BlueSci Issue 49 - Michaelmas 2020

Michaelmas 2020 Issue 49 www.bluesci.co.uk

Cambridge University science magazine

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Bacterial Art . Drug Development Staying Sane . Science at Speed

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Cambridge University science magazine

Contents Regulars

Features 6

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Plan-demic: Decoding Disease Dynamics

On The Cover News Reviews

Shavindra Jayasekera explores the role of mathematical modelling in understanding disease spread

Staying Sane in an Insane World: The Challenge of Social Distancing

FOCUS

Mirlinda Ademi explains the neuroscience underlying loneliness 10

Obesity: a Choice or ‘Fat Chance’?

Dean Ashley presents how genetics can influence metabolism

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A World Without Antibiotics?

Megan Hardy explains the importance of antibiotics and novel innovations

A Pathogen’s Dilemma: The Virulence-Transmission Trade-Off

Oakem Kyne discusses why some microbes evolve to be more harmful than others

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Pavilion: Bacterial Art

Pauline Kerekes interviews the masterminds behind ‘bacterial art’ 24

All Hands on Deck

Alice McDowell explores the benefits of sharing resources for drug development 26

Science at Speed: Publishing Amidst a Pandemic

Juliana Cudini discusses how academic journals coped with the COVID-19 ‘infodemic’

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 illustrations 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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PANGOLINS, PIGS, AND PETS: RECIPE FOR ANOTHER PANDEMIC? Tatjana Baleta, Hazel Walker and Anna Tran discuss the challenges and solutions to sustain human dependence on animal as a source of income, food, or companionship while protecting livelihoods and public health

A Vaccine for Your Mind

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The Value of Being Precautious?

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Weird and Wonderful

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Joanna Lada and Jake Rose propose inoculation theory as a weapon against misinformation

Charlotte Zemmel invites us to examine the values which underlie scientific data interpretation A Watery Twist to the Dinosaur Tale A Spoonful of Jelly Makes the RNA Go Down Peanut Butter Diamonds

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: Lisha Zhong & Emma Soh................communications@bluesci.co.uk Art Editor: Pauline Kerekes.........................................................................art-editor@bluesci.co.uk

Contents

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Issue 49: Michaelmas 2020 Issue Editor: Debbie Ho Managing Editor: Sarah Lindsay First Editors: Mirlinda Ademi, Ruby Coates, Sergio Martinez Cuesta, Grace Field, Hollie French, Matthew Harris, Ernestine Hui, Leia Judge, Lizzie Knight, Adiyant Lamba, Michelle Miniter, Maya Petek, Bao Xiu Tan, Billy Watkinson, Bryony Yates Second Editors: Salvador Buse, Jessica Corry, Sergio Martinez Cuesta, Catherine Dabrowska, Matthew Harris,Lucy Hart, Debbie Ho, Liam Ives, Anna Kirk, Miriam Lisci, Jake Rose, Holly Smith, Emma Sun, Darinka Szigecsan, Evan Wroe Art Editor: Pauline Kerekes News Team: Zak Lakota-Baldwin, Shamil Shah, Jacob Whitehead Reviews: Kate Howlett, Adiyant Lamba,Tom Wilkins Feature Writers: Mirlinda Ademi, Dean Ashley, Juliana Cudini, Megan Hardy, Shavindra Jayasekera, Oakem Kyne, Joanna Lada, Alice McDowell, Jake Rose, Charlotte Zemmel Focus Team:Tatjana Baleta, Anna Tran, Hazel Walker Weird and Wonderful: Elizabeth Brown, Adiyant Lamba, Benedetta Spadaro Production Team: Debbie Ho, Leia Judge, Pauline Kerekes, Sarah Lindsay Caption Writers: Debbie Ho and Leia Judge Copy Editors: Ruby Coates, Simone Eizagirre, Debbie Ho, Leia Judge, Sarah Lindsay, Hazel Walker Illustrators: Marie Cournut, Marida IanniRavn, Josh Langfield, Rianna Man, Marzia Munafo, Clara Munger, Eva Pillai, Rosanna Rann, Natalie Saideman, Rita Sasidharan, Erin Slatery, Zuzanna Stawicka Cover Image: Rianna Man and Rosanna Rann

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

Our Public Health When facing adversity, we have the ability to inform ourselves and work together to tackle new problems. In 2020, the COVID-19 pandemic has challenged us to use and appreciate the tools and expertise we have in place to protect public health. To address an international problem, each of us, from all walks of life, plays a role in sustaining everyone’s health and wellbeing.

Shavindra Jayasekera highlights the importance of epidemiologists and mathematicians in informing modern public health policies. He explains the basis for well-established mathematical models which quantify the effects of social contact and the risk of spreading infectious diseases. While social distancing has contributed to the control of disease transmission, humans thrive on relationships. Mirlinda Ademi discusses the challenges of social isolation, going into how we experience loneliness at the cellular level, and suggests how we can cope with it.

During this pandemic, we have become more aware that health is highly personal — illness can often be experienced differently among ourselves. Dean Ashley explains how one’s DNA can affect the individual’s risk of becoming obese, which means that a personalised approach is required to manage our metabolic health.

Beyond ourselves, we coexist in a world with microbes. While the COVID-19 pandemic lifted viruses into the limelight, we make a distinction between two types of microbes: bacteria and viruses. Megan Hardy discusses the importance of antibiotics to treat bacterial infections that were once a cause of mortality. Oakem Kyne then focuses on how pathogens including viruses and bacteria can evolve to balance their ability to spread among hosts and the severity of host disease manifestation. However, we must remember that not all microbes are harmful. In fact, some are necessary for health or have useful biotechnological applications. In the Pavilion, Pauline Kerekes interviews Dr Mehmet Berkmen, who collaborates with Maria Peñil Cobo to ‘paint’ with bacteria and create visual masterpieces.

The FOCUS is a timely piece, where Tatjana Baleta, Hazel Walker, and Anna Tran offer a global perspective on how policymakers, professionals, and consumers in the food and pet industry need to work together and responsibly manage our dependence on wild animals, livestock, or domestic animals as a source of income, meat, or companions. In unity, these communities must devise strategies to reduce the emergence of new zoonotic diseases without compromising livelihoods and public health.

Indeed, well-managed collaborations speed up solutions for biomedical problems.

Alice McDowell explains why drug development is a lengthy and expensive process.

She describes the positive impact of growing trends for open-source resources and collaboration which promote a culture of unity and inclusivity among researchers.

Beyond the research lab, during the pandemic, the scientific community also had to cope with an ‘infodemic’. Juliana Cudini interviewed Nature Editor-in-Chief Magdalena Skipper and eLife Deputy Editors Anna Akhmanova and Detlef Weigel about strategies which scientific journals have used to cope with the massive influx of research information. Furthermore, Joanna Lada and Jake Rose also spoke with Dr Sander van der Linden about how to handle misinformation and educate ourselves and those around us against fake news. Finally, Charlotte Zemmel invites us to take a step back and consider the values which underlie the interpretation of scientific data and policymaking.

In the face of hardship and amidst confusion driven by the COVID-19 pandemic, mankind has shown that unity and cooperation between professionals of diverse expertise and the general public are key to keep each other safe and adapt to unexpected challenges Debbie Ho Issue Editor #49

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On the Cover We wanted the the cover to depict scientists intrepidly heading into research by heading down test tubes and tackling big scientific problems. We have included farm animals, wild creatures, and a domestic canine as a reference to the Issue’s FOCUS on zoonotic diseases originating from wild animals, livestock, and pets. The theme of therapeutic development is loud and central here as the scientists rush around developing cures or vaccines. There is a nod to scientific publishing and policymaking as they carry files to where they need to go. The phone is hanging down and ringing off the hook to symbolise ongoing public engagement and misinformation.

Finally, a doodle of Ebola and a depiction of a bacterial culture reflect that this Issue discusses two central biological challenges in public health: viral epidemics and antibiotic resistance Rosanna Rann, Representing herself and Rianna Man as the Cover Artists

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On the Cover

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News Green Energy With Your Greens Researchers from the University of Cambridge

have demonstrated that using tinted semi-transparent solar panels with crop production can increase profits and enhance crop nutrition. The technique, known as ‘agrivoltaics’, involves harnessing a portion of solar light to generate electricity via photovoltaic panels and allowing the remaining light to be used by plants in photosynthesis. Previously, semi-transparent solar panels used in agrivoltaics have absorbed light uniformly across the visible spectrum.

This research investigated the use of tinted photovoltaic panels that selectively absorbed blue-green wavelengths and allowed orange-red wavelengths to pass through to basil and spinach crops. Due to their photosynthetic pigments, plants absorb more light in the blue, orange, and red wavelengths and reflect the rest, which explains their green appearance. Despite a lower yield in crops due to the reduction in light intensity, a reduction in electricity bills from solar power generation gave a gross financial gain of 2.5% for basil and 35% for spinach crops. Additionally, the reduced light intensity enhanced the growth of proteinrich leaves and stems over roots. With the plant-based protein market forecasted to grow by 30% annually, agrivoltaics may increase in popularity as a technique for plant production. SS Check out www.bluesci.co.uk, our Facebook page or @BlueSci on Twitter for regular science news and updates

Four-Stranded DNA: A New Dimension For Cancer Therapy?

Researchers at the University of Cambridge have found that four-stranded DNA structures play a role in certain types of breast cancer and could provide a new target for personalised medicine.

Four-stranded configurations of DNA occur in regions rich in guanine, one of the four DNA bases, which form looped structures known as G-quadruplexes.

They are involved in the process of transcription and are more likely to be found in cells that are rapidly dividing, such as cancer cells.

A team of scientists investigated the genomic distribution of G-quadruplexes in cancerous tumours, using tissue sampled from breast cancer patients at Addenbrooke’s Hospital. The study, published in Nature Genetics, showed that G-quadruplexes were most prevalent within regions of the genome containing copy number aberrations (CNAs), which arose due to incorrect DNA replication during cancer cell proliferation.

This is the first time that four-stranded DNA structures were observed in breast cancer cells, and this could have significant medical implications. There are at least 11 subtypes of breast cancer, with each of these subtypes having its own unique ‘landscape’ of G-quadruplexes. Professor Carlos Caldas, one of the lead researchers, explained, ‘Identifying a tumour’s particular pattern of G-quadruplexes could help us pinpoint a woman’s breast cancer subtype, enabling us to offer her a more personalised, targeted treatment’. ZLB

Immune Suppression — From Enemy to Therapy A joint study by the Wellcome Sanger Institute (WSI) and Medical Research Council Cancer Unit in Cambridge, UK, revealed that tumours can manipulate immune cells, known as T cells, into producing immunosuppressive steroids. While this showed that tumours have another way of evading the immune system, it indicated that it may be possible to halt steroid production and inhibit cancerous growths.

Their work was published in Nature Communications and followed from a previous discovery, which showed that T cells dampened the immune system by releasing immunosuppressive steroids to reduce activity to normal levels post-infection.

Their subsequent research in mice reported that T cells from melanoma and breast tumours behaved in a similar way. Using single-cell RNA sequencing, the team discovered that the tumours tricked T cells into producing immunosuppressive steroids, while those T cells from healthy specimens did not.

To test whether stopping steroid production could reduce tumour growth, researchers examined mice without a key steroid-synthesis gene, Cyp11a1. As expected, the tumours in these animals were dramatically smaller than those in ordinary mice. According to Dr Sarah Teichmann of the WSI, ‘Preliminary data from human tissues suggests the same tumour defence may happen in people’. If true, future drugs could target this immunosuppressive pathway as one way to treat cancer. JW Artwork by Marie Cournut

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News

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Reviews Primates – BBC One The BBC Natural History Unit’s recent series Primates was the first to focus entirely on this group of animals, exploring survival strategies, social behaviours, and the threats facing these species, such as habitat loss, the pet trade, and climate change. The series could not have come at a more important time — according to the International Union for Conservation of Nature, 0.4% of primate species are already extinct in the wild and 60% are threatened with extinction.

The programme shone a welcome light on our own group within the animal kingdom, as well as highlighting our moral responsibility to save our endangered relatives from extinction.

By drawing focus to humans’ place in the natural world, this series reminds us that despite being just another ape, we are the ones with whom the fate of all other primates rests.

Understanding our place within the animal kingdom affects our worldview. We are just one of the millions of species to inhabit our planet, and too many view us as having dominion over the rest of the planet’s biodiversity. Primates did a beautiful job of highlighting the beauty, diversity, and plight of our own taxonomic order. KH

Dish Life: The Game – Pocket Sized Hands

Stalin and the Scientists – Simon Ings

Ever wondered what it is like to be a scientist? The new game by developers Pocket Sized Hands takes the player from being a wide-eyed undergraduate interested in gaining lab experience to a fully-fledged professor of stem cell biology.

