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< Back to Issue 4 Talking to Yourself: The Biology of Hallucinations by Lily McCann 1 July 2023 Edited by Arwen Nguyen-Ngo and Yasmin Potts Illustrated by Zhuominna Ma What is consciousness? No small question. To this day it hasn’t been entirely satisfied. Consider a conversation: There are voices from the outside, stimuli that talk to all the sensory receptors that we have. They pass on messages to our fingertips that we are touching something cold; they tell our eyes that we are seeing certain wavelengths of light; and they tell the cochlea of our ears what sounds we are hearing. The sensory circuits of our bodies bring these words from outside and turn them inward, presenting them to the centre of our consciousness: Here - this is what we are experiencing. This is what we are taking from the world outside. But already, at the base of this consciousness, an idea of the world has been established. The central experience of our mind is built upon prediction: we are constantly conjuring up an estimate of how the outside world will be. The ‘Predictive Processing’ model of consciousness states that it is the conversation between this predictive perception of the world and the feedback from our sensory experience that defines what it is to feel consciousness (1). In 1971, Nature published the conclusions of a study titled, ‘Preliminary Observations on Tickling Oneself’ (2). In this experiment, a device was used to compare the experience of being tickled by an experimenter to the experience of tickling oneself, and both were compared to the intermediate of passively following the experimenter’s arm as they tickled the participant. The study concluded that the action of tickling oneself produced no effect as the planned action of tickling cancelled out the sensation of being tickled; the lack of an action in the case of the experimenter tickling the subject’s hand, allowed for a full ‘tickle’ sensation. Interestingly, the third process of passively following the tickling action was rated at a level in between these two responses. This showed that it was not the action of tickling alone that cancelled out the sensation of the stimulus as tickling, but that a knowledge of the tickle, a prediction of it, were enough to reduce the effect. This experiment reflects the idea that it is not just our planned actions and our sensory perception that drive consciousness, but that it is prediction that has a core place in driving experience. For centuries, hallucinations have been recognised as distortions of our sense of being conscious in the world. In 1838, Esquirol wrote in his ‘Mental Maladies: A Treatise On Insanity’ that the experience of a hallucination is “a thorough conviction of the perception of a sensation, when no external object, suited to excite this sensation, has impressed the senses.” (3) Anything that distorts our ‘perception’ or ‘sensation’ can therefore give rise to a hallucination. This can occur in the context of infection, psychosis, delirium, use of certain drugs - and the aptly named ‘exploding head syndrome’. Contrary to popular opinion, hallucinations are not a feature of psychotic disorders alone. In fact, analysis has shown that no single aspect of schizophrenia-related hallucinations is specific to this disease (4). In 2000, the idea of the ‘Tickling’ study was elaborated with respect to hallucinations in an investigation comparing the experience of self-produced and externally implemented stimuli for those who both did and did not suffer from hallucinations. It was shown in this study that for participants with hallucinatory disorders, there was a breakdown in the ability to differentiate between stimuli produced externally and internally (5). This study is in line with a certain theory of hallucination purported by Frith, who suggests in his discussion of positive symptoms of schizophrenia that the foundation of hallucination is a “fault in the system which internally monitors and compares intentions and actions” (6). There is another interesting theory that describes hallucinations as memories released from suppression. The authors suggest that the hallucination itself is a cacophony of memory signals set loose, where normally they are shut out of our conscious mind. One study described auditory hallucinations in those with hearing loss as an “uninhibition syndrome”. They argued that in the cases studied, a lack of sensory auditory input seemed to “uninhibit neuronal groups storing auditory memory” (7). The brain is an incredibly complex organ and theories regarding consciousness and hallucinations abound. The question of greatest practical importance is what part of the process of hallucinations can we understand and therefore, what can be targeted when we are called to treat this system in a medical setting. Recent investigations have linked various molecules, receptors and genes to hallucinatory disorders or states, whilst imaging studies demonstrate networks and regions of the brain activated during hallucinations. Investigation of certain receptor-modulating drugs has revealed the place of certain molecules in delusion and sensation; and the association of certain genes to hallucination-prone phenotypes has established a genetic cause for susceptibilities to hallucination. This research yields molecular and genetic targets for therapies that can help reduce the burden of hallucinations on an individual. It is a remarkable faculty of our minds, the ability to create a world - or aspects of the world - for ourselves and convince our own consciousness that it is real. Hallucinations reveal the capacity of the human brain for imagination; they show that all we experience is indeed creative, merely restricted by what we see as truth. But the grounding fact of knowing what is real is essential to functioning in society. Losing the ability to check our own creative experience of consciousness is exceedingly frightening and disempowering. Anything that helps us to maintain the right balance of conversation between the experiences we create and those we feel allow us to maintain a sense of self in the world. Elucidating the biology behind these conversations and the effects of hallucination itself can bring us closer to a definition of consciousness. References Hohwy J, Seth A. Predictive processing as a systematic basis for identifying the neural correlates of consciousness. Philosophy and the Mind Sciences. 