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< Back to Issue 9 Living Pixels by KJ Srivastava 28 October 2025 Illustrated by Max Yang Edited by Nirali Bhagat We’ve all seen those hypnotic videos of colour-changing animals – a cuttlefish pulsing stripes across its body, a chameleon melting from green to gold, or an octopus vanishing into coral like a magician’s smoke bomb. Their skin shifts hues like it’s nothing. But how do they actually do that? Take starfish, for instance. They don’t seem to have eyes, yet somehow they “know” what their surroundings look like. Cephalopods, your octopuses, squids, and cuttlefish, go even further, creating patterns that match their environment with uncanny precision. How can they pull that off if they can’t even see any details around them? Seeing Without Eyes? A chromatophore is a specialised cell found in animals, and even some bacteria, that contains pigment or reflects light. You’ll find them across the animal kingdom: in fish, frogs, chameleons, and even in certain bacteria (yes, microbes get to have fun too). Depending on the species, chromatophores come in different flavours. Some are pigment-based, like those filled with melanin (the same as in human skin), while others use microscopic structures to bend and reflect light, acting like natural nanotech (1). Under white light, chromatophores are often classified by the colour they show off – red, brown, blue, green, and the iridescent in-betweens. In vertebrates like fish and reptiles, these cells sit in neat layers under the skin, filtering and bouncing light to produce a kaleidoscope of shades. Chromatophores 101: Nature’s Colour Cells In creatures like octopuses and cuttlefish, chromatophores are tiny, elastic sacs filled with pigment. These sacs are surrounded by radial muscle fibres which are wired to the nervous system. When the animal wants to display a colour, it sends a signal that contracts those muscles, pulling the pigment sac open like an umbrella. The expanded pigment becomes visible on the surface. Relax the muscle and the sac snaps shut – colour gone! So instead of pigment just sitting there passively, the cephalopod is actively controlling its skin colour with muscle contractions, at speeds fast enough to create those mesmerising rippling patterns. All these changes are actively, neurally controlled; they're not automatic like blushing. They're often voluntary, and dynamic, responding to things like light, mood, temperature, and stress (2). In fact, cephalopod chromatophores are sensitive to direct electrical stimulation. One study found that when researchers applied oscillating electrical patterns to the squid Sepioteuthis lessonia, the pigment sacs expanded and contracted in synchronised, wave-like patterns under 1.5Hz; essentially, we can rhythmically ‘play’ these cells like an instrument! (1) Chromatophores in vertebrates work a bit differently. Instead of opening and closing sacs, the pigment inside the cell moves around, spreading out when the colour needs to be more visible, clustering together when it doesn't. Still responsive, still cool, just a little less… flashy. Layers, Pigments, and Light Tricks Here’s where things get really interesting. Chromatophores aren’t all for show. They’re sensitive to light, chemistry, and electrical signals, which makes them incredibly valuable for science and technology! Some fish chromatophores, for example, visibly change colour in the presence of toxins like cholera and pertussis. They detect these threats in real time, with the colour change varying with concentration, meaning you can even tell how much of a toxin is there, not just whether it is present (3). That makes them powerful candidates for biosensors, living tools that can monitor environmental or biological conditions. Why is it a big deal? Unlike traditional sensors made of synthetic materials or inert components, chromatophore-based systems are made of living cells. They keep reacting, adapting, and functioning over time, giving them an edge in sensitivity, flexibility, and longevity (2). While chromatophores already act as living, colour-changing pixels, researchers are exploring how to use them in adaptive camouflage technologies. Imagine a bandage that shifts colour when it detects infection, the moment bacteria start to grow, not just after the infection has spread. Or ocean sensors that monitor salinity and pollution, while blending seamlessly into coral reefs so as not to disturb marine life. All of these possibilities are made an achievable reality by these remarkable sacs of pigment! These amazing cells offer a glimpse at what happens when evolution builds something both beautiful and functional. Next time you see a chameleon vanish into a leaf, or an octopus ripple with light like a living mood ring, take a second to think about what’s really going on under the surface. Behind every colour shift is a tiny symphony of biology and physics, all working together in real time. And the best part? It’s still magic. It doesn't stop being magic when we figure out how it works! References Lei Y, Chen W, Mulchandani A. Microbial biosensors. Analytica chimica acta . 2006;568(1-2):200-10. doi: 10.1016/j.aca.2005.11.065 Tan L, Schirmer K. Cell culture-based biosensing techniques for detecting toxicity in water. Current opinion in biotechnology . 2017;45:59-68. doi: 10.1016/j.copbio.2016.11.026 Plant TK, Chaplen FW, Jovanovic G, Kolodziej W, Trempy JE, Willard C, Liburdy JA, Pence DV, Paul BK. Sensitive-cell-based fish chromatophore biosensor. InBiomedical Vibrational Spectroscopy and Biohazard Detection Technologies 2004;5321;265-274. doi: 10.1117/12.528093 Kim T, Bower DQ, Deravi LF. Cephalopod chromatophores contain photosensitizing nanostructures that may facilitate light sensing and signaling in the skin. Journal of Materials Chemistry C . 2025;13(3):1138-45. doi: 10.1039/D4TC04333B Previous article Next article Entwined back to

< Back to Issue 9 The Cosmos in Our Palms: A Reflection of Our Cosmic Origins by Mishen De Silva 28 October 2025 Illustrated by Heather Sutherland Edited by Nirali Bhagat The Stars and I As I lay down, head held up high, I open my eyes to the Stars and I. In silent dominion, sits the adorned sky, Scattered patterns and celestine fortresses, Locked behind veils of gas, dust and time. Where do I stand, between the Stars and I? Separated by infinities, Yet entranced by familiarity, Perhaps the Stars and I are not as different as I thought. Iron cladded blood, calcium forged bones, carbon cells, Myself, an echo to a stellar memory. What lies between the Stars and I? Long before breath touched my lungs, Fire forged my heart, And light filled my eyes, I was written in the same primordial script, Of matter and light. Seven more lines to which I exist, As a witness and whisper to our shared cosmic thread. A child of the sky, A memory, dreaming of itself, Who am I, but both the Stars and I. The universe first learned to know itself, I second, Where could it have all begun, between the Stars and I? Origins of Cosmic Matter To understand this profound connection between us and the cosmos, we must trace back 13.8 billion years to the birth of matter itself. The complex matter which encapsulates our very existence stems from one crucial cosmic event, the Big Bang (1). In this moment, hydrogen and helium were formed and became the building blocks to the universe. In the early stages of our universe forming, seas of hydrogen and helium gas were pulled by gravity to create stars, in an event known as gravitational collapse (2). These stars became the furnaces for existence. As spheres of fire, they fused atoms together to create more complex ones. This is known as stellar nucleosynthesis, where stars form heavier elements, such as carbon, calcium, nitrogen, oxygen and iron, through the nuclear fusion of hydrogen and helium (3). As time goes on, the core of a star collapses in on itself, creating a supernova. A supernova is an explosion of unimaginable heat, which is crucial in forming all the elements heavier than iron (1). In its lifetime, a star transmutes what was once darkness and barren, into a seed of complex matter. In death, they scatter the elements of their creation across the cosmos, planting them in vast fields of space, from which new stars ignite, planets take form, and life may slowly emerge (3). Through this, we can begin to appreciate our existence as something far greater than ourselves, where the iron in our blood, calcium in our bones and carbon in our cells were all created long before Earth even existed. Life on Earth As the clouds of gas and dust from countless stellar generations drift through the galaxy, they soon clump together to form planetesimals, in a process known as accretion (4). Planetesimals are small, icy and rocky cosmic bodies, which collide together