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< Back to Issue 5 Serial Killers Selin Duran 24 October 2023 Edited by Yasmin Potts Illustrated by Aditya Dey Serial killers. Do we love them or hate them? It’s hard to know, especially as the media surrounding them is increasing. From fiction to nonfiction killers, our society is obsessed with giving a voice and perspective to these people. We have movies, documentaries, TV series and even Youtube videos accounting the lives and stories of killers. Despite this, people rarely stop to ask themselves why they enjoy this style of media - some of the most wicked and gruesome acts, glorified for the interest of many. Yet, every day we are met with new shows highlighting the life of coldblooded killers. But why are we interested in them? It’s mostly a morbid curiosity; as humans, we are drawn to crime. We want to know why people choose to kill and how they do it. Jack Haskins, a University of Tennessee journalism professor, noted that "humans [are] drawn to public spectacles involving bloody death...Morbid curiosity, if not inborn, is at least learned at a very early age " (UPI Archives, 1984). As a collective, we have always wanted to explore the horrid acts of those who kill. But it’s only with the help of modern media that people enjoy them. Media loves a good story - and what makes a good story? A crazy serial killer on the loose. One of the earliest movies about a serial killer is Fritz Lang's 1931 film M . Set in Berlin, the film details a killer who targets children. Since then, a downward spiral of fictional serial killer movies has taken society by storm. Being all the craze during the mid-80s and 90s, the highest amount of serial killer media were produced in this timeframe. One of the most popular works is director Alfred Hitchcock's iconic Psycho, which won eight Academy Awards (IMDb, 2021). What is truly disturbing is the story of this film. Norman Bates, our killer, is deemed mentally insane and suffers from Dissociative Identity Disorder. Through his personality changes, he proceeds to kill two people during the film, in addition to multiple murders not depicted. Yet, when he is jailed, we learn that his actions were the result of abuse he endured when he was younger. Suddenly, we're forced to feel sympathetic towards his situation. How can that be a reasonable justification towards murder, and why do we applaud the film for this? As a society, accepting murder based on mental insanity seems more than unreasonable - but no one has questioned it thus far. This unfortunately happens not only with fictional killers, but with nonfiction ones. Our interest in killers turns into a way to inform ourselves of these situations (Harrison, 2023). We look to these documentaries and podcasts that tell the stories of the most notorious serial killers to learn something and prevent the situation from happening to us. All whilst indulging in content that emphasises these killers as being regular people, not evil individuals, who committed crimes for personal pleasure. We don’t need to see a biopic about the ventures of Ted Bundy and Jeffery Dahmer. Yet the second you search their names on Google, an all-star cast portraying the life of a man who tortured their victims fills your screen. This is certainly not an ethical thing to endorse. Despite this, not a single person thinks twice about it due to how common it is. Directors are profiting off victims and as a society, we are allowing it because of our curiosity. What happened to compassion? Because I certainly believe we have lost it. We have become so infatuated with killers that their actions seem unimportant to us. We yearn to discover more about their lives and forget that real people were implicated in these events. These killer stories provide bursts of short-lived adrenaline and then we return to our normal lives. In forgetting the consequences of these real stories, we are in many ways as bad as the killers themselves. And that is truly wicked. References Harrison, M. A. (2023). Why Are We Interested in Serial Killers? Just as Deadly: The Psychology of Female Serial Killers . Cambridge: Cambridge University Press, 17–31. https://www.cambridge.org/core/books/just-as-deadly/why-are-we-interested-in-serial-killers/B35C2243B387273749EA164318C27623?utm_campaign=shareaholic&utm_medium=copy_link&utm_source=bookmark IMDb. (2021). Psycho (1960) - Awards . https://www.imdb.com/title/tt0054215/awards/ UPI Archives. (1984). Few answers on origin of morbid curiosity. UPI. https://www.upi.com/Archives/1984/04/07/Few-answers-on-origin-of-morbid-curiosity/7976450162000/#:~:text=%27Throughout%20human%20history%2C%20humans%20have Wicked back to

< Back to Issue 9 Axolotl: The Little God of the Lake by Danny He 28 October 2025 Illustrated by Saraf Ishman Edited by Ciara Dahl Creation “When the fifth sun was created, it did not move. The god of the wind carved a destructive path through the realm, slaying all other gods to induce the Sun into movement. Xolotl, guide for the dead, escaped his sacrifice by transforming into an invulnerable salamander. Eventually, even he was captured. Upon his sacrifice, the Sun began its course. Thus began the time of man.” - Author’s creative interpretation of Aztec mythology. The otherworldly biology of the axolotl ( Ambystoma mexicanum) attracted fascination among the Aztecs, who named it after the god of fire and lightning (1). They believed the shapeshifting god Xolotl took many forms, from a chimera depicted as a dog-headed man, to a skeleton, to a deformed monster with reversed feet (1). He was a renowned shapeshifter who would guide the dead on their journey to the afterlife (1). Centuries on, the axolotl would transform from a feared deity to a beloved icon and subject of scientific marvel. Fascination “Auguste Dumeril lounged by the lake. The humidity of Lake Xochimilco was beginning to take its toll. He had recently been informed of a marvellous reptile, one that resided exclusively in the canals of ancient Aztec, capable of regrowing limbs and organs including its brain. He wondered of the scientific possibilities of studying such a creature. A self-regenerating invertebrate could fascinate the scientific community and make wonderful contributions to medicine. This creature is to be taken back home to Paris” - Imaging a day with French Zoologist August Dumeril. The axolotl exhibits many biological peculiarities. Cousin of the tiger salamander ( Ambystoma tigrinum) , it has evolved over millions of years to take advantage of the bountiful resources of the Mexican basins (2). It remains in its juvenile, tadpole-like form throughout its adulthood, retaining its gills and breathing through its skin (2). The animal’s near perfect regeneration and its potential application for medical research fascinated scientists. French zoologist Auguste Dumeril was the first to conduct research on the axolotl after discovering it during his expedition to Mexico (3). Decades later, proteins were discovered which enabled the miraculous processes of complete, scar-free regeneration of an injured axolotl (4). Scientists continue to research methods in which the axolotl’s regeneration can facilitate trauma care and cancer research (4, 5). Conservation “Pedro set his spade down, straw hat clutched close to his chest. His eyes fixated on the water before him. Just below the surface, he had thought something had moved along the river bank. It had been many years since he had last seen an axolotl. The Méndez Rosas had been working as Chinamperos for generations. The axolotl had been a welcome sight for his forefathers, now it is a sign of hope for Lake Xochilmilco.” - an interview with Pedro, a 7th generation Chinamperos (7). Chinampas are large man-made farming islands created by the Aztecs (6). The capital city was built upon an island on a vast lake using a series of complex canals to prevent their city from flooding (6). Chinamperos use the lake's nutrient-rich soil to grow crops and create a self-sustaining system resilient to pests and disease (6). Productive chinampas ensure greater food security for Mexico City. A perfect symbiosis between water and land, a healthy chinampa cannot be without a healthy body of water (6). As chinampas grow they become refuge for wildlife such as the axolotl (6). As axolotls breathe through their skin, their presence indicates excellent water quality and hence a healthy chinampa (6). However, this once thriving ecosystem is now under threat from urbanisation. Drainage of the lake has resulted in the range of chinampas being limited to Lake Xochilmilco (6). Pollution and climate change has altered the landscape, while expansion of the city has resulted in the loss of precious wetlands (6). These changes have driven axolotls to critical endangerment. A once venerated and sacred creature has been neglected and buried by the relentless incursion of human civilisation (6). It is now a race against time to save the wild axolotls as few remain in Lake Xochilmilco (2). As urbanisation continues to bear down upon the chinampas, calls have been made to protect these dwindling areas of refuge (2). The fate of the axolotl is yet to be determined, but it is certain that the loss of another species will continue to set a dangerous precedent for the conservation of our ecosystems. Aztec mythology describes the god represented by the axolotl as the caretaker of his underworld kingdom and a guide for lost souls (1). Perhaps it is now important for us to take care of the axolotl as Xolotl has taken care of us. References Spence L. Mexico and Peru [Internet]. Senate; 1994. Accessed September 29, 2025. https://archive.org/details/mexicoperu00spen The Editors of Encyclopaedia Britannica. Axolotl. Britannica . July 20, 1998. Updated 27 August, 2025. Accessed September 29, 2025. https://www.britannica.com/animal/axolotl Reiß C. Cut and Paste: The Mexican Axolotl, Experimental Practices and the Long History of Regeneration Research in Amphibians, 1864-Present. Front Cell Dev Biol . 2022;10:786533. doi:10.3389/fcell.2022.786533 Huang L, Ho C, Ye X, Gao Y, Guo W, Chen J, et al. Mechanisms and translational applications of regeneration in limbs: From renewable animals to humans. Ann Anat . 2024;255:152288. doi:10.1016/j.aanat.2024.152288 Suleiman S, Schembri-Wismayer P, Calleja-Agius J. The axolotl model for cancer research: a mini-review. J BUON . 2019;24(6):2227–31. Accessed September 29, 2025. https://www.researchgate.net/publication/338630505_The_axolotl_model_for_cancer_research_a_mini-review The Editors of Encyclopaedia Britannica. Chinampa. Encyclopaedia Britannica . July 20, 1998. Updated 26 May, 2017. Accessed September 29, 2025. https://www.britannica.com/topic/chinampa Nature on PBS. Wild axolotls are being saved by... nuns and Aztec gardens? | WILD HOPE. Youtube. September 12, 2023. Accessed September 29, 2025. https://www.youtube.com/watch?v=NL0ad3jBWRI&t=808s Previous article Next article Entwined back to

