Bluesci Issue 53 - Lent 2022

Lent 2022 Issue 53 www.bluesci.co.uk

Cambridge University science magazine

FOCUS

Temporary contracts

Lithium Extraction . Single Cell Variability Snakes . Quantum Computers

Cambridge University science magazine

Contents Regulars

Features 6

On The Cover News Reviews

Same But Different:A Short History of the Human Genome Bartek Witek discusses the clinical consequences of genetic diversity

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FOCUS

Seen One Snake, Seen Them All?

Alexandra Howard reveals variation in the diverse world of snakes 10

Something To Declare: Australia’s Cane Toad Problem Monica Killen explores invasive species and their impact on ecosystems

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Hedging Your Bets: Is Single Cell Variability Functionally Important?

Roberta Cacioppo delves into what variation between cells means at the population level

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Pavilion: Where Art Meets Artifical Intelligence

Pauline Kerekes talks to Lukas Noehrer from the Alan Turing Institute 24

How To Build A Quantum Computer

Xavior Wang explores what makes and breaks a quantum computer 26

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FLEXIBILITY OR RESTRICTION: FIVE WAYS FIXED-TERM CONTRACTS REDUCE DIVERSITY Bethan Charles

Reinventing Ourselves:What Do Advances in Artificial Intelligence Mean For Truth?

Gladys Poon discusses our increasing reliance on algorithms 22

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The Dating Game: What Role Does the Major Histocompatibility Complex Play in Sexual Compatibility?

Clodagh Bottomley asks how we choose our perfect partner

BlueSci was established in 2004 to provide a student forum for science communication. As the longest running science magazine in Cambridge, BlueSci publishes the best science writing from across the University each term. We combine high quality writing with stunning images to provide fascinating yet accessible science to everyone. But BlueSci does not stop there. At www.bluesci.co.uk, we have extra articles, regular news stories, podcasts and science films to inform and entertain between print issues. Produced entirely by members of the University, the diversity of expertise and talent combine to produce a unique science experience

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Eco-Mining For the Future: The Changing Face of Lithium Extraction

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Matthew Morris discusses the need to make lithium extraction greener

Seeds of Change: A Diverse History of Agricultural Practices in the UK

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Weird and Wonderful

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Tim Birkle argues for the importance of collective action for change to take root

Tiny Owls and Tiny Snakes: Strangest of Bedfellows?

Valuing Vaginal Variation:Why Size Matters The Large Blue(Sci) Butterfly

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Contents

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Issue 53: Lent 2022 Issue Editor: Kate Howlett Managing Editor: Georgina Withers First Editors: Laura Chilver, Tim Birkle, Adam Dray, Meng Siong Chen, Megan Hardy, Bartek Witek, Miriam Lisci, Ailie McWhinnie, Lizzie Knight, Gladys Poon, Holly Smith, Luisa Deragon, Jessica Corry, Emily Talbot Second Editors: Adam Dray, Julie Tang, Ailie McWhinnie, Devahuti Chaliha, Laura Chilver, Luisa Deragon, Emily Talbot, Miriam Lisci, Megan Hardy, Tim Birkle, Holly Smith, Bartek Witek, Rafał Wilowski Art Editor: Pauline Kerekes News Team: Adiyant Lamba, Elizabeth English Reviews: Alexandra Howard, Hazel Walker, Sarah Lindsay Feature Writers: Bartek Witek, Alexandra Howard, Monica Killen, Roberta Cacioppo, Gladys Poon, Xavior Wang, Clodagh Bottomley, Matthew Morris, Tim Birkle Focus Writer: Bethan Charles Pavilion: Pauline Kerekes Weird and Wonderful: Alexandra Howard, Benedetta Spadaro, Matt Hayes Production Team: Kate Howlett, Georgina Withers, Sarah Lindsay Caption Writer: Kate Howlett Copy Editors: Kate Howlett, Georgina Withers, Sarah Lindsay Illustrators: Josh Langfield, Mariadaria Ianni-Ravn, Sumit Sen, Biliana Tchavdarova Todorova, Anna Germon, Scott Allan Orr, Leonora Martínez-Núñez, Pauline Kerekes, Rosanna Rann Cover Image: Eva Pillai

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

Valuing Variation Variation extists both within science and in our approaches to it. Wider society's increasing emphasis on ‘listening to the science’ risks creating the narrative that science is a linear story that finds singular answers, often resulting in confusion when science ‘changes its mind’. In reality, science is a pursuit that encompasses a wide variety of approaches, a diverse range of people, and, ultimately, seeks to make sense of the variation we find in the natural world and wider universe.

In this issue, authors and artists highlight the variation found all around us, from cells and ecosystems to deep in our history and possible futures. How much variation have we already uncovered? How much is there left to find? How important is this for our health and that of our environment? How can we encourage variation within STEM academia itself?

Starting with variation within our own genomes, Bartek Witek discusses how this provides promise for personalised healthcare of the future. Moving to variation at the wholeorganism scale, Alexandra Howard reveals how snakes, often wrongly maligned creatures, display a whole assortment of approaches to life. Zooming out to the ecosystem level, Monica Killen explains how our one-size-fits-all approach to invasive species and biological control can put native biodiversity at risk. Without appreciating the nuances of different ecosystems around the world, we risk homogenising global biodiversity and endangering the delicate functioning of our environment. Next, Roberta Cacioppo explains how variability at a cellular scale contributes to diversity at the population level. Looking to the future, Gladys Poon explores what advances in artificial intelligence might mean for our understanding of truth and the changing face of the workplace.

For this issue’s FOCUS piece, Bethan Charles explores the importance of diversity amongst scientists themselves and the role of STEM academia in facilitating this.

Academia abounds in temporary, short-term contracts. What does this mean for the kinds of people able to pursue scientific research as their career?

Good communication of the latest science has never been more important. In the Pavilion, Pauline Kerekes talks to Lukas Noehrer of the AI and Arts group at the Alan Turing Institute about the integration of art with the latest scientific advances in the hope of fostering greater public understanding. Continuing the theme of accessibility, Xavior Wang bravely tackles the famously unexplainable — what goes on inside quantum computers, and why do they hold so much promise? From the abstract to the daily pertinent, Clodagh Bottomley explores the hidden role of our DNA in choosing whom we date. Matthew Morris details the latest developments in methods for lithium extraction — a vital endeavour if we are to match the expected global demand in lithium for our quest to reach net zero. Finally, Tim Birkle covers the history of agricultural practices in the UK, making the case for a return to the more sustainable, varied agricultural systems of the past.

It is possible to publish a whole issue dedicated to the variation uncovered by science itself, and another solely dedicated to the diversity of approaches and people doing science. I hope that by placing these two areas side by side, I have drawn your attention to how they are linked. If we don’t ensure everyone is welcome within science, we risk losing talent, perspectives, and ideas, potentially leaving some of the rich variation in our world, and its importance, undiscovered Kate Howlett Issue Editor #53

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On the Cover Variety is required at a primal level for survival but also for creating a rich and beautiful life. This runs the gamut from particles in the universe to the molecules that form life, to what we eat and how we learn or build new technologies. The illustration begins and ends with the central form of the diverse face of science. The variation required in thinking and contributing positively as a species is perched precariously on the instability fuelled by temporary contracts. The diversity of thought required in endeavours as distinct as mining, agriculture, and algorithm-building are represented throughout the background. Finally, I have included elements in appreciation of the wondrous variety that exists in nature at all scales, from the molecular to organ-patterning to the whole-species level, looping back to the central image of valuing variation both within and without Eva Pillai Cover Artist

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On the Cover

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News

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

Glass-Like Super Jelly: A Material for the Future

The Largest Invertebrate of All Time

What is 80% water, but ultra-hard and shatterproof?

A new material developed by a team at the University of Cambridge is all those things, and it may have applications in biomedical and bioelectronic technologies. The material is a hydrogel, which means it can swell and retain water while maintaining its integrity due to the cross-linking bonds between the network of polymers that make up the gel. ‘We use reversible cross-linkers to make soft and stretchy hydrogels, but making a hard and compressible hydrogel is difficult, and designing a material with these properties is completely counterintuitive’, said the study’s first author, Dr Zehuan Huang. The team managed nevertheless, using barrel-shaped molecules called cucurbiturils to cross-link suitable guest molecules. These barrel-shaped molecules help keep the polymer network tightly linked even when expanded, allowing it to withstand compressive forces.

Altering the property of the guest molecules in this way can affect the strength of the material.

300 million years ago, the world was a strange place. As terrestrial vertebrate life started to diversify, vast expanses of swampland were home to creepy-crawlies the size of modern-day vehicles. A recent fossil of the giant millipede Arthropleura, dating back to around 326 million years ago, reveals this creature as the largest-known land invertebrate of all time.

‘To the best of our knowledge, this is the first time that glass-like hydrogels have been made. We’re not just writing something new into the textbooks, which is really exciting, but we’re opening a new chapter in the area of high-performance soft materials’, said Huang. The researchers have used the material to create hydrogel pressure sensors for human movements, but no doubt there are many further applications of this super jelly. AL

The fossil, discovered in 2018 in Northumberland and characterised in Cambridge, was found after a large block of sandstone fell and exposed the specimen. It represents the third fossil of this species, but this is the oldest and largest one yet. The 75-cm segment discovered is thought to belong to a creature that spanned 2.7 m and weighed 50 kg, beating the previous record holder, the sea scorpion Jaekelopterus.

But how did Arthropleura get to be so large? The most common explanation for the large size of land invertebrates during the Carboniferous, when this giant millipede lived, is that the dense mass of vegetation characteristic of the period released huge amounts of oxygen, which fuelled the growth of large invertebrates. However, the new fossil seems to predate the peak in atmospheric oxygen, so this is unlikely to be the only explanation. Researchers believe that Arthropleura’s diet could also have played a role, but the exact reasons for its size remain still unknown. AL

A Breath of Fresh Air: Needle-Free COVID Vaccine Developed in Cambridge DIOS-CoVax, a next-generation coronavirus vaccine, has been developed by Professor Jonathan Heeney of Darwin College and his company, DIOSynVax. The key ingredient of most currently approved COVID-19 vaccines is the spike protein RNA sequence from the first-isolated SARS-CoV-2 variant. However, SARS-CoV-2 is prone to mutations; if SARS-CoV-2 spike proteins drastically change, new variants could be unrecognisable to our immune systems, rendering current vaccines less effective. To provide broader immune protection, the Cambridge team have identified more common antigens across coronaviruses. ‘DIOS-CoVax vaccines target elements common to all known “beta-coronaviruses” — those coronaviruses that are the greatest disease threats to humans’, says Professor Heeney. ‘These structures are vitally important to the virus life cycle…

We are confident they are unlikely to change. Therefore, DIOS-CoVax should protect us against variants we’ve seen so far and hopefully future-proof us against emerging variants’.

DIOS-CoVax is administered through a blast of air on the skin, rather than via a needle, and it takes less than 0.1 seconds, potentially speeding up the vaccination process. An appealing alternative to those with needle phobias, this technology provides hope for increased coronavirus vaccine uptake. DIOS-CoVax is currently undergoing its first safety trials as a booster dose for healthy volunteers in Southampton. If successful, DIOS-CoVax could also be manufactured as a powder to aid global vaccination efforts — a lifeline for lower income countries. EE

Artwork by Josh Langfield.

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News

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Reviews Wilding – Isabella Tree It can often feel like problems such as habitat loss and the subsequent extinctions of animals are constrained to more tropical environments.

Whether it be the deforestation of the Amazon or oil-palm plantations encroaching on the rainforests of Borneo, you would be forgiven for thinking that these are distant problems that do not affect us here in good ol’ Great Britain. But our fair isles have also seen a considerable degree of ecological change, leading to numerous extinctions of our own.