While the general public may be exposed to nuggets of scientific information, rarely do they get to see behind the curtain. In Dish Life the player has to navigate the many intricacies of research: how to maintain cells and a balanced life, how to communicate with other researchers, how to manage projects on limited time, and so on. Allowing the player to learn about how research science works both on and off the bench makes the game a novel instalment in the mobile gaming app genre, and you can dip in and out of Dish Life as you please.

The gameplay of Dish Life is somewhat repetitive, but it works well for a quick five-minute break. The player has to go through each day in the game by culturing cells, preparing solutions, and performing daily tasks (including rest). Over time the player unlocks more complicated projects and interactions. For those not in academia, the game will provide an opportunity to access the world in a fun and relatively realistic way. AL

In his 2016 book Stalin and the Scientists, Simon Ings delivers a whistle-stop tour of the role of science and those who practiced it in Russia, and then the USSR, in the first half of the 20th century. He divides this into three sections — Control, Power, and Dominion. These respectively take us through the transition of the Russian Empire into the Stalinist USSR, Stalin’s purges and his politicising of Soviet science, and finally the effect of the German invasion in 1941 and the post-war period on Soviet science. Ings chooses to tell the story of Soviet science by focusing on various protagonists. This approach is engaging but, if somewhat confusing at times due to the sheer number of characters introduced. Nevertheless, his writing style is clear and straightforward, exactly the antidote needed for this kind of structure which also aims to condense around 100 years of cultural and revolutionary history into 400 pages.

As for the themes of the book, these are clear and run throughout: the incompatibility of ideology and the scientific method, the danger of deliberate ignorance and improper application of scientific research to suit political ends, and the role political expediency plays in changing the importance of ideology in the minds of powers that be.

For example, previously impractical ‘unsoviet’ fields such as physics suddenly became much more attractive once the development of the atomic bomb became a matter of national security. In the epilogue, Ings holds a mirror up to the reader, challenging them to examine the same blind optimism they sometimes misplace in politicised science to solve modern issues of resource scarcity and consumerism as that of the early Soviets. TW Artwork by Marida Ianni-Ravn

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Reviews

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Plan-demic: Decoding Disease Dynamics Shavindra Jayasekera explores how mathematical modelling can inform plans for controlling the spread of infectious diseases The Origins Of Mathematical Epidemiology | Human civilisation has been shaped by infectious diseases. The Black Death claimed at least one-third of Europe’s population from 1346 to 1351, while smallpox from Conquistadors catalysed the collapse of Mesoamerican civilisation. This year, COVID-19 had brought much of the world to a standstill. Without a cure, public health measures to control the outbreak are essential to limit the damage caused by the disease. But which measures are most effective? When should they be deployed? Where? The answers to these questions rely on determining how the disease spreads.

Using mathematical equations to simulate outbreaks, we stand a better chance of developing strategies to tackle this ‘invisible enemy’.

Surprisingly, the foundations for modern mathematical epidemiology (the study of the incidence and spread of disease) were not laid by mathematicians, but rather by public health physicians at the turn of the 20th century.

Sir Ronald Ross, a doctor working in India in the late 1800s, discovered the malarial parasite in the mosquito and deduced that mosquitos were responsible for the transmission of the disease. This work won him the Nobel Prize in 1902, but led public health officials to believe that it was impossible to control malaria unless the mosquito population was eliminated. However, by creating a mathematical model of malaria transmission, Ross showed that if the mosquito population was reduced below a critical level, the spread of the disease could be curbed. Based on Ross’s work, policy makers in Panama decreased the mosquito population by draining pools (where mosquitoes breed), screening buildings, and killing adult mosquitoes.

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Plan-demic: Decoding Disease Dynamics

As a result, yellow fever was eradicated and deaths caused by malaria were cut-down by over 80% between 1906–1909, a major achievement in public health.

The SIR Model And Its Derivatives | One of the main approaches to modelling disease transmission is the construction of compartmental models. These models divide the population into ‘compartments’ which represent the number of individuals at a given stage of the disease. They were pioneered by Kermack and McKendrick in the early 20th century and form the foundation of many modernday epidemiological models. One of the simplest models they developed was the Susceptible-Infected-Recovered (SIR) model, in which the population is divided into those susceptible to the disease (S), infectious with the disease (I) and recovered from the disease (R). (Note that ‘recovered’ means not infectious, and therefore includes those who have passed away). Using this framework, a system of differential equations is set up describing how the number of people in each compartment changes over time as the infection runs its course. These equations can then be used to find the values of S, I, and R at any given time if we know the initial values.

The simple SIR model is powerful because it is easy to analyse and gives a qualitative description of the spread of the disease. One of its most insightful properties is that the nature of the epidemic is dependent on the reproductive number, R0, which denotes the expected number of secondary infections caused by one infected individual in a wholly susceptible population. This number can be derived from the rates of infection and recovery. If R0 is less than 1,

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then I decays and no epidemic occurs (Figure 1). If R0 is greater than 1, the number of infected individuals grows rapidly and there is a major epidemic (Figure 2).

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However, the SIR model describes a generic disease and makes several broad assumptions that may not be relevant to a real-world epidemic or are at the very least oversimplifications. Thus, more complex models are often necessary to reflect the characteristics of a particular disease that is being studied. This can involve modifying compartments and their connectivity. For instance, many diseases have an incubation time where a person has been infected but is not infectious. In this case, an SEIR model is used where E is the ‘exposed’ compartment. Some people who catch diseases such as tuberculosis remain infectious when asymptomatic so a ‘carrier’ state may be added. The flexibility of compartmental models means that it is possible to add an arbitrary number of components to describe the spread of the disease more accurately.

Another way to generalise a model is to account for more heterogeneity in the population. The generic SIR model assumes that all members of the population are equally likely to interact with each other, but in real life this is rarely the case. For instance, age structure is an important consideration when modelling ‘childhood diseases’, such as measles. Spatial structure can arise from the spread of a disease within a city or globally via international travel routes that link certain populations and not others.

These complex models provide a more accurate depiction of the disease and allow epidemiologists to make quantitative short-term predictions that are vital when forming public health policy. However, complex models come at a cost. Complicated models rarely have exact solutions, requiring approximations instead. These models are also sensitive to initial parameters so the changeable nature of viruses and global politics mean that models cannot give concrete long-term forecasts.

In addition, they require several parameters which

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need to be estimated by statisticians. However, when faced with a novel disease, there might be insufficient data to provide reliable estimates. For instance, if one were to model the spread of a pandemic in a country, modelling each town and city would not only take weeks but the data on each town would be so sparse that the cumulative errors in the model would render it useless.

As a result, mathematicians need to strike a careful balance between detail and simplicity.

Models In The 21st Century | The boundaries of mathematical modelling are constantly being pushed with modern technology. Increased computational power allows for more detailed models while the prevalence of smartphone technology offers new methods of data collection. In 2018, the BBC conducted two experiments to model the spread of a highly contagious influenza virus: one detailed study of 500 people in a small town and a national experiment with over 36,000 participants. The ‘BBC Pandemic’ app monitored the daily movements of its users and allowed them to submit a list of their contacts, similar in function to a contact tracing app. The results were harrowing — a conservative model with only a 2% mortality projected up to 900,000 deaths, highlighting the vulnerability of the UK to a global pandemic.

Information gathered by this unique experiment has provided invaluable data on social interaction in the UK and was used in models of the COVID-19 pandemic.

COVID-19 has highlighted the importance of models and the mathematicians who create them. Their expertise was instrumental in guiding government policy such as the implementation of a lockdown that prevented an overload of the NHS. The challenge now lies in the easing of restrictions and avoiding a second peak of infections. This has become the central focus of modelling efforts. Without a vaccine and the possibility of reinfection, there is a serious risk that COVID-19 outbreaks could become endemic, leading mathematicians to model control measures for a severe winter epidemic. Perhaps the most interesting avenue of research is the inclusion of behaviours in a pandemic model. This involves mathematicians working with psychologists and behavioural scientists to determine factors such as the likelihood of people obeying stay-athome orders and the effects of prolonged isolation.

Ultimately, the role of mathematicians and epidemiologists is to suggest control measures and provide clarity for policymakers, so that the consequences of their strategy and guidelines are wellunderstood. This epidemic has highlighted the need for expertise and requires the whole of the scientific community to work together with politicians to find favourable solutions, where there is no obvious answer

"This epidemic has highlighted the need for expertise and requires the whole of the scientific community to work together"

Shavindra Jayasekera is a third year undergraduate student in Mathematics at Trinity College. Artwork by Josh Langfield.

Graphs by Shavindra Jayasekera.

Plan-demic: Decoding Disease Dynamics

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Staying Sane in an Insane World: The Challenge of Social Distancing

Mirlinda Ademi discusses the neuroscience behind isolation and loneliness "A guy goes nuts if he ain't got nobody... I tell ya a guy gets too lonely an' he gets sick." — Of Mice and Men, John Steinbeck

The global COVID-19 pandemic has brought new experiences to most of us, introducing extreme changes to our work and social life. Despite social distancing measures being necessary to curb the transmission of COVID-19, the emotional distress caused by social deprivation during lockdown has been tough. Increased loneliness has been reported amongst adults, as virtual alternatives like Zoom or FaceTime are just not the same. Moreover, loneliness has been linked to depression, a health concern officially recognised by the World Health Organization. Poor living conditions and lack of social interaction are associated with poor physical and mental health and higher mortality rates. From an evolutionary perspective, seeking social connections is a deeply-ingrained instinct, essential for survival throughout the animal kingdom. Social contact is associated with an increased life span for various species, such as honeybees, mice, and macaques. When we feel lonely, many of us experience higher levels of anxiety and hypervigilance, a defence mechanism thought to have evolved as a response to potential threats. But why and how does loneliness have such an effect on the body?

The Neuroscience Of Loneliness | The effect of loneliness on the brain is poorly understood from a neuroscientific perspective. Positive social interactions such as smiling faces have been shown to activate neural reward systems. Lack of social interaction, on the other hand, is believed to create a ‘craving for company’ response in the midbrain, comparable 8

Staying Sane in an Insane World

to hunger states that trigger the search for food. Several neurotransmitters — chemical messengers important for communication between neurons — including dopamine, oxytocin, and opioid circuits, are thought to underlie the motivation for social reward. A study led by a research group at the Massachusetts Institute of Technology suggested that a cluster of dopamine-related neurons found in the brainstem region, called the dorsal raphe nucleus (DRN), form part of a neural circuit representing the subjective experience of feeling lonely. The group showed that the DRN area was extremely sensitive to acute periods of social isolation just one day after mice were isolated from their cage companions. In the same study, the group used a technique called optogenetics to switch genetically modified neurons ‘on’ or ‘off’ using light. This increased or suppressed a loneliness-like state, respectively. Activation of DRN neurons increased social preference, making mice more sociable when re-introduced to peers. In primates, negative motivational states have been mainly observed in other areas of the brain, though the role of the DRN itself remains to be properly understood.

The Stress of Social Isolation | While stress is fundamental to survival as it powers the ‘fight-or-flight’ response in dangerous situations, elevated levels of stress can be harmful to both the brain and the body. Stress causes the amygdala, the ‘fear centre’ of our brain, to contribute to the activation of our autonomic nervous system (ANS), alongside our central stress response system known as the

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hypothalamic-pituitary-adrenocortical (HPA) axis. The interactions between the brain and adrenal glands in the HPA axis release cortisol, which helps our bodies deal with acute stress. However, chronic activation of the HPA can wreck havoc on our brains, increasing amygdala activity and causing atrophy in the hippocampus, a brain region responsible for learning and memory formation.

Too much stress can remodel our brain by reducing the number of connections between neurons or shrinking the prefrontal cortex, which regulates cognitive functions such as decision making and concentration. These reactions may begin as appropriate responses to a stressful event, but set the stage for more serious conditions including clinical anxiety or major depression, leading to a vicious cycle between stress and mental health.

Furthermore, chronic stress induces inflammation in the body, which can contribute to difficulty sleeping, digestive problems, or even a weakened immune system.

A Ruffled Mind Makes a Restless Pillow | The stress from coping with social isolation and survival during the pandemic often reflects in poor sleep. They are tightly linked, as anxiety causes insomnia, which eventually increases anxiety itself.