2020;1(2). 3. https://doi.org/10.33735/phimisci.2020.II.64 Weiskrantz L, Elliot J, Darlington C. Preliminary observations on tickling oneself. Nature. 1971 Apr 30. 230: 598–599 https://doi.org/10.1038/230598a0 Esquirol J. Mental maladies: A treatise on insanity. France: Wentworth Press; 2016 Waters F, Fernyhough C. Hallucinations: A systematic review of points of similarity and difference across diagnostic classes. National Library of Medicine. 2016 Nov 21. doi: 10.1093/schbul/sbw132 Blakemore S.J, Smith J, Steel R, Johnstone E.C. The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: Evidence for a breakdown in self-monitoring. Psychological Medicine. 2000 Oct 17. 30(5): 1131-9. https://doi.org/10.1017/S0033291799002676 Frith C. The positive and negative symptoms of schizophrenia reflect impairments in the perception and initiation of action. Psychological Medicine. 1987 Aug. 17(3): 631-648. Doi: 10.1017/s0033291700025873 Goycoolea, M., Mena, I. and Neubauer, S. (2006) ‘Spontaneous musical auditory perceptions in patients who develop abrupt bilateral sensorineural hearing loss. an uninhibition syndrome?’, Acta Oto-Laryngologica, 126(4), pp. 368–374. doi:10.1080/00016480500416942. Previous article Next article back to MIRAGE

< Back to Issue 2 Making sense of the senses: The 2021 Nobel Prize in Physiology or Medicine What do spicy food, menthol lozenges and walking around blindfolded have in common? They all activate protein receptors discovered by Professors David Julius and Ardem Patapoutian, the winners of the 2021 Nobel Prize in Physiology or Medicine. by Dominika Pasztetnik 10 December 2021 Edited by Breana Galea & Juulke Castelijn Illustrated by Casey Boswell Stimuli are changes to our environment, such as heat, cold and touch, that we recognise through our senses. We are all constantly bombarded with thousands of these stimuli from our surroundings. Despite this disorder, we are somehow able to perceive and make sense of the world. The protein receptors discovered by Professors Julius and Patapoutian make this possible. Located at the surface of the nerve cell, these receptors convert an external stimulus to an electrical signal. This signal then travels along nerve cells to the brain, allowing us to sense the stimulus. Based in California, Julius and Patapoutian are scientists in the fields of neuroscience and molecular biology. The main interest of their work has been identifying and understanding the protein receptors involved in detecting stimuli. For Julius, his major focus has been to identify the receptors involved in the sensation of pain (1). For Patapoutian, it has been to identify the protein receptors involved in detecting mechanical stimuli, such as touch (2). For their past 25 years of research, Julius and Patapoutian were awarded the Nobel Prize in Physiology or Medicine in October 2021. The Nobel Prize was founded by Alfred Nobel, a Swedish scientist also famous for inventing dynamite. Prior to his death in 1896, Nobel allocated most of his money to the first Nobel Prizes. Since 1901, the Nobel Prize has been annually bestowed on those who, in Nobel’s words, have “conferred the greatest benefit to mankind” in different fields (3). Notable past laureates of the Nobel Prize in Physiology or Medicine include Sir Alexander Fleming, Sir Ernst Chain and the Australian Howard Florey. They were awarded in 1945 for their discovery of the antibiotic penicillin (4). Sir Hans Krebs received the Nobel Prize in 1953 for his discovery of the citric acid cycle (5). Also known as the Krebs cycle, it is a series of reactions used to produce energy in our cells. TRPV1: spice it up It’s a rather chilly morning. You eye the packet of Shin Ramyun that’s been sitting in your pantry for weeks. Without a second thought, you prepare the noodles, adding all the soup powder. After a few mouthfuls, your eyes start streaming and your face matches the scarlet red of the now-empty packaging. The culprit is capsaicin, a substance in the chilli flakes added to the soup powder. It binds to a protein receptor embedded at the surface of the nerve cells in your mouth. Julius discovered this receptor in 1997, and called it TRPV1, which stands for transient receptor potential vanilloid type 1 (6). TRPV1 is a channel with a gate at either end that is usually closed (Figure 1, blue) (7). Capsaicin opens these gates, allowing ions, such as calcium, to move through TRPV1 and into the nerve cell (Figure 1, red). The nerve cell then signals to the brain, causing you to feel the searing heat in your mouth. TRPV1 is also found in your skin and can be activated by temperatures above 40°C, such as when you accidentally touch the kettle full of boiling water for your noodles (8). Figure 1. TRPV1 at the surface of a nerve cell. In the absence of capsaicin or at cool temperatures, TRPV1 is closed (blue). In the presence of capsaicin or at higher temperatures, TRPV1 opens, allowing ions to flow into the nerve cell (red). TRPM8: too cool for school On your way to uni, you notice your throat’s a bit sore from going overboard with karaoke the night before, so you pop a lozenge into your mouth. The soothing, cool sensation is thanks to menthol. It is a compound that binds to TRPM8, which stands for transient receptor potential melastatin 8. It is another receptor found on the nerve cells in your tongue, as well as on your skin (9). TRPM8 was separately discovered in 2002 by both Julius and Patapoutian (10). Like TRPV1, TRPM8 is a protein channel that is usually closed. In response to menthol or cool temperatures from 26 down to 8°C, TRPM8 opens and allows ions to enter the nerve cell, which then signals the cold sensation to your brain (11). PIEZO: peer pressure During your lunch break at uni, you and your mates decide to play blindfolded tag. Because, as we all know, that's what uni students do in their free time. In the first round, you have the misfortune of being chosen as ‘it’. Blindfolded, you walk around with your hands in front of you, trying to find your mates. Despite not being able to see anything, you can still walk and wave your arms