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< Back to Issue 9 Rewilding Our Cities with Dr Kylie Soanes by Ciara Dahl 28 October 2025 Illustrated by Jess Walton Edited by Arwen Nguyen-Ngo When you think of nature, I bet the last things that come to mind are skyscrapers, freeways and footpaths. Welcome to the hidden world of urban ecology! I recently spoke to urban ecologist and prolific science communicator Dr Kylie Soanes about the challenges of conserving wildlife in urban environments, and what drives her to protect nature in our cities. Dr Kylie Soanes is determined to protect wildlife in our urban environments. (1) A research fellow at the University of Melbourne, Soanes describes herself as “your friendly neighbourhood wildlife scientist” on a mission to “save nature in cities and towns.” Her projects range from designing rope bridges to help endangered possums cross busy roads, to installing floating wetlands that bring biodiversity back to our urban waterways. Cities are a bustling weave of people and places, but where does nature belong in all of that chaos? That’s the question Soanes has dedicated much of her career to exploring. Like many of us, she grew up in a classic urban environment, longing to get into the wild. Her passion for learning about the natural world eventually grew into a career studying ecology and conservation at university. There is a common assumption that nature doesn't belong in cities. However, Soanes emphasises that cities are a “perfect place for people to connect with nature; there’s heaps of amazing biodiversity here”, adding that “it doesn't always have to look like the pristine natural conditions for it to be valuable”. She emphasises that communicating this message is the "first real step" in shifting mindsets. Soanes notes that urban ecology is often more about working with people than with science, explaining that “there are still people in this space that need to use it." Urban ecologists must be skilled collaborators, working with communities and experts across disciplines – from architects and engineers, to social scientists and artists – to reach solutions that balance the needs of nature and people. But what happens when communities don't feel seen by urban plans? A recent effort to protect swamp wallaby habitat along the Merri Creek Trail by diverting pedestrian traffic was met with concern from the community about personal safety (2). Cases like these highlight the challenges urban ecologists face every day when trying to make space for nature in our cities. Soanes argues that it is critical for urban ecologists to discuss “social risks and social justice, to make sure that we're not changing cities in a way that makes it worse for people". Public outcries like these often stem from communities that are faced with “a decision that they think that they weren't involved in”. The biggest tool in an urban ecologist's belt is community consultation, "so that everybody is brought along on the journey and we can make the right call for everyone." Some of Soanes’ favourite work is not just about protecting nature in cities, but putting it back. She speaks about creating new habitats in urban spaces, such as floating wetlands that transform bleak industrial wastelands into thriving ecosystems, or even rooftop gardens that reclaim space for nature. One of the most exciting areas of urban ecology includes restoring locally extinct species. Soanes cites the example of the endangered Key’s Matchstick Grasshopper, which was reintroduced to Royal Park in 2022 to restore the local population and support a healthy ecosystem (3). Often, such projects are overlooked in urban areas. She explains how they are frequently “put in the too hard basket”; but there is now a shift in focus towards “physically reintroducing species once we know that all the things that they need are there". So, where can we find some of Melbourne’s most exciting urban ecology projects? You can spot the floating wetlands in various locations along the Yarra River (4), and native wildflower meadows planted on roadsides throughout the city (5). Ever spotted those wooden boxes on trees around Melbourne’s gardens? They’re not decorations – they’re artificial hollows providing safe places for wildlife to nest (6). Additionally, “lots of councils are really embracing water sensitive urban design" by installing "miniature wetlands that slow rainwater down and clean it up before it hits our stormwater system" (7). The City of Melbourne has installed floating wetlands in the Yarra River since 2022. (4) Soanes also emphasises how cultural values and knowledge can be woven into urban ecology projects. She points to the revitalised Moonee Ponds Creek as an example, noting “it has a calendar for the Wurundjeri seasons and a beautiful cultural trail.” Projects like these offer valuable opportunities for communities to connect not only with nature, but with culture. So, how can we make our own homes more wildlife-friendly? Soanes encourages asking, “What can I add to make living here easier for species other than me? ”. It could be as simple as planting a few more native plants in your garden. As the warmer months approach, placing birdbaths or shallow water trays outside can help wildlife keep cool, “especially as our cities become hotter and drier”. Outside of her work as a researcher, Soanes has a strong social media presence, using it as a platform to share her conservation messages with the wider public. She emphasises that science communication is "about making your messages and your science accessible not just to the broader public, but to the people making decisions". Dr Kylie Soanes platforms her conservation messages on social media. (8) Soanes argues that "showcasing and celebrating those stories of success" gives people "hope that they can make change in their area", while inspiring councils and urban land managers to apply similar solutions. She acknowledges that wildlife conservation can feel "very heavy” at times but stresses “it is important to show that there are all these options out there.” "There are so many other people that want the same things, or would like to see their neighbourhood become a little bit better for nature," she adds. "I think almost everybody cares about nature – it just doesn't always look like wearing khaki and carrying binoculars at all times." A big thank you to Dr Kylie Soanes for taking the time to speak with us and shed light on the fascinating world of urban ecology. To keep up with her work, follow her on Instagram @drkyliesoanes or explore her research and projects at kyliesoanes.com . References Soanes K. Dr Kylie Soanes [Internet]. Dr Kylie Soanes. [cited 2025 Oct 18]. Available from: https://kyliesoanes.com/ Paul M. A “balancing act” as council votes to fence dogs out of park, sparking safety concerns [Internet]. ABC News. 2025 Aug 21. Available from: https://www.abc.net.au/news/2025-08-21/merri-creek-dog-fence-swamp-wallaby-coburg-victoria/105675854 City of Melbourne. Melbourne jumps at the chance to bring back the grasshopper [Internet]. City of Melbourne. 2022 [cited 2025 Oct 18]. Available from: https://www.melbourne.vic.gov.au/media/melbourne-jumps-chance-bring-back-grasshopper Balance Enviro. Yarra River Floating Wetlands – Balance Enviro Solutions [Internet]. 2022. Available from: https://balanceenviro.com.au/project/yarra-river-floating-wetlands/ City of Melbourne. Wildflower meadows and rare blooms boost biodiversity in Melbourne [Internet]. Vic.gov.au . 2024 [cited 2025 Oct 18]. Available from: https://www.melbourne.vic.gov.au/news/wildflower-meadows-and-rare-blooms-boost-biodiversity-melbourne#meadows Arthur Rylah Institute. Use of nest boxes in Victoria [Internet]. 2020. Available from: https://www.ari.vic.gov.au/research/people-and-nature/use-of-nest-boxes-in-victoria Melbourne Water. Constructed wetlands | Melbourne Water [Internet]. 