Research suggests lack of sleep contributes to loneliness and is a catalyst for social isolation. Sleep is more important for our brains than we may realise. On average, we spend around one third of our lives asleep. Sleep is essential for good mental and emotional health as well as adequate cognitive function. Restful sleep serves to ‘reset’ brain activity, to prepare us for emotional challenges the next day.

Dreaming during REM sleep helps us process emotional experiences, like a form of nocturnal therapy. In the long term, sleep, including well-placed naps, helps our brain consolidate information and store memories.

Brain activity after periods of sleep deprivation has been shown to be very similar to that observed in anxiety disorders. Poor sleep puts our brains on guard by triggering spikes in stress hormones early in the morning, and increases activity of the amygdala, which is also crucial for emotional processing and memory consolidation. Sleep deprivation has also been linked to changes within the medial prefrontal cortex and other brain regions associated with emotional control. People who sleep poorly are twice as likely to develop an anxiety

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disorder and other health problems such as increases in blood pressure, insulin resistance, and body weight. Some of these issues are linked to distinct changes in hungerregulating hormones associated with sleep deprivation, such as higher levels of appetite-stimulating ghrelin or lower levels of satiety-inducing leptin. Furthermore, sleep restriction modifies our endocannabinoid levels, chemical signals that affect appetite and our reward system.

Therefore, while poor sleep is a common and often underestimated outcome of altered stress levels, it can have other profound physical and psychological effects.

Coping with Late Night Loneliness | For many, the peak of loneliness comes during the evening or at night. To combat this, smartphones and the Internet have offered an important means of connection during the pandemic. However, late night screen-usage is a disruptive behaviour, affecting not only our body clock but also the levels of melatonin, our ‘sleeping hormone’.

Therefore, minimising exposure to bright lights at night can facilitate good sleep. In addition, while a nightcap before bedtime might seem tempting to help quieten the hamster wheel going in your head, it is not a good sleep aid.

Alcohol acts as a central nervous system depressant and disrupts sleep, especially in the second half of the night.

"...while poor sleep is a common and often underestimated outcome of altered stress levels, it can have other profound physical and psychological effects"

So, what can we do instead to calm our busy minds? Simple activities like reading a good book or just enjoying a cup of tea can help ease your thoughts. Alternatively, mindfulness is a more active way to better cope with pandemic loneliness and related sleeping issues. Mindfulness is like a workout for the brain — you practise awareness and concentration, resulting in general calmness and physical relaxation.

While the pandemic has come with many challenges requiring adaptation of our daily lives, it has brought another opportunity to further help destigmatise stress and its related mental health issues, as we are all trying to stay sane in an insane world Mirlinda Ademi is a third year PhD student in Clinical Neurosciences at Corpus Christi College. Artwork by Zuzanna Stawicka.

Staying Sane in an Insane World

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Obesity: a Choice or ‘Fat Chance’?

Dean Ashley explores the role of genetics in our lifestyle choices The world Health Organization estimates that

approximately 40% of people across the globe are now overweight or obese — a 20% increase since 1975. Obesity increases the likelihood of many other diseases including cardiovascular disease, stroke, Alzheimer’s disease, and cancer. As of 2019, obesity has overtaken smoking as the biggest cause of cancer, with Cancer Research UK stating that obesity is now more likely to be the cause of bowel, kidney, ovarian, and liver cancers than smoking tobacco.

Obesity is therefore a growing global health problem, but what causes it?

Obesity is driven by a combination of a lack of exercise, poor nutrition, and genetics. However, the contribution of genetics is often overlooked in comparison to the other factors. The Director of Research and Weight Stigma Initiatives at Yale University, Dr Rebecca Puhl, shows this leads to false connotations of obese individuals being lazy, weak-willed, unintelligent, and having low selfdiscipline. These stigmatisms then manifest themselves into discrimination that people justify by saying it will incentivise weight loss. Dr Puhl and others demonstrate that this is not the case. The stigmatism and prejudice are factually unfounded, reduce the mental wellbeing of sufferers, and interfere with effective treatment of the disease.

Many have discovered that if we consume more food than we need, our bodies store this excess as fat. We can then use this excess energy during exercise, heat production, and resting metabolism. However, just as the amount of energy

we use for exercise differs between individuals, the energy expended during resting metabolism also differs. These differences are caused by genetics.

Genes within our DNA hold the information needed for life. Genes are the template for creating messenger RNAs (mRNAs) which is then translated into amino acid sequences, known as proteins. To translate an mRNA into an amino acid sequence, ribosomes read three bases of an mRNA at a time and add a specific amino acid, corresponding to the three-base sequence, to a growing protein chain. Some individuals inherit gene mutations from their parents called single nucleotide polymorphisms (SNPs). A SNP occurs when a single base in a gene’s DNA and mRNA sequence is replaced with another. This one base change causes ribosomes to read the mRNA sequence differently and add a different amino acid into the protein chain. Sometimes this change in amino acid sequence prevents the protein from functioning correctly and can lead to diseases including obesity.

Therefore, someone can inherit a variety of SNPs that predispose them to obesity from their parents. This increases the probability of an individual becoming obese and is independent of will power, intelligence, or laziness.

One such SNP predisposing individuals to obesity is found in the AP-2 gene. Due to AP-2 regulating proteins involved in insulin signalling, changes to its structure can lead to insulin resistance, type 2 diabetes, and cardiovascular disease. Due to the high volume of proteins involved in regulating metabolism, the number of mutations that can

Single Nucleotide Polymorphism | (a) DNA is first transcribed into mRNA. Ribosomes translate an mRNA to produce an amino acid chain (also known as a protein) using the mRNA triple base-sequences as codes. The amino acid chain then folds into a 3D protein structure. (b) In this example, the cytosine (C)-guanine (G) base pair is mutated to a thymine (T)-adenine (A) base pair (red circle). This changes the mRNA sequence, where there is an uracil base (U) instead of a cytosine base. When a ribosome reads this mutated mRNA sequence, a different amino acid is incorporated into the amino acid chain. This change can prevent it from folding or alter its final 3D form. As a result, the protein cannot function correctly, which can predispose individuals to diseases such as obesity.

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Obesity, a Choice or 'Fat Chance'?

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predispose or protect an individual from obesity is equally as large, with over 445 SNPs being associated with obesity.

Individuals are not limited to simply having one of these SNPs either, they can possess none or all 445 at once. A strong positive correlation is seen between the number of SNPs and a person’s BMI, which clearly shows that genetics largely controls a person’s weight. This is reaffirmed by Dr Adam Locke from Washington University’s McDonnell Genome Institute, who says up to 70% of the variability between people’s BMIs can be accounted for by genetic factors.

If people know they are at risk of putting on more weight due to their genetics, surely, they should just eat less?

Genetics also plays a large role in people’s food choices, portion sizes, propensity to exercise, and more. This again is due to SNPs changing the molecular signals in our brains, which then changes how our brains think about food. One extreme example is the outcome of a mutation in the leptin pathway. Leptin is secreted by fat cells and signals to the brain that there are adequate fat stores in the body and to suppress hunger. Without this suppression, individuals demonstrate extreme overeating, so much so that fridges and freezers must be padlocked shut to prevent mass overeating.

The leptin example is a monogenic effect (one gene is responsible for the disease). However, most obesity cases are polygenic (a combination of gene SNPs with smaller individual effects which sum up to cause the disease). One such SNP is in the GAD gene leading to a lack of control over food intake and higher carbohydrate consumption in women. Another SNP in the Ghrelin gene, which substitutes a leucine amino acid for a methionine, disrupts gene function and increases the likelihood of obesity and binge eating. This is because part of the Ghrelin gene encodes the protein obestatin, which plays a role in supressing hunger.

A single base change in the TAS2R38 gene, which controls whether we can taste the bitterness in brussels sprouts, can also predispose humans to obesity.

This is because if you do not like the taste of sprouts, you are statistically more likely to avoid

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low-calorie foods in general and replace them with a more energy-dense food, which ultimately leads to a higher BMI. Clearly, this is a small effect.However, the likelihood of being overweight can be extremely high in the presence of many other obesity-causing SNPs. Even the amount of exercise we are likely to do is approximately 50% explained by genetics. For example, the melanocortin receptor gene involved in the signalling of leptin also predicts how much we exercise. Four studies discovered different regions in the human genome which either increase or decrease an individual’s likelihood of exercising. In summary, just like genes controlling metabolism, genetic variation can also influence how our brains perceive food, from the amount we eat, what we eat, and even what we burn off through exercise. Once again, this dispels the misconceptions of obese individuals lacking will power and determination.

If our genetics as well as age, sex, ethnicity, and socioeconomic background combined can determine our likelihood of becoming overweight, should individuals just accept their fate? Certainly not! These factors only increase the probability of obesity and do not mean we are destined to be overweight. We can learn a lot from man’s best friend here. 80% of Labrador guide dogs have the POMC gene which increases their food motivation. However, with the right training and education, these dogs do not pull their owners around parks chasing chocolate wrappers all day.

They have learnt that despite this urge they will receive the food they need once they get their owner home. Us humans can do the same! By spreading education on obesity, people can acknowledge their genetic predispositions but also learn and adopt healthier attitudes towards food over time.

Our collective awareness, as individuals and as a society, can change how we view obesity. Rather than regarding sufferers as lazy, I think the genetic aspects outlined above shows people are continually battling their biology. By re‑evaluating the causes of obesity, we can prevent the spread of false perceptions and prejudice, and instead enable effective treatment, education, and resolution Dean Ashley is a fourth year PhD student in Biochemistry at Hughes Hall College.

Artwork by Erin Slatery.

Obesity, a Choice or 'Fat Chance'?

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A World Without Antibiotics?

Megan Hardy discusses antibiotic resistance and the importance of antibiotic development

When penicillin, the first antibiotic,

"...the rise of antibiotic resistant strains of bacteria may mean we are entering a ‘postantibiotic era’..."

became widely available in the mid-1940s, modern medicine was revolutionised. Small wounds and childbirth no longer resulted in life-threatening incurable infections. Meningitis, tuberculosis, and chronic bone infections could all be cured. Surgery became safer since pre-operative antibiotics lowered the risk of postsurgical infection, allowing longer and more complex operations to be attempted. Disturbingly, the rise of antibiotic resistant strains of bacteria may mean we are entering a ‘post-antibiotic era’ in which antibiotics become practically useless. While there are currently 700,000 antibiotic resistance related deaths per year, this is predicted to rise to 10 million by 2050. The World Health Organization (WHO) is declaring antibiotic resistance a ‘major global threat’ in which ‘common infections and minor injuries which have been treatable for decades can once again kill’.

Pandemics of such superbugs could easily result in global quarantines and lockdowns.

Antibiotics Treat Bacterial Infections | Antibiotics are used to treat bacterial infections by interfering with processes that bacteria need to survive and grow such as bacterial cell wall production, protein synthesis, or cell division. On the other hand, viruses are not alive and cannot be killed using antibiotics. This is because viruses cannot reproduce on their own and instead rely on the host cell to make the proteins needed to produce new viruses. This process cannot be inhibited because we are the host — we would be poisoning our own cells. It is our overuse of antibiotics out of convenience which has accelerated the development of antibiotic resistant strains of bacteria. For example, global antibiotic use (average

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A World Without Antibiotics

doses per day) increased by 65% between 2000–2015, with low-middle income countries being the main driving force. Further increases are predicted for the period to 2030 in the scenario that no restrictions are introduced.

The Problem Of Antibiotic Resistance | When bacteria face a threat in the form of an antibiotic, it drives evolution for traits that help their survival. Within a population, there is a small chance that some bacteria will harbour a random genetic mutation which allows them to survive exposure to antibiotics. The presence of antibiotics selects for variants containing such a mutation — while the susceptible bacteria are killed, the resistant ones survive, reproduce, and take over the population. This has led to an ongoing evolutionary arms race between our own drug development and bacterial mechanisms to avoid their own death.

Research into new antibiotics has slowed down in recent decades, which aggravates the problem. Antibiotics are classified by their chemical structure, cellular mechanism of action, and the species of bacteria they are effective against. During the ‘golden era’ of antibiotics research (1950–1960s), scientists generally overcame problems of antibiotic resistance by developing new antibiotics at a faster rate than bacteria developed resistance. Half of the antibiotics in use today were discovered during this period. In contrast, no new classes of antibiotics have been discovered since the 1980s.

The process of discovering genuinely new antibiotics and bringing them to market is challenging and timeconsuming. It can take up to 15 years. Firstly, organisms which produce antibiotic substances are identified.

This can be difficult because these substances must also be non‑toxic to humans. Candidate drugs then move

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into clinical trials to be tested for safety and efficacy.