The concept of rewilding, reintroducing extinct species that were once present in an area, is a novel and promising method to combat these extinctions. Wilding by Isabella Tree is an in-depth look at the rewilding experiments carried out at the Knepp Estate in West Sussex. Once an arable and dairy farm, lack of profitability led Isabella Tree and her husband, Charlie Burrell, to search for an alternative purpose for the acres of land at their disposal. What followed was an incredible rejuvenation of a British ecosystem. Once starved of biodiversity, Knepp Estate is now one of the few places in the UK that has recorded an increase in the population of endangered turtle doves and has witnessed the recovery of several species of butterfly thought to be extirpated from the area. With a fine eye for ecological detail, Tree’s story is a fantastic testament to the resilience of the natural world and a rallying cry for the protection of Britain’s incredible native wildlife. AH

The Codebreaker – Walter Isaacson

Crash Course Big History – CrashCourse, YouTube

The Codebreaker recounts the discovery that CRISPR/Cas, a bacterial defence system, can be exploited to make precise edits to DNA, with huge ramifications for genetic engineering and gene therapy. Jennifer Doudna, Professor of Molecular and Cell Biology and Professor of Chemistry at UC Berkeley, shared the 2020 Nobel Prize in Chemistry with Professor Emmanuelle Charpentier for this discovery.

Starting at the very beginning with the Big Bang, 13.8 billion years ago, and ending trillions of years into the future with the end of the universe, brothers John and Hank Green, along with Emily Graslie, explore the history of the universe via YouTube. This account steers clear of the stereotypical history we learn at school: blood-shed for power or Henry VIII’s wives. Covered instead are the truly pivotal events of the past, such as the advent of single cell organisms and the five mass extinctions, as well as a glimpse into the future with John, Hank, and Emily’s logical and insightful approach to considering what this may look like.

Isaacson first tells a captivating story of scientific research, using interviews with Doudna herself, as well as her collaborators and competitors, to give an insight into how scientific discoveries are made and the drama, disagreements, and competition that might occur along the way. The second half of the book examines the ethics of genome editing and what this might hold for the future of human disease, even covering how CRISPR/Cas might be used for diagnosing and treating COVID-19. Isaacson is careful to highlight the important role that basic scientific research can play in breakthroughs related to human disease, work which is becoming increasingly difficult to secure funding for.

Overall, the book tackles complicated, modern science in an accessible way by bringing to life the people responsible for this influential work, making it an enjoyable read for experts and laypeople alike. HW

The course breaks down concepts into comprehensible chunks — no small feat when billions of years are involved. The use of engaging animations and simple, but never patronising, discussion enables scientific ideas to be grasped by all audiences. If you can get past the fast-paced speech, the strange pronunciation of ‘niche’, and the confusion between tortoises and turtles, then this is an excellent science communication channel to watch and an ideal way to learn about the vast variation and complexity that the universe has experienced over the past 13.8 billion years. SL

Willding book cover courtesy of Pan Macmillan.

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Reviews

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Same But Different: A Short History of the Human Genome Bartek Witek discusses our surprising lack of genetic diversity and its clinical consequences For a species younger than 200,000 years old, we have a surprisingly complex history etched into our genomes.

Although only emerging around 180,000 years ago, Homo sapiens has spread out across the globe over the last 100,000 years, creating pockets of isolated populations in wildly differing climates. This history can be pieced together by examining the differences in our DNA, which result from errors and adaptations, passed on through generations. Our genomes tell a story of a young species with common ancestry and very little genetic variation between us, bound much more by our similarities than divided by our differences.

However, by examining these small differences, we can begin piecing together the causes behind differences in our traits. For example, understanding how differences contribute to disease susceptibility has the potential to transform healthcare into a new era of personalised medicine.

Nucleotide Polymorphisms (SNPs), while some are caused by removals or insertions of small sections of DNA. It seems that large changes in our genomes are rare, suggesting most diseases are caused by SNPs.

A NEW UNDERSTANDING OF VARIATION | Variation can be thought of as differences in physical features, such as flower colour, beak shape or height. But what determines these differences? Ultimately, physical features are encoded by genes — basic units of inheritance — which are sequences of DNA letters. Each of us carries a slightly different, unique set of genes that interact to give complex individual traits, often difficult to predict from DNA alone. The era of genomics has allowed us to peer into our DNA, and we now know variation is heavily based on differences in our DNA sequences. We are only just beginning to uncover the true complexity of this genetic variation.

CLINICAL CONSEQUENCES | Our ability to characterise genetic variation on a global, single-letter level promises a new era in medical diagnosis. If we can accurately map differences in the genomes of healthy and ill people, perhaps we will be better able to uncover the mechanisms behind many currently poorly characterised genetic diseases.

The 1000 Genomes Project showed that some genetic changes, albeit rare, can cluster in certain populations — perhaps we can create more targeted preventative measures?

The Human Genome Project, initially published in 2001, successfully determined the arrangement of letters that make up human DNA from a mosaic of individuals, creating a reference genome that can be used as a comparison between all human genomes. It turns out that, on average, humans share 99.9% of our genetic code, and there is more genetic variation within populations than between them. The boundaries we set between ‘races’ are artificial. However, a more detailed knowledge of genetic variation between humans, from a more diverse cohort, is necessary if we are to understand geneticbased diseases and use this knowledge to improve healthcare.

To that end, in 2008, the 1000 Genomes Project was announced. This aimed to sequence the genomes of at least 1,000 people from across the world to produce a more detailed, diverse and medically useful picture of human genetic variation.

The global sequencing effort captured 2,504 individuals from 26 populations and found over 88 million genetic changes. A typical human genome differs at approximately 4-5 million sites; most differences are single-letter changes, known as Single 6

Same But Different

Populations within Africa show the greatest numbers of sites of genetic change. This is consistent with the Out of Africa hypothesis that all modern non-Africans are descended from a single exodus from the African continent around 120,000 years ago. African populations are therefore significantly older, so there has been more time for genetic differences to build up within them. Most specific genetic differences are rare in the global sample but common between cells in a single genome.

The 1000 Genomes Project demonstrated that we are more alike than different on a grand scale and are connected by a common origin.

Genome association studies have been designed to test for hundreds of known genetic differences, or SNPs, at once, to try to find those associated with a specific trait or disease.

Findings are useful but sobering. Naively, we might think that one change in our DNA will result in a dysfunctional protein which causes a disease. Unfortunately, however, the true picture is much more complex. Most traits are influenced by thousands of causal genetic differences — each on its own confers very little risk, but together they can greatly increase disease susceptibility. It is rare for a disease to be caused by just one SNP. This makes hunting for a causal gene or SNP exceedingly difficult, with no obvious place in which to start our search.

Most are found in mysterious non-coding regions — those that do not appear to code for a protein — making it hard to assign function to them. Moreover, many SNPs thought to cause a disease are often associated with other SNPs that confer no extra risk, making it hard to detangle and pin-point the real culprit. That being said, we are starting to gain a few insights.

For example, a single-letter change has been shown to be a powerful predictor of obesity, and assigning functional roles to some SNPs has helped discover a genetically encoded pathway Lent 2022

inside cells that is linked to Crohn’s disease.

While we are still a long way off identifying the mechanisms behind diseases, we have made progress in our ability to predict susceptibility. We can now assign a numerical risk-factor score for a specific disease to an individual’s genome, based on our knowledge of which SNPs are associated with a given trait.

Risk calculated from these studies is only probabilistic, with a high degree of uncertainty — low-risk individuals may still develop the disease, whilst those identified as high-risk may never do so. Many discovered risk-associated SNPs are based on European cohorts, and even small regional biases can skew results, making them less meaningful for people across the globe. Predictors are far from universal. The only solution is to increase the diversity of our sampled cohorts, making programmes like the 1000 Genomes Project key to more accurate predictors.

PROBLEMS YET UNANSWERED | We now can sequence entire human genomes in mere days at a fraction of the cost of the Human Genome Project. We do not know the function of most of the genetic differences we detect, most being in non-coding regions we know little about.

One of the biggest remaining problems is the fact that the genetic variations we have discovered do not account for the heritability of all traits, termed the missing heritability problem. Some traits, such as height, for example, are highly heritable, meaning that a large amount of the variation we see in height is encoded in our DNA, and yet, the genetic differences we have found so far are insufficient to account for all our inherited traits and diseases. Advances in longerread sequencing techniques are slowly uncovering new types of variations, but efforts even more ambitious than the 1000 Genomes Project are needed if we are to solve this conundrum to find the missing variation.

Maybe one day in the not-too-distant future, when all our genomes are sequenced at birth and we fully understand the heritability of all our traits and gene interactions, we will be able to design a truly cradle-to-grave healthcare system, with drugs and treatments uniquely designed for each individual on the basis of their genome.

Until then, we have more of a handle on our similarities than our differences, which remain so minutely small as to be undiscoverable Bartek Witek is a third-year undergraduate at St Catharine’s College studying Natural Sciences, with a Part II in biochemistry. Artwork by Mariadaria Ianni-Ravn.

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Same But Different

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Seen One Snake, Seen Them All? Think again! Alexandra Howard delves into the world of snakes to highlight their surprising diversity Snakes are a group of reptiles often perceived as scary or creepy. While some species have justifiably earned this reputation, in most cases the true threat posed is negligible.

Snakes possess a uniform, recognisable body plan — long, with no limbs — yet there is massive interspecies variation in terms of appearance, habitat, and diet. This variation exists because snakes have adapted to fill niches in many different ecosystems.

Snakes therefore represent a fascinating example of the power of adaptation, the process by which evolution shapes animals to best exploit their environment.

to avoid detection by prey or predators. However, there are some snakes that buck this trend. The distinctive red, black, and yellow colouration of the coral snakes is instantly recognisable: this kind of bright warning colouration is called

WHERE DO SNAKES LIVE? | Snakes are ectothermic, meaning they rely on external heat to regulate their body temperature. This differs from mammals and birds, which can regulate their temperature with heat produced internally. Instead, snakes regulate their body temperature through behavioural mechanisms, such as basking in the sun. Maintaining body temperature in this way is vital for snakes’ survival, as this enables them to digest prey and to move rapidly to escape from predators. The importance of temperature means the majority of snake diversity is present in the tropics. However, this does not mean that snakes are absent from cold climates, and in fact snakes are present on every continent except Antarctica. For example, the vipers (a group that includes rattlesnakes) are surprisingly tolerant of cold temperatures. The European adder, Britain’s only venomous snake, is one such viper that has made its way up north.

Vipers are able to cope with cold winter temperatures through a process known as brumation. This is a form of reptilian hibernation, in which the animal enters a dormant state with a relatively low metabolism, saving its energy for when the temperature rises again. This allows snakes to live in geographic areas that experience seasonal shifts in temperature.

WHAT DOES A SNAKE LOOK LIKE? | Snakes exhibit a wide diversity in size. At over eight and a half metres, the reticulated python is the longest snake in the world, and the heaviest is the green anaconda, clocking in at up to 250 kg.

These heavyweights of the snake world are most well recognised due to their prevalence in popular media. But snakes can also be extremely small: the world’s smallest snake is a tiny threadsnake from Barbados, measuring only 10 cm. This snake belongs to a group known as the worm snakes that spend most of their life underground, where they eat the larvae of insects such as ants and termites.

Colour is another feature in which snakes display incredible variation. Most snakes are camouflaged simply by being the same colour as their preferred environment. This is pretty common throughout the animal kingdom as a useful method 8

Seen One Snake, Seen Them All?

aposematism. Common predators of snakes such as birds or primates learn that these bright colours mean danger and avoid the animals that display them. In the case of coral snakes, the danger is a neurotoxic venom, which paralyses the breathing muscles and eventually causes suffocation. Warning colouration means that these snakes don’t need to waste their precious venom (which is energetically costly to produce) on a predator, and can instead save it for small reptiles — their preferred prey.

However, not every brightly coloured snake is dangerous.