2022. Available from: https://www.melbournewater.com.au/building-and-works/stormwater-management/options-treating-stormwater/constructed-wetlands Soanes K. Dr Kylie Soanes [Instagram page]. Instagram. [cited 2025 Oct 18]. Available from: https://www.instagram.com/drkyliesoanes/?hl=en 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 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 Axolotl: The Little God of the Lake by Danny He 28 October 2025 Illustrated by Saraf Ishman Edited by Ciara Dahl Creation “When the fifth sun was created, it did not move. The god of the wind carved a destructive path through the realm, slaying all other gods to induce the Sun into movement. Xolotl, guide for the dead, escaped his sacrifice by transforming into an invulnerable salamander. Eventually, even he was captured. Upon his sacrifice, the Sun began its course. Thus began the time of man.” - Author’s creative interpretation of Aztec mythology. The otherworldly biology of the axolotl ( Ambystoma mexicanum) attracted fascination among the Aztecs, who named it after the god of fire and lightning (1). They believed the shapeshifting god Xolotl took many forms, from a chimera depicted as a dog-headed man, to a skeleton, to a deformed monster with reversed feet (1). He was a renowned shapeshifter who would guide the dead on their journey to the afterlife (1). Centuries on, the axolotl would transform from a feared deity to a beloved icon and subject of scientific marvel. Fascination “Auguste Dumeril lounged by the lake. The humidity of Lake Xochimilco was beginning to take its toll. He had recently been informed of a marvellous reptile, one that resided exclusively in the canals of ancient Aztec, capable of regrowing limbs and organs including its brain. He wondered of the scientific possibilities of studying such a creature. A self-regenerating invertebrate could fascinate the scientific community and make wonderful contributions to medicine. This creature is to be taken back home to Paris” - Imaging a day with French Zoologist August Dumeril. The axolotl exhibits many biological peculiarities. Cousin of the tiger salamander ( Ambystoma tigrinum) , it has evolved over millions of years to take advantage of the bountiful resources of the Mexican basins (2). It remains in its juvenile, tadpole-like form throughout its adulthood, retaining its gills and breathing through its skin (2). The animal’s near perfect regeneration and its potential application for medical research fascinated scientists. French zoologist Auguste Dumeril was the first to conduct research on the axolotl after discovering it during his expedition to Mexico (3). Decades later, proteins were discovered which enabled the miraculous processes of complete, scar-free regeneration of an injured axolotl (4). Scientists continue to research methods in which the axolotl’s regeneration can facilitate trauma care and cancer research (4, 5). Conservation “Pedro set his spade down, straw hat clutched close to his chest. His eyes fixated on the water before him. Just below the surface, he had thought something had moved along the river bank. It had been many years since he had last seen an axolotl. The Méndez Rosas had been working as Chinamperos for generations. The axolotl had been a welcome sight for his forefathers, now it is a sign of hope for Lake Xochilmilco.” - an interview with Pedro, a 7th generation Chinamperos (7). Chinampas are large man-made farming islands created by the Aztecs (6). The capital city was built upon an island on a vast lake using a series of complex canals to prevent their city from flooding (6). Chinamperos use the lake's nutrient-rich soil to grow crops and create a self-sustaining system resilient to pests and disease (6). Productive chinampas ensure greater food security for Mexico City. A perfect symbiosis between water and land, a healthy chinampa cannot be without a healthy body of water (6). As chinampas grow they become refuge for wildlife such as the axolotl (6). As axolotls breathe through their skin, their presence indicates excellent water quality and hence a healthy chinampa (6). However, this once thriving ecosystem is now under threat from urbanisation. Drainage of the lake has resulted in the range of chinampas being limited to Lake Xochilmilco (6). Pollution and climate change has altered the landscape, while expansion of the city has resulted in the loss of precious wetlands (6). These changes have driven axolotls to critical endangerment. A once venerated and sacred creature has been neglected and buried by the relentless incursion of human civilisation (6). It is now a race against time to save the wild axolotls as few remain in Lake Xochilmilco (2). As urbanisation continues to bear down upon the chinampas, calls have been made to protect these dwindling areas of refuge (2). The fate of the axolotl is yet to be determined, but it is certain that the loss of another species will continue to set a dangerous precedent for the conservation of our ecosystems. Aztec mythology describes the god represented by the axolotl as the caretaker of his underworld kingdom and a guide for lost souls (1). Perhaps it is now important for us to take care of the axolotl as Xolotl has taken care of us. References Spence L. Mexico and Peru [Internet]. Senate; 1994. Accessed September 29, 2025. https://archive.org/details/mexicoperu00spen The Editors of Encyclopaedia Britannica. Axolotl. Britannica . July 20, 1998. Updated 27 August, 2025. Accessed September 29, 2025. https://www.britannica.com/animal/axolotl Reiß C. Cut and Paste: The Mexican Axolotl, Experimental Practices and the Long History of Regeneration Research in Amphibians, 1864-Present. Front Cell Dev Biol . 2022;10:786533. doi:10.3389/fcell.2022.786533 Huang L, Ho C, Ye X, Gao Y, Guo W, Chen J, et al. Mechanisms and translational applications of regeneration in limbs: From renewable animals to humans. Ann Anat . 2024;255:152288. doi:10.1016/j.aanat.2024.152288 Suleiman S, Schembri-Wismayer P, Calleja-Agius J. The axolotl model for cancer research: a mini-review. J BUON . 2019;24(6):2227–31. Accessed September 29, 2025. https://www.researchgate.net/publication/338630505_The_axolotl_model_for_cancer_research_a_mini-review The Editors of Encyclopaedia Britannica. Chinampa. Encyclopaedia Britannica . July 20, 1998. Updated 26 May, 2017. Accessed September 29, 2025. https://www.britannica.com/topic/chinampa Nature on PBS. Wild axolotls are being saved by... nuns and Aztec gardens? | WILD HOPE. Youtube. September 12, 2023. Accessed September 29, 2025. https://www.youtube.com/watch?v=NL0ad3jBWRI&t=808s Previous article Next article Entwined back to

< Back to Issue 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 4 Why Our Concept of Colours is Broken by Selin Duran 1 July 2023 Edited by Tanya Kovacevic and Megane Boucherat Illustrated by Aizere Malibek The world that surrounds us is made from a combination of three main colours: red, yellow and blue. Known as the primary colours, it's the first thing we learn in primary school art class. In illusions, however, our concept of colours becomes warped and fails us. The only question is how do we fix it? Take the infamous colour-changing dress of 2015. This dress became an internet sensation due to its ambiguity of colour with the major question being “Is the dress black and blue or white and gold?” The dress, despite causing many online debates, is actually black and blue. Nevertheless this debate raises an important question about colours. Why do we see different colours in the same image? Let's begin with colour theory. Colour theory is a set of guidelines that artists use when mixing colours within the spectrum. With the intention of provoking different psychological responses, colours are used to either complement or contrast one another [1]. We see this through the infamous dress - with black and blue complimenting each, then gold and white. Our highly subjective perception allows us to see visually appealing combinations of colours juxtaposed to contrasting combinations. However, what we also need to consider are the light sources being used. Ranging from natural light to blue light and other artificial lighting, the light that we are exposed to can alter our perspective of colour. On our devices, we see colours through a series of red, green, and blue pixels that combine to make new colours for every image that we see [2]. Similarly, the frequent manipulation of our devices’ brightness also contributes to different colours being shown on the screens. These are the primary reasons why the famous dress was perceived so differently by everyone: each device shows a different version of the same colour depending on its display settings, which affects how many red, green and blue pixels there are. In addition to the colour theory, another effect— the Bezold Effect—is at its peak with the infamous dress. The Bezold Effect is an optical illusion where a colour’s appearance is affected by the presence of colours that surround the object [3]. For this dress, it’s seen through the shadows that form on and around the bodice. With brighter surroundings, such as the sun or an overly brightened screen, the blue from the dress appears gold to the eye, while the black appears white. The dress reverts to its original colours when the screen is darkened or artificial light is used. Circling back to colour theory, the changes in colours aren’t randomly allocated: they are opposing colours of the colour wheel. The wheel is a visual illustration of colours arranged by their wavelength, used to display the relationship of primary colours to their corresponding secondary colours [4]. With blue contrasting a yellow or gold, the changes in lighting perfectly display the contrasting colours on the wheel. The fascinating nature of colours is not something we can fix. In the era of digital displays and evolving technologies, we can’t see things the “right” way because there is no notable “right” or “wrong” way to look at the world. The dress is just one of those illusions that changes depending on the context and surroundings that it’s placed in. You can manipulate these colours and force them to change by physically changing the