These clinical trials have five stages including further tests on thousands of patients even after the product is approved. According to the WHO, there are 40–50 antibiotics in clinical trials but most of these are just minor modifications of existing drugs and have little additional benefit. 250 novel antibiotics are currently in preclinical trials but it will take at least 10 years for these to reach patients and many may never be approved for use.

It is becoming increasingly difficult to find new bacterial proteins to target. This does not mean there has been no effort on this front. Pfizer, AstraZeneca, and GlaxoSmithKline ran a total of 200 ‘high throughput screens’ during the 1990s but none of these resulted in a viable drug candidate. There is a consensus within the industry that the antibiotics that were easy to discover have already been found and that expensive labour-intensive research would be required to identify new classes of antibiotics. Furthermore, these big pharmaceutical companies have recently lost interest in the development of novel antibiotics, as such drugs would be used as a last resort by only a few thousand people a year. It is not profitable for companies to invest in antibiotic development when they could instead develop drugs for chronic conditions such as asthma or diabetes, which require constant administration and therefore greater sales.

A New Wind In Development | Fortunately, there are some promising developments in the field of antibiotics research. One recently discovered compound, Irresistin, kills bacteria via a ‘poisoned arrow’ mechanism. It simultaneously punctures bacterial cell walls and destroys folate, a compound needed by bacteria to make DNA. Attacking two processes at the same time may make it harder for resistance to develop. This is a concept that will hopefully lead to new types of antibiotics in the future.

Another way to overcome the development of antibiotic resistant bacteria is with novel antibacterial medicines which have different modes of action to conventional antibiotics. Virulence blockers are drugs which effectively ‘disarm’ bacteria of their pathogenicity and prevent them from manipulating host cellular processes. For example, the type III secretion system (T3SS) is used

by Gram‑negative bacteria to directly inject toxins into host cells to help bacteria invade host tissues or suppress host immune responses. The T3SS can be inhibited by compounds such as salicylidene acylhydrazides, which are currently being trialled as an alternative to antibiotics.

Resistance to such drugs could also develop but probably not as rapidly as for conventional antibiotics. The targets of virulence blockers are found in a smaller subset of bacteria so their use will apply selective pressure on fewer organisms and only limit bacterial replication when bacteria reside in the infected host.

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Phage Therapy | Phage therapy is also a promising possibility. Bacteriophages, also known as phages, are viruses which infect and replicate within specific bacteria, ultimately leading to lysis and death of the bacterial host.

The idea of using bacterial viruses therapeutically has been around since the 1930s and phages were widely used to treat human patients in the Soviet Union during the Cold War. However, phage therapy has only recently gained traction in other countries due to the need for a response to multi‑drug resistant pathogens. For example, in France, phage therapy has been approved to treat patients with multi-drug resistant infections. Six patients with such infected burn wounds have been successfully treated.

Larger scale clinical studies are required to verify the safety and efficacy of bacteriophages as a treatment for other types of human infections.

"...we must ensure we are using the right antibiotics at the right time to slow the development of resistance to the antibiotics that still work"

Antibodies | Antibodies are proteins naturally produced by our immune systems during infection. Antibodies bind to specific bacterial proteins, inhibit pathogenicity, and make it easier for white blood cells to destroy the bacteria.

There has previously been little interest in antibodies as treatment for bacterial infections as widespread antibiotic resistance was not a problem. With the threat of a ‘post-antibiotic era’ looming, antibodies are now being investigated as a viable therapeutic alternative.

Monoclonal antibodies are identical copies of one type of antibody, produced from a clone of immune cells.

These antibodies can be bioengineered to specifically target the resistant strains of bacteria.

While these alternatives to antibiotics are exciting prospects, it is likely to be several years before any of them are commercially available. For now, we must ensure we are using the right antibiotics at the right time to slow the development of resistance to the antibiotics that still work Megan Hardy is an MSci Biological Natural Sciences student in Biochemistry at Emmanuel College. Artwork by Marzia Munafo.

A World Without Antibiotics

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A Pathogen’s Dilemma: The Virulence-Transmission Trade-Off Oakem Kyne explores why pathogens evolve to cause different levels of harm What causes some pathogens, disease-causing

microorganisms, to become more harmful than others?

How does our behaviour impact the way they evolve?

Evolutionary biology helps us consider these questions.

The Virulence-Transmission Trade-Off Model | Pathogens and their hosts have constantly been coevolving over millions of years, mainly resulting from interactions between the two species. This coevolution can be observed in a pathogen’s virulence, which is the relative ability of a microorganism to cause harm to a host organism. A common way of assessing this is by tracing mortality rates. Historically, organisms were thought to reduce their virulence over time, as the pathogen relies on the host for transmission. Thus, host mortality would reduce the amount of transmission time available to the pathogen. However, this pattern was not observed and so subsequent models of host-pathogen evolution have been proposed, with the coevolution of myxoma virus with the European rabbit being a prime example.

Myxomatosis is a lethal disease in rabbits caused by the myxoma virus, resulting in blindness and swelling. Originating from South America, the myxoma virus was intentionally introduced to the Australian rabbit population in the 1950s in an attempt to control their numbers. As these rabbits had never been in contact with this virus before, they had not yet coevolved or developed any resistance. When the virus was first introduced, it led to a dramatic reduction of the population, killing more than 90% of the rabbits. However, over time the genetic resistance of the rabbits increased due to the strong selection pressure. Eight years later, the same strain had a mortality rate stabilising at around 30%.

So, why was an intermediate level of virulence favoured in the population? Myxoma virus is transmitted via airborne droplets or arthropods, such as fleas or mosquitos. Researchers

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found that highly virulent strains quickly produced large numbers of the virus on the skin, increasing the transmission rate to the pathogen’s vectors, an organism of a different species that transmits the disease, whereas strains with low virulence never obtained numbers as high. However, strains with intermediate virulence took longer but reached higher overall levels eventually. This meant that viruses with intermediate virulence levels were more effective at transmission as they had fairly high virus numbers on the skin, for a prolonged period compared to highly virulent ones.

This is the basic concept behind the ‘virulence-transmission trade-off theory’, which argues that intermediate virulence maximises pathogenicity as a result of a trade-off between virulence and transmission. While the replication rate of a pathogen increases with virulence, the duration of transmission is negatively impacted by it, due to host mortality. As a result, there will be an optimum level of virulence, where the overall transmission of the pathogen is maximised. This will be the most evolutionarily favourable level of virulence for a pathogen.

What Causes The Observed Differences In Virulence?

As a result of coevolution, population structure can influence host-pathogen interactions. A good example is host population density. High host population densities favour increased transmission rates, as more potential hosts can be encountered over a set period of time. This implies that optimal transmission occurs with higher virulence. This may be particularly important to us as a species as our population and population density increase.

What happens to virulence when the host and pathogens have not coevolved? Pathogens crossing between species, so-called zoonotics, can lead to increased virulence. Because coevolution has not occurred, virulence is often far higher

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than optimal. This happened in the case of the myxoma virus spread, as it originated in South American rabbit species. Another good example is Ebola virus, which is so virulent that it is not transmitted very effectively. Similarly, cross-over between isolated populations can also impact virulence. A historical example from the 16th century is when European colonisation imported smallpox into North America and up to 90% of the population of the Americas died as a result of the non-native pathogen.

Implications Of The Model | The implications of current practices is most apparent in agriculture. Most farmed plants and animals are bred to reach maturity very quickly, after which they are harvested or killed. This decrease in lifespan significantly reduces the transmission time. Based on this theory, we would expect the optimal transmission rate and thus the virulence of the strain to increase. These more virulent strains could then in turn infect the wild populations, possibly causing collapse. This has been observed in some intensive aquaculture systems, but further research is still required to confirm this model.

Another interesting aspect is whether we can drive the certain pathogens to evolve to their less virulent forms. So far we have looked at viruses, however, it is important to consider virulence in other types of pathogens too, such as bacteria. Diphtheria is a disease caused by Corynebacterium diphtheriae. It is a bacterium that produces a toxin which inhibits protein synthesis and can eventually lead to severe systemic effects in the body, including heart failure and paralysis. The bacterium is found in two forms, the pathogenic form, which produces the toxin, and the benign, which causes minimal or no harm when infecting people. In an effort to eradicate the disease, people across several countries were vaccinated against the toxin produced. Due to these measures targeted against the pathogenic strain, it was nearly eradicated. As a result, the benign form became prevalent. Unfortunately, fewer people have been vaccinated in recent years, so the prevalence of the pathogenic strain has been increasing.

However, the outcome of other diseases is not this clear cut, and it is often hard to predict the consequences of different management techniques.

reproduction of the host organism, the relationship between virulence and transmission is very different.

As a consequence, the model cannot be applied in this context. Similarly, pathogens that spread by means of vectors or remain dormant for long periods of time are likely to have different virulence-transmission relationships. This means their transmission is not dependent on a living host and thus the cost of virulence varies from the model. This is one factor that contributes to the deadliness of anthrax, a bacterium that causes swelling and lesions amongst other things, as it can lie dormant as spores.

"Unfortunately, with the rise of anti-vaccine movements, the prevalence of pathogenic strains has been increasing in recent years"

The link between virulence and transmission remains largely theoretical, and it is very hard to measure this relationship. While some scientists argue that it is less direct than posited, this model is currently one of the best for explaining the patterns of virulence. Like other models, there are limitations to it. It will likely require adaptation in order to consider different environments, routes of infection or different cell types affected.

Hopefully, in the future our understanding of virulence will be such that we can control its evolution Oakem Kyne is a second year undergraduate student in Natural Sciences at Fitzwilliam College. Artwork by Clara Munger.

Limitations Of The Model | Currently, the virulence-transmission trade-off model lacks empirical support, and in many cases, needs to be expanded or is not applicable. The hypothesis regarding the relationship between transmission and virulence does not always hold true. For example, pathogens can be loosely grouped based on their mode of transmission.

Horizontal transmission happens between individuals of the same generation, for example through airborne droplets from sneezes, while vertical transmission occurs from one generation to the next, mostly through the placenta or from the birth canal during birth. As vertically transmitted pathogens rely on the

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A Pathogen’s Dilemma

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Pavilion: Bacterial Art — Unifying Art and Science Art and science are rarely brought together to the front scene. A remarkable duo, Maria Peñil Cobo and Dr Mehmet Berkmen, work in synergy to produce art with bacteria (www.bacterialart.com). Pauline Kerekes interviewed Dr Berkmen about his vision of art and science and the purpose of this project.

BLUESCI: Could you tell us a few words about your background as well as Maria’s?

DR BERKMEN: I was born in Turkey, and left Turkey at the age of 10. I went to middle school in Canada, high school in Vienna, and did my undergrad at Imperial College London.

I then received my PhD training at Houston in Texas and my degree from University of Vienna and a Postdoctoral training at Harvard Medical School. I am now a Senior Scientist at New England Biolabs where my lab conducts research on genetic engineering of bacteria to produce proteins that are difficult to make. For example, using one of the engineered strains from our lab, we were the first laboratory in the world to have produced antibodies in bacteria!

Maria is from a small town in northern Spain called San Vicente de la Barquera. It’s a small town surrounded by nature which influenced the young Maria to fall in love with nature and be inspired by it. She went to Madrid to obtain a degree in Fine Art. Afterwards, she focused on working with natural materials, like hemp and honey, and specialized in making prints using carved wood.

‘Subsurface’ bacterial art created using the following bacteria on agar plates: Arthrobacter, Deinococcus, Nesterenkonia, Xanthomonas and Bacillus.

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BLUESCI: How did you come up with that idea and how everything started?

DR BERKMEN: As a young child, I was a very good drawer, like my father and other people in the family before me. But I also liked biology and thought I had to choose between science and arts. I chose to study science, and not art, but it felt like a forced divorce. I knew I wanted to join the two entities in the future. One day at a restaurant, I saw striking pieces of print art made of wood carvings. The artist was one of the persons working in the restaurant, Maria. I gave her my card and told her to come to the lab to present her my work with bacterial art, hoping for a collaboration. Maria was immediately fascinated by the intrinsic beauty of bacteria and quickly fell in love with microbiology and bacterial art. Since 2011, we have been working together making art from living bacteria. In 2015, the American Society for Microbiology (ASM) started the first Agar Art competition, and by that time Maria and I have been working on it for four years.

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We submitted our work, and to my surprise, we won the first prize. I think the reason for that is that we have been preparing for this type of event for years. Also, most people participating were scientists and not artists, and had just weeks or months to prepare, while we had years of experience.

Winning the ASM prize was where it all began, and within months, we became viral.