< Back to Issue 8 A Psychological ‘Autopsy’ of Ludwig van Beethoven: Dissecting Genius and Madness by Kara Miwa-Dale 3 June 2025 Edited by Steph Liang Illustrated by Ashlee Yeo ‘No great mind has ever existed without a touch of madness.’ – Aristotle Preface This is not an autopsy in the traditional sense. No scalpels or specimen jars will be involved. Instead, it is an autopsy of the mind – a retrospective exploration of the inner world of the great classical composer, Ludwig van Beethoven. Beethoven was considered a genius for revolutionising Western classical music with his emotionally powerful, structurally innovative, and highly complex compositions. He broke from convention, pioneered new musical forms, and continued to create masterpieces even after becoming completely deaf. Drawing upon insights from genetics, neuroscience, psychiatry, and anthropology, alongside the testimonies of Beethoven’s peers, we will piece together an understanding of how genius, creativity and mental affliction may be intertwined. Was Beethoven’s genius a product of madness, a triumph over it, or something different altogether? The Subject Name: Ludwig van Beethoven Occupation: Composer Age at Death: 56 Reason for Autopsy : To investigate the elusive connection between creativity, mental disorder, and the mysterious concept of genius I. The Witnesses: Testimonies from the Living To those that knew him, Beethoven was a paradox. One friend called him “half crazy”, noting violent outbursts, erratic moods and obsessive tendencies (1). Others saw him as “merry, mischievous, full of witticisms and jokes” (2). His talent and creative genius, however, were never in doubt. The poet Goethe, who met him in 1812, wrote: “Beethoven’s talent amazed me. However, he is an utterly untamed personality” (3). Based on Beethoven’s letters and accounts from friends, modern psychiatrists suspect that he may have lived with bipolar disorder (4). Yet, there is no way to be sure. Like the mind itself, Beethoven resists full understanding – a genius shaped by forces we may never fully comprehend. II. The Geneticist How can DNA offer insight into Beethoven’s genius? Often described as the blueprint of life, DNA offers fascinating insights into human potential – highlighting our predispositions, vulnerabilities, and even talents. However, it only tells part of the story. In 2023, an international team of scientists sequenced the DNA of five authenticated locks of Beethoven’s hair (5). Not long after, another group of researchers used this data to calculate a polygenic score estimating his genetic predisposition for beat synchronisation, a trait believed to be linked to musicality (6). Polygenic scores add up the small effects of many different genes to estimate someone’s likelihood of expressing a complex trait – like musical ability. Because these traits are influenced by many different genes working together, polygenic scores can be a helpful tool in exploring their biological basis. Curiously, Beethoven’s polygenic score for beat synchronisation was surprisingly low, implying that he wasn’t predisposed to have a strong sense of rhythm. Does this mean that Beethoven defied his own biology? Not necessarily. Polygenic scores have significant limitations. They don’t account for environmental influences – like the years of rigorous musical training that Beethoven underwent – or complex gene-gene and gene-environment interactions. Additionally, these scores are based on modern genetic datasets, so applying them to someone from the 18th century can reduce the reliability of the interpretation. That said, the story becomes even more fascinating when we consider research linking polygenic risk scores for psychiatric conditions – such as bipolar disorder and schizophrenia – to creativity. One large study found that people with a higher genetic risk for these conditions were overrepresented in artistic and creative jobs, although the association was small (7). This doesn’t mean that mental illness causes creativity, or that all creative people have a mental disorder, but it hints at a complex biological overlap. III. The Psychiatrist How does one make a psychiatric diagnosis from the grave? It is an impossible task, and an imprecise science, but we can draw inferences from historical accounts of a person’s behaviour. Beethoven seemed to exhibit behaviours consistent with bipolar disorder, a mental health condition characterised by extreme mood swings that include emotional highs (mania or hypomania) and lows (depression). Letters written by Beethoven himself, along with observations from friends, may provide some insight. He was notably “prone to outbursts of anger, baseless suspicions, quarrels and reconciliations, fruitless infatuations, physical ills, changes of residences…and the hiring and firing of servants" (1). One friend remarked that ‘he composes, or was unable to compose, according to the moods of happiness, vexation or sorrow’, suggesting that his creative output fluctuated with his shifting emotional state (1). Individuals with bipolar disorder experience manic or hypomanic episodes marked by elevated mood, increased energy, rapid thought processes, reduced inhibition, and heightened confidence (8). These episodes may enhance creative thinking by promoting divergent thinking – the ability to generate novel ideas or unusual associations (9). Research shows that the medial prefrontal cortex, a brain region active during divergent thinking, is typically engaged during manic states (10). While it would be inappropriate to assign a clinical diagnosis based solely on anecdotal evidence, it is possible to speculate that Beethoven’s prolific composing periods might have corresponded to manic or hypomanic episodes. But how can we distinguish a clinical mood disorder from mere bursts of creative inspiration or genius? The U-shaped curve hypothesis offers one explanation, proposing that the relationship between ‘madness’ and genius is not linear (11). Mild to moderate expressions of bipolar disorder may actually enhance creativity by promoting divergent thinking, whereas severe illness can be debilitating and reduce creative output. This raises the possibility that Beethoven experienced a less severe form of bipolar disorder – one that fueled rather than hindered his musical brilliance. Building on this, psychological research also suggests that people in creative occupations tend to score higher on measures of ‘openness to experience’ (12). This personality trait describes the extent to which a person is curious, imaginative, and receptive to new ideas or unconventional beliefs. Studies have suggested that openness to experience is elevated among individuals with bipolar disorder compared to controls with no mood disorder (13,14). It is possible that Beethoven’s creative genius was influenced, at least in part, by the interplay between his personality and traits associated with bipolar. However, it is important to acknowledge the very real challenges of living with mental illness and to avoid romanticising the condition as a source of artistic inspiration. IV. The Anthropologist Cultural narratives - like the ‘mad genius’ and ‘tortured artist’ tropes - have long romanticised and distorted the relationship between mental illness and creative brilliance. However, contemporary understandings of mental health increasingly challenge the idea that extraordinary creativity requires psychological suffering. Beethoven’s life was marked by adversity. His father, believed by some to be abusive, enforced a strict practice regime for his music lessons and struggled with alcoholism – an affliction that would later cast a shadow over Beethoven’s own life. During Beethoven’s mid-twenties, he began to lose his hearing, becoming completely deaf by around 44. Yet, he continued to compose innovative symphonies, relying only on the music in his mind. Did Beethoven’s suffering fuel his brilliance? While some studies suggest a link between bipolar disorder and heightened creativity, it would be a mistake to suggest that mental illness is a prerequisite for genius. Many highly creative individuals have no history of mental illness at all. So why, then, does the ‘mad genius’ stereotype continue to endure? During Beethoven’s era – the Romantic period – suffering was often glorified as a source of artistic inspiration. Mental illness was poorly understood, and the emotional extremes exhibited by artists with mood disorders were frequently mistaken for signs of genius. Emotional intensity and instability were often seen as sources of inspiration for genius works of art. It wasn’t until the 20th century that bipolar was formally recognised as a mental illness. It is hard to say, based solely only on historical records, whether Beethoven experienced a mental health condition, or was simply an emotionally intense and unconventional individual. What we define as ‘normal’ or ‘abnormal’ behaviour is complex and deeply influenced by the social and cultural norms of the time. V. The Final Verdict So, what can we conclude from this evidence? Was Beethoven a genius because of his madness? Or in spite of it? Perhaps these are the wrong questions. Such binaries oversimply a reality that is far more nuanced. They invite us to reconsider our definitions of ‘normality’, ‘illness’ and ‘genius’. It is important to acknowledge the very real and devastating challenges associated with mental illness. Yet, it’s also true that some traits associated with conditions like bipolar disorder – such as divergent thinking – may intersect with creativity in complex ways. Rather than viewing these conditions purely as deficits, we might ask: could some features of mental disorder be better understood as extreme expressions of the broader, messier spectrum of human cognition and emotion? In the end, Beethoven remains an enigma – not because he was ‘mad’, but because he was unknowable and defied neat categorisation. Perhaps that is what genius truly is: not a clinical condition, or a byproduct of suffering, but a mystery that transcends explanation. References 1. Hershman DJ. Manic depression and creativity. Prometheus Books; 2010 Oct 5. 2. Bezane C. Bipolar Geniuses: Ludwig Van Beethoven [Internet]. Chicago: Conor Bezane; 2016 Mar 15. https://www.conorbezane.com/thebipolaraddict/thebipolaraddictbipolar-geniusesbeethoven/ 3. Carnegie Hall. Friends of Beethoven [Internet]. New York: Carnegie Hall; 2020 Mar 19 [cited 2025 May 31]. https://www.carnegiehall.org/Explore/Articles/2020/03/19/Friends-of-Beethoven 4. Erfurth A. Ludwig van Beethoven—a psychiatric perspective. Wiener Medizinische Wochenschrift. 2021;171(15):381-90. https://doi.org/10.1007/s10354-021-00864-4 5. Begg TJA, Schmidt A, Kocher A, Larmuseau MHD, Runfeldt G, Maier PA, et al. Genomic analyses of hair from Ludwig van Beethoven. Current Biology. 2023;33(8):1431-47.e22. https://doi.org/10.1016/j.cub.2023.02.041 6. Wesseldijk LW, Henechowicz TL, Baker DJ, Bignardi G, Karlsson R, Gordon RL, et al. Notes from Beethoven’s genome. Current Biology. 2024;34(6):R233-R4. https://doi.org/10.1016/j.cub.2024.01.025 7. Power RA, Steinberg S, Bjornsdottir G, Rietveld CA, Abdellaoui A, Nivard MM, et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nature Neuroscience. 2015;18(7):953-5. https://doi.org/10.1038/nn.4040 8. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR . 5th ed, text revision. Washington, DC: American Psychiatric Association; 2022. 9. Forthmann B, Kaczykowski K, Benedek M, Holling H. The Manic Idea Creator? A Review and Meta-Analysis of the Relationship between Bipolar Disorder and Creative Cognitive Potential. International Journal of Environmental Research and Public Health. 2023;20(13):6264. https://www.mdpi.com/1660-4601/20/13/6264 10. Mayseless N, Eran A, Shamay-Tsoory SG. Generating original ideas: The neural underpinning of originality. NeuroImage. 2015;116:232-9. https://doi.org/10.1016/j.neuroimage.2015.05.030 11. Richards R, Kinney DK, Lunde I, Benet M, Merzel AP. Creativity in manic-depressives, cyclothymes, their normal relatives, and control subjects. Journal of abnormal psychology. 1988;97(3):281. 12.Feist GJ. A meta-analysis of personality in scientific and artistic creativity. Personality and social psychology review. 1998;2(4):290-309. 13. Matsumoto Y, Suzuki A, Shirata T, Takahashi N, Noto K, Goto K, et al. Implication of the DGKH genotype in openness to experience, a premorbid personality trait of bipolar disorder. Journal of Affective Disorders. 2018;238:539-41. https://doi.org/10.1016/j.jad.2018.06.031 14. Middeldorp CM, de Moor MHM, McGrath LM, Gordon SD, Blackwood DH, Costa PT, et al. The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data. Translational Psychiatry. 2011;1(10):e50-e. https://doi.org/10.1038/tp.2011.45 Previous article Next article Enigma back to