brightness on a device. So out of curiosity, I decided to conduct a little experiment of my own through an Instagram poll to see what my friends thought of this dress. While only 37 people participated, it was still fun to see what would happen with the votes; however, I was surprised to see the results after 24 hours. I expected a majority to choose the “real” colour of the dress, since the dress has been around in the media for a while and the answer is also online, but people still had contrasting opinions about the dress. With only 54% of people seeing black and blue and 46% white and gold, I began questioning our vastly different perceptions. The answer always seemed obvious as the dress was always black and blue not white and gold but that didn’t mean that other people saw what I saw. My favourite response came from a friend who saw the dress as blue and gold and after that, my opinion changed. For me, the dress is now blue and with tints of gold and I can’t see it any other way. This truly goes to show that there’s more behind the dress than what meets the eye. When I first saw the image my brightness was at the lowest it could possibly be and now after looking at the image enough, it’s just blue and gold. The ambiguity of this image is what makes the dress the best example of a real-life illusion. Other colour combinations act the same way in different lighting, but what we see is completely dependent on our perceptions, and every now and then, it’s always fun to put up a debate. References Eliassen MM. Colour theory. Salem Press Encyclopedia [Internet]. 2023 Jan 1 [cited 2023 May 13]; Available from: https://discovery.ebsco.com/linkprocessor/plink?id=30f4180b-d38d-38e6-95df-fcf469ab5c8a Mertes, A. (2021, February 23). Why Computer Monitors Display the Same Colors Differently . https://www.qualitylogoproducts.com/ . https://www.qualitylogoproducts.com/promo-university/why-monitors-display-different-colors.htm#:~:text=The%20pixels%20are%20in%20some,shows%20up%20on%20the%20screen Lasikadmin. (2022, June 2). What is Bezold Effect? | Useful Bezold Effect. LASIK of Nevada. https://lasikofnv.com/blog/test-your-vision-by-bezold-effect/#:~:text=What%20is%20the%20Bezold%20Effect,one%20to%20the%20human%20eye Understanding color theory: the color wheel and finding complementary colors . (n.d.). https://www.invisionapp.com/inside-design/understanding-color-theory-the-color-wheel-and-finding-complementary-colors/ Previous article Next article back to MIRAGE

By Ashleigh Hallinan < Back to Issue 3 Space exploration in Antartica By Ashleigh Hallinan 10 September 2022 Edited by Tanya Kovacevic and Breana Galea Illustrated by Aisyah Mohammad Sulhanuddin Next The isolated southern expanse of the Earth is an alien realm, with vast expanses of white ice and blue sky that appear to stretch on infinitely. Despite its barren landscape, the Antarctic continent holds secrets to the origins of our Earth and the solar system in the form of meteorites. Meteorites are solid pieces of debris that originate in outer space, survive the journey through our atmosphere, and fall to the Earth’s surface.(1) Their unique components and pungent smells contain fascinating stories of cosmic clouds, condensing stardust and the fiery collisions of entire planets. These ‘space rocks’ can land anywhere on Earth, but the vast majority of meteorites are found in the cold deserts of Antarctica.(2) So, why Antarctica? Across the globe, meteorite abundance is dependent on two factors: the meteorites must be easy to spot, and their preservation must be guaranteed over long time periods.(3) It is the conditions of the Antarctic landscape that make all the difference when it comes to meteorite discovery. The cold, dry nature of Antarctica helps to preserve these extraterrestrial rocks, allowing for more pristine samples to be collected. In this way, we may think of Antarctica as a ‘natural freezer’. In fact, meteorites can be buried and preserved in the Antarctic ice for up to millions of years, allowing for a deep dive into the origins of the solar system upon analysis. Furthermore, meteorites are easier to find in Antarctica due to the stark contrast between the dark colours of meteorites and the white ice. And since so few rocks naturally form on ice sheets, you can be fairly certain the majority of rocks found in Antarctica are extraterrestrial. However, an expedition to Antarctica for meteorite hunting is no small feat. Thankfully, landscape processes occurring on the Antarctic continent create concentrated pockets of meteorites, making the hunt for meteorites less like trying to find a needle in a haystack. These meteorite hotspots are largely a result of the local geology and movement of ice across the Antarctic landscape.(4) As meteorites strike glaciers, they are buried and encased in the ice. These glaciers move across the landscape, acting as ‘conveyor belts’ that carry the meteorites until they reach a large barrier, such as the Transantarctic Mountains. The ice flow is blocked and builds up at the base of the mountain. Here, dry Antarctic winds slowly erode the ice, revealing a bounty of imprisoned meteorites. Traditionally, meteorites have been divided into three broad categories: stony, stony-iron, and iron.(5) While stony meteorites are made up of silicate minerals, iron meteorites are almost completely made of metal. Unsurprisingly, stony-iron meteorites are composed of nearly equal amounts of metal and silicate crystals. Alarmingly, warmer temperatures and melting ice associated with global warming may hinder our search for meteorites. This is particularly the case for iron meteorites, which conduct heat more efficiently than other meteorite types due to their higher metal content.(6) Consequently, meteorites can sink into the ice and out of sight. Despite Antarctica’s otherworldliness, it is not free of the impacts brought about by human activity occurring on landmasses separated by vast seas. However, with the help of artificial intelligence and machine-learning, the quest for meteorite discovery continues. Scientists recently estimated there are as many as 300,000 more meteorites to be discovered in Antarctica, their stories waiting to be uncovered in a never-ending game of hide-and-seek.(7) Using machine learning to combine satellite measurements of temperature, surface slope, speed of ice flow, and reflection of radar signals by ice, scientists have developed a ‘treasure map’ containing the predicted locations of concentrated meteorite zones.(7) The ’treasure map’ is accessible online,(8) so anyone can search the Antarctic continent for rocky remnants left over from the formation of the solar system. When we think of space exploration, we conjure up images of astronauts and spaceships. But Antarctica provides us with the opportunity to peer into the cosmos without ever leaving Earth, given we are brave enough to face the inhospitable conditions and pervasive alienness of the Earth’s southernmost continent. References 1. Sephton M, Bland P, Pillinger C, Gilmour I. The preservation state of organic matter in meteorites from Antarctica. Meteoritics & Planetary Science. 2004;39(5):747-54. 2. Corrigan C. Antarctica: The Best Place on Earth to Collect Meteorites. CosmoELEMENTS; 2011. p. 296. 3. Schlüter J, Schultz L, Thiedig F, Al‐Mahdi B, Aghreb AA. The Dar al Gani meteorite field (Libyan Sahara): Geological setting, pairing of meteorites, and recovery density. Meteoritics & Planetary Science. 2002;37(8):1079-93. 4. Steigerwald B. NASA Scientist Collects Bits of the Solar System from an Antarctic Glacier Greenbelt: NASA; 2018 [Available from: https://www.nasa.gov/feature/goddard/2018/antarctic-meteorites. 5. Lotzof K. Types of meteorites [Internet]. Natural History Museum; [Available from: https://www.nhm.ac.uk/discover/types-of-meteorites.html. 6. Evatt G, Coughlan M, Joy K, Smedley A, Connolly P, Abrahams I. A potential hidden layer of meteorites below the ice surface of Antarctica. Nature communications. 2016;7(1):1-8. 7. Tollenaar V, Zekollari H, Lhermitte S, Tax DM, Debaille V, Goderis S, et al. Unexplored Antarctic meteorite collection sites revealed through machine learning. Science Advances. 2022;8(4). 8. Tollenaar V, Zekollari H, Lhermitte S, Tax DM, Debaille V, S G. Antarctic Meteorite Stranding Zones [Internet]. [Available from: https://wheretocatchafallingstar.science/. Previous article Next article alien back to