BLUESCI: What is your aim with the Bacterial Art? DR BERKMEN: We do have two ambitions. The first one is to bring bacteria and humans together, and the second is to bring art and science together.

For the first ambition: there is a massive gap in public knowledge between what people know about bacteria and what bacteria really are. We depend on microbes for our own health and for the ecological balance of the planet. They are basically the engineers of this planet and they have been here for 3.5 billion years. Half of the world’s oxygen that we breathe is made by them, and the nitrogen is completely recycled by them. We have a huge link to them.

This is not new to microbiologists, however the general public usually has a disgusted reaction when they are asked about bacteria. The only times people get to hear about microbes is through infectious diseases. We are visual creatures; we believe in what we see. That’s why we use visual art to convey a positive message about bacteria using the universal language of art.

To do that, we run workshops in high-schools and conferences where I give talks on bacteria and bacterial art, Maria does a demonstration on how to do it, and then we bring plates and let other people do their own art. You don’t actually see the result of the drawing immediately and the bacteria are free to grow in different directions and communicate with each other, so you don’t have full control over the art. In bacterial art you are in collaboration with the art itself.

For the second ambition: The separation between art and science is much more important in the Western world compared to the Eastern world, where the industrial revolution did not tear apart the two entities as much. There is a more holistic view of the truth in the East. I never present myself as ‘the scientist’ and Maria ‘the artist’ and if you look at the picture on our webpage you will see that I am dressed like an artist and Maria is dressed like a scientist. Both the scientific and the artistic processes require trial and error. You try to draw something but you don’t know exactly what you are doing. Science is the same, we do not always know the outcome of our projects, but we make an informed guess.

Artists are a bit more honest with their work in that regard.

What I love is the freedom that Maria has, each time we have a contamination, she says, “It’s ok, it’s art”, whereas we can’t do that in science.

BLUESCI: Could you tell us a bit more about the third artist involved, the bacteria?

DR BERKMEN: We use three groups of natural bacteria that are not harmful to humans. First, we have production bacteria: in my company we isolate enzymes from bacteria and some of the bacteria have natural colors that we can use. Second, we have guest bacteria.

During experiments, we can have unwanted bacteria in our plates that we used to call contamination. Since we started bacterial art, we called them ‘guests’. If the guests have an interesting shape or colours we keep them for the art, and then we sequence them to check that they are non-pathogenic. The third group is Escherichia coli, engineered to produce a chromogenic protein.

This interview with Dr Berkmen was truly inspiring.

We are observers rather than controllers of science — that is the reason why it will continue to attract scientists, as long as there are humans and bacteria on Earth

‘Mask Studio’ was produced using Arthrobacter, Bacillus, and E. Coli expressing chromogenic proteins.

Pauline Kerekes is a post-doctoral researcher at the University of Cambridge. Artwork by Maria Peñil Cobo and Dr. Mehmet Berkmen

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Pavilion

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18 Focus

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Pangolins, Pigs, and Pets: Recipe for Another Pandemic?

Tatjana Baleta, Hazel Walker, and Anna Tran discuss the biorisk due to zoonotic diseases originating from the dependence of humans on animals as a source of income, food, and companionship, respectively. They highlight solutions to sustain these activities while considering the impacts on socioeconomic stability and public health.

HIV, Ebola, and SARS-CoV-2. To most, these will be familiar names, having hit headlines and caused death and suffering worldwide. Aside from that, these viruses also share one common feature — they originated in animals.

Diseases transmitted between animals and humans are termed ‘zoonotic diseases’, with The Centers for Disease Control and Prevention (CDC) estimating that three quarters of newly emerging infectious diseases originate in animals.

The ongoing COVID-19 pandemic has highlighted the devastating impact zoonotic diseases can have on a society reliant on global trade and travel, forcing us to evaluate how our actions contribute to the prevalence of such diseases.

Potential sources of zoonotic infections are numerous but can be broadly separated into three categories: wildlife, domestic livestock, and pets. All three have a well-documented history of aiding the spread of zoonotic disease and each presents unique challenges to the development of appropriate public health measures.

Paying a Price for a Taste of the Wild? | When a group of children returned to their village with the body of a chimpanzee one day in January 1996, they did not know they were harbingers of death. The remote village, Mayibout 2, in north-eastern Gabon is surrounded by the vast Minkebe forest. Ensuring no valuable protein went to waste, the chimpanzee was cooked and eaten. Within a few hours they developed a fever followed by intense fatigue, rashes, diarrhoea, kidney and liver damage, vomiting, and internal and external bleeding. The World Health Organization (WHO) was called in and the area was isolated for six weeks. Of the 31 people infected, 21 died.

Mayibout 2 had just crossed paths with a now infamous zoonotic disease: Ebola, a virulent virus with a fatality rate of up to 90%.

For a disease to jump from animal to human, the two must come into contact. One of the ways these ‘spillover’ events occur is through consumption of wildlife. This

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was the case with Mayibout 2’s Ebola encounter. With COVID-19, a wet market in Wuhan, China is the pandemic’s suspected ground zero. By definition, wet markets sell fresh produce and animal products, which can include live animals slaughtered on customer purchase.

Wet markets can be found around the world and not all sell wildlife. But at those that do, factors including unregulated hygiene standards and the indiscriminate mixing of species both wild and domesticated, sometimes combined with a tropical climate, make for the perfect meeting place for pathogens and humans.

COVID-19’s wide-reaching effects have focussed international attention on wildlife consumption and trade as public health issues. In response, many have called for wildlife trade to be banned outright. Others, like researchers at the Oxford Martin Programme, believe this would be a mistake, calling it a ‘knee-jerk and potentially self-defeating measure’ in a recent Conversation article.

While wildlife trade is a key driver of biodiversity loss and species decline, the reality is that wildlife trade, both legal and illegal, is an extremely nuanced issue and debates around its prohibition must take this into account.

When Elizabeth Maruma Mrema, the acting United Nations Biodiversity Chief, called for prohibitions on wet markets in April, she cautioned against the unintended consequences of reactionary bans on the millions of people dependent on wild animals for their livelihoods.

Wildlife trade is often perceived solely as the selling of exotic animals harvested from wild places in tropical countries, but in reality it is more complex, encompassing a wide range of species, ecosystems, and localities. These include marine and freshwater fish, fungi and medicinal plants, and game including rabbits, deer, and various bird species. Wildlife trade also encompasses various production types, including wild-caught, captive breeding, and farming of wild species. The scale of the industry is evidenced by its value: an estimated US$188–300 billion annually.

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International trade is regulated by the Convention on Trade In Endangered Species (CITES), a voluntary multilateral agreement that classifies species into categories that dictate various restrictions on their trade.

However, despite these efforts, illegal wildlife trade (IWT) is a profitable industry valued at between US$7– 23 billion annually, and remains a threat to biodiversity.

IWT is recognised as organised crime, and is often linked to drugs, arms, and human trafficking via complex transnational networks.

start versus the end of the supply chain can be staggering.

Understanding motives of the people along this chain is a vital consideration in effectively controlling trade.

A blanket ban on wildlife trade without dealing with its root causes may simply drive trade underground, where it is harder to regulate. It would also make enforcing welfare and hygiene standards more difficult, the latter a crucial factor for disease prevention. Supposed ‘quick-fix’ bans instituted without behavioural change efforts and increased enforcement will likely be ineffective.

Recreational hunting and expensive tastes for exotic wildlife products as symbols of status and wealth fuel both legal and illegal wildlife trade all over the world.

According to environmental science news platform, Mongabay, ‘an estimated 40 tonnes of bushmeat is flown into Geneva and Zurich airports every year’, the former ironically being the city home to the CITES convention.

Illegal wildlife products are also seized at the borders of other European countries and the US. These consumers represent a lucrative end point for wildlife poachers and traffickers who answer consumer demands with supply.

This is not to deny that illegal, unsustainable trade and conditions that are unhygienic and highly stressful for animals should be prevented. However, a reactionary blanket ban may fail to accommodate those who consume wildlife or engage with its trade not out of choice, but out of need, like the people of Mayibout 2 in Gabon and the bamboo rat farmers of China. The voices of these stakeholders must be heard at the policy level to avoid backlash at the community level and to ensure regulations are relevant to the real-world context.

For these consumers, wildlife consumption is a choice, but this is not the case for everyone. Many indigenous and rural communities around the world, such as the villagers of Gabon’s Mayibout 2, rely on bushmeat as an affordable source of protein. A blanket ban would mean disaster for the food security of these communities, who may have few alternatives. Charles Emogor, a PhD student at the University of Cambridge studying the pangolin in Nigeria, draws attention to the socioeconomic considerations of a ban, ‘How are you going to supplement the income levels of people who depend on wild meat? I work with hunters and see them buy clothes and food from hunting — it is a way of life’.

Wildlife trade is an economic opportunity for many.

A June 2020 New York Times article recounts the story of Mao Zuqin, whose bamboo rat farm in China lifted him out of destitution. The chubby bamboo rat is a wild species, the farming of which has been encouraged by the Chinese government in poverty alleviation efforts.

However, in the wake of the government’s ban on wildlife consumption in response to the COVID-19 outbreak as many as 100,000 people have seen their businesses become illegal overnight. At the time of writing, whether the ban (which conveniently left loopholes for the medicinal use of some animals like the pangolin) will stick remains to be seen.

A complicated web of legal and illegal activity at different scales, wildlife trade is driven by a range of people harbouring a myriad of motivations. The difference in socioeconomic status between those at the

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Wildlife consumption is just one of many ways zoonotic diseases can be introduced to humans. Since the 1940s, more than half of zoonotic outbreaks have been linked to agricultural intensification, expanding land use, and escalating livestock production. Humans’ intensifying encroachment on natural habitats results in increasing contact with wild species and the diseases they may carry. For example, Malaysia’s 1998 Nipah virus outbreak is thought to have been caused by bat migration into orchards in response to slash and burn agriculture.

Using domesticated pigs as an intermediate host, the Nipah virus jumped from bats to humans, causing over 100 deaths.

Many may view outbreaks of zoonotic disease as the result of foreign practices in ‘exotic’ places. However, they may not realise that these outbreaks can originate from common farmed meats available at the local supermarket.

Could an Appetite for Animals Trigger the Next Pandemic? | With recent media coverage focusing on the risk of zoonotic disease from wet markets, it can be easy to overlook the risk that other diets pose. Humans farm various livestock all over the world for food. Even though these animals are not wild, our interactions with them still put us at risk of disease outbreaks of pandemic proportions.

Global consumption of meat such as poultry and beef has increased rapidly over the past 50 years as diets have changed from those based primarily on cereals to an increasingly protein-rich diet, with farmed livestock as a key component. It is estimated that in Western Europe

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80–90 kg of meat is consumed per person annually. This increasing demand for cheap and abundant meat has seen a rise in factory farming practices across the globe, with close to 2,000 industrial-sized pig and chicken farms now operating in the UK. Conditions in factory farms are a virus’s dream.

Cramped conditions housing many thousands of animals provide ample opportunities for infection.

Viral spread is aided by the often identical genetic makeup of factory farm animals. Selective breeding for desirable characteristics such as larger chickens has seen the generation of breeds which grow four times faster than a typical chicken from the 1950s. While this leads to an increased meat yield, selective breeding also reduces the genetic variation within the flock.

Variation within a population helps to slow the spread of disease. A virus which can infect one individual may encounter stronger immune defences in the next, preventing infection and thus, spread of disease.

However, if animals are genetically identical, when a virus mutates such that it can successfully infect one chicken in the farm, it can quickly spread through the rest. Furthermore, substandard living conditions, such as concrete floors used in some pig farming, can impair natural instincts like foraging. Denying animals these evolutionary behaviours can result in stress-induced immunosuppression, rendering them more vulnerable to infection.

We do not need to look back very far to find a pandemic which highlights the risk of zoonotic disease transmission from farmed animals. In early 2009, an outbreak of H1N1 influenza A in pigs, ‘swine flu’, was transmitted to humans in Mexico and quickly spread throughout North America and the rest of the world.

Before the introduction of a vaccine in late 2009, this pandemic was estimated to have infected around 11– 21% of the world’s population. Over 17,000 deaths were confirmed, with some models estimating a death rate of over 150,000 people worldwide in the year following the start of the outbreak.

H1N1 is an influenza A virus made up of eight segments of viral RNA, which carry the information needed to allow the virus to survive and replicate within the cells of an infected animal. As the virus multiplies, small mistakes can be introduced into this RNA. Over time, these mutations can lead to the creation of a viral strain which differs enough from the original strain that the immune system can no longer recognise and fight it. Influenza A can also undergo more striking changes, where two or more viruses can exchange segments and form a new ‘mosaic’ virus. This is known as ‘antigenic shift’. Strains which arise from this antigenic shift are

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more likely to cause pandemics. Not only does the change happen suddenly but it is often a significant change, meaning there is little chance of pre-existing immunity in the population.