to form planets (4). The planetesimals which collided and merged to form a young Earth made an environment rich with the ingredients to create life. Over eons, elements such as carbon, hydrogen, nitrogen, oxygen, and phosphorus have worked together to create the complex chemistries we see on Earth (5). The same elements, once inside stars, became crucial hallmarks for organic life: carbon forms the backbone of DNA and protein, nitrogen is essential for amino acids, oxygen supports respiration, and phosphorus forms our energy molecules, ATP (6). In this way, every organism before us, from microscopic bacteria, to the fleeting fruit fly, across the vastness of a whale, to the depth of a human soul, were all forged in the fire of the stars. As we detangle the web of our cosmic origins, we can begin to view our existence not only as entwined with every being around us, but also a direct continuation of the cosmos and its evolution. Figure 1. Elements found in stars which make up our body (7) The Cycle of Return It is important to recognise that this cosmic history does not end with us. Matter and energy are never lost, only transformed to take on new forms. An example of this is the carbon cycle, where carbon atoms are continuously moving and taking on new forms in the atmosphere, land and oceans (8). Through death and decay, in between birth and being, our physical selves become part of the soil, water and air, being reused by plants and other organisms to create new biological cycles (9). Similar to the impermanence of our existence, the Earth too will not last forever. Just like any star, our Sun will eventually exhaust the hydrogen in its core, swelling into a giant inferno consuming our world with it (10). However, this is not the end we think it is. Over eons, through supernovae and stellar collisions, the elements to our origins of life will be scattered across different depths of space, perhaps forming new stars, planets or even life elsewhere (11). Figure 2. The Carbon Cycle (12) In the present, each organism, cell and breath of life, exists as an homage to the universe’s constant transformation and reorganisation into new forms. With each howl of a dog, cry of a baby and rustle of a tree, we all exist under a profound and truly out of this world connection. A part of a much bigger cycle, the matter which formed the stars, which created the elements giving rise to life on Earth, will one day become something new again. And so, the more we examine this complex cycle, the more we can dissolve the distance between the “Stars and I”. We were never separate from the stars, and the cosmos is no longer just ‘out there’; it is something within us, around us, and inextricably mixed with who we fundamentally are. References Muhammad, T. Why We’re All Made of Star Dust. Science News Today [Internet]. 2025 May [cited 2025 Oct 8]. Available from: https://www.sciencenewstoday.org/why-were-all-made-of-star-dust Lineweaver, C.H., Egan, C.A. Life, gravity and the second law of thermodynamics. Physics of Life Reviews. 2008;5(4): 225–242. doi: 10.1016/j.plrev.2008.08.002 Fox, R. F. Origin of Life and Energy. Encyclopedia of Energy . 2004:781–792. doi: 10.1016/b0-12-176480-x/00054-1 Halliday, A. N., Canup, R. M. The accretion of planet Earth. Nature Reviews Earth & Environment . 2022;4:1–17. doi: 10.1038/s43017-022-00370-0 The origin of life: The conditions that sparked life on Earth. Research Outreach [Internet]. 2019 Dec [cited 2025 Oct 8]. Available from: https://researchoutreach.org/articles/origin-life-conditions-sparked-life-earth/ Remick, K. A., Helmann, J. D. The elements of life: A biocentric tour of the periodic table. Advances in Microbial Physiology. 2023;82:1–127. doi: 10.1016/bs.ampbs.2022.11.001 Lotzof, K. Are we really made of stardust? Natural History Museum [Internet]. [cited 2025 Oct 8]. Available from: https://www.nhm.ac.uk/discover/are-we-really-made-of-stardust.html Pulselli, F. M. Global Warming Potential and the Net Carbon Balance. Encyclopedia of Ecology. 2008:1741–1746. doi: /10.1016/b978-008045405-4.00112-9 Huang, T., Hu, Q., Shen, Y., Anglés, A., Fernández-Remolar, D. C. Biogeochemical Cycles. Encyclopedia of Biodiversity. 2024;6:393–407. doi: 10.1016/b978-0-12-822562-2.00347-9 Staff, A. What will happen to the planets when the Sun becomes a red giant? Astronomy Magazine [Internet]. 2020 Sep [cited 2025 Oct 8]. Available from: https://www.astronomy.com/observing/what-will-happen-to-the-planets-when-the-sun-becomes-a-red-giant/ Betz, E. How will life on Earth end? Astronomy Magazine [Internet]. 2023 Aug [cited 2025 Oct 8]. Available from: https://www.astronomy.com/science/how-will-life-on-earth-end/ Sultan, H., Li, Y., Ahmed, W., Shah, A., Faizan, M., Ahmad, A., Nie, L., Yixue, M., & Khan, M. N. (2024). Biochar and nano biochar: Enhancing salt resilience in plants and soil while mitigating greenhouse gas emissions: A comprehensive review. Journal of Environmental Management. 2024; 355 :120448–120448. doi: 10.1016/j.jenvman.2024.120448 Previous article Next article Entwined back to

< 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

< Back to Issue 9 Eyeballs, a Knife, and No Fear of God by Jess Walton 28 October 2025 Illustrated by Anabelle Dewi Saraswati Edited by Chavindi Sinhara Mudalige Humans have wanted to understand our bodies the entire time we’ve had them, which is to say, the entire time. Late Classical Athens, around 300 BC, at a peak of intellectual prosperity: Herophilos cuts into a corpse. From this, he’s going to make the novel argument that the brain contains knowledge, and in doing so, he’s going to criticize Aristotle’s writing, which describes the brain as something akin to an air conditioner. Aristotle thought the brain was a cooling chamber, essentially, to prevent the heart from overheating, and that cognition happened in the heart. Much, much earlier, around 1000 BC in India, Sushruta, in his foundational surgical text, overestimated the bone count in humans by over 100. Many ancient societies had impressively detailed understanding of anatomy, considering they had no microscopes, no cameras, no X-rays; usually nothing more than their knives and eyeballs. It’s important to note as well that this article is a brief overview of a complex subject, with a major focus on Classical, meaning Ancient Greek and Roman, examples, and is in no way a complete story of early anatomical developments across the globe. Asia, Africa, the Americas and the Arab world each had their own rich and complex traditions, beyond the few examples cherry-picked here. Most societies had a few impressive hits and a few impressive misses; in a way, their approach to science isn’t all that different from ours today. What can we learn from them, and what can we learn about ourselves? In Ancient Athens, Aristotle believed the heart to be both the intellectual and emotional center of humans; the “seat of the soul” (1). Some remnants of this remain in our modern association between heart and emotion, though we know now it isn’t backed by science. His reasoning behind this was the convergence of blood vessels at the heart and its importance; from this, he also, perhaps reasonably, thought it to be the source of blood (2). Despite being deservedly considered a major anatomist, Aristotle likely made his observations from examining and dissecting the bodies of animals, particularly lower mammals, like dogs or livestock, instead of real humans (3). He unknowingly used homologous structures, long before evolution or even Charles Darwin himself was conceptualized, to essentially assume the anatomy of humans from other animals. Given this, his conclusions on the brain become a little more understandable. The brain is a strange-looking organ, critically important to life, though not obviously connected to the pulse or rich with blood; how were they to understand the structure of nerves and white matter? That it assists the heart in some way becomes a logical conclusion. So why not serve a cooling function? Blood is hot, so the heart must get hot. Overheating is usually bad; see fire. And the brain’s size makes it ideal for such a thing. The thing about anatomy and science, Aristotle’s assertion being one primordial example of many around the ancient world, is that it changes. Herophilos and Erasistratus were two more Greek anatomists who succeeded and often contested Aristotle. Unlike him, they dissected humans, having no qualms about a man’s dead—or, according to some sources, still alive—body (4). However, they offered several accurate, or at least more accurate, insights inside human bodies. Herophilus argued that the brain wasn’t a cooling chamber but contained knowledge (5). While he was at it, he argued that the heart has four chambers, unlike Aristotle, who claimed it only has three (5). Many of Herophilos and