Some snakes have adapted to take advantage of the fact Lent 2022

that aposematism is a common deterrence tactic. Afterall, it’s beneficial to be avoided by predators but energetically expensive to produce venom. So why not just look like a venomous snake? This is precisely what several species of snake have adapted to do — a tactic called Batesian mimicry. The kingsnakes exhibit the same brightly coloured red, black, and yellow striped patterns of coral snakes, but a bite from them would do no more harm than drawing a bit of blood. These snakes live in the same areas as the coral snakes, so predators will avoid them, thinking that they are a venomous coral snake.

further and has evolved to reproduce only in this way. This means the Brahminy blindsnake is clonal, with females able to start colonies whenever they want.

We also see remarkable variation in diet. While most snakes eat other vertebrates (fish, mammals, birds, reptiles, or amphibians), several species of mangrove snake have adapted to their unique environment through the evolution of a specialised diet. These snakes are specialised crab-eaters, preferring the soft-shelled, freshly moulted crabs of South East Asia. They are also the only known snakes that rip their prey into smaller pieces before eating them, forgoing the typical snake method of swallowing prey whole. This is likely due to the mechanical difficulties of swallowing a crab in one piece.

Finally, although snakes are usually thought of as solitary animals, a recent study of a species of garter snake has challenged this assumption. As a North American species, garter snakes brumate in large aggregations, emerging together in the spring to mate. Observation of wild populations has shown that large aggregations of individuals are common in many different garter snake species. Researchers from Wilfrid Laurier University in Canada investigated this phenomenon further and found that snakes will actively seek each other out in shelters, preferring to form large groups. Additionally, individual snakes associate with one another non-randomly, meaning that they preferentially spend time with the same individuals, even after being disturbed. This type of study shows not only that snakes are more social than we previously thought, but also that they have the ability to recognise and remember each other. This highlights our need to further understand snake sociality and has significant implications for snake conservation.

Snakes are a fascinating case study into the power of evolution, from extremes of body size, climate tolerance, colour, and even behaviour. By learning more about these often misunderstood animals, we stand to gain a better understanding of how adaptation has led to the diversity of life that we see today Alexandra Howard is a final-year PhD student in zoology at Trinity Hall College. Artwork by Sumit Sen.

HOW DO SNAKES BEHAVE? | Snakes also show a remarkable amount of behavioural variation across their many species. Like most animals, reproduction for snakes usually involves a male and a female. However, the Brahminy blindsnake, or flowerpot snake, is a small worm snake (the same family as the smallest snake) and is the only known snake that reproduces solely through a process called parthenogenesis.

Parthenogenesis, also known as ‘virgin birth’, is where a female animal can reproduce without the presence of a male. This occurs in many snakes and lizards, including the fearsome Komodo dragon. The flowerpot snake takes this one step Lent 2022

Seen One Snake, Seen Them All?

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Something To Declare: Australia's Cane Toad Problem

Monica Killen uses the example of cane toads to explore complexities around introduced species and the importance of research into their impact If you have ever flown to Australia, watched the TV series Nothing to Declare, or heard about the saga of Johnny Depp’s dogs in 2015, you will know that Australia has some of the strictest biosecurity laws around. But just how dangerous is your egg salad sandwich or favourite pet that you are trying to sneak in?

Invasive species introduced during early British occupation have wreaked havoc on Australia’s biodiversity, with these issues still ongoing today. Red foxes, brought in for hunting, carried disease and caused a decline in small mammal and bird populations. Rabbits, also introduced as game, had no natural predators, and despite thousands of miles of ‘rabbit-proof ’ fence, they spread to the furthest reaches of the country. Wild horses, deer, and even feral camels continue to contribute to the erosion and depletion of Australia’s native plant species.

One of the most interesting cases is that of the cane toad in the 1930s. Australia’s northern sugar cane industry was faced with a ravenous population of cane beetles, eating away at its crops. Despite some early concerns about environmental impact, industry-mounted political pressure won out in 1935, successfully lobbying to bring in the Central American cane toad as a form of biological control. The great hope was that the introduced cane toads would simply eat the cane beetles, keeping beetle numbers at bay, the sugar cane intact, and solving the industry’s pest problem. There was even a successful case study to work off — a Nature article at the time, entitled ‘Toads Save Sugar Crop’, hailed their triumphant introduction as pest control in Puerto Rico.

To say the plan failed is a massive understatement. The stomachs of cane toads found near sugar cane crops did in fact contain cane beetles, but they also contained the remains of plenty of other species, as they left the dry open fields for more plentiful food-diverse areas. They feasted on unintended insects, like ants that consume cane beetle larvae, cancelling out some of their intended pest-control benefits. But the problem was not only due to what the toads did and did not eat, but also what ate the toads. Large native species that eat cane beetles, like lizards and goannas, started to eat the cane toads and suffered poisoning from the toxic glands on the toads’ backs. Another indirect consequence was that rats, which ate both the cane toads and the valuable sugar cane, thrived.

Rats were one of very few species immune to the cane-toad toxins and increased in number, while the predators of rats, such as goannas, suffered severe population declines. Overall, 10

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the cane-beetle populations in Australia were left essentially unchanged, while the cane toads flourished.

Their numbers boomed in Australia from those first few thousand released to now well over 200 million — that’s eight cane toads for every person in Australia. Cane toads were found to have some odd commercial uses, like as a vehicle for early pregnancy testing in the 1950s and cane toad leather, which you can still buy today. Cane toads are so prolific that they have even become part of the Australian identity: a state rugby team is nicknamed after the pest, ‘toad golf ’ is a questionable eradication method, and even toad-themed festivals exist with competitions for the largest one caught. This boom in cane toad numbers has been accompanied by rapid evolutionary developments, including longer legs on toads found at the frontier as their territories expand at approximately 60 km per year. The species has also developed cannibalistic tendencies in this short span of time, likely due to their large numbers and lack of predators, leading to competition for resources.

This competition for resources, including shelter, extends to native frog and bird species, like the groundnesting rainbow beeeater,

which now produces one third fewer fledglings due to Lent 2022

nest usurping in some areas. While the cane toad has not been directly linked to any species extinction, it has a distinct effect on animal populations when it encroaches into new areas. A 75% reduction in northern quoll populations has largely been attributed to their consumption of cane toads.

Intriguing evolutionary adaptations have also occurred in native Australian species to cope with the cane toad. Crows and kites are known to turn cane toads over onto their backs to avoid contact with their poisonous glands, leaving the skin uneaten. ‘Australia’s otters’, known as rakali, use almost surgical precision, making incisions only near the edible organs and thigh muscles, expertly extracting and discarding toxic organs like the gall bladder, leaving in their wake what looks a rogue outdoor dissection class. Rakali also specifically target only the largest toads to get the greatest food reward for their hard work, with 75% of carcasses found in this way belonging in the top 3% of cane-toad size.

But if the cane toads were such a failure, why then were the toads promoted as a success story in Puerto Rico? It could be mostly due to the vast differences in ecosystems between the two locations. Another theory is that the initial Nature article failed to account for external factors that would reduce cane-beetle numbers, unique to the situation in Puerto Rico.

Following the cane toad's introduction, there were several years of uncommonly heavy rainfall, which reduced the survival of cane beetle larvae underground.

In either case, differences between results in Australia and Puerto Rico demonstrate that success in one location does not necessarily predict success elsewhere. The sugar industry failed to heed this lesson multiple times, as it had previously

(initially praised as a success in reducing rats in Jamaican cane fields) later led to a boom in ticks, declines in native species, and the mongoose becoming a prominent rabies carrier.

Similarly, the initial, hailed success of cane toads as a pestcontrol species led to ‘cane-toad fever’ and their introduction and proliferation in different ecosystems all over the Pacific Region, with varying results.

Cane toads have since been named by National Geographic as one of the most damaging invasive species in the world.

Research into control methods such as trapping, release of sterilised males, genetic modification, physical barriers, and training of native species with ‘taste aversion’ is ongoing, but reports by the Australian government conclude that the eradication of the species is unlikely and some of its damage irreversible.

SOMETHING TO DECLARE? | Actively preserving native biodiversity is increasingly important as climate change threatens habitats and the spread of disease becomes easier across the globe. Maintaining the delicate balance of our environment has intrinsic value, as we depend on it for clean air and water, pollination, waste breakdown, food, and, of course, natural pest control. One driver of biodiversity loss that could be curtailed is instances of large corporations and industries, through a desire for ever greater profits, ignoring the potential environmental impacts of their decisions.

Parallels can be drawn between the role of the sugar industry in lobbying for cane-toad introduction in Australia and pesticide companies such as Monsanto-Bayer lobbying for relaxed pesticide regulations worldwide, despite application being linked to declining bee populations. The cane toad example also illustrates how overstated claims, oversimplification of complex processes, and lack of publication of negative findings in major science journals can have far-reaching, unintended consequences.

More than ever, we need further research and legislation to safeguard our natural ecosystems for future generations. Even though we have come far with conservation and research to reverse past damage, you cannot unscramble the egg Monica Killen is a final-year PhD student in clinical neurosciences at Selwyn College. Artwork by Biliana Tchavdarova Todorova.

introduced other species to Puerto Rican cane fields in an attempt to control pests.

Introduction of the small Indian mongoose Lent 2022

Something To Declare

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Hedging Your Bets: Is Single Cell Variability Functionally Important?

Roberta Cacioppo delves into the surprising variation between cells and what this might mean at the population level Since the development of cell theory in the 19th century, the definition of cells still holds up firmly: they are the structural and functional units of life. Not only do cells store, repair, and pass on the molecule of DNA, but they can also activate the genes written in the DNA, expressing them as observable cellular traits. Therefore, if two cells activate the same genes, they acquire the same traits.

Historically, scientists used this principle to group cells into populations, hence the conventional view of cell populations as ensembles of cells that activate the same genes and so share the same features.

However, technological advancements have revealed a much more complex picture.

We now know that individual cells within a population can activate the same genes to different degrees or can even activate different genes. This distribution is referred to as single cell variability and results in cells having slightly (or very) different traits, challenging the traditional idea that cell populations are homogenous. At the heart of these cell-tocell variations lie both regulated and random events involving epigenetic marks, errors in DNA replication or rearrangements of chromosomes, to name a few. Certainly, no two cells can ever be truly identical.

The great scale at which single cell variability can manifest 12

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has therefore led researchers to ask whether it might play a role in regulating the collective behaviour of the cell population.

Indeed, many examples of the functional importance of single cell variations have been discovered. When subjected to a hostile environment, versatile cell populations that activate a diverse set of genes have a better chance of survival than their uniform counterparts, because they display a wider range of features.

Although some cellular traits might decrease the overall fitness of the population, whether or not to carry such diversity is an easy gamble: bet hedging provides the cell population with greater chances of surviving in varied environmental conditions rather than expressing a unique trait specialised for only one environment.

Variation across single cells may also allow a population to give a stratified response to external stimuli. In predator-prey dynamics, if all predators decided to hunt simultaneously, all prey would be eaten at once, causing the predator population to quickly go extinct.

Similarly, homogeneous decision-making of single cells would cause a sudden switch in the population’s behaviour, which could be detrimental: imagine if all of our cells that produce insulin uniformly programmed their death in response to an external signal — our bodies would altogether run out of insulin. Instead, fluctuations in the activation of genes within the cell population allow for fractional decision-making processes to cushion the blow of any Lent 2022

external stimulus.

There are two additional interesting cases of population-level properties emerging from single cell variability. One is termed crowd control, whereby a subset of cells responds uniquely to a perturbation, producing molecules that reprogramme the entire population’s behaviour. The other considers that single cell variability enables the coding and transfer of information.

Since the set of activated genes within a cell is like a barcode, a population that is not made of identical cells carries a higher information content than a homogenous one. Therefore, single cell variation endows a population with higher data capacity.

This is evident in the brain, where extensive cell heterogeneity within populations may increase the complexity of neural circuits, enhancing the brain’s ability to transfer information.