< Back to Issue 8 What Do Women Want? by Madeleine Kelly 3 June 2025 Edited by Rita Fortune Illustrated by May Du What do women want? Well, according to scientific research… more data is needed. As it turns out, women are a mystery to science. This mystery stems from the lack of representation of women in scientific research, both as the researcher and the subject. In its stead, sexist assumptions have leaked in and clouded results. This has very real, very scary consequences – and not just for us humans! From women to female birds and mammals, science has a habit of ignoring half the population. This gap exists in many fields, but for now let’s focus on medicine, where women are (quite literally) getting sick of being excluded. Historically, medicine hasn’t been kind to women, going all the way back to the Ancient Greeks where philosophers ingrained sexism into stone. Aristotle, considered the founder of many disciplines in Western culture including biology, thought women incomplete, “mutilated male(s)” (1). Plato, just as revered, stated that women were corrupted by a “wandering womb” – an angry uterus that would drift around the body causing all types of disease (2). The influence of these hot takes on women have shaped the fields of biology and medicine for centuries. Now we’ve ended up with a healthcare system designed by and designed for men. Looking at slightly more recent history, women weren’t included in clinical trials until the 1990s, even when looking into conditions that were specific to women (3). In the early 1960s researchers wanted to examine how the likelihood of heart disease could be decreased amongst menopausal women through hormone supplements (4). They had a respectable sample size of participants for the trials: 8,341 people. Were any of them women? No, of course not. This bias persists today. On average, only 41.2% of participants in clinical trials are female, well below their actual representation amongst patients (5). A 2022 study examined more than 20,000 clinical trials from the past 20 years and found that trials in oncology, neurology, immunology and nephrology had the lowest female representation relative to the likelihood that women would develop the disease (6). In psychiatry, as not even one of the worst fields, women still only made up 42% of trial participants, yet comprised 60% of the patients (5). Women of colour, queer women and trans women are even more marginalised in medical research (7, 8). A regular justification researchers use for excluding cis women is that their menstrual cycles would interfere with the reliability of results (which, by the way, has been proven to be unfounded) (9). This hasn’t stopped them from claiming that their results can be universally applied. Given their systematic exclusion from scientific study, it is no wonder that women are more likely to be misdiagnosed for common conditions such as a heart attack and stroke, and experience adverse side effects from medications, at twice the rate of men (3). During the period from 1997 to 2000, ten prescription drugs were taken off the market by the US Food and Drug Administration. Of these, eight posed greater health risks to women compared to men – risks which could have been caught in the trial stage if they had just included more women (10). Women are also more likely to have their physical symptoms be blamed on mental health issues — because that’s apparently better than doctors having to admit we simply don’t know how women work (11). This knowledge gap extends beyond medical research, and indeed beyond the human world. Females of all species have become victims of sexist attitudes. This is partially owed to the work of famous naturalist Charles Darwin. In his book, The Descent of Man, and Selection in Relation to Sex (1871), he labelled the female as "passive" and “coy” (12). It is the males who drive evolution, he declared. Males are the competitive ones, fighting each other and showing off their glamour in order to win the female. According to Darwin, the role of females in the animal kingdom was only to submit. Scientists that followed seemed to have a persistent case of confirmation bias. They actively looked for evidence and manipulated results to support their belief that females were monogamous, pacifistic doting mothers. This was exactly the case when in the 1990s two researchers, John Marzluff and Russell Balda, went to study the social hierarchies of the pinyon jay, Gymnorhinus cyanocephalus (13). Native to Western America, the males of this small bird go against Darwin’s claim by being absolute chillers; they don’t like to fight. Desperate to prove Darwin right, the researchers set up feeders with sweet treats to entice competition between the males. The males still refused to go up in arms. This left the researchers searching for some evidence, any evidence, that Darwin’s theory was still correct. So they claimed that there was aggressive competition between the males played out through… passive aggressive side glances. These ‘fights’ of dirty looks must have been absolutely riveting as the researchers documented over two thousand of them, stealing the show from the actual violent battles perpetrated by the females. The girlies were recorded locked in mid-air fights and stabbing each other with their beaks (yawn). This behaviour was explained away as an “avian equivalent of PMS” and that there was “little doubt that adult males are in aggressive control” (13). The myth that females are passive has been shown time and time again to be false. There are certainly some females that play this role, but just like humans, the animal kingdom is diverse. There are plenty of examples that show that females are just as impressive, competitive and violent, and all are worthy of investigation. Female topi antelopes compete for males, the female Jacana bird leaves eggs with their stay-at-home dads and matriarchal grandmother orcas pass on brutal hunting techniques to the next generation (13). Even though the myth has been busted, the consequences of it still echo in research. In 2019, it was found that there was a male bias in international natural history museum collections of mammals and birds, especially for famous name-bearing species (13). For these species, only 27% of bird and 39% of mammal types collected were female. Any studies conducted on these collections are not representative of the whole species. Given the rapid global biodiversity decline we find ourselves facing, having an accurate understanding of more than the human world has never been more important. This requires us to recognise the sexism in our studies. I know first hand that this is not simple, such as when I realised even I had internalised sexist attitudes towards animals. It took me until I was 25 to realise that the shark from the movie Jaws (1975) was meant to be a girl (15). I had just assumed (much like the director Steven Spielberg) bigger shark equals boy shark. Science doesn’t operate in a vacuum. It is not immune to society and politics, and unfortunately this has meant results can be shaped by prejudice. How do we fix this? Is there a cure for medical misogyny and can we finally discover the female species in the wild? There is no single solution, but we have many options on the table. Getting more women into STEM and leadership roles, transparency in data collection – especially being upfront about disclosing whether or not both sexes were included – and more funding for women’s health research are all essential steps (9). Already there are badass scientists out there dismantling sexist beliefs, who are armed with data and persistence (13). I also think a crucial step is to remember that knowledge is not pure. It can contain bias. As the next generation of researchers, we have a responsibility to question the assumptions baked into our methods, our questions and even our definitions of what counts as valid research. This kind of introspective, self-critical work isn’t just about academic integrity. It could save lives. So, what do women want? Aside from going back in time to set a couple ancient philosophers and a certain naturalist straight, we want you to ask us – and to never assume you know the answer before doing so. References Horowitz, MC. Aristotle and Woman. J History of Biology [Internet]. 1976 [cited 2025 May 25]; 9(2):183-213. Available from http://www.jstor.org/stable/4330651 . Adair, MJ. Plato’s View of the ‘Wandering Uterus’. The Classical Journal [Internet]. 1996 Jan [cited 2025 May 25]; 91(2): 153-163. Available from https://www.jstor.org/stable/3298478 . Why we know so little about women’s health [Internet]. Blach, B: AAMC; 2024 [cited 2025 May 25]. Available from https://www.aamc.org/news/why-we-know-so-little-about-women-s-health Dusenbery, M. New York (US): HarperCollins; 2018. Sosinsky, AZ., Rich-Edwards, JW., Wiley, A., Wright, K., Spagnolo, PA. & Joffe, H. Enrollment of female participants in United States drug and device phase 1-3 clinical trials between 2016 and 2019. Contemp Clin Trials [Internet]. 2022 Apr [cited 2025 May 25]; 115: 106718. Available from: https://doi.org/10.1016/j.cct.2022.106718 Steinberg, JR., Turner, BE., Weeks, BT., Magnani, CJ., Wong, BO., Rodriguez, F., Yee, LM & Cullen, MR. Analysis of Female Enrollment and Participant Sex by Burden of Disease in US Clinical Trials Between 2000 and 2020. AMA Netw Open [Internet]. 2021 Jun [cited 2025 May 25]: 4(6):e2113749. Available from: https: doi.org/10.1001/jamanetworkopen.2021.13749 Bierer, BE., Meloney, LG., Ahmed, HR. & White, SA. Advancing the inclusion of underrepresented women in clinical research. Cell Rep Med [Internet]. 