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< Back to Issue 8 Life Story of a Drug by Elijah McEvoy 3 June 2025 Edited by Weilena Liu Illustrated by Aisyah Mohammad Sulhanuddin From the mythical visions of church goers who took mushrooms in the infamous ‘Good Friday Experiment’ to the extreme self-reflection of those ‘tripping’ off the traditional South American hallucinogenic tea Ayahuasca (1,2), humans have been painting the extraordinary narratives of psychedelics for thousands of years in thousands of settings. Put simply, psychedelics are a class of psychoactive drugs that can alter your thoughts and senses, inducing wild experiences not thought possible in your brain’s ground state (3). One of the most famous of these drugs is LSD. ‘Lucy in the Sky with Diamonds’ is said to have inspired entire Beatles albums and shown Steve Jobs “that there’s another side to the coin” of life (4,5). LSD is also a psychedelic that stands as an enigma in many regards. It is both naturally derived and synthetically created. It has been tested in psychological therapy and psychological warfare. Even the ‘trips’ experienced by its users entail both unexplainable hallucinations and scientifically proven phenomena. While being lesser understood, the stories of LSD’s enigmatic origins, uses and effects are just as interesting as those that come from its users. The Origins Lysergic Acid Diethylamide (LSD) or ‘acid’ for short is a semi-synthetic chemical compound with humble biological beginnings. LSD is derived from a class of alkaloid metabolite molecules that are naturally produced by the fungus commonly known as ergot. Ergot fungi are members of the parasitic genus Claviceps , which have been infecting staple crops and shaping society long before acid came to distort shapes in the eyes of its users (6). Epidemics of ergotism, a disease caused by these ergot alkaloids after ingesting contaminated crops, swept across Middle Age Europe and led to the deaths of tens of thousands of people (7). Despite credible arguments to the contrary, some historians have even suggested that the Salem Witch Trials may have been sparked by a form of this disease known as convulsive ergotism. Not only were the environmental conditions in 1691 Salem reported to be optimal for ergot growth in the town’s rye, but convulsive ergotism also induces distinct muscle contractions, paranoia and audiovisual hallucinations (8). These symptoms all would have given credit to the claims of bewitchment made by the young girls that instigated the accusations of witchcraft in the town. Aside from death and dark magic, this fungus has also been used as an effective therapeutic across several eras of history. It’s use as a medication for childbirth was recorded as early as 1100 BCE in China, with midwives using ergot or it’s alkaloids to reduce bleeding during birth, expedite delivery or induce an abortion (6,7). It wasn’t until modern pharmacology advanced in the 20th century that scientists began to chemically characterise these ergot alkaloids and use them as the basis to create potent drugs. The story of how LSD was first created and consumed is one that has been immortalised in history books and unofficial holidays. Dr Albert Hoffman, a Swiss biochemist working for the pharmaceutical company Sandoz, first synthesised LSD in 1938 as the 25th substance in a series of lysergic acid derivatives being evaluated by the company (9). Initial testing of this compound indicated it had no unique pharmacological uses beyond those of pre-existing ergot alkaloid derived drugs (9). However, Hoffman couldn’t shake the nagging feeling that LSD-25 had more to offer. After making another batch of the compound 5 years later, Hoffman’s suspicions grew stronger when he was forced to leave the lab early after entering a “dream-like state… [with] a kaleidoscope-like play of colours” (9). A few days later, in a moment that demonstrated both admirable scientific curiosity and blatant rejection of OH&S, Hoffman took a large dose of LSD himself and set in for a trip of a lifetime (9). Like all good scientists, he recorded his experience in a journal, writing at 3pm on 19 April 1943: “visual distortions, symptoms of paralysis, desire to laugh” (9). Hoffman’s notes for the day stopped there. The Uses April 19th has come to be celebrated as ‘Bicycle Day’, commemorating the seemingly endless and surreal bike ride home Hoffman undertook after this self-experimentation. However, a wacky trip was not the only thing that followed this discovery. After Hoffman distributed the drug to his superiors to try for themselves, LSD was sold on the market by Sandoz under the name Delysid. This drug was employed by psychiatrists throughout the 1950s as a treatment for alcoholism or simply ‘psychotherapy-in-a-pill’ for patients suffering psychological trauma (10,11). LSD not only garnered therapeutic interest from scientists but also more nefarious intrigue from the CIA. Seeking to get an upper hand in the department of mental warfare during the Cold War, the CIA bought up 40,000 doses of LSD from Sandoz and performed a variety of unethical experiments on unknowing prisoners, heroin addicts and even other CIA agents in an attempt to understand the drug’s potential for ‘mind control’ under the MKUltra project (12). Moving into the 60s, LSD’s use amongst budding leaders of the Hippie and Yippie movements gave the drug its countercultural status. Harvard Professor Timothy Leary, who was dismissed from his position due to experimenting (literally) with LSD, promoted the drug as an agent of revolution that allowed the youth of America to “turn on, tune in, drop out” (10) of repressive society. Due to its increasing association with these disruptive movements and eventual outlawing by the US government in 1966 (11), acid’s place in culture shifted out of labs and psychologist offices and into illicit recreational usage by experimental hippies and enlightened artists. The Trip Whether accompanied by an experienced monitor or listening to some soothing vinyl records yourself, the experience of taking LSD is predictably unpredictable. ‘Dropping acid’ is unique in that only micrograms of the drug are enough to elicit a palpable psychedelic experience (13), with most users diluting the dosage on tabs of blotting paper or sugar cubes (11). Following consumption, it takes as little as 1.5 hours for LSD to cross the blood-brain barrier, dilate the pupils and bring users to the peak intensity of the drug’s psychological effects (13). The bizarre experiences perceived by those ‘tripping’ on LSD is rooted in a now well-characterised receptor binding interaction in the brain. The nitrogen-based chemical groups of the LSD molecule first anchor themselves within the 5-HT2A serotonin receptors found in the synapses of neurons (14). While the serotonin neurotransmitter typically helps regulate brain activities like mood and memory, LSD binding instead causes the activation of distinct intracellular cascades within these brain cells (3). The importance of this interaction was demonstrated in experiments that proved blocking this receptor can cancel the acid trip all together (3). Recent studies that have further characterised the chemical structure of this interaction have also shown that 5-HT2A forms a lid-like structure that locks LSD into this receptor protein’s binding site and sets the user in for a long trip (14). From these individual cellular interactions, LSD ignites a burst of brain activity. Modern brain scanning technology has revealed that LSD first disrupts the capacity of the thalamus to filter and pass on sensory stimuli from the body to the cortex of the brain. Upon injection of LSD, patient’s brains demonstrated both an overflow of information running between the thalamus and posterior cingulate cortex and restriction of signals going to the temporal cortex (15). Not only does LSD modify the brain’s ability to sort out important stimuli from the outside world, but this small molecule has also been found to temporarily form new connections between different parts of the brain. Hoffman’s recount of how “every sound generated a vividly changing image” (9) on the first Bicycle Day can be explained by the increased connectivity of the brain’s visual cortex on LSD. This causes areas of the brain responsible for other senses or emotions to become involved in creating the images perceived in the user’s head, causing visual hallucinations and geometric distortion that have no basis in real stimuli coming from the eyes (16). In contrast, Hoffman’s feeling of being “outside [his] body” (9) likely came from decreased connectivity between the parahippocampus and retrosplenial cortex, two regions of the brain responsible for cognition. This severance has been correlated with the greater meaning that those tripping on LSD find in objects, events or music along with their characteristic ‘ego dissolution’ (16). This is a phenomenon where users no longer see the world through the lens of their own ‘self’ and instead feel an increased sense of unity with everything around them (17). Very Hippie ideas with a very scientific explanation. The Comedown and Beyond The float back down from the peak of an LSD trip takes up to 10 hours and leaves its users with a variety of stories and outcomes. Contrary to the fearmongering of parents and politicians, LSD does not leave holes in the brain, does not lead to addiction and has not directly led to the death of anyone as a result of overdosage (3). While the risk of a ‘bad trip’ and the feelings of severe anxiety, fear and despair that come with it may be traumatic, these are typically experienced when taking LSD in unsupportive environments without proper mental preparation (13). In fact, when LSD is taken in a manner closer to the controlled ritual practices surrounding psychedelics of old (3), acid is suggested to have long-lasting positive impacts on the user’s attitude and personality (13). It is these experiences that have rejuvenated the field of LSD research from its abrupt stop in the 60s. Modern investigations have picked up where these scientists left off and are evaluating the potential of utilising LSD-assisted therapy to alleviate anxiety and depression. Studies have focused particular attention on addressing these mental health conditions in those suffering from life-threatening illnesses like cancer (18). While some of these experiments lack the controls or data to make strong generalised conclusions, several studies have demonstrated that patients supplied with LSD reported lasting decreases in anxiety surrounding their condition, greater responsiveness to their families and improved quality of life (3,18). All of this is not to promote LSD as a harmless wonder drug. While rare, LSD has been linked to Hallucinogen Persisting Perception Disorder, a condition in which people experience distressing ‘flashbacks’ to the effects and experiences of past psychedelic trips in a normal setting. Additionally, the changes in visual perception, emotion and thought while one is tripping can also cause users to make reckless decisions in dangerous situations (18). However, continuing to wage war against controlled experiments and supervised therapeutic trials with LSD only serves to limit the attempts of scientists in better understanding the balance between this drug’s risks and benefits. While our trip through the life of LSD may end here, there is still much to explore. The greater story of how we use it, how we view it and how it fits into our society is far from over. References Illing S. Vox. 2018 [cited 2024 Oct 23]. The brutal mirror: what the psychedelic drug ayahuasca showed me about my life. Available from: https://www.vox.com/first-person/2018/2/19/16739386/ayahuasca-retreat-psychedelic-hallucination-meditation Majić T, Schmidt TT, Gallinat J. Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences? J Psychopharmacol. 2015 Mar 1;29(3):241–53. Nichols DE. Psychedelics. Barker EL, editor. Pharmacol Rev. 2016 Apr 1;68(2):264–355. Gilmore M. Beatles’ Acid Test: How LSD Opened the Door to “Revolver” [Internet]. Rolling Stone. 