and roughly know where your arms and legs are in space. This is due to a sense called proprioception. You lunge forward and nearly grab someone, only to feel their jacket brush your fingers. Both proprioception and the detection of light touch, such as of the jacket brushing your fingers, are made possible by another class of protein receptors called PIEZO2. Discovered by Patapoutian in 2010, its name comes from piesi, the Greek word for pressure (12). Like TRPV1 and TRPM8, PIEZO2 is an ion channel at the nerve cell surface. However, the structure of PIEZO2 is nothing like that of TRPV1 and TRPM8. PIEZO2 has three protruding blades, which form a dent, called a nano-bowl, in the outer surface of the cell (13). When the outside of the cell is prodded, the blades straighten and the nano-bowl flattens. This allows the channel in the centre of the PIEZO2 to open, so ions can flow into the nerve cell (Figure 2). The nerve cell then sends an electrical impulse to the brain, letting you know you’re failing at blindfolded tag. Figure 2. PIEZO at the surface of a nerve cell. When force is applied to the surface of the nerve cell, the PIEZO channel opens, allowing ions to move into the cell. Apart from being essential for playing blindfolded tag, PIEZO2 is also important in various other aspects of the human body’s functioning we often take for granted. For example, PIEZO2 prevents you from breathing in too much air (14). It is also present on the cells lining your digestive tract. PIEZO2 detects pressure exerted onto these cells by food, causing the cells to release hormones that help with digestion (15). Furthermore, PIEZO2 helps monitor the fullness of your bladder, saving you from embarrassment (16). If there is a PIEZO2, what about PIEZO1? Although it has a similar structure to PIEZO2, PIEZO1’s role is quite different. PIEZO1 handles the background maintenance required to keep your body healthy. This includes bone formation (17) and preventing your red blood cells from bursting (18). People with a particular mutated form of PIEZO1 have a reduced risk of getting malaria (19). Patapoutian found that this mutation causes red blood cells to shrivel, preventing the malaria parasite from infecting them. Many people living in malaria-affected areas, such as Africa, have this mutation. Therefore, knowledge regarding these receptors is improving our understanding of related diseases. Drug development Researchers are currently using information about the receptors discovered by Julius and Patapoutian to develop new drugs to treat various conditions. Knowing the identities and structures of these receptors is helping researchers design compounds that bind to them, either blocking or activating them. In this way, Julius and Patapoutian’s work is helping provide a “benefit to mankind”. For example, during a migraine, the TRPV1 channel opens more frequently in the nerve cells of the meninges, the envelope surrounding the brain (20). These nerve cells contain more TRPV1 at their surfaces. This causes the nerve cells to send more electrical signals to the brain and so increases the sensation of pain. Using a drug to block the TRPV1 receptor could reduce the number of these electrical impulses and lessen the pain associated with migraines. It’s been a busy day activating all these receptors, which, as it turns out, are part of your daily life as a uni student. So next time you eat chilli flakes, have a menthol lozenge or play blindfolded tag, you will know which tiny sensors to hold responsible for your pleasant — or unpleasant — experiences. Further reading Press release: The Nobel Prize in Physiology or Medicine 2021 The Nobel Prize in Physiology or Medicine 2021 - Advanced Information References: University of California San Francisco. “Biography of David Julius.” UCSF. Accessed November 10, 2021. https://www.ucsf.edu/news/2021/09/421486/biography-david-julius. Nobel Prize Outreach AB 2021. “Press release: The Nobel Prize in Physiology or Medicine 2021.” The Nobel Prize. Accessed November 10, 2021. https://www.nobelprize.org/prizes/medicine/2021/press-release/. Nobel Prize Outreach AB 2021. "Alfred Nobel’s will." The Nobel Prize. Accessed November 10, 2021. https://www.nobelprize.org/alfred-nobel/alfred-nobels-will/. Nobel Prize Outreach AB 2021. “The Nobel Prize in Physiology or Medicine 1945.” The Nobel Prize. Accessed November 10, 2021. https://www.nobelprize.org/prizes/medicine/1945/summary/ Nobel Prize Outreach AB 2021. “The Nobel Prize in Physiology or Medicine 1953.” The Nobel Prize. Accessed November 10, 2021. https://www.nobelprize.org/prizes/medicine/1953/summary/ Ernfors, Patrik, Abdel El Manira, and Per Svenningsson. "Advanced information." The Nobel Prize. Accessed November 10, 2021. https://www.nobelprize.org/prizes/medicine/2021/advanced-information/. Liao, M., E. Cao, D. Julius, and Y. Cheng. "Structure of the Trpv1 Ion Channel Determined by Electron Cryo-Microscopy." Nature 504, no. 7478 (Dec 5 2013): 107-12. doi: 10.1038/nature12822. Ernfors et al., “Advanced information.” McKemy, D. D. "Trpm8: The Cold and Menthol Receptor." In Trp Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades, edited by W. B. Liedtke and S. Heller. Frontiers in Neuroscience. Boca Raton (FL), 2007. Ernfors et al., “Advanced information.” McKemy, Trp Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Coste, B., J. Mathur, M. Schmidt, T. J. Earley, S. Ranade, M. J. Petrus, A. E. Dubin, and A. Patapoutian. "Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels." Science 330, no. 6000 (Oct 1 2010): 55-60. doi: 10.1126/science.1193270. Jiang, Y., X. Yang, J. Jiang, and B. Xiao. "Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels." Trends in Biochemical Sciences 46, no. 6 (Jun 2021): 472-88. doi: 10.1016/j.tibs.2021.01.008. Nonomura, K., S. H. Woo, R. B. Chang, A. Gillich, Z. Qiu, A. G. Francisco, S. S. Ranade, S. D. Liberles, and A. Patapoutian. "Piezo2 Senses Airway Stretch and Mediates Lung Inflation-Induced Apnoea." Nature 541, no. 7636 (Jan 12 2017): 176-81. doi: 10.1038/nature20793. Alcaino, C., K. R. Knutson, A. J. Treichel, G. Yildiz, P. R. Strege, D. R. Linden, J. H. Li, et al. "A Population of Gut Epithelial Enterochromaffin Cells Is Mechanosensitive and Requires Piezo2 to Convert Force into Serotonin