2022 Mar [cited 2025 May 25]; 3(4): 100553. Available from: https://doi.org/10.1016/j.xcrm.2022.100553 Kelly, T & Rodriguez, SB. Expanding Underrepresented in Medicine to Include Lesbian, Gay, Bisexual, Trasgender, and Queer Individuals. Acad Med [Internet]. 2022 Nov [cited 2025 May 25]; 97(11) 1605-1609. Available from: https://doi.org/10.1097/ACM.0000000000004720 Beery, AK. & Zucker, I. Sex Bias in Neuroscience and Biomedical Research. Neurosci Biobehav Rev [Internet]. 2010 Jul [cited 2025 May 25]; 35(3): 565-572. Available from: https://doi.org/10.1016/j.neubiorev.2010.07.002 . Carey, JL., Nader, N., Chai, PR., Carreiro, S., Griswold, MK. & Boyle KL. Drugs and Medical Devices: Adverse Events and the Impact on Women’s Health [Internet]. 2018 Jan [cited 2025 May 25]; 39(1): 10-22. Available from: https://doi.org/10.1016/j.clinthera.2016.12.009 Jackson, G. Pain and Prejudice. Crows Nest (AUS): Allen & Unwin; 2019. Cohen, C. Darwin on woman. Comptes Rendus Biologies [Internet]. 2010 Feb [cited 2025 May 25]; 333(2): 157-165. Available from https://doi.org/10.1016/j.crvi.2009.12.003 Cooke, L. Bitch: What does it mean to be female? London (UK): Penguin Books; 2022. Cooper, N. Bond, AJ., Davis, JL., Miguez, RP., Tomsett, L & Helgen, KM. Sex bias in bird and mammal natural history collections. Proc. R. Soc. B. [Internet]. 2019 Oct [cited 2025 May 25]; 286: 20192025. Available from https://doi.org/10.1098/rspb.2019.2025 What did Hollywood get wrong about great white sharks in Jaws? [Internet]. Ladgrove, P. & Smith, B: ABC News; 2024 [cited 2025 May 25]. Available from: https://www.abc.net.au/news/science/2024-11-16/jaws-what-did-hollywood-get-wrong-shark-attack-humans/104538116 Previous article Next article Enigma back to

< Back to Issue 5 On the Folklore of Fossils Ethan Bisogni 24 October 2023 Edited by Arwen Nguyen-Ngo Illustrated by Aisyah Mohammad Sulhanuddin We inhabit an incredible world, one shaped by the ancient mysteries of our past and the imaginative stories they inspire. Throughout human history, we have tried to comprehend the bigger picture - using mythology and science to explain the presence of any natural phenomena we can observe. Between the movement of the stars and shape of the land, most scientific explanations of our world share a fascinating mythical counterpart. One particular area of science that has been bestowed with some truly incredible folklore is palaeontology. A History of Palaeontology To best understand some of the amazing mythologies surrounding fossils, we should first briefly explore the history of modern palaeontology. Some of the earliest attempts at understanding fossils can be seen in ancient Greece and Rome, where philosophers such as Herodotus understood that the presence of petrified shells indicated the recession of a past marine environment (Forli & Guerrini, 2022a). However, much of the groundwork for modern palaeontology was only developed in the late 17th century (Boudreau et al., 2023). Regarded as one of the most influential figures in modern geology, Nicholas Steno had outlined the Principles of Stratigraphy in his 1669 Dissertationis Prodromus - to be used as a jumping board for many earth scientists to come (Berthault, 2022). In the early 1800’s, William Smith had utilised his fossil knowledge to differentiate and match layers of rock known as strata, published in Strata Identified by Organised Fossils (Scott, 2008). And perhaps one of the largest contributions to modern palaeontology, Darwin's theory of evolution outlined in On the Origin of Species allowed for natural scientists to better understand the evolution of species throughout time. Considering how much of what we know about modern palaeontology was only published in the last 350 years, it becomes clear why so many cultures had developed their own interesting interpretations of fossils. From magical spells to infernal beasts, these legends highlight the prominent ideologies of their time. So let us explore some of the more interesting and diverse fossil myths from the ages. Merlinia To start, we will be discussing the folklore origin of Merlinia, an extinct genus of trilobite from the Early Ordivician age, 470 million years ago (British Geological Survey, n.d.). Trilobites were small sea-faring invertebrates who first appeared following the Cambrian Explosion, and were prominent throughout the fossil record until their unfortunate extinction 250 million years ago during the Late Permian mass extinction (American Museum of Natural History, n.d.). According to the British Geological Survey, this genus of trilobite was extensively found throughout the rocks of Carmarthen - a Welsh town famous for being the supposed birthplace of Merlin, the legendary wizard and advisor to King Arthur (‘P550303’, 2009). Often mistaken by the townspeople as stone butterflies, these fossils were naturally attributed to Merlin and thought to be the product of a petrification spell (American Museum of Natural History, n.d.). Whilst disheartening for the butterflies, the real trilobites behind the myth likely faced a much more wicked and sorrowful demise. Snakestones Much like Merlinia, snakestones were also named after a prominent figure with a habit for turning creatures to stone. Saint Hilda of Whitby was the abbess of the local town monastery during the sixteen hundreds, and was widely credited for the creation of these fossils - which are otherwise known as Hildoceras, after herself (Lotzof, n.d.). With the town facing a plague of snakes, St Hilda was said to have performed a miracle that petrified the serpents and forced them to coil into the fossils we see today (National Museums Scotland, n.d.). These stony serpents however are really just ammonites, a group of molluscs that went extinct alongside the dinosaurs 66 million years ago (Osterloff, n.d.). The legend of St Hilda isn’t the only instance of snake-repellent folklore either, with St Patrick earning himself a holiday after supposedly clearing the snakes out of Ireland. Much of the rise of European anguine-based legends can be attributed to growing Christian influences during the second millennium. The biblical depiction of snakes as tempting and disingenuous has caused them to be portrayed harshly throughout older western media (Migdol, 2021). Unsurprisingly, this isn't the only time that palaeontology and Christianity have crossed paths. The Devil Perhaps the most infamous figure in human culture, the Devil is outlined in Christian doctrine as the embodiment of sin and evil. References to their influence can be found throughout human history, and have naturally found their way into geological folklore. Many geological features have been attributed to a satanic presence, thought to be remnants from when the Devil would walk the earth (Forli & Guerrini, 2022b). Gryphaea was a fossil widely mistaken as the authentic nails of Satan himself, hence nicknamed the ‘Devil’s Nails’, and was used as a proxy to determine areas of evil (Forli & Guerrini, 2022b). However, these fossils were not the byproduct of Satan’s occasional beauty treatments, but rather an extinct genus of mollusc from the early Jurassic, 200 million years ago (Forli & Guerrini, 2022b). Nail clippings were not the only features observed that people considered to be a sign of the Devil’s unholy pilgrimage. Devilish hoof-shaped steps embedded into stone have been reported throughout the world. Referred to as ‘il-passi tax-xitan’ by the Maltese, meaning ‘the devil's footsteps’, these tracks were considered further proof of the Devil's presence amongst mankind (Duffin & Davidson, 2011). In Malta these footprints were really just fossilised echinoids - innocent former sea urchins facing unkind accusations of being demonic (Duffin & Davidson, 2011). That's not to say all Maltese fossils were considered unholy: some 16th century priests conversely believed them to be the footsteps of St Paul the Apostle, following his shipwrecking on the island in the 1st century (Mayor & Sarjeant, 2001). Dragons Dragons are some of the most well known mythical creatures, with many cultures around the world having their own rendition of a mystic dragon-like beast. Unlike some of the other legends explored so far, it is unlikely that fossilised remains were the initial cause of this myth, but were rather used as evidence to cement it in truth. Dragons were considered prominent creatures throughout the Indian mountains, with evidence of dragon hunts being displayed in the ancient city of Paraka (Mayor, 2000). Apollonius of Tyana, a 1st century Greek philosopher, was said to have observed these dragons during his passage through the Siwalik Hills - an Indian range known for its preservation of larger fossils (Mayor, 2000). Described by Apollonius as considerable tusked creatures, these dragon remains were more than likely the fossils of extinct elephants and giraffids - such as Elephas hysudricus or Sivatherium giganteum (Mayor, 2000). India is not the only country to have experienced this phenomenon either, with many Asian and European societies said to have also continuously misdiagnose large vertebrate fossils as dragon