2016 [cited 2024 Oct 23]. Available from: https://www.rollingstone.com/feature/beatles-acid-test-how-lsd-opened-the-door-to-revolver-251417/ Hsu H. The Lingering Legacy of Psychedelia. The New Yorker [Internet]. 2016 May 17 [cited 2024 Oct 23]; Available from: https://www.newyorker.com/books/page-turner/the-lingering-legacy-of-psychedelia Haarmann T, Rolke Y, Giesbert S, Tudzynski P. Ergot: from witchcraft to biotechnology. Molecular Plant Pathology. 2009 Jul;10(4):563–77. Schiff PLJ. Ergot and Its Alkaloids. American Journal of Pharmaceutical Education. 2006 Oct 15;70(5):98. Woolf A. Witchcraft or Mycotoxin? The Salem Witch Trials. Journal of Toxicology: Clinical Toxicology. 2000 Jan;38(4):457–60. Hofmann A. How LSD Originated. Journal of Psychedelic Drugs. 1979 Jan 1;11(1–2):53–60. Massari P. Harvard Griffin GSAS News. 2021 [cited 2024 Sep 28]. A Long, Strange Trip | The Harvard Kenneth C. Griffin Graduate School of Arts and Sciences. Available from: https://gsas.harvard.edu/news/long-strange-trip Stork CM, Henriksen B. Lysergic Acid Diethylamide. In: Wexler P, editor. Encyclopedia of Toxicology (Third Edition) [Internet]. Oxford: Academic Press; 2014 [cited 2024 Sep 28]. p. 120–2. Available from: https://www.sciencedirect.com/science/article/pii/B9780123864543007442 Stuff You Should Know. Did the CIA test LSD on unsuspecting Americans? - Stuff You Should Know [Internet]. [cited 2024 Aug 25]. (Stuff You Should Know). Available from: https://www.iheart.com/podcast/1119-stuff-you-should-know-26940277/episode/did-the-cia-test-lsd-on-29468397/ Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. The Pharmacology of Lysergic Acid Diethylamide: A Review. CNS Neurosci Ther. 2008 Nov 11;14(4):295–314. Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, et al. Crystal structure of an LSD-bound human serotonin receptor. Cell. 2017 Jan 26;168(3):377. Sample I. Study shows how LSD interferes with brain’s signalling. The Guardian [Internet]. 2019 Jan 28 [cited 2024 Nov 10]; Available from: https://www.theguardian.com/science/2019/jan/28/study-shows-how-lsd-messes-with-brains-signalling Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, et al. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences. 2016 Apr 26;113(17):4853–8. Sample I. LSD’s impact on the brain revealed in groundbreaking images. The Guardian [Internet]. 2016 Apr 11 [cited 2024 Nov 10]; Available from: https://www.theguardian.com/science/2016/apr/11/lsd-impact-brain-revealed-groundbreaking-images Liechti ME. Modern Clinical Research on LSD. Neuropsychopharmacol. 2017 Oct;42(11):2114–27. Previous article Next article Enigma back to

< Back to Issue 4 Fool Me Once by Julia Lockerd 1 July 2023 Edited by Tanya Kovacevic and Elijah McEvoy Illustrated by Sonia Santosa I have rabies. I’m absolutely sure of it. I mean, I can't really tell, but that’s the silent killer, right? You don’t know you’re rabid till it’s all over, and you’re foaming at the mouth and biting your student tutor on the leg. Despite being completely safe here in Australia with its complete lack of rabies-having animals, I’m still pretty sure I’ve managed to catch it. Next week it will all be over for me and my tutor. Sorry, James. Of course, it’s not actually rabies that I’ve contracted, but a much more common condition: Medical Student Syndrome (1). Last week in my lectures, we learned all the ins, outs, and symptoms of the rabies virus. So, naturally, now we all have it. This health-related anxiety is a prime example of how our human brains can trick us into experiencing phantom symptoms. The same cognitive veil is used in clinical trials all over the world in order to test the efficacy of new drugs. We’ve all felt it. That moment when you question, ‘Is this real, or is my mind making its reality?’ We call this the placebo effect. The placebo effect is crucial to modern and historical experimental design. The ‘trickable’ nature of the human mind has changed the course of drug development as we know it. The effects’ success hinges on a patient's belief that they are receiving treatment for their ailment. The simple belief in a cure can often result in real physiological changes in an individual. This makes the placebo effect a very powerful tool in the development of new drugs for the market. In a placebo-controlled trial, half of the sample population will be blindly given a placebo, and the other half of the drug being tested. In order for a potential treatment to be considered effective, it must produce more significant results than the placebo group (2). We must improve our approach to designing and researching hypotheses. Can we use what we know about the placebo effect to make more accurate claims about modern pharmaceutical development? Well, in 2017, Dr. Sara Vanbheim of the Arctic University of Norway published a study that brought into consideration the possible effects of differing sexual characteristics on placebo efficacy (3). This idea could restructure the way experiments are designed going forward and potentially provoke a possible review of drugs already on the market. Is it possible that traditionally marginalised groups are underrepresented in the clinical trial process? Can we restructure experiments to be more inclusive? Are changes even really necessary? These questions were investigated through the compilation and calculation of placebo and nocebo effects on men and women over multiple previously conducted studies mostly centering around physical pain and the administration of analgesia. The term ‘nocebo’ defines the antithesis of a placebo (4), referring to adverse side effects a subject feels when given an inert version of the test drug. While placebos tend to have an analgesic effect, nocebos often cause negative effects or emotions when the subjects are told that they should expect/anticipate them. Before discussing any of these questions, it is worth noting that the Norwegian study focuses solely on classic sexual differences between cis-gender men and women. Though both keywords ‘gender’ and ‘sex’ were included in the study, research surrounding the specific effects of gender identity and gender-affirming therapies on placebos has not been thoroughly conducted as of 2023. It is with this focus that the following hypotheses are stated (3): “1) placebo responses would be stronger or more frequently observed in males than in females, 2) nocebo responses would be stronger or more frequently observed in females than in males, 3) verbally induced placebo responses would be more frequently observed in males than in females, and 4) conditioned nocebo responses would be more frequently observed in females than in males.” Results concluded that there was indeed a significant correlation between sex and placebo/nocebo effects when concerning pain relief. But what is truly fascinating is that while men received elevated levels of a placebo effect, such as reduced symptoms and analgesia, women were more susceptible to hyperalgesia and negative emotions. Those supposed ‘side effects’ appear to weigh more heavily on women (3). What does this say about how men and women process pain and information? The Norwegian study discusses the role of ‘psychophysiological mechanisms’ in pain pathways. Or, more simply, How stress and anxiety can affect the pain the brain perceives. In 8 of the 12 studies, men experienced significantly stronger analgesic effects from the placebo than women (3). It is plausible that men react more strongly to pain induced by stress hormones. This would explain why when taking a placebo, their anxiety level would decrease, and they would receive higher levels of analgesia than their female counterparts (3). Another study, upon which the Norwegian argument builds, investigates placebo delivery methods and their effect on perceived pain in men and women. In this study, men relied far more on verbal queues to provide analgesia, whereas women received a more significant effect from classic conditioning (5). These studies bring into question both the methodological and physiological effects of placebos on different sexes. What do these differences tell us about how men and women perceive the world? And what does this mean for the future of the placebo? The result of all of these studies is to show not whether placebos are bad or good, reliable or unreliable, but instead to highlight the differences in the physiological and psychological links when looking at different groups of people. At its core, a placebo is simply a trick of the brain, a psychological mirage. While the basis and reliability of placebos can be debated at length, their effect on the human brain teaches us something about ourselves societally. In all areas of medicine, the inclusion of people from all different backgrounds, genders, ethnicities, and ages is crucial so professionals know how to identify and treat various manifestations of a disease with grace and care. Now I know James responds better to verbal commands; I’ll be sure to tell him he has rabies the next time I see him. References Henning Schumann J. I contracted medical student syndrome. You probably will too. [Internet]. AAMC. [cited 2023 Jun 22]. Available from: https://www.aamc.org/news/i-contracted-medical-student-syndrome-you-probably-will-too Harvard Health Publishing. The power of the placebo effect - Harvard Health [Internet]. Harvard Health. Harvard Health; 2021. Available from: https://www.health.harvard.edu/mental-health/the-power-of-the-placebo-effect Vambheim S, Flaten MA. A systematic review of sex differences in the placebo and the nocebo effect. Journal of Pain Research. 2017 Jul;Volume 10:1831–9. National Cancer Institute NCI. Definition of nocebo effects [Internet]. www.cancer.gov . 2011. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nocebo-effect Enck P, Klosterhalfen S. Does Sex/Gender Play a Role in Placebo and Nocebo Effects? Conflicting Evidence From Clinical Trials and Experimental Studies. Frontiers in Neuroscience. 2019 Mar 4;13. 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Issue 5: Wicked 24 October 2023 This issue spotlights the mischievous, malevolent and morally dubious. Dive into a fascinating selection of articles by our talented writers below! A Message from the Editors in Chief Rachel Ko & Ingrid Sefton A word from our Editors-in-Chief. Columns Chatter Why Do We Gossip? Lily McCann Rumours, reputation and reciprocity: Lily debates the connotations we make with gossip and whether our assumptions of its malicious nature are justified. Ethics in Science Three-Parent Babies? The Future of Mitochondrial Donation in Australia Kara Miwa-Dale Cutting edge IVF technology is challenging our perceptions of what it means to be a parent. Kara deconstructs the social issues and ethics of mitochondrial donation. Features When Dark Matters Ingrid Sefton Dark matter: it has a name, yet no identity. Ingrid untangles the enigmatic nature of dark matter, probing into just what we do and don’t know about this cosmological puzzle. Black Holes: Defying Reality and Challenging Perception Mahsa Nabizada Black holes: portals into the unknown? Mahsa guides us through the mind warping and perception defying nuances of black holes. On the Folklore of Fossils Ethan Bisogni Ethan traverses the interface of palaeontology and mythology, considering the insights fossils provide into both natural phenomena and human nature. Wicked Invaders of the Wild Serenie Tsai In this article, Serenie examines the detrimental and dastardly effects of invasive species and their future implications. Griefbots: A New Way to Grieve (or Not) Akanksha Agarwal Akanksha considers the efficacy and ethics of AI Griefbots, exploring the implications for grieving, and the boundaries between life, death and human connection. Serial Killers Selin Duran Ever find yourself falling down the rabbit hole of gory true crime stories? Selin explores why our society is so infatuated with the lives of cold-blooded killers.