Pigs are particularly well placed to host antigenic shifts and are often referred to as ‘mixing vessels’ due to their susceptibility to infections by both avian and human viruses. This means that if a pig is infected with human, avian, or swine influenzas at the same time, these viruses could combine to form a new strain of virus which is capable of crossing the species barrier and infecting a new host species. In work published in Nature, researchers traced the family tree of the H1N1 strain responsible for the 2009 pandemic, showing that it was made up of multiple influenza A strains that had been circulating amongst pig farms in North America and Eurasia for decades. The journey of these viruses to Mexican pig farms, where they eventually recombined to form the 2009 strain, follows the movement of live pigs across continents for global trade. The worldwide trade of any live animals, whether wild or domesticated, increases the chances of bringing viruses together with the potential to form a deadly strain.

With the Food and Agriculture Organization of the United Nations stating in a 2013 report ‘livestock health is the weakest link in our global health chain’, it is evident that to prevent future pandemics livestock populations must be prioritised. In the wake of the 2009 H1N1 pandemic, Dr Garcia-Sastre, director of the Icahn School of Medicine’s Center for Research on Influenza Pathogenesis, told Science Daily, ‘We need to monitor the viruses that are circulating, and try to stop mixing influenza strains from different geographic locations’.

The importance of such screening is underscored by the results of influenza virus surveillance of pigs in China during 2011–2018. Published in the Proceedings of the National Academy of Sciences in June, the results show that a new strain of H1N1 with the potential to infect humans has been circulating in pigs since 2016. Early warning of the emergence of strains with epidemic potential is vital for preventative measures.

There are multiple strategies already employed to reduce the risks of an outbreak. These measures include quarantining of new animals and extensive hygiene training of staff as well as the development of vaccines for both livestock and humans. Other innovative research could see the development of transgenic livestock which has been genetically modified so that it is unable to spread disease or, better still, become infected in the first place.

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The rapid growth of factory farming is juxtaposed with an increasing interest in a more plant-based diet. A survey conducted by the Vegan Society reported that more than 20% of Britons have reduced their meat consumption during the COVID-19 lockdown, citing reasons such as reduced meat availability in supermarkets as well as health, environmental, and animal rights concerns. A recent report, carried out by a team of global experts, made more than 100 suggestions of how to reduce the risk of another pandemic, including adoption of a more plant-based diet. Reduced demand for both wildlife and domestic farming could lead to a decreased need for the agricultural intensification of the past decade, in turn lessening the risk of disease spillover from animals to the human population.

From factory farms to homeowners with their own flocks of chickens and everything in between, there is no denying the risk that while our attention is focused on wet markets, the next pandemic virus could be making its way into existence in farm animals.

A further human interaction with animals that may be overlooked is right within our own homes. The risk of zoonotic transmission from pets gained traction in light of the COVID-19 pandemic when at one point it was thought that pets may be able to spread the virus to their owners.

Hidden Right under Our Noses? | As revealed through photos of dogs donning face masks during the COVID-19 pandemic, pets are important parts of many people’s lives. Dogs and cats have been close companions of ours for more than 10 millennia, gaining their present status as pets, or more fondly as family members, within households in modern society. The global trade in wildlife is estimated to be worth US$30.6–42.8 billion annually, of which approximately US$22.8 billion is legal and substantially driven by the global demand for pets.

In fact, about 50% of adults in the UK own a pet, with 26% of UK adults owning dogs and 24% owning cats.

However, like their wild counterparts, common household pets can also be carriers of various viral diseases. Rabies infections are among the most commonly known of these diseases, accounting for anywhere between 30,000–70,000 deaths annually worldwide, the majority of which are caused by dog bites in developing countries. Although rabies among domestic dogs in the developed world is largely under control, more than 99% of human rabies infections continue to be canine-related in many other parts of the world.

In 2008, a fisherman landing on the Bali peninsula of Indonesia unknowingly introduced a rabies epidemic

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to the island by bringing his dog who was incubating the virus, leading to over 130 human deaths.

Although Bali was historically rabies-free until 2008, activities such as pet trade and dog adoption between countries can lead to the accidental emergence or reemergence of the virus, even in countries that have eradicated canine rabies.

Dogs are just the tip of the iceberg. Many small pet animals can also carry diseases transmittable to humans, including reptiles and rodents. One of the most popular choices for small pets is the Syrian or golden hamster. A survey by the American Veterinary Association in 2012 suggested that more than a million individuals owned pet hamsters in the US. Golden hamsters were carriers of the lymphocytic choriomeningitis (LCM) virus, which infected 48 lab staff at the University of Rochester Medical Center between 1971–1973. Dozens of pet hamster-associated LCM cases have been identified since, with 181 cases being reported within three years in the US during the mid-1970s, prompting the release of a national alert by the CDC. This marked the adorable household pet as a major link to human disease, largely through airborne infection.

In humans, LCM can lead to severe symptoms, such as brain inflammation and other neurological symptoms.

While human-to-human transmission of the LCM virus appeared to be rare, a disturbing development in 2005 surfaced — a severe and often fatal LCM was identified among transplant patients. Four organ recipients had their LCM traced back to transmission from an organ donor who kept golden hamsters as pets. These pets were later found to have been sourced from the same commercial hamster breeding and distribution location where the outbreak began. As alarming as that is, LCM virus transmission through solid organ transplant is a rare phenomenon, albeit a formidable one.

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It is no surprise that the exotic pet trade also comes with similar risks. The term ‘exotic pets’ does not have a set definition, but here it refers to animals that are non-native to a region and can be domesticated or wild.

Ownership of exotic pets has been on the rise since the 2007 modification to The Dangerous Wild Animals Act (1976).

Previously, owners had to acquire licenses to keep specific exotic species as pets in the UK. However, this requirement was removed for some species on the list. As a result, the increased convenience of owning these exotic animals encouraged the trade and led to the emergence of new zoonotic infections.

An example of these infections is the 2003 outbreak of human monkeypox in Texas. This disease was previously unrecorded in the Western hemisphere. It was brought over by an international shipment of pet prairie dogs from Ghana to Texas. In Wisconsin, the first case was a three-year-old girl who was bitten by her infected pet prairie dog and was sent to hospital with monkeypox symptoms. Eventually, 80 other patients fell victim to the disease. According to the WHO, although monkeypox was once considered a rare disease confined within remote rainforests in central and western Africa, it is now the most important orthopoxvirus infection in humans following the eradication of the closely related smallpox virus.

Outside of home, several outbreaks were linked to zoos, particularly petting zoos where visitors can freely approach and feed animals. Animal exhibits were associated with over 25 outbreaks of infectious diseases between 1990–2000 alone. For example, the Komodo dragon at a Colorado Zoo was the starting point for a salmonella outbreak in 1996 with 65 cases identified, in which most patients were children. Surprisingly, it had nothing to do with directly interacting with this nearmythical beast itself — it was associated with touching the wooden barrier around its exhibit.

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These are all nightmarish cases, but are relatively rare and preventable. Similar to livestock, adequate surveillance and control policies for breeding facilities, distribution centres, and laboratories can lower the risk of human infection. For example, periodic testing of these animals may lead to early identification of potential infections before animal-to-human transmission occurs.

On an individual level, maintaining basic hygiene practices such as proper handwashing can keep owners and pets healthy. Bringing pets to the vet for regular check-ups, tests, and vaccinations can also be great opportunities to ask and learn more about the risks involved with having pets, how to responsibly care for them, and how to appropriately deal with their waste products. This is especially important to consider for the young, elderly, and immunocompromised, who may be more prone to infections.

Despite the risks of zoonotic infections, pets continue to hold a special place in many of our hearts. Taking appropriate precautions can decrease the risk of transmission of zoonotic illnesses, allowing us to safely enjoy our companionship with animals.

Across the globe, we rely on animals for food, companionship, and survival. Our interactions with them — be it pangolins, pigs, or pets — provide a myriad of benefits, but if unregulated may also plague us with disease. We are quick to vilify specific species or people in the wake of a pandemic, but it is up to all of us to safely mediate our interactions with nature. Investing in understanding the mechanisms through which zoonotic diseases spillover, taking steps to minimise those risks, and preventing indiscriminate natural resource use will protect us and the flora and fauna around us.

Our collective survival depends on this finely balanced co-existence. Zoonotic diseases have the power to take thousands of lives, cause widespread panic, immense economic loss, and shake the world to its core. In all this destruction, perhaps there is one seed of hope — an opportunity for us to review our relationship with the natural world and with each other Tatjana Baleta completed her MPhil in Conservation Leadership (Class of 2020) at Wolfson College; Hazel Walker is a fourth year PhD student in Immunology at Fitzwilliam College; Anna Tran was a visiting BSc student in Human, Social, and Political Sciences at Pembroke College (Class of 2020). Artwork by Rosanna Rann and Rianna Man. Background art from pngtree. com (七七的7, 杨浩, 588ku) and Vecteezy.com

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All Hands on Deck Alice McDowell explores the need for collaborative drug discovery programmes

Drugs have been a fundamental component of medicine for most of human history — traditional knowledge of plant extracts, passed down for many centuries, is the origin of around a quarter of all modern medicinal drugs. Opium, for instance, has been used for pain relief for 5,000 years and willow bark was used to reduce fevers for at least 3,000 years before the chemical structure of its active component was discovered, synthesised, and marketed as aspirin. For those of us fortunate enough to have access to them, the drugs available today protect and prolong our lives in innumerable ways. With anaesthetics to facilitate surgical interventions, antibiotics to protect us from deadly infections, and hormones that enable us to manage conditions such as diabetes, it can be easy to take modern medicine for granted.

When disaster strikes, it is the absence of drugs for diseases like cancer, multiple sclerosis, dementia, and (at the time of writing) COVID-19, of which we are most acutely aware.

So the question becomes: what do we do when we need new drugs?

At present, the drug development pipeline is lengthy, expensive, and inefficient. Drug discovery often begins with screening large libraries of small-molecule compounds against biological targets. These targets are usually proteins which can potentially be manipulated for therapeutic benefit.

Hits from these screens then undergo further validation in cultured cells and animal models of human disease. A long process of preclinical testing and improvement follows, in which a number of pharmacological properties of the drug candidate are determined. If a candidate is successful up to this point, several rounds of human clinical trials can begin to further gauge safety, dose, and efficacy of the drug.

If the drug passes all of these trials and gains approval by regulatory bodies, only then can the structure of the final product be patented, and the drug manufactured, marketed, and distributed. This system requires massive financial investment, because so much work goes into drug candidates that eventually fail and produce no financial return. Despite 24

All Hands on Deck

improvements like the use of artificial intelligence for target identification, bringing a new drug to market takes an average of 10 years and ÂŁ1 billion.

Financing is a natural stumbling block to drug development, but fundraising becomes nearly impossible if the drug in question must be provided at low cost, or to a relatively small number of rare disease sufferers. The financial motives of pharmaceutical companies inevitably cause progress on less profitable drugs to stagnate. Research on partially-developed drugs that are not profitable enough to take further is locked away. For drugs that do make it to market, researching alternative applications to potentially extend their benefits is almost impossible until their patents expire. Even then, accessing the original research can be difficult and expensive.

In contrast, when pharmaceutical companies do agree to share data, significant discoveries can be made. For example, AstraZeneca has provided anti-cancer antibody-drug conjugates (ADCs) to researchers wishing to repurpose them as a treatment for African sleeping sickness, an often fatal parasitic disease caused by African trypanosomes. Existing drugs for this disease are not always fully effective and often have severe side effects, which means that new drugs are desperately needed. Recent experiments by Dr Paula MacGregor (University of Cambridge) and her collaborators have shown that changing the antibody in an ADC to one that targets trypanosomes can produce an anti-trypanosomal therapy that is effective in mice. Since ADCs have been trialled extensively for their safety already, bringing them to market may prove cheaper and faster than would be possible for a completely novel drug.

The success of projects like this is contingent on the cooperation of large pharmaceutical companies which often lack the incentives to provide it — but what if sharing data and materials that might advance medicine was the

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norm? Proponents of what is known as ‘open-source medicine’ believe it will revolutionise drug discovery.

One key principle of this movement is that the results of unsuccessful research should be made openly available, to prevent unnecessary duplication of scientific efforts.

Substantial progress has been made on this issue in response to initiatives like AllTrials, a campaign that calls for all past and present clinical trials to be registered and their results reported. It is much harder to promote a similar culture in the preclinical stages of drug discovery.