bones. Whether it is mischievous spellcasting or the indication of a demonic evil, myths surrounding fossils have existed throughout centuries of human society. These legends provide a fascinating window into the creative minds of past cultures, and their beliefs at the time. While modern palaeontologists have proven these legends to be no more than captivating stories, it is important to view this folklore with a certain understanding and respect. These early attempts at trying to understand the world around us provides an interesting insight into human nature, and our innate desire to search for answers. References American Museum of Natural History. (n.d.) End of the Line - The demise of the Trilobites . American Museum of Natural History. https://www.amnh.org/research/paleontology/collections/fossil-invertebrate-collection/trilobite-website/trilobite-localities/end-of-the-line-the-demise-of-the-trilobites Berthault, G. (2002). Analysis of Main Principles of Stratigraphy on the Basis of Experimental Data . Lithology and Mineral Resources, 22(5), 442-446. https://doi.org/10.1023/A:1020220232661 Boudreau, D., McDaniel, M., Sprout, E., & Turgeon, A. (2023). Paleontology . National Geographic Society. https://education.nationalgeographic.org/resource/paleontology/ British Geological Survey (n.d.). Trilobites . https://www.bgs.ac.uk/discovering-geology/fossilsand-geological-time/trilobites/ Duffin, C. J., & Davidson, J. P. (2011). Geology and the dark side . Proceedings of the Geologists’ Association, 122(1), 7-15. https://doi.org/10.1016/j.pgeola.2010.08.002 Forli, M., & Guerrini, A. (2022). Bivalvia: Devil’s Nails, Reflections Between Superstition and Science. In The History of Fossils Over Centuries (pp. 181-206). Springer, Cham. https://doi.org/10.1007/978-3-031-04687-2_2 Forli, M., & Guerrini, A. (2022). Fossilia and Fossils: Considerations on Their Understanding Over the Centuries . In The History of Fossils Over Centuries (pp. 5-25). Springer, Cham. https://doi.org/10.1007/978-3-031-04687-2_12 Lotzof, K. (n.d.). Snakestones: The Myth, Magic, and Science of Ammonites . Natural History Museum. https://www.nhm.ac.uk/discover/snakestones-ammonites-myth-magic-science.html Mayor, A. (2000). CHAPTER 3 Ancient Discoveries of Giant Bones . In The First Fossil Hunters (pp. 104-156). Princeton University Press. https://www.jstor.org/stable/j.ctt7s6mm.11 Mayor, A., & Sarjeant, W.A.S. (2001). The Folklore of Footprints in Stone: From Classical Antiquity to the Present . An International Journal for Plant and Animal Traces, 8(2), 143-163. https://www.jstor.org/stable/j.ctt7s6mm.11 Migdol, E., Morrison, E., & Grollemond, L. (2021). What Did People Believe about Animals in the Middle Ages? Getty Conservation Institute. https://www.getty.edu/news/what-did-people-believe-about-animals-in-the-middle-ages/ National Museums Scotland (n.d.). Snakestones . https://www.nms.ac.uk/explore-our- collections/stories/natural-sciences/fossil-tales/fossil-tales-menu/snakestones/ Osterloff, E. (n.d.). What Is an Ammonite? Natural History Museum. https://www.nhm.ac.uk/discover/what-is-an-ammonite.html P550303. (2009). British Geological Survey . http://geoscenic.bgs.ac.uk/asset- bank/action/viewAsset?id=113713&index=4&total=6&view=viewSearchItem Scott, M. (2008). William Smith (1769-1839) . NASA Earth Observatory. https://earthobservatory.nasa.gov/features/WilliamSmith Wicked back to

Science Ethics Should We Protect Our Genetic Information? By Grace Law What is a top story that has been brewing in our news in recent months? This column provides an introduction to the topic and why we should care about it. For this issue, our focus is on the security of our genetic and biometric data. Edited by Juulke Castelijn & Khoa-Anh Tran Issue 1: September 24, 2021 Illustration by Aisyah Mohammad Sulhanuddin Our genetic and biometric data, like DNA and fingerprints, make each of us unique and identifiable. This information is invaluable in allowing us to verify our identity, predict personal characteristics, identify medical conditions, and trace our ancestry. But there are consequences we should be aware of when we are sharing this data. It is often not known exactly what our information is used for. We must make a more informed decision about the services we obtain in exchange for our biometric and genetic information. The unknown consequences of medical tests Most of us would not hesitate to get a blood or genetic test. These tests have been instrumental in allowing us to identify genetic abnormalities, monitor our health, and provide peace of mind in pregnancies. However, some companies and 3rd parties have exploited the trust patients placed in them to analyse these data beyond the original medical intentions. Reuters reported in July 2021 of a Chinese gene company, BGI, using leftover genetic data from their prenatal test to research population traits (1). The test is sold in at least 52 countries to detect abnormalities like Down’s syndrome in the fetus but it also captures genetic and personal information about the mother. The company confirmed that leftover blood samples are used for population research, and the test’s privacy policy states that data collected can be shared when “directly relevant to national security or national defence security” in China (2). This is not the only instance of genetic data being exploited by a state for mass examination and surveillance purposes. The Australian Strategic Policy Institute (ASPI) published a research paper identifying the Chinese Government Ministry of Public Security’s mass DNA collection campaigns on millions of men and boys (3). It aims to ‘comprehensively improve public security organs’ ability to solve cases, and manage and control society’ (4). Certainly such databases are useful to forensic investigations, but the mass collection of genetic data raises serious human rights concerns regarding ownership, privacy and consent. Furthermore, it opens the possibility of surveillance by the government (5). Everyone should be giving fully informed consent for the usage of their genetic information in accordance with international human rights law (6). ‘At-home’ genetic kits are not guaranteed to be secure Although there is no evidence of such scales of surveillance in Australia, we are not immune to exploitation and questionable practices. Direct-to-consumer (DIC) genetic tests are widely available, often through online purchases. These tests advertise as being able to indicate predisposition to various diseases, including diabetes, breast cancer and heart disease (7). However, as these processes don’t always involve the advice and interpretation of a doctor, there are concerns that data may be analysed beyond current medical understanding. Misinformation, such as misdiagnosis or exaggeration of the certainty of the user’s health conditions, can cause unnecessary anxiety. The discovery of medical predispositions can have ongoing consequences, including refusal of coverage from insurance companies and discrimination by society (8). Under the US Genetic Information Nondiscrimination Act, employees cannot discriminate against employers on the basis of genetic information. Australia currently relies on existing Commonwealth, state and territory anti-discrimination laws to protect against discrimination in public domains (9). Companies are also not regulated by the law in what they do with the information collected. Many have been found to use the information beyond providing results to consumers, such as for internal research and development, or providing it to third parties without additional consent (10). Ancestry tests are another type of DIC test facing similar scrutiny. As we all share genetic information with our relatives, these tests allow us to identify distant relatives, and even help solve mysteries and capture a serial killer (11). Testing companies therefore have portions of genetic information from relatives without needing to obtain their consent, as well as being able to identify familial lineages. These examples highlight the difficulty of protecting consumer privacy and maintaining ownership of our genetic information. The daily convenience of biometric data and its unintended side-effects Most of us do not encounter the aforementioned tests daily, but we often use our biometric data in many aspects of our lives. As technology advances, fingerprint readers, facial scanners, and even retina/iris scanners are available on our phones to replace traditional PINs. These have been widely adopted due to their convenience. However, our security is being compromised in the process. Not only is your device easier to hack compared to passwords, but the collection of biometric data can also be illegally obtained from improper storage (12, 13). We cannot change our biometric data like a password. Once it is compromised, it is beyond our control. Meanwhile, technology is advancing to include new types of biometric data like voice recognition, hand geometry and behaviour characteristics. As our lives become more public through social