic field), the light induces a collective, coherent oscillation of electrons in the gold nanoparticle.

This electron oscillation around the nanoparticle surface induces a charge separation across the nanoparticle. The amplitude of the oscillation reaches its maximum at a specific frequency, this is termed the surface plasmon resonance. Surface plasmon resonance induces a strong absorption of the light, which can be measured using a spectrometer.

A Golden Way of Delivering Drugs | Gold nanoparticles are now being used as drug delivery systems. Through controlled fabrication, gold nanoparticles sized 1-150 nm (1 nm is one billionth of a metre) can be bound directly to drugs. This binding can be applied to several different metals, however, the key benefit to using gold nanoparticles is that the gold â&#x20AC;&#x2DC;coreâ&#x20AC;&#x2122; is non-toxic, biocompatible, and inert thus will not promote an immune response in the body. Prodrugs are drugs that are inactive when administered and are then metabolised into pharmaceutically active drugs in the body. The conjugation of a prodrug to a gold nanoparticle enables the delivery of a drug to a cell and the drug can then be released to the cells via external stimuli such as ultraviolet (UV) radiation.

This approach is now becoming applicable in genetic modification. DNA is bound to gold nanoparticles via

A Sprinkling of Gold Dust

The surface plasmon resonance is much stronger in gold than other metals due to its electron structure. The surface plasmon resonance intensity and wavelength depends on the factors affecting the electron charge density on the particle surface such as the metal type, particle size, shape, structure, and composition.

Absorption or Scattering | Upon light striking a nanoparticle, there is energy loss. The two contributors of this loss are absorption and scattering. When light is absorbed, the energy is lost to the surroundings and converted to heat. On the other hand, scattering occurs when the energy causes electron fluctuations in the nanoparticle which in turn emits a form of scattered light.

The absorption and scattering of light is largely dependent on the size of the nanoparticles. For the smaller gold nanoparticles, nearly all of the energy loss

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is contributed by absorption. However, the ratio of light scattering to absorption increases dramatically for larger particles and this sliding scale guides the choice of which gold nanoparticle to use in science. Due to their higher scattering ability, larger nanoparticles are preferred for biomedical imaging, whereas smaller nanoparticles are preferred for photothermal therapy, as light is mainly adsorbed and is efficiently converted to heat for cell and tissue destruction.

Gold Nanoparticles for Photothermal Cancer Therapy | Gold nanoparticles can be used in the treatment of skin cancer. Cancer cells are cells that are growing uncontrollably and can be recognised because they display certain cancer-specific markers on their surface. In research laboratories, antibodies recognising these markers can be manufactured and conjugated to small gold nanoparticles. The antibodies will direct the gold nanoparticles specifically to cancer cells in the skin. Upon exposure to a light source, the gold nanoparticles will convert the light to heat, killing the cancer cells. This treatment does not cause harm to normal cells, which is a major problem with other non-targeted cancer treatments, such as chemotherapy.

Gold nanoparticles can also be used as medical imaging aids. For example, in regenerative stem cell therapies, the tracking of injected stem cells within the body is vital in order to understand the location and mechanisms of their therapeutic effects. By labelling stem cells with large gold nanoparticles, light scattered from the particle can be used to track the stem cell within the body.

The gold can donate electrons to the hydrogen ions (H+) to produce hydrogen atoms (H), which can be stored until required. Therefore, the gold nanoparticles act as photocatalysts, using sunlight to make chemical reactions occur faster and more readily in renewable energy devices. Furthermore, the ability to store hydrogen means the major drawback for using solar panels (the intermittent availability of a solar source) is overcome.

When we think of gold, we normally think â&#x20AC;&#x2DC;the more there is, the more valuable it isâ&#x20AC;&#x2122;. However, when we consider gold on the nanometre scale, its chemical properties seem much more valuable than its use in jewellery. Gold can be used for drug delivery systems, cancer therapies, stem cell tracking devices, or even to solve the issues of inefficient renewable energy sources.

Maybe there is some magic in a sprinkling of gold dust?

"Gold nanoparticles have revolutionised renewable energy by increasing the efficiency of producing hydrogen power."

William Hotham is a third year PhD student in Surgery at St. Catherines College. Artwork by Josh Langfield.