Release." Proceedings of the National Academy of Sciences of the United States of America 115, no. 32 (Aug 7 2018): E7632-E41. doi: 10.1073/pnas.1804938115. Marshall, K. L., D. Saade, N. Ghitani, A. M. Coombs, M. Szczot, J. Keller, T. Ogata, et al. "Piezo2 in Sensory Neurons and Urothelial Cells Coordinates Urination." Nature 588, no. 7837 (Dec 2020): 290-95. doi: 10.1038/s41586-020-2830-7. Li, X., L. Han, I. Nookaew, E. Mannen, M. J. Silva, M. Almeida, and J. Xiong. "Stimulation of Piezo1 by Mechanical Signals Promotes Bone Anabolism." Elife 8 (Oct 7 2019). doi: 10.7554/eLife.49631. Cahalan, S. M., V. Lukacs, S. S. Ranade, S. Chien, M. Bandell, and A. Patapoutian. "Piezo1 Links Mechanical Forces to Red Blood Cell Volume." Elife 4 (May 22 2015). doi: 10.7554/eLife.07370. Ma, S., S. Cahalan, G. LaMonte, N. D. Grubaugh, W. Zeng, S. E. Murthy, E. Paytas, et al. "Common Piezo1 Allele in African Populations Causes Rbc Dehydration and Attenuates Plasmodium Infection." Cell 173, no. 2 (Apr 5 2018): 443-55 e12. doi: 10.1016/j.cell.2018.02.047. Dux, M., J. Rosta, and K. Messlinger. "Trp Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches." International Journal of Molecular Sciences 21, no. 1 (Jan 4 2020). doi: 10.3390/ijms21010342. Previous article back to DISORDER Next article

< Back to Issue 6 A Frozen Odyssey: Shackleton’s Trans-Antarctic Expedition by Ethan Bisogni 28 May 2024 Edited by Rita Fortune Illustrated by Aisyah Mohammad Sulhanuddin The Heroic Age of Antarctic Exploration South of the 66th parallel lies a continent desolate and cruel, where the experiences of those who dared to challenge it are preserved in its ice. Antarctica was deemed Earth’s final frontier by 19th-century explorers, and at the cusp of the 20th century, the ‘Heroic Age of Antarctic Exploration’ was underway (Royal Museums Greenwich, n.d. a). Those who answered the call of the wild, to face the polar elements, would be remembered as heroes. Among the pantheon of Antarctic explorers, none are more celebrated than Sir Ernest Shackleton. An Irishman whose name became synonymous with adventure and peril, Shackleton emerged at the forefront of Britain’s polar conquests. During his Nimrod expedition to reach the magnetic South Pole, Shackleton and his crew found themselves within 100 miles of their goal—only to be thwarted by their human needs (Royal Museums Greenwich, n.d. b). His ambition outmatched the capabilities of those he commanded, so they withdrew for want of survival. Despite the supposed failure of the two-year expedition, Shackleton’s romanticism of exploration, leadership, and unwavering optimism earned him a knighthood in 1909 (Royal Museums Greenwich, n.d. b). In the years following, as other explorers performed increasingly remarkable polar feats, Shackleton was left in limbo. It was during this time that an impossibly ambitious expedition was put forward to him. The plan was as follows: a crew would sail a wooden barquentine, the Endurance, into the Weddell Sea, and land on the Antarctic coast. There, the men would split into groups, and Shackleton would pursue a daring transcontinental journey across Antarctica (Smith, 2021). Despite the questionable feasibility of this plan, a benefactor named James Caird sought to help fund the expedition (Smith, 2021). Thus, these plans were translated into reality, and with a finalised crew of 27, the Endurance was set to sail under the helm of New Zealand captain Frank Worsley. On August 1st, 1914, the Endurance departed Plymouth (PBS, 2002). Explorers of the Antarctic, from left: Ronald Amundsen, Sir Ernest Shackleton, Robert Peary (Antarctica 21, 2017) The Imperial Trans-Antarctic Expedition Into the Weddell Sea, December 5th, 1914 After their momentary recess in South Georgia, and the recent pickup of a stowaway, the Grytviken whaling station remained the crew's last semblance of civilisation (PBS, 2002). Shackleton was well aware of the challenges that loomed ahead—notorious for its hostility, the Weddell Sea was Antarctica’s first line of defence (Shackleton, 1919). In the coming days, the Endurance encountered pack ice, severely slowing its progress. A nightmarish phenomenon for any explorer, pack ice was an abundant drift of sea ice no longer connected to land. While plentiful, navigating it was not impossible—it only required patience, caution, and an intuitive hint of wisdom. But even with worsening conditions, Shackleton proceeded into unclear waters (Shackleton, 1919). The Endurance in the Weddell Sea (Hurley, 1914) Icebound, January 18th, 1915 The Endurance was again ensnared in ice, and this time the ship would not budge. Plagued by regret in pushing ahead, but desperate to break free, Shackleton ordered his men to cease routine. Once again, his ambition outpaced his capabilities, but Shackleton was also a man of determination. They would wait until an opening cleared (Shackleton, 1919). The ship began to drift northward with the ice, but as months passed, so too did any hope of landing. Time was running out, and with winter approaching, the Endurance would soon be engulfed by the long polar night (PBS, 2002). For this expedition to succeed, the crew needed to remain optimistic. A brotherhood formed on the ice, with theatre plays and celebrations to ease their dire worries. The eerie creak of the hull did not deter them from trekking the very ice that imprisoned them. The ship’s Australian photographer, Frank Hurley, captured these moments of perseverance on photographic plates, including the hauntingly beautiful Endurance beset amongst the snow (Shackleton, 1919). The Endurance in the night (Hurley, 1915) Abandon Ship, October 27th, 1915 True to its name, the Endurance weathered the dark winter months. But despite the comfort of a newly rising sun, disaster did not fade with the darkness. A catastrophic ice shift had violently imploded the ship’s hull, and with its fate sealed, the Endurance would not hold. Shackleton gave the order to abandon ship (Shackleton, 1919). Any hope of the expedition continuing was now lost alongside the Endurance , which was silently withering on the ice. Though this was not Shackleton’s first time in Antarctica, nor was it his first disastrous expedition. Stations of emergency supplies established by himself and other explorers