One approach to examining the idea that single cell variability in a given gene is functionally important is to determine whether it is evolutionarily conserved between species, known as the comparative approach. Suppose we measure how much the activation of a particular gene varies across single cells in species A and, after comparing this with the same measurement taken in species B, we note that there is a difference. How do we know that this difference is significant? To address this, one could first assess the degree of cell-to-cell variability of that gene in relation to the degree of variability of other genes within the same species, and only then use this corrected measurement for comparisons among species.

To complicate things more, the use of the comparative approach faces several other significant issues. One problem is that there is no robust model to predict the single cell variability of activation associated with each gene. Such a model would be useful to rectify the variability that one measures experimentally. One further issue is biological: a gene may have conserved high cell-to-cell variability of activation because it may be directly responsible for some of the population-level functions discussed above, or, conversely, it may have conserved low single cell variability because its activation must be tightly regulated. But if so, how can we be sure that a low variability of activation is not functional to population behaviour? We cannot exclude the possibility that population-level properties result from a non-specific degree of activation of random genes, rather than being dependent on the precise level of activation of specific genes. To distinguish between these two possibilities is not at all easy.

would exist regardless of the specific genes whose activation varies across single cells. On the other hand, by suppressing specific genes, one could pinpoint the molecular players whose activation must vary from cell to cell for the population to acquire a given behaviour.

All in all, we now think of individual cells as existing in a population, just as individual organisms exist in a community: each cell’s traits and behaviours contribute to the population’s properties, just as traits and behaviours of different organisms serve community dynamics in an ecosystem. Some speculate that single cell variation may follow a kind of Darwinian mechanism for driving population-level decisions and might therefore offer a platform through which natural selection can occur. Even more broadly, single cell variability could represent a way of integrating environmental cues into the functioning of organisms.

Still, the hypothesis that single cell variability has evolved for certain functions is complementary to the more conservative idea that biological mechanisms evolve to allow function despite variability. Surely, cohesive behaviour of individual cells is important for the existence and survival of cell populations.

At the same time, if the examples above have taught us anything, it is that single cell variability per se is indispensable for a population’s survival. Either way, there is no doubt that understanding the population-level functions that originate from single cell variability will be key to unravelling the complexities of multicellular systems Roberta Cacioppo is a third-year PhD student in molecular biology at Corpus Christi College. Artwork by Sumit Sen.

However, one thing that we can directly test is how deactivating genes in the cell population affects the population’s behaviour. Several methods now exist to achieve this, one of which is using short RNA molecules called small interfering RNAs (siRNAs). These are purposely designed to stop the activation of genes. Importantly, siRNAs can be designed to target genes either specifically or randomly. If a particular cell population’s behaviour is not altered following deactivation of random genes, then that property is gene-independent: it Lent 2022

Hedging Your Bets

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Reinventing Ourselves: What Do Advances in Artificial Intelligence Mean for Truth?

Gladys Poon discusses how our increasing reliance on algorithms affects the world we live in and our perception of it No knowledge remains absolutely true if we wait for long enough. The train is no longer the fastest way to commute, and the quartz watch is no longer the most accurate way to keep time. Throughout our long history, we have had to relearn facts and theories, and this discovery process has been picking up speed — from evolution to the cause of infectious diseases — many scientific theories have been superseded in the last few hundred years. With the advance of artificial intelligence (AI), the dismantling of old knowledge is like the accelerated breaking off of gigantic glaciers at the poles and similarly overwhelming in its sheer scale.

Often, rapid paradigm shifts in our understanding of the world are accompanied by identity crises (remember the social outcry back in the 16th century when we discovered that the earth is not at the centre of the universe?) Algorithms are becoming smart enough to eclipse human intelligence and already show signs of superhuman capabilities in games such as chess and Go. Is this the demise of the dominance of human intelligence? On the other hand, humans see themselves as agents of judgement, decision-making, and action — our narrative of history is a drama underpinned by these keywords, which shape our cognitive identities. Resolving an identity crisis is no easy task. Will we be able to reinvent ourselves?

SPECTATORS | What do you think of as the more defining characteristic of humans — the ability to act or the ability to perceive? Most readers of this article would probably choose the former, thanks to our result-oriented culture, but this question of whether humans are defined by the active life (vita activa) or the contemplative life (vita contemplativa) has been subject to debate for centuries.

Ancient philosophers in many cultures insisted on the superiority of vita contemplativa. Zhuang Chou in China focused on the contemplative nature of human life: his famous paradox in which he dreamt of becoming a butterfly, but pondered whether it was instead the butterfly dreaming of becoming him, was his means of approaching human consciousness. The view that human consciousness begins with contemplation was also shared by the celebrated 17thcentury French philosopher Descartes: ‘I think therefore I am’.

Contemplation is, after all, the domain of philosophers, so it is no wonder that most agree on its superiority, but, as ever, exceptions do exist.

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Karl Marx, for instance, flipped the hierarchy to place vita activa on top of all else, claiming that without labour, humans would cease to be humans. Ironically, this idea is shared by many who are embroiled in the workaholic culture of the modern day, driven by a full-blown capitalist, global economy.

Hannah Arendt purports that vita activa is neither superior nor inferior to its counterpart and needs to be better understood in terms of three concepts: labour, work, and action. With the advance of AI, we will soon be free from repetitive labour, of which the sole aim is to meet our biological necessities, and be outcompeted in areas of work Lent 2022

that produce longer-lasting entities like architecture. Music and arts may seem secure, but it is not impossible to imagine a world where machines write better poems and music: today’s natural language processors are already capable of producing literary works that are difficult to differentiate from those of humans by a layperson’s eye. In ancient Greek culture, action belonged solely to free men in the public realm where they could distinguish themselves through great deeds and great words, whereas subordinated slaves and women were confined to labour and work. Will AI one day take the place of subordinated slaves so that we can all be like the free men of ancient Greece?

AI will most certainly wipe out a great number of jobs in many arenas that presently depend on human labour. Depending on your philosophical and social outlook, it may be considered either unsettling or emancipating to know that the value of any of us is no longer determined by the works we produce. Is it time that we retreat to the spectators’ stand and sit back to enjoy the unfolding of a story that is now no longer ours?

REINVENTING TRUTH | Machines and algorithms not only change the way we interact with the world but also our perception of it. Already, truth is increasingly defined by the top result on a Google search.

Deepfake, a technology that can generate videos of anybody saying anything, makes misinformation ever more indistinguishable from fact.

Reality has always been evasive, and humanity has struggled for thousands of years in pursuit of knowledge. So far, our crowning glories are language and the scientific method. Language ascribes a ‘concreteness’ to abstract, generalised concepts we know as reality by attaching to them small things meaningful only to our individual selves. On the other hand, the scientific method reduces reality to the fewest, simplest premises that all of us can agree upon, and anything that cannot be deduced from therein are not nominally regarded as parts of reality.

It is easy to fall into thinking that because machines are less likely to make mistakes than humans, human endeavours should be relegated to a position of irrelevance. However, the conduction of extraordinary sciences through asking questions beyond the current framework shows that science is inherently a human endeavour and not just the manifestation of objectivity. For example, the choice of p-value thresholds is, to some extent, an arbitrary measure for testing credibility Lent 2022

of scientific claims, dependent on the scientist’s insight.

Take another example: unless there is a meaningful prior, maximum likelihood calculations are not forms of proof, and ‘meaningfulness’ is constructed by the brain mostly through language, not numbers!

REINVENTING OURSELVES | As AI replaces some of our physicians and drivers, new jobs will emerge and disappear more quickly. Humans will have to retrain ourselves constantly as jobs become more volatile, but this is not insurmountable, once we set up the right infrastructure for continuous education. Also, the element of human touch warrants that some jobs should remain human. For instance, we will never completely replace our actors and dancers if we consider art as an expression of the human experience.

More centrally, as we begin to rely more on algorithms than on trusting ourselves to make decisions — for example, Google Maps decides for us the best route to our destination — human judgement is at risk of becoming increasingly irrelevant. This has become the case even in courtrooms. Judges in New York (and other jurisdictions including Wisconsin and California) use a proprietary risk-assessment algorithm called COMPASS to predict how likely a defendant would be to re-offend to inform decisions on jail sentences. Indubitably, algorithms remove the human biases that flaw the judicial system: it has been repeatedly shown that judges are affected by cognitive biases and personal circumstances, which serves as justification for the involvement of AI. However, algorithms are not without biases of their own: they learn from existing information, so inevitably they will perpetuate historical biases. Hence, the best way forward is to combine the use of algorithms with human judgement.

Limiting the power of algorithms is our responsibility. We should test them and fix them if necessary. More importantly, we should always retain the power to veto machine decisions if something looks wrong on the surface.

Machines work with numbers. Therefore, non-numerical entities like justice will always remain in the human remit — that is, until we decide to write an algorithm for its definition.

As the human experience changes (perhaps as we someday move out into space), we will be rewriting our personal and social algorithms as well. We will need to use our imagination and creativity, as we have many times throughout history, to find our new place in the new world Gladys Poon is a final-year PhD student in oncology at Magdalene College. Artwork by Sumit Sen.

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Flexibility or Restriction: Five Ways Fixed-Term Contracts Reduce Diversity Bethan Charles explores the dominance of temporary contacts in academia and what this means for diversity ​​E arly - career researchers in pursuit of an academic career can expect to spend years jumping between temporary roles. While these contracts offer opportunities to explore new science, institutions, and cultures, they also act as a barrier to an untold number of people who cannot afford years of insecurity with little promise of a permanent job at the end. This issue’s FOCUS article dives into the murky waters of fixed-term contracts and asks what impact they have on diversity in scientific research.

THE UNCERTAIN WORLD OF ACADEMIA | As a postdoctoral research associate, I exist in a perpetual state of reflection, striving to answer the question ‘What next?’

It is a situation that will resonate with many early-career researchers, or ECRs, the precariously defined term used to group people within about eight years of completing their PhDs. So, although I am not yet applying, my mornings sometimes include scrolling through job advertisements on LinkedIn, saving or dismissing roles from potential future employers as though they were profiles on Tinder.

One morning, I discovered a post advertising an academic position requesting a PhD in physical science, five additional years of research experience, proven expertise in a vast list of specialised skills, leadership experience, product management experience, a portfolio of topquality publications, and a catalogue of soft skills. And the duration of the job? 10 months. What is most shocking about this short-term role is its normality. Fixed-term — or temporary — contracts are keystones of academia, with approximately 70% of UK researchers in higher education tied to one. These contracts end on a specific date, usually a handful of months or years in the future.

In 2002, the House of Commons Science and Technology Committee published a report examining how 40,000 of the UK’s researchers found themselves employed on fixed-term contracts, some as short as one month. The Committee found ‘widespread dissatisfaction and demoralisation’ among researchers who saw ‘no career structure’ and ‘little hope of obtaining a permanent position’ in their futures.

The report concluded that universities ‘deflected the risk’ of employing researchers longer than the project grants they were associated with onto ECRs themselves. This ‘added to the plight’ of junior researchers.

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Despite the report being older than some of the University of Cambridge’s current undergraduates, many of its findings still ring true today. In the past decade, the number of UK researchers on fixed-term contracts has risen by 12,000. However, individuals and institutions are increasingly highlighting the issues surrounding academia’s reliance on temporary contracts. Indeed, the University and College Union (UCU) is running a national campaign to improve employment stability and continuity amongst ECRs. This campaign contributed to the strike action on working conditions that UCU members voted to support in November 2021.

Universities appear reluctant to update the fixed-term contract system despite simultaneously wanting to create diverse and inclusive communities. However, academia cannot ignore its reliance on fixed-term contracts when addressing the diversity issues which run rife through higher education institutions.