The efficiency of individual researchers would suffer if they had to publish every negative result, and for most, the principles of open data must be balanced against the possibility of being ‘scooped’, something that can seriously hinder their ability to acquire funding for future work. However, progress can be made when grant-makers acknowledge the value of open data and when scientific journals change to open-access models available to all researchers.

It is not only data that can be made openly available.

There are growing trends for open-source hardware (e.g.

3D-printable microscopes), consumables (e.g. locally manufactured enzymes made using freely-available methods) and software (for anything from modelling drug effects to data mining from scientific literature).

As well as making science fairer and more accountable, these changes will greatly improve the ability of the world’s researchers to work on improving global health, with the greatest impact being on those in underfunded institutions or research areas.

all hands on deck — a fact rarely clearer than during a pandemic. The response to COVID-19 has largely been a collaborative effort: in January 2020, less than two weeks after the virus was first reported to the World Health Organization, a draft of the genetic sequence of SARS-CoV-2 was published by Chinese researchers. This enabled scientists around the world to begin developing tests, treatments, and vaccines — some of which, six months later, are already in clinical trials. To support this work, pharmaceutical companies searched their archives for drugs that could be repurposed and agreed to combine resources to expedite the drug development process. With luck, these efforts will prove to be a catalyst for the movement towards a more open and collaborative approach to drug development and medical research as a whole. The sooner we all learn to work together, the better. The benefits to global health could be enormous

"When it comes to matters of public health, we need all hands on deck — a fact rarely clearer than during a pandemic"

Alice McDowell is a third year PhD student in Biochemistry at Jesus College. Artwork by Eva Pillai.

Expanding and diversifying the medical research community is not simply a social justice project. It is important to remember that while large investments by big companies are responsible for the brute-force, high throughput methods by which many drugs have been discovered, the technologies underlying some of our most revolutionary therapeutics were developed in smallscale academic laboratories. For example, the best-selling drug of 2019, Adalimumab, is a humanised antibody used to treat arthritis, Crohn’s disease, psoriasis, and other inflammatory conditions. The technology behind Adalimumab owes its existence to the work of researchers at the Laboratory of Molecular Biology (Cambridge), the Scripps Research Institute (San Diego), and the German Cancer Research Centre. The ideas, perseverance, and collaborative spirit of these researchers has led to the creation of an entirely new class of drug and largescale production of these medicines by pharmaceutical companies has allowed them to benefit many people.

As well as universities and research institutes, private companies, national governments, and international bodies all have a role to play in developing new drugs.

When it comes to matters of public health, we need

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All Hands on Deck

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Science at Speed: Publishing Amidst a Pandemic Juliana Cudini speaks with Nature Editor-in-Chief Magdalena Skipper and eLife Deputy Editors Anna Akhmanova and Detlef Weigel about the rapidly rising tide of COVID-19 publications On my first day of remote working, I set up a journal alert for research relating to the COVID-19 pandemic. As an infectious disease researcher, I had a surreal feeling that I was a living dot on a scatterplot I would later be charged with analysing, and to prepare, I wanted to keep up with important SARS-CoV-2 findings. The next morning, I woke up to 20 new publications in my inbox. By the end of the week, it was over 300.

The rate at which research on the novel coronavirus is being churned out is unprecedented. The Chief Editor of Nature Medicine tweeted that submissions to the journal had increased by 150-200% since mid-March. According to a report by research technology company Digital Science, over 42,000 articles relating to the COVID-19 pandemic were released in just four months from January to April.

To put that in perspective, the entire field of ‘deep learning’ in artificial intelligence, one of the fastest growing research sectors according to Digital Science, contains around 150,000 publications in total. Use of preprint servers — online repositories hosting unreviewed scientific findings and often heralded as the fastest route to disseminate results — has also skyrocketed. The website Rxivist,

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which collects statistics on the life science pre-print server bioRxiv, recorded a 10-fold increase in the monthly rate of new submissions to the server between January and May 2020, compared to the previous 9 months. It quickly became clear to publishers that access to these results is essential in shaping a pandemic response. The Wellcome Trust stated that by mid-March over 30 leading publishers had removed paywalls on any content related to COVID-19, granting access to those without subscriptions to their journals.

At the time of writing in June, though the initial peak of the publication boom appears to have plateaued, the waterfall of information is far from petering out. In fact, the flood of research relating to the pandemic continues to serve as a fascinating test of strength for the levees employed by scientific publishers against rising tides of unsupported or misleading information.

Journal editors subject any new finding to rigorous review by experts in the field to critically assess both the study’s design and reported conclusions. Depending on a number of factors, this process takes anywhere from weeks to

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months. Amidst a global a new sense of urgency. A recent report in Nature Human Behaviour found while the median time to publication before the pandemic sat at 93 days, for COVID-19-related submissions, this figure plummeted to just six days. A similar ‘rush’ was observed during the first 12 weeks of the 2014 Ebola outbreak in West Africa, with median time to publish reduced to 15 days. Even outside of a public health emergency one can find peerreviewed research released less than a week following initial submission, but what makes this pandemic different is largely the novelty of the SARS-CoV-2 virus, coupled with its unprecedented global reach and level of societal disruption. As many researchers are busy adapting to lab shutdowns and remote working setups, expert reviewers can be difficult to find. ‘Many experts in the relevant areas are writing their own papers and have less time to review the work of others’, said Anna Akhmanova, a Deputy Editor at eLife, ‘Also, the fact that many SARS-CoV-2 virus-related studies are put together rather quickly and often not very profound makes it difficult to find reviewers’.

Despite these efforts, the unusually invested interest of the global lay audience in research output from the field occasionally leads to the misinterpretation and spread of poorly supported claims in both preprints and published articles by researchers, media outlets, and even world leaders. In the early days of the pandemic, preliminary results touting the use of antimalarial drug hydroxychloroquine as a treatment for COVID-19 gained international traction, leading to shortages of the drug in the United States and at least one lethal administration.

The study has since been retracted, and further research has found the drug potentially ineffective in treating the disease. Additional retractions of research published in the Lancet and the New England Journal of Medicine, this time attempting to track the spread of viral cases, also made international headlines. These incidents, while widely reported, are exceedingly rare. In July 2020, of the tens of thousands of available papers relating to the pandemic, the website Retraction Watch has recorded at least 22 (including preprints) as officially retracted.

A dwindling pool of available reviewers and accelerated turnaround times, however, do not mean that editorial standards have been loosened. A group of publishers including eLife, PLOS, and The Royal Society released an open letter in late April stating their commitment to ensuring rapid but thorough assessment of new coronavirus research. In the statement, they address the ‘expertise drought’ by calling for the names of reviewers willing to commit to fair but rapid review. According to Magdelena Skipper, Editor-in-Chief of Nature, ‘the pandemic is putting immense pressure on everyone — including authors and reviewers — and we’re grateful to each and every one of them for working with such dedication and prioritising this work’. It is the combined efforts of researchers, reviewers, and editorial staff, she says, that keeps the vast majority of poorly supported information at bay.

The responsibility remains with researchers to continue to independently critically assess any new findings, peerreviewed or not. ‘There is no way around judging for yourself the merit of work published as a preprint or in a journal’, says Weigel, ‘yes, reviews increase the chance that the work shows what the authors claim, but we all know that reviewers can make mistakes’. Akhmanova adds, ‘it is also the responsibility of the media to provide a clear background about their sources of information (e.g. peerreviewed papers vs. non-peer-reviewed preprints) when they further disseminate this information to the public’. This is a sentiment shared by Skipper at Nature. She advocates for better dataset availability as a means of helping individual researchers locate shortcomings in a study that might have been missed in the peer-review process, ‘assessing data quality and appropriateness of a dataset to address a given question can also be key. This is why we encourage (and in some cases mandate) data sharing — it facilitates a more thorough peer review and, post-publication helps others to further verify and build on a given set of findings’.

The pandemic continues to provide unique challenges for researchers, policymakers, publishers, and news outlets to adapt to. Personally, I have had to turn off my journal alert for the sake of my overwhelmed email client, but have discovered my own new ways of accessing and critically appraising research that I will continue to employ long after the pandemic is over. As is the case for so many in this pandemic, we are all still learning to keep our heads above the surging stream of information and stay afloat

Skipper also believes the pandemic has helped to highlight the important alliance between peer-reviewed journals and preprints. Both Nature and eLife advocate for authors to submit their findings on preprint servers while the peer review process takes place. ‘We view the relationship between preprints and journals as symbiotic’, says Skipper, ‘preprints surface research in its earliest form, facilitating early access to research for the wider scientific community, whilst journals provide curation and deliver the rigorous peer review process, and scrutiny, alongside other functions’.

Detlef Weigel, also a Deputy Editor at eLife, explains how the publisher is also trying to bridge the gap between the two platforms, ‘one of our initiatives, Preprint Review, aims to fast-track reviews for preprints, so that research in preprints is vetted more quickly — independently of formal acceptance for publication in a traditional journal’.

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"The responsibility remains with researchers to continue to independently critically assess any new findings, peer-reviewed or not"

Juliana Cudini is fourth year PhD student in Infection Genomics at Gonville and Caius College. Artwork by Rianna Man.

Science at Speed

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A Vaccine for Your Mind Joanna Lada and Jake Rose look at the increasing prevalence of ‘fake news’ and discuss ways to combat misinformation with inoculation theory

Social connectedness is allowing misinformation to

spread further and faster than ever before. Can the spread of misinformation ever be contained, or better yet, prevented?

We live in times dominated by uncertainty. Headline-news events are swiftly followed by a myriad of online responses, proposed causes and remedies, cries of ‘conspiracy’, and demands for transparency. The emergence of the COVID-19 pandemic has worsened the situation. False information are used to construct attention-grabbing stories that propagate mistruths. This is not new, but in our increasingly connected world it is becoming a more severe problem. Tedros Adhanom Ghebreyesus, the director-general of the World Health Organization put it perfectly when he said “we’re not just fighting an epidemic; we’re fighting an infodemic”. Perhaps a solution lies in a vaccine — a psychological vaccine.

False information can be described as misinformation (unknowingly incorrect) and disinformation (knowingly incorrect). Like a biological virus, they can spread through

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social networks. The ongoing pandemic highlights that they can be just as dangerous. A widely discredited belief that injection or consumption of bleach can cure COVID-19, which began with an offhand remark by Donald Trump, led to 100 people calling an emergency hotline in Maryland alone with cases of bleach intoxication, with an overall spike in cases across America. Despite the poorly worded statement from the President, this likely would never have had such a large impact if it were not for the quick proliferation of the claim via social media accounts, notwithstanding its refutal within 24 hours

by Dr Anthony Fauci, one of the key members of the White House Coronavirus Task Force. Information, no matter how incorrect, can rapidly spread regardless of expert opinion.

Today, where every individual can go viral, the barriers to misinformation are low.

The new ways of freely spreading information via social media require innovative countermeasures to contain the spread of misinformation. Social media giants such as Facebook have pushed to promote content from reputable

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sources and lessen the reach of misinformed posts.

Google alone has committed £5 million to fund fact checkers fighting misinformation related to the pandemic.

Independent organisations have employed advanced artificial intelligence (AI) in an attempt to identify misinformation outbreaks in their infancy to channel debunking efforts into the appropriate networks. But AI is prone to error, and these methods only control the spread once it has begun. Once mistruths have taken hold, debunking loses much of its efficacy. As such, preventative measures could be more effective.

One preventative approach which comes from the world of psychology is inoculation theory.

To understand the theory, it helps to first understand how a biological vaccine works. The latter typically acts by showing our bodies a version of a pathogen that is incapable of causing illness, whether due to having been weakened in a lab or broken into fragments. In response, our bodies build defence mechanisms so that, in the case of a real infection, they can quickly eliminate the agent before any significant damage is done. Inoculation theory works in an analogous way, preparing the brain by showing a weakened form of misinformation and allowing the subject to form their own counter arguments. This process will strengthen the mind's ability to counter newer and more complex arguments in the future.

Implementing the theory is somewhat of a balancing act, since supplying an argument that is too convincing for the subject (although still wrong) and not countering effectively can actually cement the idea one is trying to defend against.