By Rachel Ko < Back to Issue 3 “Blink and you’ll miss it”: A Third Eyelid? By Rachel Ko 10 September 2022 Edited by Ashleigh Hallinan and Yvette Marris Rachel Ko Next The creature snarls a deep, thundering growl, tensing its protruding muscles that are covered in layers of thick, green, armour-like scales, individually rattling by the sheer force of its stance. Clenching its claws, the lizard glares with a bizarrely human expression, a villain trapped in a peculiar hybrid humanoid form. As the screams of terrified students fill the air, the camera zooms into the mutant’s glistening yellow eye, and it blinks; a slimy, translucent covering flickers across its eyeball, leaving a trail of moisture - grotesque proof of its reptilian form. A charm of the cinematic world is that aliens, radioactive spider superheroes and giant mutant lizards can exist in the same universe as the regular person. On a recent movie night, watching The Amazing Spiderman, the villain Lizard caught my eye. The creature is a metamorphosed version of human scientist Dr Curt Connors, who had attempted cross-species genetic regeneration on himself. Largely CGI, the Lizard’s primitive no-frills characterisation makes him an unconventional superhero antagonist. However, upon focus, these exaggerated reptilian characteristics are wha become staples of the Lizard’s uniquely villainous appeal: the alien-green colouring, the razor-sharp claws, the terrifying teeth and, of course, the glistening yellow eyes. Figure 1: Spiderman's 'The Lizard' In reference to the creation of these eerie eyeballs, animation supervisor David Schaub confirmed the purposeful inclusion of a nictitating membrane (1). This membrane is a slimy skin-like covering more commonly known as the Third Eyelid. In animals such as birds, reptiles, fish, amphibians, and some mammals (2), it acts as a bizarre protective mechanism that maintains moisture while retaining vision (3) - and also gives the Lizard’s glare that extra kick. Acting like a windscreen wiper, the membrane ‘nictitates’, meaning it blinks, to keep debris and dust out of the eye while simultaneously hydrating it. Its transparency also allows vision underground or underwater (4). Figure 2: A bird blinking! There is just one primate species known to have a prominent nictitating membrane: the Calabar angwantibo, also known as the golden potto, which is a rare African prosimian primate found only in Cameroon and Nigeria (5). Figure 3: Look at the Calabar's nictating membrane! The membrane is a major characterising feature of The Amazing Spiderman’s creepy mutant reptilian aura. However, this Third Eyelid actually has a homologous counterpart in Dr Connors’ eyes too. In fact, it is found in all humans, and is known as our plica semilunaris, a vertical fold of conjunctiva in the inner corner of the eye (6). Although it plays a minor role in eye movement and tear drainage (7), the plica semilunaris has nowhere near as great a function in humans as the nictitating membrane does in animals (8). The plica semilunaris and its associated muscles are merely an evolutionary remnant of the nictitating membrane that existed in our reptilian ancestors millions of years ago (9). Evolution is driven by selective advantage: the traits that allow organisms to survive and reproduce are the ones that are selected for and thrive within the population, passed down from one generation to the next (10). Traits that are disadvantageous to organisms decrease their chance of survival and reproduction, meaning fewer offspring will inherit the trait, causing it to eventually disappear from the population (11). The mystery remains as to why human ancestors lost the nictitating membrane in the first place, but it is likely that changes in habitat and lifestyle regarding eye physiology made it selectively advantageous to lose the Third Eyelid, rather than wasting precious energy on maintaining a no-longer-vital mechanism (12). For some reason, though, once the nictitating membrane had evolved into nothing more than a miniscule pink fold in the corner of the eye, it still persisted. Some argue that this is because humans have had no evolutionary incentive to completely lose them (13) – the plica semilunaris is just harmless enough that it has flown under the radar of evolution’s cut. Having suggested that, however, the primary clinical significance of the plica semilunaris has been connected to allergies of the eye, in which release of inflammatory molecules like histamine causes the tissue to become swollen and itchy (14). Thus, it is worth considering another argument: that the persistence of the plica semilunaris may be indicative of some beneficial function, particularly in its role in human eye protection. It has been found that the tissue observed in early intrauterine (within the uterus) development has a dense infiltration of immune cells like macrophages and granulocytes that serve to engulf and destroy foreign invaders of the tissue (15). Along with the abundance of blood vessels and immune chemical signalling, this has suggested a specialised role in eye protection, a benefit that may have very well ensured the plica semilunaris’ survival within human populations until this day (16). One fascinating clinical case, which showcases the outlandish capabilities of this vestigial feature, is of a child for whom it was not a question of why the plica semilunaris persisted, but an actual nictitating membrane. This peculiar instance was presented on a 9 year-old girl whose left eye had a non-progressive translucent membrane covering it horizontally. The globe of the eye was able to move freely beneath the membrane, suggesting that there was no attachment. However, it was causing amblyopia (also known as a lazy eye), and poor vision, so the nictitating membrane was successfully removed by simple excision (17). Figure 4: The plica semilunaris Figure 5: A clinical case of a human nictating membrane The only other recorded case of persisting nictitating membrane was an infant boy born prematurely with Edwards syndrome, who had nictitating membranes in both eyes (18). However, due to the baby’s infancy and condition, membrane imaging was unobtainable. Thus, arguably, the most striking aspect of the 9 year-old girl’s case was the pre-procedure imaging of her eye: an intriguing, almost alien-like fusion of the human eye and that of our reptilian ancestors. This case study can be interpreted as an exaggerated example of an existing link between the nictitating membranes we see in animals today, and the plica semilunaris that exists, tucked away, in the corner of our very own eyes. So, next time you find yourself staring into your partner’s baby blues, or putting on eyeliner in the mirror, keep an eye out for this fascinating evolutionary remnant; but be quick because - blink and you’ll miss it. References Sarto D. 'Spider-Man'’s Lizard Part 1: The Animation [Internet]. Animation World Network. 2012 [cited 4 May 2022]. Available from: https://www.awn.com/vfxworld/spider-mans-lizard-part-1-animation Butler A, Hodos W. Comparative vertebrate neuroanatomy. Hoboken (New Jersey): Wiley-Interscience; 2005. Why do cats have an inner eyelid as well as outer ones? [Internet]. Scientific American. 2006 [cited 4 May 2022]. Available from: https://www.scientificamerican.com/article/why-do-cats-have-an-inner/ The Equine Manual [Internet]. Elsevier; 2006. Available from: http://dx.doi.org/10.1016/B978-0-7020-2769-7.X5001-1 Montagna W, Machida H, Perkins EM. The skin of primates. XXXIII. The skin of the angwantibo (Arctocebus calabarensis) [Internet]. Vol. 25, American Journal of Physical Anthropology. Wiley; 1966. p. 277–90. Available from: http://dx.doi.org/10.1002/ajpa.1330250307 Plica semilunaris [Internet]. Merriam-Webster.com medical dictionary. [cited 4 May 2022]. Available from: https://www.merriam-webster.com/medical/plica%20semilunaris LaFee S. Body and Whole [Internet]. UC Health - UC San Diego. 2016 [cited 4 May 2022]. Available from: https://health.ucsd.edu/news/features/pages/2016-06-30-listicle-body-and-whole.aspx Dartt D. Foundation Volume2, Chapter 2. The Conjunctiva–Structure and Function [Internet]. Oculist.net. 2006 [cited 4 May 2022]. Available from: http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v8/v8c002.html Gonzalez R. 10 Vestigial Traits You Didn't Know You Had [Internet]. Gizmodo. 2011 [cited 4 May 2022]. Available from: https://gizmodo.com/10-vestigial-traits-you-didnt-know-you-had-5829687 Sukhodolets V. V. (1986). K voprosu o roli estestvennogo otbora v évoliutsii [The role of natural selection in evolution]. Genetika, 22(2), 181–193. Sukhodolets V. V. (1986). K voprosu o roli estestvennogo otbora v évoliutsii [The role of natural selection in evolution]. Genetika, 22(2), 181–193. Gonzalez R. 10 Vestigial Traits You Didn't Know You Had [Internet]. Gizmodo. 2011 [cited 4 May 2022]. Available from: https://gizmodo.com/10-vestigial-traits-you-didnt-know-you-had-5829687 Kotecki P, Olito F. We No Longer Need These 9 Body Parts [Internet]. ScienceAlert. 2019 [cited 4 May 2022]. Available from: https://www.sciencealert.com/we-no-longer-need-these-9-body-parts Bielory L, Friedlaender MH. Allergic Conjunctivitis [Internet]. Vol. 28, Immunology and Allergy Clinics of North America. Elsevier BV; 2008. p. 43–58. Available from: http://dx.doi.org/10.1016/j.iac.2007.12.005 Arends G, Schramm U. The structure of the human semilunar plica at different stages of its development a morphological and morphometric study [Internet]. Vol. 186, Annals of Anatomy - Anatomischer Anzeiger. Elsevier BV; 2004. p. 195–207. Available from: http://dx.doi.org/10.1016/S0940-9602(04)80002-5 Arends G, Schramm U. The structure of the human semilunar plica at different stages of its development a morphological and morphometric study [Internet]. Vol. 186, Annals of Anatomy - Anatomischer Anzeiger. Elsevier BV; 2004. p. 195–207. Available from: http://dx.doi.org/10.1016/S0940-9602(04)80002-5 Vokuda H, Heralgi M, Thallangady A, Venkatachalam K. Persistent unilateral nictitating membrane in a 9-year-old girl: A rare case report [Internet]. Vol. 65, Indian Journal of Ophthalmology. Medknow; 2017. p. 253. Available from: http://dx.doi.org/10.4103/ijo.IJO_436_15 García-Castro JM, Carlota Reyes de Torres L. Nictitating Membrane in Trisomy 18 Syndrome [Internet]. Vol. 80, American Journal of Ophthalmology. Elsevier BV; 1975. p. 550–1. Available from: http://dx.doi.org/10.1016/0002-9394(75)90228-7 Images Figure 1: Galloway, R. (2022, January 25). Lizard originally had a different look in 'Spider-Man: No way home'. We Got This Covered. Retrieved August 9, 2022, from https://wegotthiscovered.com/movies/lizard-originally-had-a-different-look-in-spider-man-no-way-home/ Figure 2: Hudson T. (2010, July) Retrieved Sep 13, 2022, from https://en.wikipedia.org/wiki/Nictitating_membrane#/media/File:Bir d_blink-edit.jpg Figure 3: Sharma R. Calabar angwantibo - Alchetron, The Free Social Encyclopedia [Internet]. Alchetron.com. 2018 [cited 7 May 2022]. Available from: https://alchetron.com/Calabar-angwantibo Figure 4: Amir, D. (2019, January 16). Twitter. Retrieved August 9, 2022, from https://twitter.com/dorsaamir/status/1085557444196 081664 Previous article Next article alien back to