were scattered across the islands of the Weddell Sea, each offering glimmers of hope. However, at over 500 kilometres away, they all required a potentially fatal journey (Shackleton, 1919). Frank Wild overlooking the wreck of the Endurance (Hurley, 1915) Ocean Camp, November 1st, 1915 A plan was conjured—they would march across the unforgiving ice, bringing themselves to one of the few sanctuaries along the Antarctic Peninsula. Concerns of risk from Captain Worsley fell on deaf ears; undeterred, Shackleton knew waiting was futile (Worsley, 1931). Leading up, a difficult decision was made to conserve the crew’s rations. Mrs. Chippy, the beloved ship cat of carpenter Harry McNish, was to be killed amongst the other animals (Canterbury Museum, 2018). Although believing it necessary, Shackleton’s remorseful orders to cull the animals aboard had cast a shadow over his leadership (Scott Polar Research Institute, n.d.). The march soon commenced, but horrendous conditions had led the men into a frozen labyrinth. After a pace of only a kilometre a day, the march was abandoned. The crew instead erected ‘Ocean Camp’, and were to wait for the ice to clear a path for their lifeboats (PBS, 2002). Weeks in, the crew's evening was interrupted by the ghostly wailing of the Endurance wreck . Beckoning in the distance, the men gathered to watch its final breaths. On November 21st, the ice finally caved in, and the Endurance was swallowed into the forsaken depths of the Weddell Sea (Worsley, 1931). Ocean Camp (Hurley, 1915) The Rebellion on the Ice, December 27th, 1915 With the crew’s last tether to the world severed, a depression had settled over the camp. Now dragging their lifeboats to open water, a quiet but persistent discontent was beginning to grow. Most of the crew still admired Shackleton as their resolute leader, but some were beginning to lose faith. A frustrated and grieving McNish made his stand, arguing that the loss of the Endurance had nullified Shackleton's command. Shackleton, furious but sympathetic, was able to successfully de-escalate the situation (Scott Polar Research Institute, n.d.). The mutiny was short-lived, but McNish was now under Shackleton's watchful eye. He knew that he would have to inspire hope, and that a rift in the crew would only prompt death. Dragging the lifeboats (Hurley, 1915) Elephant Island, April 14th, 1916 With three lifeboats in possession, a proposal to island-hop was presented. McNish had spent his time reinforcing the boats for open waters, and after careful deliberation, a destination was chosen. Elephant Island was a barren, windswept landscape—a false sanctuary harbouring an inhospitable environment. Landing there was not Shackleton’s first choice, but a fast approaching winter left no alternative (Shackleton, 1919). With Elephant Island looming over the horizon, the boats set forth. Battling the arduous sea, one of the lifeboats, the Dudley Docker , was torn away from the rest during an unprecedented storm. Fading into the vast darkness, the men aboard were presumed dead. No amount of enthusiasm from Shackleton could lift the crew's spirits, who were now delirious and grief stricken (Fiennes, 2022). The following day, a landing was imminent. Nearing the shore, a boat was noticed soaring in the distance. The Dudley Docker pierced through the waves—the crew still alive and following in hot pursuit. Ecstatic and revived with hope, landfall was made. A major milestone had been reached; the crew were now unified and ashore for the first time since South Georgia (Fiennes, 2022). Unfortunately, Elephant Island’s taunting winds carried no whispers of hope. The silence was apparent: this island would be their grave unless contact was made with civilisation. A party must be formed, one that would take the risk and sail into the heavy seas of the Southern Ocean (Shackleton, 1919). The shores of Elephant Island (Hurley, 1916) The Voyage of the James Caird, April 24th, 1916 Shackleton selected a route to a South Georgia whaling station neighbouring the one they had departed in 1914—a harrowing 1500 kilometres across notoriously restless seas. In one of their modified lifeboats, they were to utilise the prevailing westerlies to attempt an impossible sailing feat (Pierson, n.d.). Six men were selected to commander the James Caird : Shackleton, Worsley, McNish, Crean, Vincent, and McCarthy. As the James Caird set sail, a vast ocean of uncertainty lay between Elephant Island and South Georgia (Pierson, n.d.). The voyage was tortuous, with the men severely ill-prepared. From storm-fed waves to frigid winds, the James Caird and those aboard were unlikely to survive the journey. At each turn, however, the determined men managed to stay afloat and push ahead. 17 days passed before the dominant mountains of South Georgia came into view (PBS, 2002). Shackleton, fearing his men would not survive another day at sea, hastened a plan to land on the rocky western shores (Pierson, n.d.). The six men found themselves on the wrong end of the island to the station, and James Caird was in no state to navigate the coast. The capable individuals would have to perform the first trans-island crossing of South Georgia—a far cry from their original ambitions, but daring nonetheless. With only Shackleton, Worsley, and Crean able to attempt the task ahead, McNish, Vincent, and McCarthy were left to establish ‘Peggotty Camp’ in the landing cove (Pierson, n.d.). Waving goodbye to the James Caird (Hurley, 1916) The Crossing of South Georgia, May 10th, 1916 The three men began their journey northward towards the Stromness whaling station. Encountering menacing snow-capped peaks, the men were so close to potential rescue only to be divided by insurmountable odds. Needing to race the approaching night down a 3000-foot mountainside, a makeshift sled was constructed from their little equipment. Rocketing downhill, a rare moment of joy and exhilaration accompanied the men along their daredevilish tactics (Antarctica Heritage Trust, 2015). Exhausted and verging on collapse, the men were now nearing the outskirts of their destination. A whistle in the air had lured them closer, and on May 20th, 1916, contact was finally made. The men were tended to by the distraught station managers, and a rescue party was sent