DIVERSITY IN ACADEMIA | Before exploring how fixed-term contracts affect diversity, I should ask the following: what are the diversity issues in academia? A quick Google search reveals a plethora of articles that hint at the scale of the problem. For example, a 2018 report by the Royal Society of Chemistry revealed that only 9% of UK chemistry professors are female, despite women making up 44% of the undergraduate cohort and 39% of PhD students. This mass exodus of female staff in STEM careers is a well known phenomenon and forms part of the so-called ‘leaky pipeline’ — a topic discussed in issue 52 of BlueSci. According to 2020 data from the Higher Education Statistics Agency, out of around 23,000 professors in the UK, 6,300 are women. Of those women, just 35 are black.

In late 2021, the University of Cambridge ran an exhibition titled Phenomenal Women: Portraits of UK Black Female Professors, which highlighted this absurd disparity in the top echelons of academia.

The under-representation of marginalised groups is a significant problem within scientific research, and universities are taking steps to combat this. For example, the Cambridge Equality and Diversity unit offers grants, FOCUS 17

runs events, and fosters networks designed to improve diversity by increasing awareness and helping to amplify the voices of marginalised groups in STEM research.

However, the slow rate of change is worrying. In 2021, the Royal Society published a report examining the diversity observed in applications to their earlycareer fellowship programmes. Although fellowships are not permanent positions, they are often seen as the next step in a postdoctoral researcher’s career. But the Royal Society’s results are troubling. Between 2018 and 2020, applications were not representative of UK postdoctorates. For example, in the call for the Royal Society’s prestigious University Research Fellowships, out of an ‘eligible pool’ of 42%, only 28% of applicants were women. There was also low representation of Asian and multi-ethnic groups, and no applications were put forward by black researchers.

Therefore, marginalised groups are not only underrepresented as recipients of competitive academic fellowships, but they are not applying. Why? As the rest of this article explores, fixed-term contracts contribute to the exclusion of minority groups, exacerbating existing diversity issues in academia.

BENEFITS OF FIXED-TERM CONTRACTS | It would be unfair to dive into the issues temporary contracts cause without first acknowledging their advantages. Fixed-term contracts offer an abundance of opportunities to ECRs, which would be difficult to match in any other profession.

When researching this article, I reached out to current Cambridge-based ECRs who cited ‘freedom to move’ as a major benefit of temporary posts. ECRs enjoy the flexibility to ‘try out different projects and challenges’, ‘build a network in another country’, and experience other cultures and institutions ‘without the need to permanently settle’.

Academia is almost unparalleled in the mobility it grants its employees, and few other professions could lead you to five different countries in as many years. Being a researcher means you are part of a global network, and the opportunities can feel limitless. The temporary nature of roles and access to thriving scientific communities means ECRs can swap topics within or even outside their discipline, so broadening their career prospects and providing the opportunity to discover research they may hold more passion for than their PhD work. This might sound ideal, and for many, it is. However, this freedom comes at a cost.

HOW FIXED-TERM CONTRACTS RESTRICT DIVERSITY

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1) INCREASED FINANCIAL STRAIN | A few years ago, I quit my job at a large multinational firm to start a PhD for ‘my love of science’ because, as I told my baffled friends, I was ‘not in it for the money’. Indeed, after a second master’s degree and a PhD, I earn less than I did as a 22-year-old graduate, although I am far more suited to research and much happier with my day-to-day work.

Besides the discrepancy between qualifications and remuneration, the concrete end date printed on fixedterm contracts serves as a constant reminder that, one day, the money will stop. As the end of an ECR’s contract looms, they must confront their options: line up an extension, win more funding, or find another job. ECRs must meticulously plan these next steps to coincide with their contract’s end date, cutting into the time they can spend on their current project, else endure weeks or months eating into their financial savings.

Many researchers struggle to move up the career ladder despite gargantuan efforts in the lab, publication records longer than Netflix’s lists of home makeover shows, and CVs saturated with accolades. The nature of the academic job market does not guarantee researchers a permanent position after their temporary roles. In fact, just 10% of postdoctoral staff in the UK achieve permanent jobs.

Financial insecurity alienates people who cannot afford to risk periods with little or no pay, including those from low socio-economic backgrounds, those on visas with strict salary requirements, and researchers with families.

As one ECR explains, ‘When it was just me, [changing contracts] was a lot more fun and exciting’, but ‘with a young family, and as the main income earner, the responsibility changes completely. Last-minute extensions [to contracts] are not OK and do not help’.

2) FAMILY PLANNING PRESSURE | It is impossible to make long-term plans whilst on a temporary contract, and ECRs often face a choice between progressing their career or starting a family. While the insecurity of fixedterm contracts has considerable effects on men’s family planning choices, reports consistently highlight that women are disproportionately affected. Perhaps one of the most significant impacts of fixed-term contracts on inclusion and diversity is their role in maintaining the ‘glass ceiling’ — the metaphorical barrier halting the career progression of marginalised groups, especially women.

The average age of a UK PhD graduate is 27. If this graduate — let’s call her Olivia — wants a career in academia, she can expect to be on fixed-term contracts well into her thirties. As most women this age know, society will bombard Olivia with unsolicited opinions on her fertility, despite the possibility of her choosing not to

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have children or wanting to wait. However, if she starts a family at 30 — the average age for a first-time mother in the UK — she will probably be on a temporary contract.

During this time, she faces the possibility of having no right to maternity leave because of the insecure nature of her role. For safety reasons — due to, for example, chemical hazards — she may also have to spend nine months away from the lab she works in, eating into the limited time her contract grants her, with little or no support to complete her experiments. Or she may find herself stuck in the grey area where her contract ends before her due date. Since Olivia faces so many concerns due to the temporary nature of her role, she may prefer to leave academia altogether.

Lack of support for young mothers is one of the many reasons behind the low number of women progressing up academia’s career ladder or choosing not to start the climb in the first place. The 2018 report by the Royal Society of Chemistry investigating women’s retention and progression in the chemical sciences concluded that ‘the dominance of short-term contracts creates unnecessary pressure and uncertainty’. Many researchers the Royal Society of Chemistry interviewed cited fixed-term contracts as the main reason female postdoctoral staff leave academia, helping to account for the conspicuous absence of female chemistry professors.

3) LACK OF SUPPORT FOR PARENTS AND CARERS | If an early-career researcher stays in academia while starting a family, the insecure nature of their contract may lead to problems beyond parental leave.

The term ‘early-career’ covers a vast range of people, funded by a myriad of different organisations with no standard set of rights written into their contracts. This diversity of roles leads to considerable variation in the benefits researchers can access. For example, when I was researching this article, an externally funded ECR I talked with said that not only was she denied maternity leave, but she also did not have access to university childcare or funding to help with costs.

Restricted access to childcare is not uncommon. In 2020, Nature published the results of their first survey of postdoctoral staff, gathering data on over 7,600 researchers from 93 nations. Only half of respondents had access to paid parental leave, and just 14% could then apply for subsidised childcare — this lack of support recalls the first issue I discussed, financial strain.

Childcare is expensive. In the UK, the average cost of a part-time nursery place stands at £7,000 a year. Flexible working may help alleviate these costs, but such benefits are rare in fixed-term contracts. In addition, ECRs must spend a significant amount of time searching and applying for their next role, on top of their current fulltime job. These time and financial pressures can present

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significant challenges for a parent with a partner and insurmountable ones for single parents.

Lack of flexibility also affects carers. The NHS defines a carer as anyone who ‘looks after a family member, partner or friend who needs help because of their illness, frailty, disability, a mental health problem or an addiction and cannot cope without their support’. However, carers may not always ask for direct support because, as the NHS notes, a person takes ‘an average of two years to acknowledge their role as a carer’ — a length of time comparable to a typical fixed-term contract. Little data exists on the opinions and quality of support available to carers working in research. Still, universities are running initiatives to help, for example, the Supporting Parents and Carers @ Cambridge — or SPACE — network.

SPACE offers a range of initiatives designed to support parents and carers in maintaining a positive work-life balance.

While UK research institutions acknowledge the need to help parents and carers, ECRs on temporary contracts still face the question ‘What next?’ What support is there once the end date of their contract passes? What happens if the researcher’s only option is a role in a different institution or country? Then, the mobility that can be a desirable benefit to fixed-term contracts becomes a major obstacle: moving means relocating a family or dependents.

4) VULNERABILITY TO BULLYING, HARASSMENT, AND DISCRIMINATION | In recent years, bullying within academia has made major news headlines. In 2018, an investigation by The Guardian revealed 300 academics at UK universities faced accusations of bullying between 2013 and 2018.

However, this only hints at the true scale of the problem.

A recent study conducted by Moss and Mahmoudi investigating bullying in STEM found an incredible 84% of researchers they surveyed had first-hand experience of bullying, but less than 30% had reported it. Why? Claims of bullying and harassment are often downplayed or ignored by host institutions, contributing to victims being hesitant to report issues. In addition, ECRs can also face severe implications for their career if they speak out. Moss and Mahmoudi noted that ‘perpetrators were more likely [to be] from the highestranked institutions, and they were most likely PIs’. PIs — or principal investigators — are the senior academics responsible for a research group and who often hold the grants that fund early-career researchers.

The nature of fixed-term contracts means ECRs depend on their PIs for career progression. For example, an ECR’s PI is often the only suitable reference for job applications.

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This leaves researchers vulnerable to the opinions and behaviours of one person. The Academic Parity Movement — a non-profit organisation aiming to protect students and ECRs from bullying — identifies several examples of PIs abusing their positions to influence an ECR’s career negatively. Examples include giving an unfair reference, cancelling job offers, extending contracts unnecessarily, and offering no support when an ECR expresses an interest in moving on. The over-reliance of career progression on PIs, coupled with the vast power imbalance between senior and early-career academics, puts the careers of those vulnerable to bullying, harassment, and discrimination at serious risk.

Nature’s 2020 survey of postdoctoral staff revealed that 40% of respondents had experienced gender discrimination, of which 90% were women. Female staff are subjected to intolerable levels of bullying and harassment, often manifesting so subtly that incidents are dismissed or go unnoticed by colleagues. The problem is so severe that the Royal Society of Chemistry identifies a ‘culture of secrecy and lack of accountability around harassment’ as a key barrier to women’s progression in chemical science.

A quarter of the postdoctoral researchers surveyed by Nature in 2020 had experienced racial discrimination, and an increasing number of BAME researchers are opening up about their experience of racism in academia.

They cite problems such as being subjected to racist comments, being side-lined by senior colleagues and having to defend their abilities as scientists when others see their appointment as reaching a ‘diversity quota’.

Discrimination against the LGBTQ+ community is also a serious problem. A joint report run by the Institute of Physics, the Royal Astronomical Society, and the Royal Society of Chemistry in 2019 found that 28% of LGBTQ+ researchers had ‘considered leaving their workplace’ because of discrimination and intolerance within their institutions. For LGBTQ+ researchers, the mobile and international culture within academia — supported by the prevalence of temporary contracts — increased anxiety because of the prospect of ‘interacting with cultures that were not yet inclusive of LGBT+ people’.

While issues of bullying, discrimination and harassment against marginalised groups are not unique to universities, higher education’s reliance on fixedterm contracts leave ECRs more vulnerable to bullying than employees in many other workplaces. When this compounds with the discrimination and harassment marginalised groups face, it is no wonder many leave scientific research in favour of more stable jobs, where they are less reliant on one person for career progression.

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5) DISENCHANTMENT WITH ACADEMIA | An extensive study conducted by the UCU in 2019 found that 81% of researchers considered short-term contracts to have negatively affected their own research. This alludes to the vicious cycle in which ECRs can become trapped, as time pressure created by fixed-term contracts limits research activity. To improve their output and thus their chance at landing a permanent position, ECRs take on many extracurricular roles on top of applying for short-term grants.

However, grants and fellowships can have thousands of applicants for only a handful of places. Therefore, most applications an ECR makes are likely to be unsuccessful.