By Andrew Lim From Fusion to Submarines: A Nuclear Year By Andrew Lim 23 March 2022 Edited by Tanya Kovacevic Illustrated by Quynh Anh Nguyen A press conference in April, pledging millions of dollars to nuclear medicine. A university address in November, rethinking Australia’s nuclear attitudes. A fusion reaction in December, promising a clean energy revolution. No matter where you were or who you were listening to, the world of nuclear science was inescapable in 2022. It has been a year of great progress and, at times, even greater controversy – pairing milestone triumphs and landmark facilities with old fears and vast challenges. So, what has defined the year in nuclear science – and what comes next? Powering the Future Image 1: LLNL’s National Ignition Facility, where the successful fusion ignition experiment was conducted in December. Perhaps the year’s most eye-catching discovery came near its end. On 13th December, scientists at the Lawrence Livermore National Laboratory (LLNL) in California announced that for the first time, they had produced more energy out of a nuclear fusion reaction than they had put in. It seemed to herald the beginnings of a new era – nuclear power without toxic nuclear waste. However, to report this as the USA’s civilian nuclear energy story of the year perhaps fails to capture the whole picture. It’s an important discovery, sure, but it stands on another development, far less well known: the congressional funding battles of the preceding months. Crafted from intense negotiations led by Majority Leader Chuck Schumer (D-NY) and Senators Todd Young (R-IN), Mark Warner (D-VA) and John Cornyn (R-TX), the bipartisan CHIPS and Science Act (1) authorized and appropriated funds for nuclear research en masse. It provided everything from a five-year $50 million p.a. plan for “Foundational Nuclear Science” (2), to a $1.09 billion Electron Ion Collider (3) and a “National Nuclear University Research Infrastructure Reinvestment” scheme that included LLNL (4). Even private sector fission work received a boost in the form of the Inflation Reduction Act of 2022 (5), built on a compromise between Schumer and Senator Joe Manchin (D-WV), allocating billions of dollars in tax credits and loan guarantees for the sector. These funding boosts (and their predecessors), the work of years of lobbying and negotiations across multiple political factions, helped create the environment necessary for this research to thrive – and the breakthrough is as much a reminder of their importance as a triumph of nuclear physics. Health and Safety Image 2: Prime Minister the Hon Scott Morrison MP, flanked by Health Minister the Hon Greg Hunt MP (L) and backbencher Gladys Liu MP (R), announces a $23 million APME grant in April. The year’s nuclear focus extended into the medical sector, too. President Biden’s 2022 State of the Union address announced an appeal beyond partisan lines, one pillar of which was the use of the Advanced Research Projects Agency for Health (ARPA-H) to “drive breakthroughs in cancer” (6). His call was answered in budget appropriations bills, funding accelerators and reactors to research new radioisotopes, while also investigating safer handling methods for natural and artificial nuclear sources (7). Such emphases echoed as far away as our antipodean shores. While Australia may already produce 80% of the radioisotopes used in its own nuclear medical procedures (8), both major parties took 2022 to advance nuclear medicine production. In April, the Coalition government launched new grants for the Australian Precision Medicine Enterprise (APME) in Melbourne, with the Hon Greg Hunt MP, then Minister for Health, declaring nuclear medicine “the next stage of precision medicine.” (9) Mere months later, in the October Budget, his Labor successor the Hon Mark Butler MP pledged funds for medical supplies of Gallium-67 (10). Across party lines, nuclear innovation became key to funding in the health sector. Securing Tomorrow Image 3: Australian Deputy Prime Minister and Minister of Defence Richard Marles (L) meets with US Secretary of Defence Lloyd J Austin III (R) at the Pentagon to discuss AUKUS submarine arrangements in December. All that said, no article about nuclear science, especially these days, would be complete without a discussion of AUKUS. In late October, an interview with Australian Vice Admiral Jonathan Mead was published in The Australian, in which he underscored the importance of building a nuclear workforce – that is, building the educational pathways required to produce all the crews, builders, architects, regulators and scientists a nuclear submarine capability would entail (11). With Australia’s first nuclear submarine captains likely in high school, the infrastructure needed to train them simply doesn’t exist – and time is running out. This urgency was emphasised by academics at ANU, home of the only postgraduate qualifications dedicated to nuclear science in the country. In November, Vice-Chancellor Brian Schmidt AC spoke of an approaching “transformation in Australia’s cultural relationship” with nuclear science (12). In December, Dr AJ Mitchell, an ANU academic leading the development of a national program for nuclear science and education, reiterated Schmidt’s arguments. In comments provided to The Sydney Morning Herald and The Age, he advocated for a “sovereign capability…start[ing] yesterday,” to ensure an Australian nuclear workforce capable of meeting requirements not only for defence but also for health, regulation, space exploration and much more (13). However, this attitude was not without controversy. In today’s world, where the word ‘nuclear’ carries connotations of Chernobyl, Fukushima, and the Cold War, increased nuclear funding (even if only to regulatory or medical bodies) often sparks fear in the public imagination. In response to Mitchell’s comments, A/Prof Peter Christoff, a University of Melbourne climate policy researcher, expressed worries about increased “anxiety in our region”. More than anything else, this perhaps underscores the biggest issue facing the nuclear sector: the long-held apprehensions from media, governments and beyond that can often lump anything vaguely nuclear – from medication to missiles – under the same roof. What's Next? Image 4: US President Joe Biden delivering his 2023 State of the Union Address, advocating for increased cancer research funding, flanked by Vice-President Kamala Harris (L) and Speaker Kevin McCarthy (R). Over the first months of 2023, the tense balancing acts and decisions of the past year have only continued to grow. In the USA, President Biden’s 2023 State of the Union speech, delivered in early February, saw him reinvigorate his call to “end cancer as we know it” (14) – the same call that led to all that radioisotope funding last year. However, Biden faces a Republican House of Representatives seemingly hell-bent on blocking his legislation. With the resultant impasse threatening a wholescale government shutdown, the funding necessary for scientific leaps of the kind seen in 2022 remains in doubt. On the Australian front, our lack of a ready nuclear workforce is causing jitters amongst our allies – with leaked letters from US Senators Jack Reed (D-RI) and James Inhofe (R-OK) expressing concern to the Biden administration about Australia relying on American production lines for stopgap submarines. Australian Defence Minister Richard Marles spent the December-January period allaying these concerns with the support of US Representatives Joe Courtney (D-CT-02) and Mike Gallagher (R-WI-08) while in the US and UK, but the issue is certain to remain a hot topic for this year. Even closer to home, Rio Tinto’s loss of a Caesium-137 capsule in Western Australia captured the imaginations of people across the nation and the world. At once it seemed to represent the long-standing fear of nuclear research and its importance in fuelling the same regulatory efforts that helped track down the capsule. Perhaps more than a story of scientific discoveries, of neutrons, protons and physics, the story of nuclear science in 2022 and beyond is the story of people. Of those legislators and politicians, balancing visions of the future with messy political compromises. Of those scientists and researchers, balancing plans and facilities with the capacity of their institutions. Of us, the ordinary public, balancing long-held phobias with exciting aspirations. Will we meet the challenges that lie before us? Are we ready to have a nuanced discussion about how we want to use our nuclear knowledge? Can we balance the possibilities of the future with the fears of the past? Well... that’s entirely up to us. Andrew Lim is an Editor and Feature Writer with OmniSci Magazine and spent the summer as a Summer Research Scholar at the Australian National University’s Heavy Ion Accelerator Facility, working on studying nuclear structure through particle transfer reactions. Image Credits (in order): Lawrence Livermore National Laboratory; Monash University; US Department of Defence; The White House Author's Note Between the submission of this article in late February and its publication in mid-March, a notable development took place, one that necessitated this additional note. On March 14, at an announcement held in San Diego, President Biden, Prime Minister Albanese and Prime Minister Sunak revealed plans for Australia to purchase three to five American Virginia-class submarines in the early 2030s. The Royal Navy and the Royal Australian Navy would then work out of their shipyards to develop and produce new SSN-AUKUS submarines (based off plans for successors to the British Astute-class models), coming into service in the late 2030s. If anything, this timeline accentuates the dramatic expansions required from Australia’s nuclear workforce, as presented in the original article. Meanwhile, the narrative that surrounded the announcement – one solely focussed on nuclear research’s military capabilities (and, at that, often conflating nuclear weaponry with nuclear power) – seems only to indicate the same throughlines of 2022 repeating themselves in the year to come…and nuanced and subtle discussion of nuclear research being left for another day. References CHIPS and Science Act, Pub L No 117-167, 136 Stat 1366 (2022). See ibid, div B tit I § 10102(d), 136 Stat 1415-6. See ibid, div B tit I § 10107, 136 Stat 1449-50, esp. sub-s (b)(4). See ibid, div B subtitle L § 10741-5, 136 Stat 1718-21. Inflation Reduction Act of 2022, Pub L No 117-169, 136 Stat 1818. The White House Office of the Press Secretary, Remarks by President Biden in State of the Union Address. March 2, 2022. https://www.whitehouse.gov/briefing-room/speeches-remarks/2022/03/02/remarks-by-president-biden-in-state-of-the-union-address/ See House Committee on Appropriations, Report to Accompany H.R. 8295, H.R. Rep No 117-403 (2022), esp. at 65, 104, 235, 238. Taylor A, Birmingham S and Hunt G, Safeguarding the future of critical medicine supply [Media Release]. September 30, 2021. https://www.minister.industry.gov.au/ministers/taylor/media-releases/safeguarding-future-critical-medicine-supply. “Precision medicine is the ‘future of medicine’: Greg Hunt”. The Australian. April 4, 2022. https://www.theaustralian.com.au/nation/politics/precision-medicine-is-the-future-of-medicine-greg-hunt/video/9ec9b0942bfb18757e3fbf4f3e95e0f4 Garvey, P. “Butler steps in to ease nuclear medicine crisis”. The Australian. October 27, 2022. Nicholson, B. “Defence Special Report: Cultivating a Nuclear Mindset”. The Australian. October 27, 2022. ANU Communications & Engagement, Building Australia’s AUKUS-ready nuclear workforce: Address by Professor Brian Schmidt AC. November 9, 2022. Mannix, L. “‘Cherish’ the power: Physicists issue call to arms over nuclear skills gap”. The Sydney Morning Herald. December 28, 2022. https://www.smh.com.au/national/cherish-the-power-physicists-issue-call-to-arms-over-nuclear-skills-gap-20221228-p5c92s.html The White House Office of the Press Secretary, Remarks by President Biden in State of the Union Address. February 7, 2023. https://www.whitehouse.gov/briefing-room/speeches-remarks/2023/02/07/remarks-by-president-biden-in-state-of-the-union-address-2/ Previous article Next article