Erasistratus’ insights required Aristotle’s, or some other prior Mediterranean scholar’s, claims to give them something to criticise. Praxagoras was one such anatomist, from about 400 BC, about 100 years earlier. He correctly associated the pulse with natural movement within the body, but also asserted that arteries carry air (6). There is, possibly because of this claim, debate as to whether he had any practical anatomical experience or observed any dissections. If so, it’s quite impressive to miss the blood in arteries. He did, however, note that veins carry blood (2). Thus, he was later included in Herophilos’ critique. Before we criticise how long it took for them to realise seemingly obvious facts, we must remember that bloodletting as an acceptable treatment persisted into the 19 th Century. Modern and recent understandings are far from flawless. A couple of hundred years later, Galen, a Roman from the late 2 nd Century AD, would voice similar critiques (2). Galen would later become famous for his theory of the four humors: blood, yellow bile, black bile, and phlegm, each with associated personalities and elements (7). While these are all real liquids found somewhere in the human body, they do not really work as the four-way counterbalance he describes. Galen made some incredible leaps forward in Roman anatomy, including developing more elaborate tools for dissection and surgery processes, which would be instrumental in allowing future developments in the field. However, he also learned more anatomy from treating severe gladiator injuries—which is awesome—or like Aristotle, from dissections and studies on lower mammals (7). This led to some interesting conclusions; his description and diagrams of a human uterus match that of a dog’s uterus exactly, for example (7). He did well with the tools he had, but guesswork has its limits. Three hundred years before Aristotle, and over seven centuries before Galen, the ancient Indian physician Sushruta, a continent away, was revolutionizing, and if there was nothing to revolutionise, inventing surgeries and surgical techniques. He also valued an understanding of human anatomy, which likely contributed to his surgical skill, and dedicated a portion of his seminal Sanskrit work, Sushruta Samhita , to anatomy, calling it the Sharira Sthana . In his work, he describes in detail the head, which he correctly identified as the major center of essentially all function, particularly the cranial nerves (8). He also includes the first detailed guide to human dissection, alongside the anatomy of the embryo at various developmental stages; this is described as arising from seven skins, each with their own associated ailments, and while the skins are anomalous, many of the ailments correlate impressively with known diseases (8). There’s also, incredibly, a detailed description of cataract surgery procedure, where exceptionally specific incision locations in the cornea are interspersed with instructions to sedate the patient with wine mixed with cannabis, which makes sense in a world far predating modern anesthesia, then to spray the eye with breast milk (9). This part seems outlandish and harder to explain, but anyone who has studied immunology can tell you that breast milk contains antibodies and antibacterial proteins. Sushruta likely made some link between breast milk and reduced post-op infections, even if there were not yet microscopes to see bacteria with. Even if they couldn’t see why on the molecular scale, ancient anatomists were able to understand what worked and what didn’t and justify it to the best of their knowledge. When Sushruta describes the bones of the human body, he does so in great detail, and also counts more than 300 of them. Humans typically have 206 bones, give or take a rib: Sushruta mildly overestimated. This is thought to be from him, largely basing his skeletal insights off child cadavers, before many bones have fused together (9). Hindu religious law calls for the cremation of any body over two years old, in its natural and thus undissected state; though there are accounts of Sushruta performing dissections, presumably on adults, the bodies he likely had the most exposure to were infants. Sushruta was working within the confines of the society and world that he lived in, as was Herophilos. Medical insights which seem obvious to us today, like that the brain is for thinking and the heart is for beating blood, and that blood goes through the arteries and is most definitely a liquid, rely upon prior knowledge reached with tools that hadn’t even been invented yet. These firsts—surgeons, anatomists, scientists—would probably have to be physically pried away from microscopes and X-rays, if ever introduced to them. They often didn’t even have a human body to dissect, yet drew human anatomical conclusions regardless. And it’s easy to marvel at their mistakes, but it’s even easier to marvel at how much they got right; Herophilos correctly uncovered nerves and linked them to sensation and response, which is impressive in itself. Could you find a nerve in some meat, with just your naked eye? He also linked the heart and the pulse. The Huangdi Neijing , for example, is a Chinese medical text said, though disputed, to be from 2600 BC, which describes the relationships between organs in military terms: the heart as a king, the liver as a commandant, and the gallbladder as an attorney-general responsible for coordination (10). However, both like and before Herophilos, it also correctly identifies the cyclic nature of blood flow and links it to the heart (10). The Edwin Smith Papyrus, dating from 1700 BC in Ancient Egypt, is the oldest known surgical text, describing 48 different injuries with treatments; all shockingly accurate (11). Sushruta may have miscounted the bones, but he described their shapes accurately and suggested legitimate therapies for particular bone breakages and dislocations. Nowadays, little has changed: in just the 1950s, lobotomies became the standard cure for a headache; even long after we developed microscopes, we were recommending treatments, like scrambling our brains, that only 70 years later seem ridiculously stupid. We’re far from done charting our own bodies, either. In 2018, an entirely new type of tissue all throughout the body was found: the interstitium, which is critical in cell and organ communication across the body (12). It’s been there the whole time, but no one had noticed before. Humans are humans; it is only natural to want to understand ourselves, and as a part of that, our bodies. We now study our ancestors as they studied themselves; the same mix of awe, confusion and confidence. Their methods and conclusions may be fallible, but their curiosity was not, and as long as we remain, never will be, dead. These examples were only a fraction of those whose work has been preserved, who themselves were only a fraction of the ancient people across the globe who investigated human anatomy. A millennium from now, our descendants will laugh at our misconceptions, when they have mapped every neuron in the human brain with instruments we could not conceive of. But without us, they wouldn’t know what they know, and without our original anatomists, we wouldn’t know what we know. Our modern granular understanding of our own structure is built on the bodies we looked in before ours. So, we should perhaps extend some empathy to our predecessors. They had only eyeballs, a knife, and our own curiosity. Different tools, same bodies. References Aird WC. Discovery of the cardiovascular system: from Galen to William Harvey. J Thromb Haemost. 2011;9(Suppl 1):118–29. Johnston IH, Papavramidou N. Galen on the Pulses: Medico-historical Analysis, Textual Tradition, Translation [Internet]. De Gruyter; 2023 [cited 2025 Oct 10]. Available from: https://www.degruyterbrill.com/document/doi/10.1515/9783110612677/html Crivellato E, Ribatti D. A portrait of Aristotle as an anatomist. Clin Anat. 2007;20(5):447–85. Papa V, Varotto E, Vaccarezza M, Ballestriero R, Tafuri D, Galassi FM. The teaching of anatomy throughout the centuries: from Herophilus to plastination and beyond. Med Hist. 2019;3(2):69–77. Bay NSY, Bay BH. Greek anatomist Herophilus: the father of anatomy. Anat Cell Biol. 2010;43(4):280–3. Wright J. Review of: Praxagoras of Cos on Arteries, Pulse and Pneuma. Studies in Ancient Medicine, 48 . Bryn Mawr Class Rev [Internet]. [cited 2025 Oct 10]. Available from: https://bmcr.brynmawr.edu/2017/2017.07.34/ Ajita R. Galen and his contribution to anatomy: a review. J Evid Based Med Healthc. 2015;4(26):4509–16. Bhattacharya S. Sushruta—the very first anatomist of the world. Indian J Surg. 2022;84(5):901–4. Loukas M, Lanteri A, Ferrauiola J, Tubbs RS, Maharaja G, Shoja MM, et al. Anatomy in ancient India: a focus on the Sushruta Samhita . J Anat. 2010;217(6):646–50. O’Boyle C. TVN Persaud, Early history of human anatomy: from antiquity to the beginning of the modern era. Med Hist. 1987;31(4):478–9. van Middendorp JJ, Sanchez GM, Burridge AL. The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on spinal injuries. Eur Spine J. 2010 Nov;19(11):1815–23. Benias PC, Wells RG, Sackey-Aboagye B, Klavan H, Reidy J, Buonocore D, et al. Structure and distribution of an unrecognized interstitium in human tissues. Sci Rep. 2018;8(1):4947. Previous article Next article Entwined back to