Hence, an ECR is likely to spend a tremendous amount of time applying for short-term funds to extend their short-term contracts all to continue their research, which should be their full-time job. This begs the question: why bother? Why not leave for a permanent position elsewhere? Many people do. Universities are allowing talent to slip away.

In almost every industry, organisations employ separate teams to sell, design, implement, and communicate work.

Each stage requires a very different skillset, so having specialists is a sensible decision. But academia expects researchers to excel at selling, designing, implementing, and communicating their work, alongside being worldclass teachers. Unachievable expectations lead to fantastic researchers having no time for science because they must concentrate on other tasks, brilliant teachers with little energy left for their students, and extraordinary science communicators who feel their work is side-lined. These people often choose to leave for permanent roles in the areas they are passionate about. Therefore, universities are missing out on an incredibly diverse range of talent by continuing to fixate on an outdated opinion that professors must be polymaths.

LOOKING TO THE FUTURE | A survey conducted by the UCU in 2019 revealed that 97% of respondents on fixed-term contracts in higher education would prefer a permanent position. Over the past few years, ECRs have become increasingly outspoken against their uncertain employment status, and support for campaigns pushing for change, such as the UCU’s ‘stamp out casual contracts’, has grown. And universities are listening.

In 2020, the Russell Group — an association of twenty-four research-intensive UK universities, including Cambridge — commented on academic working practices. In the report, the universities admitted the ‘over-reliance on some forms of employment models and associated contractual arrangements may not serve the best interests of staff, for example, in supporting their development and career aspirations. Ultimately, they may

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also affect the wider academic mission and the staff and student experience at university’.

Although the vast majority of ECR contracts continue to be temporary, positive change appears to be underway.

An increasing number of permanent teaching and research development roles within universities seem to scatter my job searches on LinkedIn. However, change is a slow beast, and academia’s reliance on fixed-term contracts will probably be an issue for many more ECR cohorts. Therefore, universities will continue to lose the researchers they invested so much time and money in training.

without being inclusive, and we cannot improve inclusivity without addressing fixed-term contracts

Bethan Charles is a postdoctoral researcher in the Depar tment of Materials Science and Metallurgy. Ar twork by Anna Germon.

Leaving academia is often seen as taboo for early-career researchers, but it is the correct decision for many. Researchers should not feel obliged to continue pursuing an academic career if the negatives outweigh the positives. Losing talent is a failure of the system, not the person. An academic career is a journey of manageable steps up a well trodden path for some.

For others, it is a game of snakes and ladders. As with most professions, the people who reach the top are likely those for whom the journey was smoothest.

Ultimately, the power to demolish the barriers driving the diversity issues plaguing academia lies with universities and funders. For real change to happen, more must be done than simply issuing statements supporting diversity, holding seminars, or offering awarenessraising online equality courses. One concrete action would be examining academia’s over-reliance on temporary contracts and implementing alternative working practices. We cannot form a diverse research community

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Pavilion: Where Art Meets Artificial Intelligence Pauline Kerekes talks to Lukas Noehrer at the Alan Turing Institute

O ne of the most fascinating aspects of the growing field of Artificial Intelligence (AI) is trying to get interpretable meaning from its output. A novel approach to this question is being developed in the AI and Arts group at the Alan Turing Institute (https://www.turing. ac.uk/research/interest-groups/ai-arts). With around 70 members, encompassing multiple stakeholders drawn from academia to cultural heritage institutions to the creative industries to policy makers, the AI and Arts group delivers excellence in research and provides broad means of engagement through their website, webinars, publications, events, and conferences. BlueSci met with Lukas Noehrer, one of the group’s organisers, to gather insights on this innovative and multidisciplinary research project.

BlueSci: Could you tell us who you are and what your role is in the group?

Lukas Noehrer: I’m a PhD researcher and research assistant at the University of Manchester. The Arts and AI group was formed in 2019 as part of the Turing Institute’s so-called interest groups. I joined the group as a representative for Manchester, and I recently became one of the group organisers.

BS: You use algorithms to interact with art material.

Could you tell us how machine learning works?

LN: We use different methods. We are a very sciencedriven group, but we also draw a lot of input from arts practices and the creative industries. Being aware of the interplay between these various research fields is useful in helping us answer each other's questions. We use a very broad set of machine learning (ML) algorithms due to the variety of applications we are working with: these range from supervised, semi-supervised, and unsupervised models to deep learning approaches. ML is a method of teaching computers to learn from data, typically by finding patterns or distinct groupings — something that would be difficult for a human to do by hand. There are a variety of approaches used in ML, but they broadly fall into one of two categories: supervised and unsupervised. In supervised learning, labelled datasets — that is, datasets where you know the outcome, e.g., house prices — are used to teach the computer to classify or predict the outcomes accurately.

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Whereas, in unsupervised learning, you do not know the outcome, so you teach the computer to identify groups (otherwise known as clustering) in the dataset. ML has found applications across a wide range of sections and in everyday life, from healthcare to suggesting movies.

BS: Your use of machine learning to work with arts is multifaceted, and one of the goals is directed towards cultural heritage. Could you give us an example of work you develop in this field?

LN: Yes. For example, in the group, we work with semantic image segmentation to get a systematic observation of castle walls to show how they change over time in terms of vegetation. Image segmentation in this case allows us to define what is a window, what is the wall, or other objects that could be present on the wall, such as vegetation, to see how they change over time.

This is definitely very useful in supporting conservation and restoration of those castles, but it also saves time and resources compared to traditional methods of observation.

BS: One important notion in machine learning is the concept of explainability. Could you define this term and tell us to what extent the arts help in achieving it?

LN: Explainability in AI is the process of making sense of the machine’s output from a human perspective. The artistic practice gives different methods and tools to investigate datasets and human life. It gives a broader view of how things work. For instance, museum collection managers or curators, who have been working with the art data for years on a day-by-day basis, bring critical insights to interpret post hoc why certain algorithms work in the way they do. Explainability is also intersecting with ethics, which is a huge topic and issue in the field. It’s really important for people who work in the AI world to always question the data they are using — this is what we do in the group. For instance, in museum collections, the datasets have been accumulated through centuries. There have been bias issues due to, for example, their colonial past or the misrepresentation of gender. A good example are collections that were established by a primarily white bourgeoisie, who mainly collected white male artists.

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BS: Another of your group’s projects is in the use of AI to support, enhance, simulate, or replicate creativity. How would you define machine creativity?

LN: Machine creativity is a very narrow-minded understanding of creativity. ‘Autonomous creator’

doesn’t mean we put the machine at the level of the artist. Machines are autonomous in the sense that their outputs are not completely human-controlled, meaning that all the instructions to produce a result are not all hard-coded or pre-determined. These are deep learning approaches where we attribute some kind of creativity to the machine when we can’t completely explain what the output will be, or if a very specific algorithm performs very well in executing a human-like task, e.g., composing a piece of music or painting an image in a certain style. A trending example would be the applications of Generative Adversarial Networks (GANs) to multimedia data, a ML approach that tries to recreate an output so similar to its original training data that humans can’t tell if it’s an original or machine-made.

BS: Could you give an example of a partnership between an artist and a machine to produce a creative outcome?

LN: An interesting example would be a digital art exhibition that took place at the Edinburgh International Festival and is called the New Real (https://efi.ed.ac.uk/ events/the-new-real/).

BS: What is the most long-term goal of the AI and Arts group?

LN: The whole Turing Institute is going through a re-visioning, re-missioning phase and received recently a budget of £10 million from the Engineering and Physical Sciences Research Council, on behalf of UKRI, to support this project. The goal of our group, within this scheme, is to develop a collaborative and fruitful community that respects all various disciplines and fields that equally feed into the AI and Arts remit Pauline Kerekes is a postdoctoral researcher in the Department of Physiology, Development and Neuroscience. Lukas Noehrer is a third-year PhD student in museology and computer science at the University of Manchester. Artwork by Scott Allan Orr.

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How to Build a Quantum Computer Xavior Wang explores what makes and breaks a quantum computer Quantum computers are notorious for being prohibitively difficult to wrap our heads around. ‘If you think you understand quantum mechanics, you don't understand quantum mechanics’, said Richard Feynman, a brilliant theoretical physicist and eloquent communicator. Therefore, to understand them is impossible, and we are not going to try. But although we cannot truly envisage wavefunctions and quantum spins, an intuitive understanding of quantum computation can still be achieved without having to clamber through the horrible maths.

Let us look at how classical computers work and build our understanding of the quantum version from there.

RETURN TO THE CLASSICS | So, what is inside your run-of-the-mill computer? The digital theatrics have two key components: information (the actors) and instructions (the script). In the computer’s memory, information is stored as bits — an endless stream of 0s and 1s. The infinite monkey theorem states that given enough time, a monkey smashing at a typewriter could produce the complete works of William Shakespeare. Likewise, a sufficiently long string of bits can represent anything between ‘this pixel is blue’, ‘the time is 4am’, and ‘the answer is 42’. The intricate drama between bits is orchestrated by the instructions. With every click of the mouse and tap on the keyboard, you ask the computer to process a set of instructions on a sequence of bits. These instructions come in the form of logic gates. For instance, the NOT gate takes a single bit and flips it, while the OR gate takes two bits and outputs 0 only when both inputs are 0.

These bits and gates are not just abstract entities floating in the computer’s digital consciousness. There are many ways bits can be represented. Generally, the 0s and 1s are encoded by tiny magnets that point one way for 0 and the other for 1, or by the absence or presence of electrical charges in little units.

The gates take the form of transistors — tiny circuits that take in input bits as little currents of electricity, control their flow, and release currents that represent output bits.

THE QUANTUM VARIANT | Fundamentally, quantum computers differ from classical ones in the way they store and process information — not as bits but as qubits. Think of these as indecisive bits, like little magnets spinning round and round, only landing on a 0 or 1 when you force them to stop.

Of course, real qubits are not spinning magnets. How best to realise these indecisive bits is still an area of ongoing research.

Essentially, we need tiny objects with two possible states, and the likelihood of them being in one state over another is determined by the laws of quantum mechanics.

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Naturally, a quantum computer is not a computer if we cannot implement logic gates as we do for classical computers.

Instead of transistors, each variant of qubits demands a unique toolbox of physical processes to perform the necessary operations. Take a primitive example of a qubit — an electron in a hydrogen atom either in the low-energy ground state (0) or high-energy excited state (1). The aforementioned OR gate can be implemented by ‘connecting’ two input electrons to an output, and, if either or both inputs are excited by a photon (10, 01, or 11), then at least one of them can pass the energy and excite the output (1). In other words, only when none of the input is excited (00) will we get a non-excited output (0).

Returning to the idea of ‘indecisiveness’, if we then ‘connect’ one excited input to two outputs, then we know for sure that either of the outputs will be 1 and the other will be 0, but the electrons are undecided about which is which, and there is no way to tell them apart until you measure one of them. This is what physicists mean when they say, ‘qubits can exist in a superposition of states, which collapses when measured’.

PEAKS AND TROUGHS | In sum, qubits can be manipulated with logic gates analogous to their classical counterparts, but their quantum behaviours also enable proprietary gates exclusive to quantum objects. Our previous one input-two output setup illustrates two such properties: superposition (the output electrons are in both the ground and excited state until measured) and entanglement (the state of one output atom implies the state of the other). Herein lies the strength of quantum computers. In terms of computability, any problem that a classical computer can solve, a quantum version can do likewise, and the reverse is also true. However, in terms of complexity, quantum computers can reinterpret and simplify certain problems with quantum logic gates to solve them faster, sometimes exponentially so.

There is a caveat here: quantum computers are not substitutes for classical computers. The quantum infrastructure, while promising, has its own host of problems. For one, while nature is immensely powerful in that she orchestrates quantum interactions of unimaginable complexity, she also communicates the result cryptically — a waveform of dense information disperses when observed, leaving behind a single hint — 0 or 1. Our best attempt to grasp the underlying truth is to query nature again and again, reconstructing the message one letter at a time. Consequently, quantum results are always statistical. Not only that, but to manipulate qubits into doing our bidding is like moving a balloon using hands of needles through lava. Qubits only work as qubits if they stay quantum, but any interaction with stray molecules or radiation reduces them to normal bits in a process called decoherence.