< Back to Issue 9 Knot Theory and Its Applications. Why Knot? by Ryan Rud 28 October 2025 Illustrated by Saraf Ishmam Edited by Elijah McEvoy Knot theory is a theoretical study in mathematics, where your brain thinks of an imaginary knot, and manipulates it to your heart’s desire. Yes, the kind of knot you are probably thinking of now, it might be a shoelace, a knot in a piece of string or some utility knot. Good job, but it’s missing one detail: the knot needs to be tied at its ends. Think of this as a string with both ends tied together so that it can’t come undone when you play with it. Now you can pull at and twist this knot, as long as you don’t break it. Congratulations, you now understand the basics of knot theory. (1) So why should we care about a niche field of maths that you will probably never use in your everyday life? Well, the first answer to that is simply ‘for the love of the game’. For some people problem-solving is an endless endeavour that satisfies an urge to understand and be intellectually stimulated. But that’s not for everyone. So then we remember all the times when random elements of pure mathematics became essential when applied to seemingly unrelated topics. Such as how number theory became applied to information transmission, cryptography and computing. (2) How quaternions made for more efficient digital transformations in computer science. (3) Or how graph theory was used to strongly conjecture that any two people have 6 degrees of separation between each other. (4) Although we may not routinely ponder these discoveries, it is because of the works of pure mathematicians that we can admire certain facts that we could not prove otherwise or appreciate how they silently helped to make all the digital devices in your homes. But before we get into the applications, it is good to be familiar with some general terminology. That knot which you pictured earlier with its ends tied is called a standard knot. In 1867 Lord Kelvin thought of the revolutionary idea that what we know as elements - the ones made of protons and neutrons - are actually types of standard knots. (5) He wasn’t right, but it inspired his assistant Peter Guthrie Tait to begin the rigorous study of knots and we have been trying to find applications ever since. Here are the first knots in the greater sequence of the periodic table of knots (see cover image for more!): Figure 1. An ordered table of the first 15 prime knots. (6) There are knots made from one piece of string (prime knots) and knots made from multiple knots joined end-to-end (composite knots) (Fig.2b). There are also links, where two closed knots are combined without gluing the string (Fig.2a). Understanding any further implications of this terminology is not necessary here, but it may help to have a visual understanding of them for the next part. Figure 2. a) Showcasing types of mathematical links; unlink on the left, Hopf link in the centre and whitehead link on the left. b) Demonstrating how two prime knots are combined into a composite knot. c) Demonstrating chirality in trefoil knots, notice the overlapping pattern. Lastly, like many things in mathematics we need a way to systematically and efficiently describe how we manipulate the knots. Luckily, Kurt Reidemeister had the pleasure of providing us with a knot-manipulating moveset in the 1930s through rigorous proofs.These are the legal set of moves that can be done to a knot without changing the knot structure. If we were to cut the knot, twist or untwist the string and then reattach the ends, this is called a crossing switch and it changes the knot. Again, this is not an extensive course but it helps to know of the terminology and visualise it. Feel free to do more research into the details of these topics using the references below! Figure 3. A depiction of the Reidemeister moves. DNA and knot theory Deoxyribonucleic acid (DNA) is the most important and relevant knotting molecule. Each cell nucleus contains (on the millionth order) DNA that is regularly knotting, coiling and compressing to fit into this tight space. However, the best application of knot theory is to the closed end, circular DNA in bacteria. During DNA replication, the unwinding of DNA at one end creates immense torsional strain on the other side of the loop, which is enough supercoiling that prevents replication and leads to cell death.To counter this, bacteria utilise an enzyme known as type II topoisomerase which makes double-stranded cuts in the DNA, followed by a rearrangement of the tangle and reconnecting of the strands, a crossing switch! Without this adaptation, all cellular life would have evolved differently. If you gave this DNA to a mathematician and asked which position in the DNA would be best for this enzyme to cut with the intent of untangling, they could spend a lifetime performing Reidemeister moves and contemplating, never knowing where or how many cuts to make. In contrast to our world’s best mathematicians, topoisomerase is incredibly efficient in where it cuts. We have yet to understand what mechanism allows for such accurate cuts, but practical research into topoisomerase could potentially help knot theorists solve the immensely inscrutable question of the minimum number of crossing switches to simplify any knot. Furthermore, if an understanding of the mechanisms for topoisomerases in bacteria and humans is possible, then humanity can access a new form of control over DNA. It has been speculated that there are possible uses of topoisomerases to inhibit cancer growth, or as a revolutionary way to treat bacterial disease. While we do not have this intel right now, this is one of the ways knot theory could be integral to applied sciences and given time and research funding, it can prove itself useful. (7-8) Knots in chemistry So what other molecules can form knots? Chemists have been creating molecules which involve the basic knots and links since the 1960s (see Fig 4), when topological isomerism was discovered and characterised. Topological isomers are chemicals that are similar in many properties, but differ in spatial arrangement. We can think of it like chirality for knots (see Fig 2c). Chirality is the property of an object not being the same as its mirror image, like a right and left hand. Subsequently, these molecules were made through a technique called ‘templating’, where a metal ion or some template structure was used to produce a desired product, based on how the template interacts with the reactants. There is also another category of knot called a ravel (Fig 4h), where a knot has multiple strings connected at vertices. Altogether, the study of topological isomerism and templating techniques have been advanced by the experimental desire to produce these beautiful molecules. This then indirectly contributes to the production of new molecules and drugs that can go on to have real world impacts. (9) Figure 4. a) The first molecular trefoil knot produced in 1989. c) The first molecule pentafoil knot produced in 2011. d) First molecular Borromean rings, a type of link produced in 2004. f) The first molecule solomon link produced in 2013. h) The first molecular ravel produced in 2011. (9) The recent breakthrough in knot theory I admit, progress in knot theory is slow and perhaps you did not find the scientific revelation of knot theory here that you were hoping for. But that does not mean that current research is ineffective. As recent as June of this year, there was a groundbreaking proof. Think back to the prime and composite knots (scroll up if you have to). Prime knots have an unknotting number, which is the number of crossing changes needed to simplify it to the unknot, similar to what the topoisomerase does. If we merge two prime knots into a composite knot, it can be easily seen that it takes as many crossing switches to simplify the composite, as it does the crossing switches for the sum of the primes. In other words, to untangle a composite knot, you cut and reglue it as many times as the prime knots that make it up. Now, the breakthrough was a proof that it is possible to untangle some composite knots through less crossing switches than the sum of its prime knots. This may seem bleak, but it disproves a widely believed conjecture and now theorists are one step closer to solving the question of the minimum number of crossing switches needed to simplify a knot. (10) Conclusion I will end this with a quote from Dr Arunima Ray, a mathematician that specialises in knot theory and low-dimensional topology at the University of Melbourne, and a dear professor of mine. Hopefully this is just more proof (pun intended) that the work us mathematicians do is tangible: “I had never imagined that mathematics could be used to describe something so abstract as knot theory, but to me the appeal was its tangibility. No matter who you are, there really is something in mathematics for you.” References Pencovitch M. What’s not to love? [Internet] Mathematics Today . 2021. Available from: https://ima.org.uk/17434/whats-knot-to-love/ Koblitz N. A course in number theory and cryptography . 2nd ed. Springer Science & Business Media; 1994. Jeremiah. Understanding quaternions. 3D Game Engine Programming [Internet]. June 25, 2012. Available from: https://www.3dgep.com/understanding-quaternions/ Zhang L, Tu W. Six degrees of separation in online society [Internet]. Research Gate. 2009. Available from: https://www.researchgate.net/publication/255614427_Six_Degrees_of_Separation_in_Online_Society Wilson RM. Holograms tie optical vortices in knots. Physics Today. 2010. https://doi.org/ 10.1063/1.3366639 Li M, Wang T, Kau A, George W, Petrenko A. Knots. Brilliant. 2025 [Internet]. Available from: https://brilliant.org/wiki/knots/ Catherine. All tangled up: an introduction to knot theory [Internet]. Gleammath. April 28, 2021. Available from: https://www.gleammath.com/post/all-tangled-up-an-introduction-to-knot-theory Skjeltorp AT, Clausen S, Helgesen G, Pieranski P. Knots and applications to biology, chemistry and physics. In: Riste T, Sherrington D, editors. Physics of Biomaterials: Fluctuations, Selfassembly and Evolution. Dordrecht: Springer Netherlands; 1996. p.187–217. https://doi.org/10.1007/978-94-009-1722-4_8 Horner KE, Miller MA, Steed JW, Sutcliffe PM. Knot theory in modern chemistry [Internet]. Chemical Society Reviews. 2016;45(23). Available from: https://durham-repository.worktribe.com/output/1394834 Brittenham M, Hermiller S. Unknotting number is not additive under connected sum [Internet]. Arxiv . 2025. Available from: https://arxiv.org/html/2506.24088v1 Previous article Next article Entwined back to

By Caitlin Kane, Rachel Ko, Patrick Grave, Yvette Marris Message from the Editors in Chief By Caitlin Kane, Rachel Ko, Patrick Grave, Yvette Marris 23 March 2022 Edited by the Committee Illustrated by Quynh Anh Nguyen Another year in science has passed, with 2022 disappearing into 2023. With a mandated return to campus life at the University, there seems a tangible break from the past three years of lockdowns, isolation and online existence. Over the summer holidays, four of our wonderful OmniSci contributers—Andrew, Julia, Lily and Yvette—have written about science that has made a mark in 2022, with topics spanning DNA of the ancient past to the future of art crafted by artificial intelligence. Our writers were supported by editors, Tanya and myself, and the cover and article art for this issue has been created by Quynh Anh. Thanks also goes to our behind-the-scenes events duo, Andrew (again!) and Aisyah, who have been working hard on promotion to showcase the work of our team on this mini-issue, and our treasurer-secretary, Maya, who keeps us all in line. On behalf of the whole team, we're incredibly excited to share our summer issue, 2022: A Year in Science. If you would like to support our work, you can sign up as a member, join our mailing list or get in touch at omniscimag@gmail.com—all this and more on our About Us page. Most importantly, please read on! Previous article Next article

< Back to Issue 9 Conferring with Consciousness by Ingrid Sefton 28 October 2025 Illustrated by Heather Sutherland Edited by Steph Liang Down the rabbit hole Indulge me for a moment, will you? I value your opinion. Your opinion, as in, one which has arisen from your mind. I would assume. It would seem unusual to consider that, perhaps, your thoughts are not your own. Stranger still to ponder the possibility that they did not arise from your mind. I digress – or maybe not. For it is this dilemma which I wish to pick your brain on. The mind. The brain. You. Are they one and the same; entwined? What do you think? Again, assuming it is you thinking. Assuming you feel certain enough to agree with this. Really, with what certainty can we say anything? You may be wondering who “I” am. I am but you, of course! I kid, but not entirely. Think of me as the brain; your brain if you wish. An excellent name I gave myself, if you ask me. Before we spiral any deeper into this chasm that is consciousness – because that is what this is about, is that not what this, life, is all about? – I must disclose a few things. One, I do not expect you to have answers to these questions I pose. Because two. We do not have answers. I apologise that I have not come bearing the answers to our existence, that I have not yet unpicked these questions of “who?”, “how?”, “why?”