media, others may be using this opportunity to collect more information. TikTok’s update on its privacy policy recently included permission to gather physical and behavioural characteristics, but it is unclear what it is being used for (14). These examples highlight why we should be aware of the consequences and compromisation we make in using biometric data for daily convenience. Looking to the future There is certainly no shortage of interest in our genetic information and biometric data. Unfortunately, current legislation is fairly general and therefore not equipped to deal with the variety of issues that emerge with specific technologies. Exacerbating this effect are the continual advances made in this technology, with the law simply not keeping up. But that does not mean we are helpless. A landmark case found that an Australian worker being fired for refusing to use a fingerprint scanner at work was unjust (15). This shows our rights over our genetic information are still in our own hands. While we should be vigilant at all times, it should not deter us from accessing the necessary medical tests or saving us a few seconds each time we access our phones. It is more important to protect ourselves: be aware of our rights, the policies we are consenting to, and the possible implications of a service. Whilst appropriate legislation still needs to be developed, we can hold companies accountable for their policies. We should also be critical in whether we publicise all of our information, and be cognizant of the way our data is stored. This is an instance where we really should read the terms and conditions before accepting. References: 1 . Needham, Kirsty and Clare Baldwin. “Special report: China’s gene giant harvests data from millions of women.” Reuters, July 8, 2021. https://www.reuters.com/legal/litigation/chinas-gene-giant-harvests-data-millions-women-2021-07-07/ . 2. Australian Broadcasting Corporation. “China’s BGI group using prenatal test developed with Chinese military to harvest gene data.” July 8, 2021. https://www.abc.net.au/news/2021-07-08/prenatal-test-bgi-group-china-genetic-data-harvesting/100276700 . 3. Dirks, Emile and James Leibold. Genomic surveillance: Inside China’s DNA dragnet. Barton, ACT: Australian Strategic Policy Institute, 17 June, 2020. https://www.aspi.org.au/report/genomic-surveillance . 4. Renmin Net. “Hubei Yunxi police helped to solve a 20-year-old man’s duplicated household registration issue.” 18 November, 2021. https://www.abc.net.au/news/2021-07-08/prenatal-test-bgi-group-china-genetic-data-harvesting/100276700 . 5. Wee, Sui-Lee. “China is Collecting NDA From Tens of Millions of Men and Boys, Using U.S. Equipment.” 17 July, 2020. https://www.nytimes.com/2020/06/17/world/asia/China-DNA-surveillance.html . 6. United Nations Human Rights Office of the High Commissioner. Universal Declaration on the Human Genome and Human Rights. Paris, France: United Nations, 11 November, 1997. https://www.ohchr.org/en/professionalinterest/pages/humangenomeandhumanrights.aspx . 7. Norrgard, Karen. “DTC genetic testing for diabetes, breast cancer, heart disease and paternity,” Nature Education 1, 1(2008): 86. https://www.nature.com/scitable/topicpage/dtc-genetic-testing-for-diabetes-breast-cancer-698/. 8, 10. Consumer Reports. “The privacy risks of at-home DNA tests.” Washington Post, September 14, 2020. https://www.washingtonpost.com/health/dna-tests-privacy-risks/2020/09/11/6a783a34-d73b-11ea-9c3b-dfc394c03988_story.html . 9. National Health and Medical Research Council. Genetic Discrimination. Canberra, Australia: November, 2013. https://www.nhmrc.gov.au/about-us/publications/genetic-discrimination. 11. Jeong, Raehoon. “How direct-to-consumer genetic testing services led to the capture of the golden state killer.” Science in the News, 2 September, 2018. https://sitn.hms.harvard.edu/flash/2018/direct-consumer-genetic-testing-services-led-capture-golden-state-killer/ . 12. Lee, Alex. “Why you should never use pattern passwords on your phone.” Wired UK, 3 July, 2020. https://www.wired.co.uk/article/phone-lock-screen-password . 13. Johansen, Alison Grace. “Biometrics and biometric data: What is it and is it secure?” NortonLifeLock, 8 February, 2019. https://us.norton.com/internetsecurity-iot-biometrics-how-do-they-work-are-they-safe.html . 14. McCluskey, M. “TikTok Has Started Collecting Your ‘Faceprints’ and ‘Voiceprints.’ Here’s What It Could Do With Them.” Time, 14 June, 2021. https://time.com/6071773/tiktok-faceprints-voiceprints-privacy/ . 15. Perper, Rosie. “An Australian worker won a landmark privacy case against his employer after he was fired for refusing to use a fingerprint scanner.” Business Insider Australia, 22 May, 2019. https://www.businessinsider.com.au/australian-worker-wins-privacy-case-against-employer-biometric-data-2019-5?r=US&IR=T.

< Back to Issue 7 A Coral’s Story: From thriving reef to desolation by Nicola Zuzek-Mayer 22 October 2024 edited by Arwen Nguyen-Ngo illustrated by Amanda Agustinus The sun is shining. Shoals of fish are zooming past me, leaving their nests where I let them stay for protection from bigger fish. I look to my right and the usual fish have come to dine from me, filling their bellies with vital nutrients. I feel proud of our coexistence: I feed the big fish and provide shelter to small fish, whilst they clean algae off of me. I am the foundation of the reef. I am the architect of the reef. Without me, there would be nothing. I can’t help but think that the reef is looking vibrant today. A wide variety of different coloured corals surround me in the reef, with some of my closest friends a stone’s throw away. We’ve all known each other for our entire lives, and it’s such a close knit community of diverse corals. Life is sprawling in this underwater metropolis, and it reminds me of how much I love my home. But recently, I’ve heard some gossip amongst the city’s inhabitants that this paradise may change soon – and for the worse. Something about the land giants destroying our home. I refuse to believe such rumours – why would they want to destroy us? Our home is so beautiful, and we have done nothing to hurt them. Our beauty attracts many of them to come visit us, and most never hurt us. But sometimes I feel pain when they visit on a particularly sunny day, when I see white particles drop down to the reef and pierce my branches, polluting the city. My friends have told me that these giants wear something called ‘sunscreen’ to protect themselves from the sun, but their ‘protection’ is actually poisoning us. I hope that they realise that soon. Another thing that I’ve noticed recently is that the ocean is feeling slightly warmer than before, and my growth is slowing more. Yes, I’m concerned, but I don’t think that the issue will get worse. 30 years later… The sun is blisteringly hot. I feel sick and the water around me is scorching hot. The vibrant colours of the reef are disappearing, and there are fewer organisms around. We used to be so diverse, but so many species of fish have died out. It’s eerie to see the area so desolate. My body is deteriorating and I feel so much more fragile than before. I feel tired all the time, after using so much energy to repair my body in the acidic water. I sense myself becoming paler, losing all colour in my body. I struggle to breathe. My coral friends and family are long gone, perished from the acidity of the ocean. I am the last one remaining. In my last moments, I can only wish to go and relive the past. I wish that the land giants had done more to help not only my city, but other reef cities around the world. All the other cities are empty now, and all ecosystems are long gone. If only someone had helped our dying world. Previous article Next article apex back to