Issue 8: Enigma 3 June 2025 This issue unspools the long-hidden threads in science. Come make sense of the puzzles and mysteries with us! Or perhaps, leave just as addled. Editorial Cracking the Code: A Word from the Editors-in-Chief by Ingrid Sefton & Aisyah Mohammad Sulhanuddin A word from our Editors-in-Chief. Facial recognition Friend or Foe?: The Mechanisms Behind Facial Recognition by Mishen De Silva What's in a face? Mishen walks us through the ingenious ways our brains make meaning of the faces we see everyday. Human evolution The Lost Link: A Mystery in Evolution by Eymi Gladys Carcamo Rodriguez The theory of human evolution conjures textbook timelines of ape to man, but as Eymi explores, biology has never been that simple. Celebrity culture Glowing Limelight, Fashioned Stars by Aisyah Mohammad Sulhanuddin Chronically online or not, society sure loves its stars. Aisyah investigates the messy sociology behind our relationships with celebrities in past decades. Astronomy Why Are We So Fascinated by Space? An Exploration of Human’s Fascination with Outer Space by Emily Cahill What make the night sky impossible to ignore? Emily uncovers how culture, commercialisation and science have fuelled our cosmic curiosity. Prehistoric predators Terror Birds: The Discovery of Prolific Hunters by Jason Chien Giant, flightless and carnivorous - Jason pieces together the rise of terror birds as fearsome apex predators Psychology A Psychological ‘Autopsy’ of Ludwig van Beethoven: Dissecting Genius and Madness by Kara Miwa-Dale Elusive and erudite, even beyond the grave. Dissect the inner world of Beethoven with Kara - when can we call genius, madness? Fungi Fungal Pac Man by Ksheerja Srivastava No matter how good of a gamer you are, Ksheerja proves why biosensensing fungi should be crowned as our worlds best Pac-Man player. Dreams In Your Dreams: Unpacking the Stories of Your Slumber by Ciara Dahl Where do our minds go every night? Ciara explores the mysterious science best theories behind dreaming Neurology Functional Neurological Disorder by Esme MacGillivray What if your nervous system just stopped working? Esme explains FND, and how it affects someone, beyond symptoms. Slime moulds Thinking Outside the Body: The Consciousness of Slime Moulds by Jessica Walton I think, therefore I am... a slime mould? Jess ponders whether this humble, single cell protist may exhibit conciousness without a brain. Psychadelics Life Story of a Drug by Elijah McEvoy From 'Bicycle Day' to brain receptors, Elijah takes us on a trip through the enigmatic origins, uses and psychadelic effects of LSD. Gut microbiome Microbic Mirror of The Self by Sarah Ibrahimi Microbes: Humanities greatest enemy or our best friend? Sarah explores the relationship between the gut microbiome and our health. Infantile amnesia Mental Time Travel: How Far Can I Remember? by Sophie Potvin Step inside the hippocampus, as Sophie illustrates the mechanisms of memory formation and our power to make the past come alive again. Consciousness A Headspace of One’s Own by Andrew Irvin At what point does a computer become conscious? Andrew delves into technology that blurs the line between artificial intelligence and the human brain. Prejudice in Science What Do Women Want? by Madeleine Kelly The question we should be asking is not what we know, but what we don't know about women.

By Gavin Choong < Back to Issue 3 Love and Aliens By Gavin Choong 10 September 2022 Edited by Khoa-Anh Tran and Niesha Baker Illustrated by Ravon Chew Next Neither Daniel Love nor Brendan Thoms were Australian citizens, but they were both recognised as First Nations Australians by law. Under legislation, “aliens” who commit crimes with a sentence of over a year may be removed from the country. (1) Due to their non-citizenship, the then Minister for Home Affairs Peter Dutton classified these men as aliens and tried to deport them after they were convicted of serious crimes. This attempt failed. The High Court of Australia ruled, in the hotly contested landmark decision of Love v Commonwealth, that Indigenous Australians could not be considered aliens under Australian law because of the “spiritual connection” they hold with the lands and waters of the country we live in. (1) Effectively, this barred the deportation of Love and Thoms but also sent astronomical ripples through the fabric of our nation’s legal framework. This year, major challenges to the decision made in Love v Commonwealth have arisen. Of the arguments put forward, some protest the judicial activism of the judges – that is, them going above and beyond written law to produce a fairer ruling. For example, many contend the term spiritual connection bears no actual legal meaning. However, with a history dating back upwards of seventy-thousand years, two hundred and fifty languages and eight hundred dialects, complex systems of governance, deeply vested religious and spiritual beliefs, and a profound understanding of land, it would be ignorant to argue this rich culture should simply be disregarded in the face of the law. This article adopts a scientific lens and delves into an empirical basis for the spiritual connection Aboriginal Australians share with country, traversing from Dreamtime to spacetime and beyond. THE DREAMING: FROM NOTHING, EVERYTHING From nothing came everything. Nearly fourteen billion years ago, a zero-volume singularity held, tightly, all the energy, space, and time from our current universe. In the moment of creation, temperature and average energies were so extreme all four fundamental forces which shape the universe, as we know it, acted as one. Cosmological inflation followed, allowing for exponential expansion and rapid cooling. Within a picosecond, the four fundamental forces of nature – gravity, electromagnetism, weak interactions, and strong interactions – emerged independently. These forces interacted with matter, resulting in the formation of elementary particles now coined quarks, hadrons, and leptons. For twenty more minutes, elementary particles coupled to form subatomic particles (protons, neutrons) which in turn underwent nuclear fusion to create simple early atoms such as hydrogen and helium. From nothing, came everything. In an eternal present, where there had once been flat and barren ground, Ancestral and Creator spirits emerged from land, sea, and sky to roam the Earth. As they moved, man and nature – mountains, animals, plants, and rivers – were birthed into existence. Once these spirits had finished, instead of disappearing, they transformed into the world they had created, existing in sacred sites such as the night sky, monolithic rocks, and ancient trees. The Dreaming is a First Nations peoples’ understanding of the world and its creation. Importantly, it is an event which cannot be fixed in time – “it was, and is, everywhen,” continuing even today. Countless retellings have caused Dreamtime tales to diverge slightly, leading communities of Aboriginal Australians to identify with different variations of similar stories. (2) These fables refer to natural worldly features and sacred sites, whilst also incorporating favourable values such as patience, humility, and compassion. An example is the tale of the Karatgurk, told by the Wurundjeri people of the Kulin nation, about seven sisters representing what we now consider as the Pleiades star constellation. (3) The Karatgurk These seven sisters once lived by the Yarra River, where Melbourne now stands. They alone possessed the secret of fire, carrying live coals at the end of their digging sticks. (Crow ("trickster, cultural hero, and [another] ancestral being") called the sisters over claiming he had discovered tasty ant larvae. (3) The women began scouring, only to find viscious snakes underneath the dirt which they beat using their digging sticks. As they did so, the live coals flew off and were stolen by Crow who brought fire to mankind. The Karatgurk sisters were swept into the sky, with their glowing fire sticks forming the Pleiades star cluster. In theory, the extreme physical reactions occurring minutes after the Big Bang, paired with hyper-rapid cosmic inflation, should have resulted in a completely homogeneous universe with an even distribution of all existing matter and energy. Cosmological perturbation theory explains, however, that