the following day to those abandoned at ‘Peggotty Camp’ (Pierson, n.d.). After multiple attempts to obtain a suitable vessel, the 22 remaining souls holding steadfast on Elephant Island were finally rescued by the Yelcho on August 30th, 1916. Hope was not lost amongst them, as even in his absence their belief in Shackleton kept their spirits alive. Bringing their ordeal to a close, and without a man’s life lost, the crew’s troubles were left behind in the frozen Antarctic (Shackleton, 1919). The Yelcho arrives to rescue the crew (Hurley, 1916) Legacy Published in 1919, ‘South’, Shackleton’s autobiographical recount of the expedition, brought these remarkable stories into the limelight. However, records stricken from the novel hide some concerning truths. While omitting the incident regarding McNish’s mutiny, it was clear Shackleton resented him for introducing doubt during their time of turmoil. Despite his redemption during their voyage to South Georgia, Shackleton recommended McNish not be awarded the Polar medal—a decision still considered mistakenly harsh (Scott Polar Research Institute, n.d.). But despite his flaws and misjudgments, Shackleton was undoubtedly the optimistic and courageous leader you would seek in times of crisis. In 1922, aboard his final expedition to circumnavigate Antarctica, Shackleton suffered a fatal heart attack - and was buried in South Georgia. Regarded as a defining moment, his death signalled the end of the ‘Heroic Age of Antarctic Exploration’ (Royal Museums Greenwich., n.d. b). Exactly one century following, the Endurance was found preserved at the bottom of the Weddell Sea. Its mast still bearing its inscription, the ship remains an enduring remnant of a heroic past. This inspiring tale of survival continues to live on, as one of the greatest stories of human perseverance in the face of the elements. The crew of the Endurance (Hurley, 1915) References Antarctica 21. (2017). Famous Antarctic Explorers: Sir Ernest Henry Shackleton. Antarctica 21 . https://www.antarctica21.com/journal/famous-antarctic-explorers-sir-ernest-henry-shackleton/ Antarctica Heritage Trust (2015). Crossing South Georgia. Antarctic Heritage Trust. https://nzaht.org/encourage/inspiring-explorers/crossing-south-georgia/ Canterbury Museum (2018), Dogs in Antarctica: Tales from the Pack. Canterbury Museum https://antarcticdogs.canterburymuseum.com/themes/hardships Fiennes, R (2022). Remembering a Little-Known Chapter in the Famed Endurance Expedition to Antarctica. Atlas Obscura, https://www.atlasobscura.com/articles/shackleton-endurance-elephant-island Hurley, F. (1914-1916). Imperial Trans-Antarctic Expedition Photographic Plates. [Photographs]. National Library of Australia. https://www.nla.gov.au/collections/what-we-collect/pictures/explore-pictures-collection-through-articles-and-essays/frank PBS (2002). Shackleton’s Voyage of Endurance. PBS Nova. https://www.pbs.org/wgbh/nova/shackleton/1914/timeline.html Pierson, G (n.d.), Excerpt: The Voyage of the James Caird by Enerest Shackleton. American Museum of Natural History. https://www.amnh.org/learn-teach/curriculum-collections/antarctica/exploration/the-voyage-of-the-james-caird Royal Museums Greenwich. (n.d. a). History of Antarctic explorers. Royal Museums Greenwich. https://www.rmg.co.uk/stories/topics/history-antarctic-explorers Royal Museums Greenwich. (n.d. b). Sir Ernest Shackleton. Royal Museums Greenwich. https://www.rmg.co.uk/stories/topics/sir-ernest-shackleton Scott Polar Research Institute (n.d.). McNish, Carpenter. University of Cambridge, Scott Polar Research Institute. https://www.spri.cam.ac.uk/museum/shackleton/biographies/McNish,_Henry/ Shackelton, E (1919). South: The Endurance Expedition. Heinemann Publishing House Smith, M (2021). Shackleton's Imperial Trans-Antarctic Expedition. Shackleton. https://shackleton.com/en-au/blogs/articles/shackleton-imperial-trans-antarctic-expedition Worsley, F (1931). Endurance: An Epic of Polar Adventure. W. W. Norton & Co Previous article Next article Elemental back to

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

The Greenhouse Unpacking the Latest IPCC Report - What Climate Science is Telling Us By Sonia Truong The most comprehensive climate science report to date, this sixth assessment report reveals the reality of climate change and stresses that we need to take action urgently. Edited by Jessica Nguy & Yen Sim Issue 1: September 24, 2021 Illustration by Jess Nguyen On the 9th of August 2021, the United Nations Intergovernmental Panel on Climate Change (IPCC) released its first instalment of the IPCC Sixth Assessment Report from Working Group I, Climate Change 2021 — The Physical Science Basis of Climate Change. The IPCC is one of the world’s leading authorities on climate change and its reports provide an important scientific framework for governments to develop climate policies. With the collaborative effort of 234 leading climate scientists and more than 1,000 contributors, the latest IPCC report provides the most up-to-date information about the scientific basis of climate change and the effects of human activity on Earth’s systems. The report can be found online — it features a ‘Summary for Policymakers’ document exploring key findings across four topic areas as well as a comprehensive ‘Full Report’ which assesses and compiles peer-reviewed literature on climate science from across the globe. The report also features the IPCC WGI Interactive Atlas which explores observed and projected regional climate changes across different emissions and warming scenarios. Three key takeaways from the IPCC report are described below. #1: Human activity has contributed to climate change It in unequivocal that human influence has warmed the atmosphere, ocean and land. Headline statement from the IPCC’s ‘Summary for Policymakers’, AR6 2021 Advancements in attribution studies have allowed scientists to better simulate Earth’s responses to natural and anthropogenic factors and estimate the extent of human influence on observed climate trends. For the first time, the IPCC report has been able to state with a very high level of certainty that anthropogenic factors have been the main driver of increasing temperature extremes since the mid-19th century. Figure SPM.1 shows that simulated