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Another natural enemy of quantum computers is noise. Initialising the states of qubits, applying quantum operations, and even taking measurements can, and will, introduce errors. When you add all this up, you have a calculator that writes ‘6’ when you press ‘9’, and reads ‘4’ when it means ‘20’. These constraints deny the possibility of a quantum monopoly. In fact, a quantum-classical hybrid infrastructure looks to be leading the impending computational succession.

A QUANTUM LEAP | Between an infallible promise and inevitable demise, where is the quantum revolution heading?

Whether quantum supremacy — the phenomenon wherein quantum computers outspeed classical computers in a particular calculation — has been achieved is still up for debate, and while tech giants worldwide have their hopes and money in the quantum future, quantum computers are still a work-in-progress. On the theoretical front, idealists are formulating quantum algorithms that assume perfect, large-scale quantum networks, swearing to leave classical computers in the dust when they eventually have the hardware to realise the codes. Concurrently, development is underway for noisy intermediate-scale quantum (NISQ) algorithms and error correction techniques that make do with the dozens of noisy qubits we currently have to produce some interesting results.

In experimental labs under impenetrable radiation shields, within cryogenic chambers and between crisscrossing lasers, the search for the holy grail of sturdy but obedient qubits continues.

Although the quantum revolution may not be just around the corner, it sure is coming. Just as classical computers evolved from vacuum tubes and magnetic drums filling entire rooms in the 1940s to the coin-sized microelectronics today, we can expect the same for quantum computers. The vacuum tubes and magnetic drums of quantum computers today will eventually give way to supercomputers that can simulate complex systems, develop life-saving drugs, rewire financial markets, transform cybersecurity, and advance artificial intelligence, all within our lifetime

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Xavior Wang is a second-year undergraduate at St Edmund’s College studying Natural Sciences. Artwork by Josh Langfield.

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The Dating Game: What Role Does the Major Histocompatibility Complex Play In Sexual Compatibility?

How do we choose our perfect partner? Clodagh Bottomley suggests our DNA has a greater role to play than we might think It is a scientific cliché that humans share 99.9% of our DNA with each other, making us remarkably similar. Yet, despite this apparent homogeneity, even 0.1% difference confers a huge degree of variation, largely centred around the Major Histocompatibility Complex (MHC). This region of the genome encodes around 200 genes implicated in many functions which primarily involve immunity, but also influence the brain, gut, and other organs. In fact, the MHC may even bias whom we are attracted to and who is attracted to us.

The MHC is a section, or locus, of our DNA encoding cellsurface proteins called MHC molecules. These are expressed on nearly all cells and present protein fragments, or peptides, to the immune system to help identify pathogens. The MHC locus is both highly polygenic, meaning it includes many genes, and highly polymorphic, meaning each gene has many alleles.

Individuals can be grouped by their particular combination of MHC alleles, known as their MHC haplotype. Importantly, MHC genes are expressed codominantly, so if chromosomes with different haplotypes are inherited from each parent, children will express both haplotypes and have a wider range of MHC molecules. This extends the repertoire of peptides that can be presented to immune cells, leaving us better equipped, both individually and as a population, to survive disease.

In this context, the importance of maintaining this variation is clear. Firstly, progeny of parents with dissimilar MHC loci will have an increased range of peptides to prime immune cells so the body is better prepared to attack pathogens and resist attacking itself. Secondly, similar MHC haplotypes may indicate familial relation, so choosing a partner with a dissimilar haplotype, a process known as MHC disassortative mating, helps to prevent inbreeding. For these reasons, disassortative mating is expected to improve species survival.

Given this predicted evolutionary benefit, scientists wondered whether MHC haplotypes contribute to mateselection in practice. To investigate this, Kunio Yamazaki and colleagues observed the mating choices of caged inbred mice.

They isolated the effect of MHC variation by using mice strains with different MHC haplotypes against an otherwise indistinguishable genetic background. When a male mouse was presented with two females, MHC genes influenced mate choice. Similar results were seen for stickleback fish, showing 26 The Dating Game

that at least for non-human animals, the MHC has a definite role to play in partner selection.

How can these MHC differences be detected? One muchresearched theory is by smell. Olfactory stimulation is a well characterised method of sexual attraction, the archetypal example being sex pheromones. MHC or bound peptides could act in a similar way. Several theories have been proposed to explain the effect of MHC on body odour, which tend to centre around volatile MHC-derived or MHC-bound molecules, or, more indirectly, around MHC genes influencing the ‘friendly bacteria’ in our gut. Perhaps a likely explanation is that MHC molecules restrict the available pool of MHCbinding peptides, which are then degraded and made volatile by our gut bacteria to produce a scent. This olfactory mediation is affected by both partners, meaning that odours may not be universally attractive — instead, it may be that individuals are attracted to particular smells given off by individuals with dissimilar MHC genes.

Several years after their initial experiment, Yamakazi and colleagues conducted follow-up experiments demonstrating that mice can differentiate the odours of mice differing only at MHC loci. This ability is conserved between species: mice and rats are able to distinguish between urine from humans with different MHC genes, possibly through volatile molecules.

HUMAN PHEROMONES? | However, whereas many mammals rely heavily on smell, humans prioritise sight and sound. Additionally, human mate selection includes more factors (or so we would like to think). The next step, therefore, was finding evidence for olfactory-mediated MHCdisassortative mating in humans.

One way of investigating this is analysis of MHC haplotypes in isolated populations. Christopher Ober and his team studied mate choice in Hutterite populations — colonies near the USA-Canada border isolated by religious beliefs. To find partners, adolescents travel to other Hutterite colonies, resulting in repeated patterns of marriages and higher levels of homozygosity in Hutterite genomes. Despite this, MHC haplotypes of Hutterite spouses are more different than would be expected by chance, and their progeny have more heterogeneous MHC loci than the rest of their genomes. This Lent 2022

indicates a preference for MHC-dissimilar partners, confirming the results from mice. Furthermore, Ober found that foetal loss increased significantly when parents had similar MHC haplotypes. Whilst he could not conclude that MHC similarity caused this (rather than linked genes, for example), MHC may be implicated in the role of immune cells in distinguishing foetal cells as ‘self’ rather than invasive. This is supported by further research showing this bias is solely dependent on maternal, rather than paternal, MHC genes. Put simply, humans are attracted to partners with MHC genes different from their mothers. (Take that, Freud!)

Through this analysis, Ober showed a tendency towards MHC-disassortative mating in humans, but it was Claus

relative contribution of MHC haplotypes in partner selection in 833 European and Middle Eastern couples. Across Northern Europe, spouses were more MHC-dissimilar than random pairs of individuals, and this pattern of dissimilarity was exceptional compared to the rest of the genome. These results were significant in terms of reliability, but the effect was small, suggesting that MHC has a minor but definite contribution to mate-selection. Interestingly, this trend was not as strong in the Middle East, and in Israel there was even evidence for MHC-assortative mating. This could be explained by common marriages between cousins and social homogeneity.

Additionally, the similarities between MHC genes were not significantly stronger than would be seen with totally random mating, supporting this hypothesis. These observations indicate

Wedekind who conducted a now-fabled experiment to assess smell-dependence. Wedekind instructed 44 males and 49 females to prime their sense of smell using nasal spray for 14 days and, amusingly, to read Perfume by Patrick Süskind.

Following this, the men wore the same T-shirts for two nights and abstained from activities that might change their scent, including sex, smoking, or drinking. The women then ranked the T-shirts’ attractiveness. Wedekind found that women found the smell of partners with dissimilar MHCs more attractive.

This demonstrated that MHC preference aims to maximise progeny heterozygosity rather than favouring specific alleles or MHC combinations.

that, whilst the MHC may play a role in sexual decisions, contextual factors can supersede this.

Since these experiments, access to genomic data has increased massively, allowing large-scale analysis of MHC variation.

A 2019 study published by the Royal Society analysed the

Clodagh Bottomley is a second-year undergraduate at Trinity College studying Natural Sciences. Artwork by Biliana Tchavdarova Todorova.

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So how do all of these findings affect how we will find our match? Already, websites such as genepartner.com invite users to take a DNA test and have their MHC analysed. Users are then matched with someone who has ‘compatible’, i.e., dissimilar, MHC genes. It is possible that in the future, catfishes on Tinder may soon be manipulating their MHC sequencing results instead of profile pictures, but, for now, it is hard to imagine preferring a date who reeks of a repeatedly worn T-shirt over the cool, refreshing scent of deodorant

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Eco-Mining for the Future:The Changing Face of Lithium Extraction Matthew Morris discusses the need to make lithium extraction greener and how we are bringing this closer to home in more ways than one Our world is undergoing an energy transition. Fossil fuels are being phased out as renewable energy paves the way to net zero. To drive this change, there is a rapidly increasing global demand for the materials of the future. Lithium is one of these materials, being a key component in Li-ion batteries — a crucial part of electric cars, alongside other commercial battery systems. With demand for these batteries increasing by the day, the need for lithium is expected to increase by over 300% by 2030. However, despite the central role of lithium in green technology, traditional lithium extraction is often damaging to our natural environment.

Australia is currently the world’s largest lithium producer, accounting for over half of the global supply. Here, lithium is mostly mined via hard-rock methods, where it is extracted primarily from a mineral called spodumene. Although this method is efficient for extracting lithium, it comes with many downsides. For example, the opencast mines have a large physical impact on the landscape and are associated with high carbon footprints due to the energy required to extract the rock and process the minerals.

Chile, the world’s second largest producer, extracts lithium through a very different process. Due to the high solubility of lithium, it is often found dissolved in subsurface fluids.

These fluids are circulating in underground reservoirs beneath Chile, and miners pump this water to the surface where it evaporates under the harsh Chilean sun in artificial evaporation ponds. Unfortunately, this method is also problematic.

Chile is a relatively dry country and, for the process to remain sustainable, the underground reservoirs must be recharged by rainfall. However, extraction rates are already outpacing recharge rates. This is having a serious impact on local communities, who are deeply opposed to new lithium extraction projects due to the relatively unknown future impact on their natural environment and drinking water. In addition, the evaporation ponds require vast expanses of land and, like hard-rock methods, have a large physical impact on the landscape, being easily visible from space.

Alongside the environmental issues associated with extraction, the global distribution of lithium reserves also causes problems. The US, EU, and UK are big players in the energy transition but lack the domestic lithium production to develop significant battery supply chains. Since shipping these raw materials across the world has a large environmental impact, 28

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a local source would be strongly preferred; however, typical lithium reserves in Europe are small and often very low-grade.

This has historically prevented companies from developing them. Nowadays, the ever-increasing global demand, alongside more sophisticated extraction techniques, has brought these lower-grade deposits into the economic spotlight. The Jadar Valley in Serbia and Cinovec project in the Czech Republic are two sites currently being explored in Continental Europe. Here in the UK, the focus is on Cornwall.

Why Cornwall? The regional geology is distinct from the rest of the UK due to a large body of granite, called the Cornubian batholith, lying beneath much of the South West peninsula.

This stretches from the Isles of Scilly in the west to Dartmoor in the east and is responsible for Cornwall’s rich mining history.

Copper and tin deposits associated with the granite have been exploited for millennia. Of greater interest today, however, is that areas of this granite, particularly around the St Austell area, contain certain lithium-rich minerals. These minerals are micas (a category of mineral), specifically zinnwaldite and lepidolite.

Although the Cornish granite is considered low-grade for lithium on the global scale, interest is growing. Currently, there are a number of companies attempting to extract the lithium-rich micas from the granite and commercially produce lithium. Trial projects are currently mining small volumes of granite to test both whether this is feasible and sustainable, with the redevelopment of brownfield sites and the use of renewable energy in the extraction process. This has caught the attention of many investors as well as the UK Government.