micro-fluctuations in material properties create gravitational wells resulting in the random grouping of matter. These aggregations formed the first stars, quasars, galaxies, and clusters throughout the next billion years. It took, however, another ten billion years for the solar system to form. Similar to Saturn’s planetary rings, the early Sun had its own rotating, circumstellar disc composed of dust, gas, and debris. According to the nebular hypothesis, over millions of years, enough particulates coagulated within the Sun’s spinning disc to form small, primordial planets. Early Earth was a hellish fire-scape as a result of constant meteoric bombardment and extreme volcanic activity. The occasional icy asteroids which collided with Earth deposited large amounts of water, vaporising upon contact – as our planet began to cool, these gaseous deposits condensed into oceans, and molten rock solidified into land mass. In the blink of an eye, early traces of modern humans fluttered into existence at the African Somali Peninsula. They were a nomadic people, travelling westwards and then north through modern day Egypt and into the Middle East. Ancestral Indigenous Australians were amongst the first humans to migrate out of Africa some 62,000 to 75,000 years ago. While other groups travelled in different directions filling up Asia, Europe and the Americas, ancestral Indigenous Australians took advantage of drastically lower sea levels during that time to travel south, as, back then, mainland Australia, Tasmania, and Papua New Guinea formed a single land mass (Sahul) while South-East Asia formed another (Sunda). In spite of this, the wanderers still had to possess the requisite sea-faring skills to traverse almost ninety kilometres of ocean. When the last ice age ended 10,000 years ago, rising waters from melting ice caps covered many of the terrestrial bridges early humans had once journeyed over. This severing allowed Indigenous Australians to foster culture and tradition in their very own passage of time, uninterrupted and independent until a British fleet of eleven ships approached Botany Bay thousands of years later. Significant parts of Australia’s coast were also submerged due to ice age flooding. As coastal Indigenous Australians observed this phenomenon, they recognised its significance through their tales. The Gimuy Walubara Yidinji, traditional custodians of Cairns and the surrounding district, are one of the many groups which reference coastal flooding in their geomythology. Gunya and the Sacred Fish Gunyah, who had lived on Fitzroy Island, went out to hunt for fish one day. Spotting a glimmer in the water, he plunged a spear towards it only to find he had attacked the sacred black stingray. The stingray beat its wing-like fins, causing a great, unending storm. Gunyah fled from the rapidly rising sea and managed to find refuge in a clan living on the cliffs of Cairns. Together, they heated huge rocks in a fire and threw them far into the sea. The pacific was once again pacified, and the Great Barrier Reef created. Isaac Newton proposed, in Principia Mathematica, that the strength of the force of gravity between two celestial bodies would be proportional to both of their masses. At the beginning of the twentieth century, Albert Einstein refined this concept with the theories of Special and General Relativity. His mathematical models suggested time and space were woven into a four-dimensional canvas of spacetime, and the presence of massive objects such as black holes and stars created gravitational wells which distorted spacetime. Within these distortions, bodies closer to large masses would conceive time and space differently than those further away. This unique phenomenon, for example, means astronauts living onboard the International Space Station age fractionally slower relative to us grounded on Earth. Einstein was also able to find that as the velocity of any given body increased to that near the speed of light, it would gain an almost-infinite mass and experience a drastically slowed perception of time relative to their surroundings. These once inconceivable findings had monumental implications in the sphere of theoretical physics, with two examples below. (4, 5) Dark Matter ‘Visible’, baryonic matter humanity is familiar with makes up less than a fifth of the known universe, with a hypothetical ‘dark’, non-baryonic matter comprising the rest. Dark matter lies between and within galaxies, driving baryonic matter to aggregate, forming stars and galaxies. As it cannot be detected using electromagnetic radiation, gravitational lensing provides the strongest proof of its existence. Gravitational lensing occurs when there is an interfering body between us, here on Earth, and a given target. As per Einstein’s relativity, the interfering body has mass which will bend space and therefore distort the image we receive of the target. There exists a mathematically proportional relationship between mass and distortion – the more massive an interfering body, the greater the distortion. Scientists performed calculations but found that the levels of distortion they observed correlated to masses much greater than that of the interfering body. Dark matter accounts for this invisible and undetectable missing mass. String Theory At its core, quantum physics deals with interactions at the atomic and subatomic level. This body of work has borne unusual findings – including that light can act both as a particle and wave, that we may never identify a particle’s position and momentum simultaneously with complete certainty, and that the physical properties of distant entangled particles can fundamentally be linked. On paper, however, there has been great difficulty reconciling quantum physics with relativity theory, as the former deals with interactions which occur in “jumps…with probabilistic rather than definite outcomes”. (4) String theory, however, seeks to settle this tension by proposing the universe is comprised of one-dimensional vibrating strings interacting with one another. This theoretical framework has already bore fascinating fruit – it has been hypothesised that the universe has ten dimensions (nine spatial, one temporal) and during the Big Bang, a “symmetry-breaking event” caused three spatial dimensions to break from the others resulting in an observable three-dimensional universe. (5) On 21 September 1922, astronomers in Goondiwindi, Queensland, used a total solar eclipse to successfully test and prove Einstein’s theory of relativity. Aboriginal Australians present believed they were “trying to catch the Sun in a net”. (6) Western academics were far from the only ones who sought to explain natural phenomena. From the ancient Egyptians to Japanese Shintoists and South American Incas, many civilisations of the past revered the Sun and Moon, having been enthralled by the two celestial bodies. Indigenous Australians were one such people, wanting to understand why the sun rose and set, how moon cycles and ocean tides were related, and what exactly were the rare solar and lunar eclipses. Such occurrences had a mystical property about them, reflected in a rich collection of traditional tales which looked to illuminate these astronomical observations. (7) Walu the Sun-woman Told by the Yolngu people of Arnhem Land, Walu lights a small fire every morning to mark that dawn has arrived. She paints herself with red and yellow pigment with some spilling onto the clouds to create sunrise. Walu lights a bark torch and carries it across the sky from East to West, creating daylight. Upon completing her journey, she extinguishes her torch and travels underground back to the morning camp in the East. While doing so, she provides warmth and fertility to the very Earth surrounding her. Ngalindi the Moon-man Told by the Yolngu people of Arnhem Land, “water fill[s] Ngalindi as he rises, becoming full at high tide”. (6) When full, he becomes gluttonous and decides to kill his sons because they refuse to share their food with him. His wives seek vengeance by chopping off his limbs, causing water to drain out. This is reflected by a waning moon and ebb in the tides. Eventually, Ngalindi dies for three days (New Moon) before rising once again (waxing Moon). Bahloo and Yhi Told often by the Kamilaroi people of northern New South Wales, Yhi (Sun-woman) falls in love with Bahloo (Moon-man) and tries to pursue him across the sky. However, he has no interest in Yhi and refuses her advances. Sometimes, Yhi eclipses Bahloo and tries to kill him in a fit of jealously, but the spirits holding up the sky intervene allowing Bahloo to escape. In 1788, British colonists prescribed the fictitious doctrine of terra nullius which treated land occupied by Indigenous peoples as “territory belonging to no-one,” susceptible to colonisation. (8) It is apparent, however, that Indigenous Australians did and still do belong, having a greater, more unique, and nuanced relationship to our lands and waters than we can ever hope to have. This article shows that as detailed and prescriptive our modern scientific understanding is, First Nations peoples will have an equally if not richer perspective, woven through their stories, languages, and practices. To argue that the spiritual connection Indigenous people share with country is not recognised by law would be wilfully making the same mistake our early settlers made two and a half centuries ago. It would be allowing the continuance of intergenerational trauma and suppression. For those reasons, despite the assertive legal challenges being brought against Love v Commonwealth, its judgement must be upheld. References 1. Love v Commonwealth; Thoms v Commonwealth [2020] HCA 3. 