natural factors do not come close to explaining the observed increase in global surface temperature since the mid-19th century. Figure SPM.1: A powerful comparison of changes in global surface temperature since 1850 with and without human factors. This figure shows that the effects of natural climate drivers on global warming have been negligible compared to human influence on the climate. IPCC AR6, ‘Summary for Policymakers’ Atmospheric greenhouse gas concentrations are higher than what they have been in the last two millennia and have been increasing at an unprecedented rate, mainly due to human activities in greenhouse gas combustion and deforestation. According to the report, greenhouse gas emissions from human activities have caused warming of approximately 1.1°C above pre-industrial average. In fact, human activities have caused enough emissions for even greater warming, but this has been partially counteracted by the cooling effect of aerosols in the atmosphere. Some recent heat extremes would have been virtually impossible without the influence of human forcing factors. Siberia’s prolonged heatwaves of 2020, for example, would have occurred less than once every 80,000 years without human-induced climate change. Moreover, the onset of Siberia’s wildfire season saw record-high temperatures throughout 2020 and 2021 as well as the burning of over 16 million hectares of land. Even in today’s climate, such extreme weather events are unlikely, but have been predicted to become more frequent by the end of this century. #2: Every region will experience environmental changes due to climate change The IPCC report states that the “widespread, rapid and intensifying” effects of climate change will be experienced by every region in a multitude of ways. Since the release of the last IPCC report in 2018, the world has observed an increase in acute weather events such as widespread flooding, storms, drought, fire weather and heatwaves. These are predicted to increase in frequency and severity as a result of human-induced climate change. Many changes in the climate system become larger in direct relation to increasing global warming. They include increases in the frequency and intensity of hot extremes, marine heatwaves, and heavy precipitation, agricultural and ecological droughts in some regions, and proportion of intense tropical cyclones, as well as reductions in Arctic sea ice, snow cover and permafrost. B.2 from the IPCC’s ‘Summary for Policymakers’, AR6 2021 Several environmental changes due to climate change are already irreversible. Notably, global sea level rise and ocean acidification are set in long-term motion and will proceed at rates which will depend on future emissions. Glacial retreat is occurring synchronously across the world and glaciers will continue to melt for decades or centuries. All emission scenarios within the 21st century described in the report have revealed that global temperature changes will exceed a 1.5ºC increase, even in the lowest emissions scenario (SSP1-1.9). Thus, warming will reach a critical level regardless of actions that the world takes now. We can, however, prevent further temperature increases with deep reductions in global greenhouse gas emissions (especially carbon dioxide and methane). Figure SPM.5: All regions of the world (with one exception) will experience warming as a result of climate change, although not at an equal level. IPCC AR6, ‘Summary for policymakers’ Environmental changes at a 2ºC warming will be more pronounced and widespread, and extremes are likely to exceed critical tolerance thresholds in human health, ecological systems and agriculture. Australia, in particular, is vulnerable to experiencing scarce water resources in drought-prone areas and flooding and landslide events due to heavy rainfall events. Australia’s coastlines are also prone to erosion and flooding from rising sea levels and extreme meteorological events. The IPCC report examines evidence for climate ‘tipping points’ which, due to uncertainty about the Earth’s feedback systems, “cannot be ruled out” in climate projections. These tipping points are key thresholds that will lead to large-scale and irreversible damages to the Earth’s systems if breached. One of these tipping points is the loss of the Greenland ice sheet which is melting at an unprecedented rate. Surface melt of this major ice sheet involves a number of positive feedback loops which exacerbate the melting as the ice surface gets darker and less reflective of solar radiation. Scientists warn that, while highly unlikely, there is a possibility that we will reach a tipping point with current warming trends. #3: We need to make drastic reductions in greenhouse gas emissions immediately The Sixth Assessment Report tells us, with greater certainty than ever before, that human activities over the past six decades have caused global warming trends and affected climate extremes globally. These trends are likely to continue on a long-term scale. Most importantly, the report stresses that if we want any chance of limiting global temperature rise to 1.5ºC above pre-industrial levels, we must urgently make strong, sustained reductions in global greenhouse gas emissions. The current global carbon budget to remain below 1.5ºC warming is estimated to be at an additional 500 billion tonnes of greenhouse gas. To remain within this budget, we need to achieve net zero carbon dioxide emissions by 2050. Reductions in greenhouse gas emissions will only be achieved with meaningful climate action. If we can drastically reduce emissions now, we will still have a chance of averting the climate crisis. The two succeeding instalments of the IPCC Sixth Assessment Report will cover the impacts of climate change and mitigation of climate change and are planned to be released in 2022. References: IPCC, 2021: Summary for Policymakers. In: Climate Change 2021: The Physical Science Basis. Contribution of Working Group I to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [MassonDelmotte, V., P. Zhai, A. Pirani, S.L. Connors, C. Péan, S. Berger, N. Caud, Y. Chen, L. Goldfarb, M.I. Gomis, M. Huang, K. Leitzell, E. Lonnoy, J.B.R. Matthews, T.K. Maycock, T. Waterfield, O. Yelekçi, R. Yu, and B. Zhou (eds.)]. Cambridge University Press. In Press.