A Golden Renewable Energy Source | Gold nanoparticles have revolutionised renewable energy by increasing the efficiency of producing hydrogen power. Currently, titanium dioxide is used as a catalyst in hydrogen production, requiring illumination with UV light. However, this is not efficient due to low levels of natural UV light. Instead, scientists now use gold nanoparticles in the form of tiny stars, which are coated with a semiconductor to give them the capacity to generate hydrogen from water. This is four times more efficient than gold-free methods. The gold nanoparticles can be excited using visible or infrared light from the sun, causing the electrons to oscillate (surface plasmon resonance). The oscillating electrons then break the chemical bonds in water to form hydrogen ions and oxygen.

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A Sprinkling of Gold Dust

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Weird and Wonderful Illuminating the Northern Lights The Northern Lights, or ‘aurora borealis’, are without a doubt one of the most beautiful sights in nature and have inspired many stories to explain their cause, from the twinkling of the Valkyrie’s shields to the spirits of the dead playing football with a walrus skull. However, my personal favourite is that which is told by physics.

Kristian Birkeland was the first to suggest a scientific theory for the Northern lights in the early 1900s but even now the details are not fully understood. The phenomenon involves a complex interplay of solar physics, electrodynamics, and atomic physics. Here I will focus on the most visually spectacular part; how do the Northern Lights get their colours?

The Northern Lights are caused by the interaction of the solar wind with the Earth’s magnetic field. The solar wind consists of a plasma of particles including protons and electrons which are directed towards the Earth’s poles by its magnetic field. When these particles reach the upper regions of the atmosphere, they collide with atmospheric atoms and molecules and gain energy, which excites them.

After a particle has been excited, it moves back to a lower energy state by emitting a photon, the colour of which is determined by the energy difference between its excited and final states. These energy differences are unique to each element meaning each one will emit a unique spectrum of colours. Most of the colours we see in the Northern Lights are caused by just two elements: oxygen and nitrogen.

Oxygen is responsible for the green and yellow hues whereas nitrogen causes the reds, purples, and sometimes blue. LH

Stepped-drum Calculators to Math Grenades

Why Position Matters

How much do you know about the development of the calculator? Today we see calculators as a useful feature on our phone. Yet when they were first invented, they were considered to be technological masterpieces, accomplishing calculations in a fraction of the time that would leave even the greatest mathematicians hunched over their desks for days.

The mathematician and philosopher Gottfried Leibniz developed the concept of stepped-drum calculators (also known as Leibniz’s wheel) as early as 1673. This involved a cranked system, which coupled a counting wheel with ten different sprockets and cogs of varying sizes to give an output in decimal representation. Invented in the 1870s by Baldwin and Odhner, separately, the pinwheel mechanism built on Leibniz’s concept to further improve the mechanical calculator. Both the steppeddrum and pinwheel calculators performed multiplication and division by successive addition and subtraction, while the Millionaire calculator, 1893, was the first direct multiplication machine.

A standout mechanical calculator is the Curta, often referred to as the ‘Math Grenade’, as it resembles the shape of a stereotypical hand grenade. This pocket-sized creation was the first portable calculator. It was developed in the 1930s by Curt Herzstark, an Austrian engineer. Curta calculators were widely considered the best portable calculators available until they were displaced by electronic calculators in the 1970s. KB

Enantiomers are molecular mirror images of each other. This means they have the same chemical composition, however their bond positions are reflected in such a way that the two molecules can no longer be superimposed. This can confer different biological properties to each molecule.

These chemical differences can be experienced in the kitchen. One of the major essential oils in citrus fruit is limonene, which comes in two different enantiomers. The R form of limonene is responsible for the smell of oranges and the S form for lemons. One small change in positions of the atoms causes a drastic change in how we perceive the chemical. It is worth giving them a sniff!

A more extreme example of the effect of enantiomers is thalidomide, a drug which was historically used to treat morning sickness. One thalidomide enantiomer causes birth defects and high infant mortality rates, whilst the other is an effective morning sickness treatment.

The problem arose because the molecule tested was obtained from biological sources and only contained one enantiomer; the one that treats morning sickness. However, when the drug was chemically synthesised, a ‘racemic’ mixture was produced, which contains a 50:50 ratio of the two enantiomers. Whilst these chemicals have the same chemical composition, enzymes can distinguish the different enantiomers and respond differently to them. Enantiomers present a big problem in terms of chemical synthesis, especially when making medicines. In some cases the dose simply has to be increased, while for others the enantiomers must be separated or chemically converted into a single enantiomer. One tiny difference has the potential to cause a dramatic change! OK

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Weird and Wonderful

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