2. Stanner WE. The Dreaming & other essays. Melbourne (AU): Black Inc.; 2011. 3. Creation Stories [Internet]. Victoria: Taungurung Lands & Waters Council [cited 2022 Apr. Available from: https://taungurung.com.au/creation-stories/ 4. Powell CS. Relativity versus quantum mechanics: the battle of the universe [Internet]. The Guardian; 2015 Nov 4 [cited 2022 Apr 17]. Available from: https://www.theguardian.com/news/2015/nov/04/relativity-quantum-mechanics-universe-physicists 5. Wolchover N. String theorists simulate the Big Bang [Internet]. Live Science; 2011 Dec 14 [cited 2022 Apr 17]. Available from: https://www.livescience.com/17454-string-theory-big-bang.html 6. Hamacher DW. On the astronomical knowledge and traditions of Aboriginal Australians [thesis submitted for the degree of Doctor of Philosophy]. [Sydney]: Macquarie University; 2011. 139 p. 7. Mathematics, moon phases, and tides [Internet]. Melbourne: University of Melbourne [cited 2022 Apr 17]. Available from: https://indigenousknowledge.unimelb.edu.au/curriculum/resources/mathematics,-moon-phases,-and-tides 8. Mabo v Queensland (No 2) [1992] HCA 23. Previous article Next article alien back to

< Back to Issue 6 Proprioception: Our Invisible Sixth Sense by Ingrid Sefton 28 May 2024 Edited by Subham Priya Illustrated by Jessica Walton What might constitute a sixth sense? Perhaps, it involves possessing a second sight or superhuman abilities. A classic example of this would be Spider-Man and his ‘spidey-sense’ — an instinctual warning system that alerts him to imminent danger. Enhancing his reflexes and agility, his sixth sense enables him to evade threats with precision. Turns out Spider-Man is not the sole bearer of a ‘spidey sense’. While we may not be scaling walls anytime soon, we too possess a special sense that unconsciously guides our movements. It might sound peculiar, but knowing your arm is indeed your own arm involves a unique form of sensory processing. Considered by neuroscientists as our own ‘sixth sense’, proprioception is our own way of helping the brain to understand the position of our body and limbs in space (Sherrington, 1907). Consider a typical scenario: your first sip of coffee in the morning. Eyes shut, you savour your latte before the day begins. Such a simple act, yet impossible without proprioception. With closed eyes, how do you know where your mouth is? How do you gauge the position of your arm to ensure the coffee cup reaches your lips? Proprioception seamlessly transmits information about muscle tension, joint position, and force to the brain, making drinking your coffee an automatic and coordinated process. Proprioception operates on principles akin to those guiding our other senses. Specialised cells, known as receptors, are found in each sensory organ and receive information from the environment. Receptors in your eyes capture visual information, while those in your ears detect auditory stimuli. This sensory information is transduced through signals to the central nervous system – through the spinal cord and to the brain – where it’s integrated and processed to determine an appropriate response. Analogously, proprioceptive information is mediated by proprioceptors, a unique type of receptors located in your muscles and joints (Proske & Gandevia, 2012). Unlike our other senses, proprioception does not rely on input from the external environment. Rather, it provides feedback to the brain about what the body itself is doing. Changes in muscle tension and the position of our joints are relayed to the brain, ensuring awareness of the body’s whereabouts at any given moment. One implication of this ‘internal’ feedback loop is that proprioception never turns ‘off’. When you cover your ears, you experience silence. If you hold your nose, you can block out the smell. Yet even when still, in motion, or unconscious, your brain continuously receives proprioceptive input. Imagine this in the context of going to bed each night. What exactly prevents you from falling out of bed, once asleep? While most senses are subdued when sleeping, proprioception remains active, informing the brain about the slightest changes in the position of the body. This ensures a perpetual awareness of our body in space – and luckily for us, stops us from rolling out of bed (Proske & Gandevia, 2012). It can be hard to appreciate what our proprioceptive system allows us to do, given its unconscious nature and integration with our other senses. Rare neurological disorders affecting proprioception highlight just how critical this sense is in our daily lives. The case of Ian Waterman – now known as ‘the man who lost his body – offers profound insights into the significance of proprioception (McNeill et al., 2009). Following a fever in 1971 at age 19, a subsequent auto-immune reaction destroyed all his sensory neurons from the neck down–a condition termed ‘neuronopathy’. Despite retaining his intact motor functions, Waterman lost all proprioceptive abilities, rendering him unaware of his body's position in space. Although the viral infection’s initial effect was that of immobility, this loss was not due to paralysis. Rather, it was Waterman’s lack of control over his body that inhibited his ability to move. Sitting, walking, and manipulating objects became impossible tasks as a result of the absence of any proprioceptive feedback from the body. Remarkably, Waterman has been able to teach himself precise strategies to walk and function with a degree of normality (Swain, 2017). Yet, all movement requires concerted planning and relies entirely on vision to compensate for the unconscious proprioceptive processing. In the absence of any light, Waterman is unable to see his limbs, thus restricting his ability to move. An understanding of the molecular mechanisms underlying proprioception remains somewhat of a mystery compared to that of our other senses. However, recent genetic advancements are paving the way for the development of novel therapies aimed at neurological and musculoskeletal disorders (Woo et al., 2015). A study involving two young patients with unique neurological disorders affecting their body awareness revealed a mutation in their PIEZO2 gene (Chesler et al., 2016). Both individuals experienced significant challenges with balance and movement, coupled with progressive scoliosis and deformities in the hips, fingers, and feet. The PIEZO2 gene typically encodes a type of mechanosensitive protein in cells, r esponsible for generating electrical signals in response to alterations in cell shape (Coste et al., 2010). Mutations to this gene prevent signal generation and render the neurons incapable of detecting limb or body movement. These findings firmly establish PIEZO2 as a critical gene for facilitating proprioception in humans, a sense that is crucial for bodily awareness. PIEZO2 mutations have also been implicated in genetic musculoskeletal disorders (Coste et al., 2010). Joint problems and scoliosis experienced by the patients in a study suggest that proprioception may also indirectly guide skeletal development. These insights into the role of the PIEZO2 gene in proprioception and musculoskeletal development open up promising avenues for understanding and treating neurological and musculoskeletal disorders. It’s more than fitting to regard proprioception as our sixth sense. The capacity of our nervous system to seamlessly process vast amounts of information from our joints and muscles, all without any conscious effort on our part, is truly remarkable. So, the next time you have that eyes-shut first sip of coffee, give yourself a pat on the back. With your sixth sense at play, you’re clearly a superhero! References Chesler, A. T., Szczot, M., Bharucha-Goebel, D., Čeko, M., Donkervoort, S., Laubacher, C., Hayes, L. H., Alter, K., Zampieri, C., Stanley, C., Innes, A. M., Mah, J. K., Grosmann, C. M., Bradley, N., Nguyen, D., Foley, A. R., Le Pichon, C. E., & Bönnemann, C. G. (2016). The Role of PIEZO2 in Human Mechanosensation. N Engl J Med , 375 (14), 1355-1364. https://doi.org/10.1056/NEJMoa1602812 Coste, B., Mathur, J., Schmidt, M., Earley, T. J., Ranade, S., Petrus, M. J., Dubin, A. E., & Patapoutian, A. (2010). Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science , 330 (6000), 55-60. McNeill, D., Quaeghebeur, L., & Duncan, S. (2009). IW - “The Man Who Lost His Body”. In (pp. 519-543). https://doi.org/10.1007/978-90-481-2646-0_27 Proske, U., & Gandevia, S. C. (2012). The Proprioceptive Senses: Their Roles in Signaling Body Shape, Body Position and Movement, and Muscle Force. Physiological Reviews , 92 (4), 1651-1697. https://doi.org/10.1152/physrev.00048.2011 Sherrington, C. S. (1907). On the proprio-ceptive system, especially in its reflex aspect. Brain , 29 (4), 467-482. Swain, K. (2017). The phenomenology of touch. The Lancet Neurology , 16 (2), 114. https://doi.org/10.1016/S1474-4422(16)30389-1 Woo, S. H., Lukacs, V., de Nooij, J. C., Zaytseva, D., Criddle, C. R., Francisco, A., Jessell, T. M., Wilkinson, K. A., & Patapoutian, A. (2015). Piezo2 is the principal mechanotransduction channel for proprioception. Nature Neuroscience , 18 (12), 1756-1762. https://doi.org/10.1038/nn.4162 Previous article Next article Elemental back to