. I come offering an alternative. I wish to present to you these entangled threads of consciousness: of what we currently know, of what we hope to know and of where we can proceed from here. Then it’s back to you. You get to decide what you think (again, with the thinking). Maybe, for you and the workings of your inner mind, consciousness and all it entails will be revealed in full clarity. Maybe not. You certainly won’t know unless you try. A brief neural memoir Many a Nobel prize has been awarded for discoveries relating to the nervous system: from the morphology of neurons (Golgi and Cajal 1906) and their electrical signalling properties (Eccles, Hodgkin and Huxley 1963), to the nature of information processing in the visual system (Hubel and Wiesel 1981) (1). Despite some obvious gaps remaining in what is known about the brain (ahem, that slight issue of consciousness), the field of neuroscience has rapidly progressed over the last century. Gone are the days of thinking I was nothing more than a cooling mechanism for the blood, as Greek philosopher Aristotle once believed (2). How dismissive of my intellect! I assure you, I have far more important things to be doing. Generating the experience of “you”, as one small matter. The techniques developed to study the brain have also rapidly advanced. It was not until the invention of microscopes in the 19 th century that the neuron doctrine even came about . Pioneered by Santiago Ramón y Cajal, this is the (now) well-accepted concept that the nervous system is made up of discrete cells known as neurons, challenging older theories which proposed a continuous neural network (3). Today, neuroscientists have the ability to appreciate my anatomical and functional complexity at a huge range of temporal and spatial resolutions. Whole-brain connectivity can be studied using functional magnetic resonance imaging (fMRI), while the electrical activity of single neurons can be recorded using patch-clamp electrode technology. Not to mention optogenetics, chemogenetics, viral transduction: while the available experimental techniques are still unable to address all our brainy questions, the field of neuroscience has never been in a better position to get closer to answers. The potential of neurons Neurons: those special, excitable cells that make up the squishy entity I seem to be. The mechanisms of how neurons detect, generate and transmit signals have been described in utmost precision. When I talk of excitable cells, I am not referring to a bunch of cheerful, eager neurons. Excitability, in this context, refers to the fact that neurons can respond to a sensory stimulus by generating and propagating electrical signals, known as action potentials. Clearly, I am made up of slightly more than two neurons cheerfully signalling to each other back and forth. Try 86 billion, between the cortex and cerebellum combined (4). Yet, despite our deep understanding of neural signalling mechanisms, this has yet to reveal an explanation for consciousness. Individual neurons in isolation, it would appear, don’t hold the answers we want. In turn, a focus of neuroscience research has been on the wider “neuronal correlates of consciousness”, the minimal neuronal mechanisms that are sufficient to generate a conscious experience (5). This relates broadly to the generation of consciousness itself, but also to studying the neural underpinnings of specific conscious experiences. For example, which collective neural substrates support the process of visual object recognition. This is often a focus of fMRI studies, which examine brain activity in an attempt to pin-point where in the brain a particular cognitive function may be performed. Fancy techniques aside, some of the most fundamental insights into my regional specialisations have arisen from careful observation following selective lesions or damage to the brain. The critical, yet specific role of Broca’s area in speech production was discovered in 1861 by surgeon Paul Broca’s observations of his patient “Tan”. Tan had lost his ability to produce meaningful speech, yet was still able to comprehend speech; Broca identified a lesion in Tan’s left frontal lobe post-mortem, drawing the conclusion that this region is selectively involved in speech production (6). But what does all of this show us? Perhaps the only thing that neuroscientists can agree on, is that conscious experience is fundamentally, in some way, somehow, related to my activity: the brain. In turn, the activity of the brain is related to the activity of neurons; firing and signalling and transforming information. A lot is known about neurons. Less can be said about specific cognitive functions, yet we can see correlations between the regional brain activity and particular conscious experiences. Here lies my problem. The elephant in the room. How do we get from individual neurons to conscious experience? A map with no destination Enter “The Connectome” and the Human Connectome Project: a collective attempt to map the neuronal connections of the human brain, in an effort to connect structure to function (7). And in turn, for our purposes, to ideally connect this to consciousness. The rationale is that by modelling and trying to “build” a brain using a bottom-up approach, we may therefore understand the mechanisms of how cognitive functions arise. I’m sure it will come as no surprise that this isn’t the simplest of tasks. To measure, record and model billions of neurons and synapses requires techniques, time, and resources that are incredibly hard to come by in sufficient quantities. Excitingly, scientists have recently managed to successfully map a whole brain. That is, of a fly (8). With 3016 neurons and 548000 synapses, this was no simple feat. In case you had forgotten my own complexity, however, let me remind you of my 86 billion neurons, and estimated 1.5 x10 14 total synapses in the cortex alone (4). Progress has also been made on the human front, nonetheless. It was recently announced that a cubic millimetre of human temporal cortex has been completely reconstructed using electron microscopy, involving 1.4 petabytes of electron microscopy data (1000 Terabytes or one quadrillion bytes) (9). One cubic millimetre down, approximately a million to go. Putting practicalities aside, let us suppose we do, one day, manage to map and model an entire human brain, in all its intricacies. What now? What does one actually do with this data, and how would this allow us to better understand how consciousness arises? Up until now, we have been following the train of thought that consciousness, somehow, results from the activity of neurons, yet does not arise from the activity of individual neurons. This leads us to the notion that perhaps consciousness is due to the collective, computational activity of neurons working together – that with enough complexity, and enough information processing, together this will lead to the first-person experience of being “you”. Does this actually make sense? You tell me. Wishful thinking and conscious rocks The notion that, at a certain level of complex neuronal signal processing, a first-person perspective of “being you” (i.e. consciousness) arises is often termed “strong emergence” or “magical emergence” (10). With what we currently know about the properties of neurons, there is fundamentally no reason why this should happen. The “property” of consciousness, which cannot be predicted from the principles of how individual neurons function, seemingly just emerges. Consciousness, therefore, must somehow be greater than the sum of its parts, only emerging when neurons interact as a wider network. Maybe, the answer to this is merely that we don’t understand the mechanisms of neurons as well as we think we do. It could be that we have missed a fundamental property of how neurons operate and upon discovery of this, it would suddenly be completely explicable how consciousness arises. Or maybe, computation and neural signalling is not all there is to it. An alternative line of thinking is that rather than consciousness being a property that “arises”, it is a basic constituent of the universe that is missing from our current model of standard physics (11). That is, consciousness has been present all along and exists in everything. The philosophical view of ‘panpsychism’ embraces this idea to the extreme, proposing that everything within the universe is, to some degree, conscious (12). As in yes, that rock over there might just be conscious. Other theories suggest that consciousness only emerges in a recognisable form in certain conditions or at some critical threshold; myself and all my neurons apparently being one such example of the “right” conditions. Theories of consciousness don’t just stop at computation and fundamental properties of the universe. Quantum physics, microtubule computations, electromagnetic fields; all have been proposed as part of this web of “why” (13). While some theories arguably veer more towards pseudoscience than well-founded scholarship, they all make one thing clear. At this stage, just about every idea remains fair game in the quest for answers. Pondering hard, or hardly pondering? The question of consciousness is far from limited to the field of neuroscience. Philosophers too have long wracked their brains in an attempt to rationalise and unpick this problem. What unites the work of neuroscientists and philosophers alike, along with the many theories of consciousness, is that nothing provides a satisfactory explanation for why consciousness should emerge from the activity of neurons. Philosopher David Chalmers has termed this the “hard problem”. “Why should physical processing give rise to a rich inner life at all? It seems objectively unreasonable that it should, and yet it does” (14). If consciousness is simply the result of high-level processing and the computational activity of neurons, why would we even need to be conscious? If all the brain is doing is computation, and thus everything can be done via computation, there would appear to be no purpose in having a subjective experience of being “you”. Whichever side of consciousness we may be inclined to take, computational, fundamental, or otherwise, the fact remains. We cannot seem to move beyond mere description, to explanation. We have not solved the “hard problem”. A final conundrum, and a sole certainty Physicist Emerson M Pugh once made the somewhat sceptical remark that “if the human brain were so simple that we could understand it, we would be so simple that we couldn't.” (15) Is the reason that we have yet to understand consciousness simply, frustratingly, that we are not meant to? Logical conundrums aside, I rest my case. I hope I have given you some food for thought, or at the very least, not set off too dramatic an existential crisis. Somewhere between the neural wirings of the brain and the experience of consciousness lies an answer, regardless of whether we are destined to find it out. Make of this what you will. And if nothing else, let me try reassuring you once again with the wisdom of René Descartes. “ Cogito, ergo sum ” “ I think, therefore I am ” (16). If you are here, and you are thinking, you are conscious. You, my friend, are you. References Nobel Prizes in nerve signaling. Nobel Prize Outreach. September 16, 2009. Accessed October 18, 2025. https://www.nobelprize.org/prizes/themes/nobel-prizes-in-nerve-signaling-1906-2000/ . Rábano A. Aristotle’ s “mistake”: the structure and function of the brain in the treatises on biology. Neurosciences and History . 2018;6(4):138-43. Golgi C. The neuron doctrine - theory and facts . 1906. p. 190–217. https://www.nobelprize.org/uploads/2018/06/golgi-lecture.pdf Herculano-Houzel S. The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci . 2009;3:31. doi: 10.3389/neuro.09.031.2009 Koch C, Massimini M, Boly M, Tononi G. Neural correlates of consciousness: progress and problems. Nature Reviews Neuroscience . 2016;17(5):307-21. Broca area . Encyclopedia Britannica; 2025. Accessed October 18, 2025. https://www.britannica.com/science/Broca-area Elam JS, Glasser MF, Harms MP, Sotiropoulos SN, Andersson JLR, Burgess GC, et al. The Human Connectome Project: A retrospective. NeuroImage . 2021;244. doi: 10.1016/j.neuroimage.2021.118543 Winding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, et al. The connectome of an insect brain. Science . 2023;379(6636). doi: 10.1126/science.add9330 Shapson-Coe A, Januszewski M, Berger DR, Pope A, Wu Y, Blakely T, et al. A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution. Science . 2024;384(6696). doi: 10.1126/science.adk4858 Chalmers D. Strong and Weak Emergence. In: Clayton P, Davies P. The Re-Emergence of Emergence: The Emergentist Hypothesis from Science to Religion . Oxford University Press; 2008. Kitchener PD, Hales CG. What Neuroscientists Think, and Don’t Think, About Consciousness. Frontiers in Human Neuroscience . 2022;16. doi: 10.3389/fnhum.2022.767612 Goff P, William Seager, and Sean Allen-Hermanson. Panpsychism . The Stanford Encyclopedia of Philosophy. Summer 2022. Seth AK, Bayne T. Theories of consciousness. Nature Reviews Neuroscience . 2022;23(7):439-52. doi: 10.1038/s41583-022-00587-4 Chalmers D. Facing up to the hard problem of consciousness . In: Shear J. Explaining Consciousness: The Hard Problem. MIT Press; 1997. Pugh GE. The Biological Origin of Human Values . Routledge & Kegan Paul; 1978. Descartes R. Principles of Philosophy . 1644. Previous article Next article Entwined back to