The argument needs to be ‘strong enough to trigger the antibodies but not so strong that you convince people of something that isn’t true’, says Dr Sander van der Linden, Professor of Social Psychology at Cambridge University and Director of the Cambridge Social Decision-Making Lab. Dr van der Linden is one of the leading experts in tackling fake news. Much of his research concerns controlling its spread on social media, where most resources are invested in time consuming fact checking and debunking. But with the recent explosion in fake news surrounding the pandemic, social media companies have been struggling to keep up. ‘Everyone is running behind the curve’, says Dr van der Linden. Feeling overwhelmed, social media companies are turning to ideas like inoculation theory, pre-emptive strategies to stop the problem before it is one. His team has already entered into partnerships with Google and WhatsApp who are interested in employing tactics based on their research.

the trade in a fun way. Large-scale studies of the game have shown that by exploiting techniques such as impersonation, polarisation, and emotional appeal, the players become more sensitive to their use in real life, and thereby develop resistance to those methods. Teaching these skills on a wide scale would be the equivalent to providing a psychological ‘herd immunity’ for the population — another idea borrowed from biology. One appeal of this tactic is that its entertainment factor can help it reach a wider audience.

In fact, it has already gone viral on reddit. This is one place where the biological analogy fails — biological vaccines do not spread, but psychological ones can.

"The key to inoculation theory’s success may be in its wide scale adoption by our biggest social media sites"

The key to inoculation theory’s success may be in its wide scale adoption by our biggest social media sites. However, Dr van der Linden believes it can also be applied on smaller scales, even in everyday conversations, provided both sides are knowledgeable enough on the subject that they can express and counter the basic fallacies of the argument.

One such approach is the Fact-Myth-Fallacy framework developed by Dr John Cook. This strategy involves presenting a fact and a conflicting myth, followed by an explaination of the factual distortion. For example, the fact could be: ‘Human CO2 emissions are the main causes of climate change’. Subsequently, a conflicting misinformation is presented: ‘Human CO2 emissions are tiny compared to most other sources’. In the final step, the fallacy within the myth is revealed: ‘Human CO2 emissions are small relative to other sources, but small changes in a balanced system can create big effects. Climate models show that the imbalance induced by human emissions is the cause of recent climate changes’.

"Although misinformation is a problem that will stay, we can fight against it using innovative strategies"

While our connected world has allowed misinformation to spread faster and further than before, each of us has a voice within this network. Although misinformation is a problem that will stay, we can fight against it using innovative strategies. For the ills of misinformation, inoculation theory is a promising defence Joanna Lada studied Mathematics (Class of 2020) at St John's College; Jake Rose is an MSci student in Astrophysics at Magdelene College. Artwork by Marie Cournut.

One tactic the researchers have investigated is an online browser game, Bad News. Players are guided through a comical exercise in which they impersonate ‘fake news’ experts promoting conspiracies, thereby learning the tools of

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A Vaccine for Your Mind

29

The Value of Being Precautious?

Charlotte Zemmel discusses the precautionary principle and how it shaped the UK response to COVID-19 The COVID-19 pandemic has revealed diversity in the world's attitude towards healthcare and public welfare.

One particularly striking aspect is how social values beyond scientific evidence shaped recommendations in Evidence Based Medicine. Here, I explore how COVID-19 response teams operated according to the principle of precaution.

Precaution, as a guiding principle of theory and policy, encourages us to choose the intervention, evidence, and prognosis that is most pessimistic and cautious with respect to the future. Perhaps one key lesson to be learned from the post-COVID-19 ‘new normal’ is that the background values which shape our scientific models have fundamental consequences for our interpretation of scientific knowledge.

Here, I explore the analysis and critique of these values by discussing the impact of being precautious on the epidemiological models produced by the UK’s leading COVID-19 response teams.

On 26th March 2020, Imperial College London’s COVID-19 response team published their report, The Global Impact of COVID-19 and Strategies for Mitigation and Suppression. Based on a series of models, they predicted that SARS-CoV-2 would cause 40 million deaths globally if left unchecked. The report came at a critical time in public health debates — the UK was set to follow a policy whereby the country would remain entirely open in order to generate herd immunity, where spread of the virus is prevented by enough of the population gaining immunity by contracting the disease and recovering. Imperial’s bleak prognosis catalysed the Prime Minister’s revision of the herd immunity stance whilst the shocking numbers in the report drove many to take the threat of the virus seriously.

assessing the implications of choosing an incorrect hypothesis or disposing of a correct one.

According to Rudner’s argument, the choice between a herd immunity response or a lockdown response requires the inclusion of judgements beyond the confines of evidence and data. This is where the precautionary principle was exercised.

The poor quality of data in the early stages of the pandemic seemed to further justify a method that proceeded with maximum caution when designing effective public health responses. Furthemore, Rudner’s argument from inductive risk highlights that the less reliable the evidence is, the more essential extra-scientific values become. From looking at practitioners’ opinions on the quality of evidence during the pandemic, it was clear that values akin to the precautionary principle were necessary for good reasoning. Assistant Professor of history and philosophy of science at the University of Pittsburgh, Jonathan Fuller, explained that the focus on modelbased strategies in COVID-19 epidemiology, as opposed to other evidence-based approaches such as population sampling, was the result of the dire quality of evidence collected at the

Which Values Should We Value? | At times when scientists and policymakers are expected to make decisions with potentially harmful consequences for the public, it is intuitive that they should consider the most possible detrimental outcomes of each option in their decision making process. This is the rationale that sits behind the precautionary principle.

Since the 1960s, philosophers of science have worked hard to devise an account for how scientists do and should use values such as the precautionary principle in their work. The clearest justification for the use of such values was first articulated

by Richard Rudner in 1953: Argument from Inductive Risk (AIR). The argument states that: since no amount of evidence can guarantee that one hypothesis is correct over and above its closest rival, hypothesis choice is always underdetermined.

Hence, scientists must use value judgements such as the social, ethical and political implications to navigate the choice by

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The Value of Being Precautious?

Michaelmas 2020

beginning of the pandemic. The epidemiologist Professor John Ioannidis at Stanford University even labeled the scientific response to the virus an ‘evidence fiasco’. He also highlighted how the disparate methods of data collection across the globe have made the information on the rate of spread and the virus’s deadliness ‘utterly unreliable’.

A Deeper Look at Imperial’s Report | Precautionary judgements were entrenched in the report from Imperial College, highlighting the centrality of this principle in guiding COVID-19 science and policy decisions. The shocking prediction that there would be seven billion infections and 40 million deaths globally were reached through worst-case-scenario modelling, whereby the R-number (the number of healthy people a single sufferer will infect on average) was set to 2.4–3.3, which was the upper band of postulated values estimated at the time. In mid-May, for example, Public Health England and the University of Cambridge calculated that the R-number in the UK was between 0.5–0.9. The fact that Imperial opted for such a high R-number highlights the depth to which being precautious and postulating on the worst-case scenario was rooted in this report.

The report concluded that, ‘given these results, the only approaches that can avert health system failure in the coming months are likely to be the intensive social distancing measures currently being implemented in many of the most affected countries’.

It is no surprise that this would be the recommendation of a report that compared how a highly infectious virus

would spread freely through a population undertaking no mitigation strategies, against simulations where extensive preventive measures were put in place. In other words, the recommendation of the model is a direct result of maximally dangerous premises and investigating only one avenue of mitigation, namely restrictions on movement. Thus, as one looks deeper into the Imperial report, the impact of the precautionary principle on the modelling style and interpretation of results was wide reaching, emphasising the need to scrutinise the justification for this value further.

A Viable Alternative? | The question will always remain on how different our COVID-19 journey could have been if a precautionary approach was exchanged for something else.

One viable contender was offered by Professor Alex Broadbent, who discussed a ‘rational cost-benefit analysis’ approach. His suggestion was that our response to the current pandemic should be the result of careful compromise between a myriad of different problems, such as the supreme danger the virus poses to the sick and elderly, the damage to children’s educations from school closures, and the unprecedented impact on the economy lockdown has and will have.

He thinks that the most rational way to construct public health policy is to consider all possible consequences of COVID-19 strategy and trade-offs between them. It is important to note that Imperial’s report purposely excluded socio-economic considerations of the social distancing measures they adamantly endorse: ‘we do not quantify the wider societal and economic impact of such intensive suppression approaches’.

As we enter a post-lockdown period of trying to restore our businesses, schools, and industries, only time will tell how successful the precautionary principle was at mediating the extremely complex landscape of irreducible and irreconcilable public health, social, and economic issues.

The celebrated and influential 20th century sociologist, William Edward Du Bois, defended a science free of values by emphasising that in a democratic society, scientists do not have the sufficient expertise to make judgements concerning what the outcomes of the knowledge they produced will be. That is the job for democratically elected politicians. Whilst precaution has been the watchword of risk assessment during the COVID-19 pandemic, perhaps allowing philosophers of science to scrutinise the values that we use to conduct epidemiological research in times of crisis would not only expose the values that shape our research, but also allow us to spend time conceptualising what the best values to use should be.

The lesson to be learned here is that the scheme of values that we prioritise in society has immediate and fundamental consequences for the science that we make and spread. Perhaps the outcome of this pandemic will inspire more careful evaluations of the judgements that sit behind our models and predictions so that we can justifiably say that we have learnt for the future to better evaluate our methods of judgement in situations of uncertainty Charlotte Zemmel is an MSc student in History and Philosophy of Science at Newnham College. Artwork by Natalie Saideman.

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The Value of Being Precautious? 31

Weird and Wonderful A Watery Twist to the Dinosaur Tale The word ‘dinosaur’ may once have conjured up the image of a lizard-like beast galloping across prehistoric lands, but that perception has changed. It is currently agreed amongst scientists that many dinosaurs were indeed feathered or fluffy, and it is well known that birds are living remnants of the dinosaurs themselves. New research has now provided an added twist in our understanding of the magnificent creatures that once populated our Earth.

It had previously been thought that non-avian dinosaurs were restricted to terrestrial environments, with only a few hints that some dinosaurs may have had a more versatile lifestyle. In particular, it was suggested that the spinosaurids — giant, sail-finned carnivores — may have had ‘semi-aquatic’ behaviour. The latest research from Dr Nizar Ibrahim and colleagues, however, has suggested that one Spinosaurus species may have significantly inhabited the waters, opening up the possibility for a ‘substantial invasion of aquatic environments by dinosaurs’. The researchers found Spinosaurus tail bones with long spikes, suggesting that this creature had a large tail fin that could propel its body through water. Reconstructions of the Spinosaurus tail fin have shown that it has a thrust and efficiency more comparable to crocodiles than other similar dinosaurs.

Artwork by Rita Sasidharan.

All in all, perhaps the name ‘terrible lizard’ (deinos sauros) is not as representative as ‘destructive bird’ or ‘tyrannical crocodile’. AL

A Spoonful of Jelly Makes the RNA Go Down Bees are well-known for their innate ability to turn nectar into a sweet, pancake-friendly substance, honey. However, there is much more to these little creatures. Honey bees expertly adapt to their environment by expressing different parts of their genome.

Normally, genetic information is transmitted through DNA, from parents to offspring. However, research showed that bees can transmit information outside parenthood in an RNA-containing jelly given to larvae. Larvae that feed on jelly made by worker bees become workers and royal jelly causes larvae to develop into queens.

RNA is bound to stabilising proteins which target it to specific cells.

These discoveries are relevant to the field of gene therapy and vaccines, where RNA delivery has been challenging to achieve because RNA cannot cross cell membranes unless chaperoned by membrane proteins or lipid nanoparticles and have low stability in the gut. RNA therapeutics hold promise in treating hereditary defects, targeting aberrant gene expression in cancers or even acting as vaccines.

Understanding the composition of bees’ RNA-jelly could reveal biological processes to design improved RNA drug formulations.

After honey, RNA-jelly could be the second sweetest gift that bees offer to humanity. BS

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Weird and Wonderful

Peanut Butter Diamonds In a quest to mimic conditions deep inside the Earth, scientists have discovered a method for producing diamonds from a rather unlikely source of carbon… peanut butter!

To form this precious gem, everyday peanut butter is sandwiched between the tips of two diamonds in a piston press and squeezed, creating a ‘stiletto heel effect’. As diamond is one of the hardest substances on Earth, this set up can create the extreme pressure (approximately 1.3 million times that of atmospheric pressure) needed to break down the carbon bonds in peanut butter. The carbon atoms then rearrange from a peanut butter structure to a tetrahedral, diamond crystal structure. In addition to diamonds, the same method has previously been used to create red crystals out of oxygen.

Unfortunately, you are unlikely to make your millions by heading to the preserves aisle of your local supermarket as the extreme pressure must be maintained for several weeks to form a diamond of merely two to three millimetres. Also, hydrogen gas released from the process can cause small explosions.

However, this method is still of significance because it could be used by scientists to generate artificial diamonds for use in superconductors and quantum computing. EB

Michaelmas 2020

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