The Government is understandably keen to develop a domestic source of lithium and has funded a range of endeavours, such as Li4UK. This feasibility study involves the company Cornish Lithium and the Natural History Museum, and aims to secure a domestic lithium supply chain for the UK. However, can lithium mining in Cornwall be truly sustainable enough to be labelled ‘eco’? And what is ‘ecomining’ anyway? Traditionally, mining has been viewed in a negative light; stripping the planet of resources, leaving unsightly scars on the landscape, and emitting huge volumes of greenhouse gases into the atmosphere. Even though minerals are essential for society, the methods used to extract them have often caused tension between mining companies, environmentalists, and the wider public. However, significant technological advancements are now providing new, near Lent 2022

carbon-neutral methods of extraction.

Alongside the traditional hard-rock extraction method, Cornish Lithium are trialling a new technique known as direct lithium extraction, or DLE. In 1864, during previous mining operations, it was noted that lithium-enriched geothermal waters were circulating deep below Cornwall. Cornish Lithium began drilling operations in 2019 and have managed to pump this water successfully to the surface and extract the lithium without the need for huge evaporation ponds. This constitutes a significant improvement in the environmental footprint of mining operations. Cornwall is not, however, the only place

where this novel technique is being tested. For locations where significantly lithium-enriched brines are circulating, DLE provides an effective, green method for lithium extraction.

Trials are taking place across the world, with test-phase extraction plants being built even in countries without a significant history of lithium mining, such as the US and Japan. DLE is also being trialled in Chile, in an attempt to find an alternative to the problematic evaporation ponds.

Many of the lithium-enriched brines also have the potential for use in geothermal energy. Fluids extracted from shallow depths of around 1 km are not hot enough for commercial geothermal electricity production, but the heat can still be used to help power the extraction of the lithium itself. Meanwhile, deep fluids from over 5 km below the surface can be hot enough for use in full-scale geothermal energy projects, with the electricity produced helping to make the lithium extraction process an overall net-zero venture.

If this new method proves effective, it could help to decarbonise the lithium extraction process, eliminate the environmental impact of evaporation ponds, and allow the commercial production of lithium in areas where extraction was previously uneconomical. This last point is particularly important. Not only does this allow the creation of large-scale domestic battery production lines, but it significantly reduces the carbon footprint of shipping the raw materials across the globe. Lithium extraction directly from geothermal waters is set to revolutionise the lithium extraction industry and help to meet the global demand necessary for the energy transition Matthew Morris is a MASt student in earth sciences at Queens’ College. Artwork by Leonora Martínez Núñez.

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Seeds of Change: A Diverse History of Agricultural Practices in the UK Tim Birkle delves into the history of crop rotations in the UK, modern farming practices, and the role of collective action in allowing important changes to take root The UK’s industrialised farming sector produces a little over 60% of our food with just 1.5% of the working population. A key characteristic of this system is a reliance on intensive monocropping, whereby the same highly profitable, high-yield crop is grown on the same land year after year.

However, the so-called Green Revolution of the 1960-70s, culminating in these practices today, was a decisive shift away from sustainability after a millennia-old evolution of crop rotations in the UK. To tackle today’s threats of ecological degradation, we now need to appreciate these sustainable farming practices of old once more.

NEW GROWTH | The first domestication of crops originated from the Neolithic and Bronze Ages, approximately 6,000 years ago. However, although certainly adopted by countless societies and indigenous peoples already, the systematic application of crop rotation practices in the UK only appeared two millennia ago with Roman society. This prescribed a three-field crop rotation system: one fallow year during which livestock was to be secured overnight, a winter sowing year of wheat or rye corn, and finally a summer crop of oat or barley. The growth of varied species, the fallow recovery year, and livestock returning nutrients to the land together provided maintenance of soil health and pest control.

These attributes meant that it endured far beyond the Roman Empire, and, despite its simplicity, this system is still practised in parts of the UK today.

However, shifting socio-political views would eventually alter these long-held farming regimes. From the early 17th century, Enclosure Acts redistributed land ownership and weakened tenant farmers’ rights. This included limiting the movement of livestock onto fallow land, destabilising a critical pillar of the three-field system. Positively, however, bolstered profit incentives led to reclamation of unused land and the development of innovative methods such as the Norfolk fourcourse rotation in the 18th century, underpinning the so-called British Agricultural Revolution. This latter improvement to crop rotations was massively successful. A clover ley year was typically used to restore soil nitrogen while also allowing livestock to graze, which strengthened soil fertility and sustainability.

At this point, an exciting era of experimentation in crop variety and rotation design began. Some rotation practices entailed cycles spanning anywhere from five to eight years, 30

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with the growing appreciation of the benefits that certain crop types afford soil health in the long run. For example, root vegetable crops allow efficient weeding of the fields at the same time as production of an energy-rich food. Certain crops allow simultaneous grazing of livestock and thus increased provision of natural fertiliser to arable land. Overall, the returns in productivity were significant and helped fuel a sharp increase in the UK population during this time.

Despite its strengthening up to the 1900s, industrialisation and globalisation nonetheless began to threaten UK agriculture.

The advent of refrigeration allowed for lengthened supply chains, and this, in combination with increased wider European productivity, would lead to an increase in imported competition. Along with the acute pressures of the World Wars, the long-term prospects for our food supply system were uncertain.

However, these conflicts also emphasised the importance of selfsufficiency. In response, the modern era of agriculture began to take shape.

This Green Revolution of the 60s and 70s fuelled an impressive recovery from WWII and led us directly to where we stand today — for better or for worse.

FORGETTING OUR ROOTS | Most crucial to this fresh phase of UK agriculture was the new availability of cheap artificial fertilisers and pesticides that replaced the need for natural soil recovery through crop rotations. In an effort to prevent food shortages reminiscent of WWII, investment into new technologies and mass farming techniques of monocropping quickly soared.

Old practices of crop rotation were soon a distant memory. Global trade pressures further incentivised regional specialisation in production to achieve economies of scale and outgrow competition.

Beyond rapid growth, a recent Lent 2022

research paper by Dr George Cusworth and colleagues at the University of Oxford describes how this revolution became ‘locked-in’: the aggregated social, political, and economic factors of the time disadvantaged other farming regimes in a self-reinforcing manner. For example, popular new crop strains bred for modern monocropped fields and cheapening requisite materials only made the industry more profitable. This further engrained the new methods with little thought given to the long-term consequences.

The effects are only now being fully realised, as reported recently by the UK Government and the Intergovernmental Panel on Climate Change. Indeed, Cusworth and colleagues identify four primary consequences: biodiversity loss, soil degradation, greenhouse gases, and water nitrification. In 2017, then environment secretary Michael Gove reported that the UK is around 40 years away from ‘the fundamental eradication of soil fertility’, largely a result of taking so much from the land while giving nothing but damaging chemicals in return.

A NEW LEAF | Could huge system change happen once again? On a practical level, our knowledge of the past combined with modern-day scientific research means we understand the principles underlying a sustainable food production system better than before. However, as for much of modern life, the challenges we face are more political than

technological. We understand the benefits that diversity in our soils brings to our environment, but only by truly valuing this both in thought and practice will we move forward.

In fact, social, political, and environmental pressures are slowly being felt. In their recent paper, Cusworth carries out interviews across the farming sector in an attempt to document this and in doing so to exemplify how we can collectively and individually advocate progress. They propose three key factors shaping our current agricultural landscape: government policy and subsidies; research and appreciation of the impacts of different practices; and consumer demand. For example, the need for modern regulations to fill the space left by Brexit has encouraged the introduction of new Environmental Land Management Schemes currently being trialled. Interviewed farmers were enthusiastic about such schemes potentially allowing more sustainable yet still profitable farming. They further expounded the benefits of crop rotations and increased legume crop inclusion in particular. UK consumer demand for plant-based products is also skyrocketing, growing by 40% in 2019 alone. With this, the viability of cultivating more diverse leguminous crops is improving steadily. As remarked by one interviewee: ‘You know, these vegans want something to eat, so the market’s there!’.

Thus, knowledge of our agricultural history, combined with modern pressures even at the level of individual choices, is propagating a movement back towards the higher agricultural diversity and crop rotations from years past. Importantly, these seem set only to accelerate. Voting, spreading knowledge about these issues, and individual actions all let us enact change — and it is a change that our soils urgently need.

This piece drew inspiration and key information from a recent publication by Cusworth et al. (2021, Journal of Rural Studies) and from Knox et al. (2011, Journal of Sustainable Agriculture) Tim Birkle is a third-year PhD student in biochemistry at Christ’s College. Artwork by Pauline Kerekes.

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Weird and Wonderful Tiny Owls and Tiny Snakes: Strangest of Bedfellows?

If you found tiny snakes in an owl nest, you would be forgiven for thinking that they were perhaps intended to be food for growing owlets.

After all, owls are predatory birds that prey on a wide variety of animals. However, an unusual relationship between the eastern screech owls and blind snakes of central Texas seems to suggest something different is happening.

Researchers from Baylor University, Texas, were surprised to find these usually secretive blind snakes in the nests of owls. The snakes are a group of miniature underground species that eat the larvae of insects, most often ants and termites — so how were they getting up into trees? In an unexpected twist, rather than killing the snakes before bringing them to their nest in the way owls usually treat their prey, eastern screech owls were picking them up and dropping them off alive. Surprisingly, it appears that the presence of snakes in these owl nests significantly increases the growth rate and decreases the mortality rate of chicks. This is probably due to blind snakes’ dietary preferences as these little snakes will eat any parasites that might negatively impact the owl chicks — not a bad job for such a tiny snake. AH

Valuing Vaginal Variation: Why Size Matters

The Large Blue(Sci) Butterfly

While 50% of the world’s population could benefit from a better understanding of vaginas, it appears a male-centric approach to research has led to neglect of the topic. In her book about the gender data gap, Invisible Women, Caroline Criado Perez presented basic yet surprisingly poorly answered questions: What are the shapes and sizes of vaginas? How do these vary with age and childbirth? A limited number of studies have explored these questions. Two studies identified five broad shapes based on just 77 samples: parallel-sided, conical, heart, slug, and pumpkin seed. Penis size, on the other hand, has been investigated through systematic reviews and in studies with over 15,000 samples.

When thinking of the weird and wonderful, few animals seem to fit the bill as well as the large blue butterfly. This unassuming insect might look like any other, but its caterpillars hide a sinister secret. Left out in the open to fend for themselves, they are adopted by ants, mistaken for one of the ants’ own grubs which has strayed far from the safety of the nest. Once carried back to the colony by the ants, the caterpillars are terrible guests and proceed to eat the real ant grubs!

The lack of data on vaginal anatomy has significant clinical implications. Millions of women are suffering from hard-to-treat conditions related to vaginal and pelvic-floor health. Similarly, devices like the vaginal speculum have retained their uncomfortable designs for years. Luckily, we may be witnessing a shift in attitudes: start-ups have begun to value variation in vaginas, leading to the development of more comfortable devices for examination and pelvic-floor training. Moving away from a onesize-fits-all approach, vaginas are finally starting to be appreciated for their fundamental role in menstruation, sex, childbirth, and pelvic health. Hopefully, soon enough, they will not be considered weird anymore but variably wonderful. BS

It turns out that the large blue butterfly caterpillars mimic the chemical signature of the ant grubs, acting as social parasites not unlike cuckoos. This mimicry is remarkably specific to a particular species of red ant. This was not well understood for much of the large blue’s documented history in the UK, and, unfortunately, this lack of understanding contributed to the extinction of the large blue from the UK in 1979.

However, research into the host ant species and improved management allowed the butterfly to be successfully reintroduced just a few years later. The UK now hosts some of the densest populations of the large blue butterfly anywhere in the world, making this a rare but welcome conservation success story. MH

Artwork by Rosanna Rann.

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