< Back to Issue 7 Tip of the Iceberg: An Overview of Cancer Treatment Breakthroughs by Arwen Nguyen-Ngo 22 October 2024 edited by Zeinab Jishi illustrated by Louise Cen Throughout the history of science, there have been many firsts. Anaximander, a Greek scholar, was the first person to suggest the idea of evolution. Contrary to popular belief, the Montgolfier brothers were the pioneers of human flight by their invention of the hot air balloon, as opposed to another pair of brothers, the Wright brothers. In 1976, the first ever vaccine was created by an English doctor, who tested his theory in a rather peculiar manner that would not be approved by today’s ethics guidelines (Rocheleau, 2020). While there have been many extraordinary discoveries, there continue to be many firsts and many breakthroughs that have pathed the way for the next steps in research. In particular is research into ground-breaking treatments for cancer patients. 1890s: Radiotherapy (Gianfaldoni, S., Gianfaldoni, R., Wollina, U., Lotti, J., Tchernev, G., & Lotti, T. 2017) In the last decade of the 19th century, Wilhelm Conrad Rцntgen made the discovery of X-rays, drastically changing the medical scene for treating many diseases. From this discovery, Emil Herman Grubbe commenced the first X-ray treatment for breast cancer, while Antoine Henri Becquerel began to delve deeper into researching radioactivity and its natural sources. In the same year that Rцntgen discovered X-rays, Maria Sklodowska-Curie and Pierre Curie shared theirs vows together, and only three years later, discovered radium as a source for radiation. By then, during a time where skin cancers were frequently treated, this discovery had kick-started the research field into X-rays as well as the use of X-rays in the medical field. Scientists and clinicians have gained a greater understanding of radiation as treatment for diseases, but the research does not stop there and the advancement of radiotherapy only continues to thrive. 1940s: First Bone Marrow Transplant (Morena & Gatti, 2011) Following World War II, the physical consequences of war accelerated research into tissue transplantation. Skin grafts were needed for burn victims, blood transfusions needed ABO blood typing, and the high doses of radiation led to marrow failure and death. During this time, Peter Medawar started his research into rejection of skin grafts as requested by the Medical Research Council during World War II. It was a priority for the treatment of burn victims. Medawar had concluded that graft rejection was a result of an immunological phenomenon related to histocompatibility antigens. Histocompatibility antigens are cell surface glycoproteins that play critical roles in interactions with immune cells. They are unique to every individual and essentially flags one’s cell as their own, therefore making every individual physically unique. 1953: First Human Tumour Cured In 1953, Roy Hertz and Min Chiu Li used a drug, methotrexate, to treat the first human tumour — a patient with choriocarcinoma. Choriocarcinoma is an aggressive neoplastic trophoblastic disease, and can be categorised into two types — gestational and non-gestational (Bishop & Edemekong, 2023). The cancer primarily affects women, as it grows aggressively in a woman’s uterus (MedlinePlus., 2024). However, it can also occur in men as part of a mixed germ cell tumour (Bishop & Edemekong, 2023). Methotrexate is commonly used in chemotherapy as it acts as an antifolate antimetabolite that induces a cytotoxic effect on cells. Once methotrexate is taken up by cells, it forms methotrexate-polyglutamate, which in turn inhibits dihydrofolate reductase, an enzyme important for DNA and RNA synthesis (Hanood & Mittal, 2023). Therefore, by inhibiting DNA synthesis, the drug induces a cytotoxic effect on the cancerous cells. Since the first cure of choriocarcinoma using methotrexate, the drug has both been commonly used for chemotherapy and other applications, including as an immunosuppressant for autoimmune diseases (Hanoodi & Mittal, 2023). 1997: First ever targeted drug: rituximab (Pierpont, Limper, & Richards, 2018) Jumping ahead a few decades and 1997 was the year that JK Rowling published Harry Potter and the Philosopher’s Stone . It was also the year that the first targeted anti-cancer drug was approved by the U.S Food and Drug Administration (FDA), rituximab. Ronald Levy created rituximab with the purpose of targeting malignant B cells. B cells express an antigen – CD20 – which allows B cells to develop and differentiate. Rituximab is an anti-CD20 monoclonal antibody, meaning that it targets the CD20 antigens expressed on malignant B cells. It had improved the progression-free survival and overall survival rates of many patients who had been diagnosed with B cell leukemias and lymphomas (Pavlasova & Mraz, 2020). Much like the Philosopher’s Stone, you may consider rituximab to increase longevity of patients diagnosed with B cell cancers. Although Levy created this drug, his predecessors should not be ignored. Prior to his research and development of rituximab, research and development of monoclonal antibodies can be dated all the way back to the late 1970s (Pavlasova & Mraz, 2020). César Milstein and Georges J. F. Köhler developed the first monoclonal antibody in the mid-1970s, and first described the method for generating large amounts of monoclonal antibodies (Leavy, 2016). Milstein and Köhler were able to achieve this by producing a hybridoma – “ a cell that can be grown in culture and that produces immunoglobulins that all have the same sequence of amino acids and consequently the same affinity for only one epitope on an antigen that has been chosen by the investigator” (Crowley & Kyte, 2014). They had produced a cell with origins from a myeloma cell line and spleen cells from mice immunised against sheep red blood cells (Leavy, 2016). Going forward: CAR T Cells The most recent and exciting development in cancer research has been the development and usage of chimeric antigen receptor (CAR) T cells. CAR T cell therapy is a unique therapy customised to each individual patient, as the CAR T cells used are derived from the patient’s own T cells. The process involves leukapheresis, where the patient’s T cells are collected, and these collected T cells are then re-engineered to include the CAR gene. The patient’s own CAR T cells are produced, expanded and subsequently infused back into the patient. The first concept of CAR T cells to be described was in 1987 by Yoshihisa Kuwana and others in Japan. Following this, different generations of CAR T cells have now been developed and trialled, leading to the FDA’s first two approvals for CAR T cells (Wikipedia Contributors, 2024). This research avenue has only scratched the surface, with many individuals now exploring the best collection methods and how best to stimulate the “fittest” T cells - the apex predator of immune cells. A recent paper was published where CAR T cells were trialled as a second line therapy to follow ibrutinib-treated blood cancers. The phase 2 TARMAC study involved using anti-CD19 CAR T cells to treat patients with relapsed mantle cell lymphoma (MCL) who had been exposed to ibrutinib, a drug used to treat B cell cancers by targeting Bruton Kinase Tyrosine (BTK) found in B cells. The study showed that 80% of patients who had previous exposure to ibrutinib and were treated with CAR T cells as a second-line therapy achieved a complete response. Furthermore, at the 13-month follow-up, the 12-month progression free survival rate was estimated to be 75% and the overall survival rate to be 100% (Minson et al., 2024)! It is without a doubt that as humans, we are naturally curious creatures. It is with this curiosity that we have journeyed through the many scientific breakthroughs and innovations. And within each special nook and cranny of countless fields of science, from flight to evolution, from vaccines to cancer treatments, there have been multitudes of discoveries. There is no doubt that the number of innovations will only continue to grow. References Bishop, B., & Edemekong, P. (2023). Choriocarcinoma. StatPearls . Crowley, T., & Kyte, J. (2014). Section 1 - Purification and characterization of ferredoxin-NADP+ reductase from chloroplasts of S. oleracea . In Experiments in the Purification and Characterization of Enzymes (pp. 25–102). Gianfaldoni, S., Gianfaldoni, R., Wollina, U., Lotti, J., Tchernev, G., & Lotti, T. (2017). An overview on radiotherapy: From its history to its current applications in dermatology. Open Access Macedonian Journal of Medical Sciences, 5 (4), 521–525. https://doi.org/10.3889/oamjms.2017.122 Hanoodi, M., & Mittal, M. (2023). Methotrexate. StatPearls . Leavy, O. (2016). The birth of monoclonal antibodies. Nature Immunology, 17 (Suppl 1), S13. https://doi.org/10.1038/ni.3608 MedlinePlus. (2024). Choriocarcinoma. MedlinePlus . https://medlineplus.gov/ency/article/001496.htm#:~:text=Choriocarcinoma%20is%20a%20fast%2Dgrowing,pregnancy%20to%20feed%20the%20fetus Minson, A., Hamad, N., Cheah, C. Y., Tam, C., Blombery, P., Westerman, D., Ritchie, D., Morgan, H., Holzwart, N., Lade, S., Anderson, M. A., Khot, A., Seymour, J. F., Robertson, M., Caldwell, I., Ryland, G., Saghebi, J., Sabahi, Z., Xie, J., Koldej, R., & Dickinson, M. (2024). CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: The phase 2 TARMAC study. Blood, 143 (8), 673–684. https://doi.org/10.1182/blood.2023021306 Morena, M., & Gatti, R. (2011). A history of bone marrow transplantation. Haematology/Oncology Clinics, 21 (1), 1–15. Pavlasova, G., & Mraz, M. (2020). The regulation and function of CD20: An "enigma" of B-cell biology and targeted therapy. Haematologica, 105 (6), 1494–1506. https://doi.org/10.3324/haematol.2019.243543 Pierpont, T. M., Limper, C. B., & Richards, K. L. (2018). Past, present, and future of rituximab: The world’s first oncology monoclonal antibody therapy. Frontiers in Oncology, 8 , 163. https://doi.org/10.3389/fonc.2018.00163 Rocheleau, J. (2020). 50 famous firsts from science history. Stacker . https://stacker.com/environment/50-famous-firsts-science-history Wikipedia contributors. (2024, October 6). CAR T cell. In Wikipedia, The Free Encyclopedia . Retrieved October 17, 2024, from https://en.wikipedia.org/w/index.php?title=CAR_T_cell&oldid=1249695600 Previous article Next article apex back to