< Back to Issue 7 Neuralink: Mind Over Matter? by Kara Miwa-Dale 22 October 2024 edited by Weilena Liu illustrated by Aisyah Mohammad Sulhanuddin What if I told you that you could control a computer mouse with just your thoughts? It sounds like something straight out of a sci-fi movie, doesn’t it? But this isn’t fiction… Welcome to the brain-computer interface, a device which is able to record and interpret neural activity in the brain, enabling direct communication between your mind and a computer. Tech billionaire Elon Musk founded ‘Neuralink’, a company developing coin-sized brain-chips that can be surgically inserted into the brain using a robot. Neuralink made headlines a few months ago by successfully implanting their brain-chip, dubbed ‘Telepathy’, into their first trial patient, Noland Arbaugh. While there were a few technical glitches, it seems to be working relatively well so far. Noland has been able to regain some of the autonomy that he lost following a devastating spinal cord injury. He is even able to play video games with a superhuman-like reaction speed, thanks to the more direct communication route between the Neuralink implant and his computer. But it doesn’t stop there; Elon Musk’s ultimate vision is to have millions of people using Neuralink in the next 10 years, not only to restore autonomy to those with serious injuries, but to push the boundaries of what the human brain is capable of. He thinks that Neuralink will allow us to compete with AI and vastly improve our speed and efficiency of communication, which is ‘pitifully slow’ in comparison to AI. Neuralink implants may seem like an incredible leap in scientific technology, but what will happen if they become normalised in our society? Let’s imagine for a moment … Jade, April 7th 2044 Shoving my jacket into my bag, I dart out of the hospital and pull onto the main road in my Tesla. As I speed past the intersection, I see a giant advertisement plastered on a sleek building: ‘Neuralink: Seamless Thoughts, Limitless Possibilities’. When I signed up to get a Neuralink implant, all I’d thought about were the infinite possibilities of how it would change my life – not what could go wrong. I wish I could say that I was brainwashed into getting a Neuralink, or that I had no choice in the matter. But the truth? I got an implant so that I could be ‘ahead of the crowd’ and because I was so frustrated at feeling inadequate compared to the other doctors at my hospital. When I graduated medical school, at the top of my class, people told me that I would do ‘great things’ and ‘change the world’. I followed the standard path, landing my first job and climbing the ranks one caffeine-fuelled shift at a time. I loved my job. Every time I saved a life, it felt like all my effort had paid off. Then Neuralink happened. I still remember the day Dr Maxwell - a doctor I worked with - proudly announced that he’d ‘bitten the bullet’ and gotten the implant. Over the coming weeks, we watched in awe: his diagnoses were quicker and more accurate than any human could imagine, and he went home as energetic as he’d arrived. Now, the extra hours I spent figuring out tricky cases were no longer a representation of my work ethic, but a symptom of my inadequacy compared to the Neuralink-enhanced doctors. One by one, my colleagues signed up for the implant. I hated the thought of having something foreign nestled in my brain, recording my brain’s neurons every second of the day. I told myself I wouldn’t let peer pressure get to me. But, as I watched those around me get promoted while I continued to work endless days, the frustration started to build. One afternoon, the department head came into my office to tell me that they were reconsidering the renewal of my contract. I wasn’t ‘keeping up’ with my Neuralink-enhanced colleagues. “We respect your personal decision, of course,” she said with hollow politeness. I wasn’t keen on being pressured into it, but at the same time, I genuinely believed that the implant would improve my life. When I told my friends and family about getting an implant, they were concerned. They tried to list all the things that could go wrong, but I came up with enough reasons to convince myself that it was the right decision. Once they saw how incredible the Neuralink device was, I thought, they would want one too. *** I’m jolted back to reality as the car veers slightly left, and I manually yank the wheel to correct it. Perhaps my implant glitched for a second… *** Everything changed after I had my Neuralink implanted. I was the only person in my family who had one, although a couple of friends did. At first, I felt invincible. The phenomenal speed with which I was able to come up with previously challenging diagnoses was thrilling. I was able to process enormous amounts of data and draw connections that I had never been able to before. It was addictive to feel that I was working at my full potential, using my newfound ‘superpower’ to save more lives than ever. About a month in, my thoughts began racing uncontrollably, until I felt like I was drowning in a flood of information. Sometimes, the input was so overwhelming that my head pounded and I struggled to breathe. My thoughts didn’t even feel like mine anymore. Family and friends started to grow more and more distant from me. This device was stuck inside my brain like superglue, and sometimes I just wanted to dig it right out of my skull. When I asked the doctor about removing it, he looked at me and smirked, “Why on earth would you want to get rid of such a game-changing device? Neuralink’s the new normal, honey. Get used to it.” *** A honk startles me as a car zooms past, nearly colliding with mine. I turn into a quieter street to regain my composure. But then – suddenly – thoughts of accelerating the car bombard my mind – so loud that I can barely hear myself think. The speedometer rises from 60 to 80 to 100 km an hour. I desperately try to disconnect my Neuralink from the car, to manually override the system – anything that will slow the car down. I start pushing random buttons hoping that I will get some kind of response. A red light flashes on my dashboard. ERROR. SIGNAL DISRUPTED BY UNKNOWN USER. I look up and meet the panicked eyes of a woman pushing a man in a wheelchair. Noah, April 7th 2044 The sun makes its final, glorious descent below the horizon, painting a beautiful array of pinks and oranges across the sky. I take a deep breath as Sophia, my support worker, pushes me along the road. We’re on our way to the grocery store, just in time for the end of day specials, which are all I can afford right now. Since my accident, I’ve tried my best to appreciate what I have, but it isn’t easy. Some days, I’m filled with rage as I struggle to complete daily tasks that I did on autopilot before my accident – back when I wasn’t confined to a wheelchair. It’s been hard to come to terms with this new body that I’m stuck with, and all the ways it seems to betray me. I miss the simple things – going to the grocery store by myself or playing board games with friends. But most of all, I miss working as an architect. I loved seeing my clients’ faces light up as they imagined the memories they would make in the new homes I had designed. This sense of satisfaction was taken from me the moment I was paralysed from the neck down. It’s why I’m so desperate to get a Neuralink implant. I would get one right this second if they weren’t so expensive. The Neuralink device isn’t covered by my insurance because the government claims that it wouldn’t be ‘cost effective’. While it won’t restore movement in my arms and legs, this implant would give me some precious freedom back. Maybe if I keep saving and take out a loan, I’ll have just enough to cover it and get my life back … *** “God, these Tesla drivers think they own the road!” I chuckle at Sophia, as a Tesla races towards the crossing in this 40km zone. As we begin to cross the road, I realise that the Tesla is showing no signs of slowing down. The car swerves violently, hurtling towards us without mercy. Sophia’s face pales as she frantically tries to push me out of the road. I squeeze my eyes shut, bracing for impact. Bibliography: Cernat, M., Borțun, D., & Matei, C. (2022, April). Human-Computer Interaction: Ethical Perspectives on Technology and Its (Mis) uses. In International Conference on Enterprise Information Systems (pp. 338-349). Cham: Springer Nature Switzerland. https://doi.org/10.1007/978-3-031-39386-0_16 Fridman, Lex. (Host). (2024, August 3rd). Elon Musk: Neuralink and the Future of Humanity (No 438). [Audio podcast episode]. In Lex Fridman Podcast. https://lexfridman.com/elon-musk-and-neuralink-team/ Jawad, A. J. (2021). Engineering ethics of neuralink brain computer interfaces devices. Perspective , 4 (1). https://doi.org/10.23880/abca-16000160 Oravec, B. Neurotechnology, Ethical Privacy, and Information Technology. Knighted , 36. https://www.mga.edu/arts-letters/docs/knighted-journal/Issue-6.pdf#page=37 Youssef, N. O. A., Guia, V., Walczysko, F., Suriyasuphapong, S., & Moslemi, C. (2020). Ethical concerns and consequences of Neuralink. Natural Science. https://rucforsk.ruc.dk/ws/files/75503337/NIB3_Group1_Neuralink.pdf Previous article Next article apex back to

By Yvette Marris Behind the Mask By Yvette Marris 23 March 2022 Edited by Tanya Kovacevic Illustrated by Quynh Anh Nguyen It would be hard to write about A Year in Science without the obligatory COVID article. We hear constantly about the stresses of being a frontline healthcare worker, the signs and symptoms of long COVID, and the endless vaccine scepticism. I’d like to tell a slightly different story. During the COVID pandemic, other infections didn’t just take a holiday and cancers didn’t just stop growing. More ordinary illness and injury continued behind the headlines. As a consequence of the pandemic, healthcare workers are additionally dealing with an abundance of patients, delays with diagnosis and some very complex medical cases. Megan Gifford worked in a hospital that didn’t primarily treat COVID-19 patients, but still had to adapt to the constant changing of rules, regulations and policies put in place to protect staff and patients alike from the virus. Now at the Peter MacCallum Cancer Centre in Melbourne, Gifford spoke to me about her experiences working at Townsville University Hospital in the only bone marrow transplant ward servicing a large population across regional Queensland. Gifford experienced the stress and burden of trying, not only to assuage their own anxieties but to also provide current, up-to-date information to patients and deliver high quality care. There were the frustrations of unavoidable logistical problems like border closures, stay-at-home orders, preventing access to crucial materials and patient transport. There was heartbreak of watching transplant patients deteriorate mentally, as their will to persist with treatments began to fade. Pathologists and haematologists also found themselves facing an unprecedented logistical nightmare, including re-allocation of diagnostic equipment and protective equipment for mass COVID testing. Access to essential biomedical material like blood and plasma became increasingly difficult and many suffered as a result. While pandemic consequences like long COVID and the increased prevalence of affective disorders, like depression and anxiety, are well documented in media and academia, post-traumatic stress disorder (PTSD) hasn’t gotten the same amount of attention. Statistics and anecdotes alike are staggering, both for patients and healthcare workers. With stressors like an unprecedented number of critically ill patients, capricious disease progressions, high mortality, and ever-changing treatment guidelines the world was sympathetic to healthcare workers’ struggles (3). Yet with the lockdowns and restrictions over, it would be naïve to think everything would just return to normal. It was found that 29% of healthcare workers had clinical or sub-clinical symptoms of PTSD (1), and that this figure was significantly higher for healthcare workers directly treating COVID patients (2). Gifford recalled anecdotes of “patients suffering anxiety attacks when they smell the hospital alcohol rub and hear the familiar beeping of the various equipment”. Even beyond the mental health scope, logistical issues like delayed learning for medical students or the backlog of elective procedures is still placing an enormous burden on healthcare workers, despite the immediate threat seemingly behind us. But to say that everything remains in shambles would frankly be insulting to healthcare workers, who are working tirelessly to deliver good quality healthcare. The speed at which pathologists and scientists have adapted to limited resources and supply shortages, and the way in which doctors and frontline workers have shifted their style of care and developed new problem-solving skills, are exceptional and should not go unnoticed or unappreciated. Importantly, the COVID-19 pandemic and its ripple effects have brought centre stage the consequences of under-resourced healthcare centres in a way that affected all people, irrespective of geography, class or reputation. The reality is that the conditions in which many metropolitan hospitals found themselves in, with never enough staff or supplies, is a condition that some hospitals experienced long before COVID-19 ever appeared, particularly in rural settings. To say that every dark cloud has a silver lining would be horribly cliché, but in this case, there may be truth to it. This edition of A Year in Science is a chance for us to reflect on all that COVID-19 has called attention to and decide to do something about it. References Carmassi C, Foghi C, Dell’Oste V, Cordone A, Bertelloni CA, Bui E, et al. PTSD symptoms in healthcare workers facing the three coronavirus outbreaks: What can we expect after the COVID-19 pandemic. Psychiatry Research. 2020 Oct;113312. Janiri D, Carfì A, Kotzalidis GD, Bernabei R, Landi F, Sani G. Posttraumatic Stress Disorder in Patients After Severe COVID-19 Infection. JAMA Psychiatry. 2021 Feb; Johnson SU, Ebrahimi OV, Hoffart A. PTSD symptoms among health workers and public service providers during the COVID-19 outbreak. Vickers K, editor. PLOS ONE. 2020 Oct 21;15(10):e0241032. Previous article Next article

< 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 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

Issue 6: Elemental 28 May 2024 This issue explores the building blocks that comprise the world we live in. Our talented writers braved the elements - have a read below! Editorial by Ingrid Sefton & Rachel Ko A word from our Editors-in-Chief. Fire and Brimstone by Jesse Allen The world has long been subject to the fury of fire and volcanic eruptions. Technology to predict seismic activity may allow us to tame this elemental force. Hidden in Plain Sight: The dangerous chemicals in our everyday products by Kara Miwa-Dale Drink bottles, tinned food, receipts: a recipe for disaster? Interviewing A/Prof Mark Green, Kara exposes the hidden dangers of endocrine disrupting chemicals. A Frozen Odyssey: Shackleton’s Trans-Antarctic Expedition by Ethan Bisogni A pursuit of knowledge and a testament to survival, Ethan navigates the enthralling legacy of Sir Ernest Shackleton's Trans-Antarctic Expedition. Everything, Everywhere, All at Once: The Art of Decomposition by Arwen Nguyen-Ngo Arwen breaks down the intricacies of decomposition, leading us to consider the fundamental power not only in creation, but destruction. Out of our element by Serenie Tsai Following the industrial revolution, humankind has exploited and degraded the Earth's natural resources. Serenie shows how nature resists, maintaining the capacity to restore what humans have destroyed. Cosmic Carbon Vs Artificial Intelligence by Gaurika Loomba Carbon constitutes life and death, shaping conscious human existence. What threat could AI hold to the power of this element? Proprioception: Our Invisible Sixth Sense by Ingrid Sefton Our mysterious, yet omnipresent sixth sense - proprioception is the reason we know where our body and limbs are, even in the dark. A Brief History of the Elements: Finding a Seat at the Periodic Table by Xenophon Papas There's hydrogen and helium, then lithium, beryllium - or is there? The periodic table we know today was not always so, as Xen recounts.