< 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

< Back to Issue 4 From the Editors-in-Chief by Caitlin Kane, Rachel Ko, Patrick Grave, Yvette Marris 1 July 2023 Edited by the Committee Illustrated by Gemma van der Hurk Scirocco, summer sun, shimmering on the horizon. Salt-caked channels spiderweb your lips, scored by rivulets of sweat. Shifting, hissing sands sting your legs. You are the explorer, the adventurer, the scientist. A rusted spring, you heave forward, straining for each step, hauling empty waterskins. ----- The lonely deserts of science provide fertile ground for mirages. An optical phenomenon that appears to show lakes in the distance, the mirage has long been a metaphor for foolhardy hopes and desperate quests. The allure of a sparkling oasis just over the horizon, however, is undeniable. The practice of science involves both kinds of stories. Some scientists set a distant goal and reach it — perhaps they are lucky, perhaps they have exactly the right skills. Other scientists yearn to crack a certain problem but never quite get there. In this issue of OmniSci Magazine, we chose to explore this quest for the unknown that may be bold, unlucky, or even foolhardy: chasing the ‘Mirage’. Each article was written entirely by a student, edited by students, and is accompanied by an illustration that was created by a student. We, as a magazine, exist to provide university students a place to develop their science communication skills and share their work. If there’s a piece you enjoy, feel free to leave a comment or send us some feedback – we love to know that our work means something to the wider world. We’d like to thank all our contributors — our writers, designers, editors, and committee — who have each invested countless hours into crafting an issue that we are all incredibly proud of. We’d also like to thank you, our readers; we are incredibly grateful that people want to read student pieces and learn little bits from the work. That’s enough talking from us until next issue. Go and read some fantastic student writing! Previous article Next article back to MIRAGE

By Juulke Castelijn < Back to Issue 3 Believing in aliens... A science? By Juulke Castelijn 10 September 2022 Edited by Tanya Kovacevic and Ashleigh Hallinan Illustrated by Quynh Anh Nguyen Next The question of the existence of ‘intelligent life forms’ on a planet other than ours has always been one of belief. And I did not believe. It was probably the image of a green blob with multiple arms and eyes squelching across the ground and emitting noises unidentifiable as any form of language which turned me off the whole idea. But a book I read one day completely changed my mind; it wasn’t about space at all, but about evolution. ‘Science in the Soul’ is a collection of works written by the inimitable Richard Dawkins, a man who has argued on behalf of evolutionary theory for decades. Within its pages, you will find essays, articles and speeches from throughout his career, all with the target of inspiring deep rational thought in the field of science. A single essay gives enough food for thought to last the mind many days, but the ease and magnificence of Dawkin’s prose encourages the devourment of many pages in a single sitting. The reader becomes engulfed in scientific argument, quickly and completely. Dawkins shows the fundamental importance of the proper understanding of evolution as not just critical to biology, but society at large. Take, for instance, ‘Speaking up for science: An open letter to Prince Charles,’ in which he argues against the modelling of agricultural practices on natural processes as a way of combating climate change. Even if agriculture could be in itself a natural practice (it can’t), nature, Dawkins argues, is a terrible model for longevity. Instead, nature is ‘a short-term Darwinian profiteer’. Here he refers to the mechanism of natural selection, where offspring have an increased likelihood of carrying the traits which favoured their parents’ survival. Natural selection is a reflective process. At a population level, it highlights those genetic traits that increased chances of survival in the past. There is no guarantee those traits will benefit the current generation at all, let alone future generations. Instead, Dawkins argues, science is the method by which new solutions to climate change are found. Whilst we cannot see the future, a rational application of a wealth of knowledge gives us a far more sensitive approach than crude nature. Well, perhaps not crude per se. If anyone is an advocate for the beauty and complexity of natural life, it is surely Dawkins. But a true representation of nature, he argues, rests on the appreciation of evolution as a blinded process, with no aim or ambition, and certainly no pre-planned design. With this stance, Dawkins directly opposes Creationism as an explanation of how the world emerged, a battle from which he does not shy away. Evolution is often painted as a theory in which things develop by chance, randomly. When you consider the complexity of a thing such as the eye, no wonder people prefer to believe in an intelligent designer, like a god, instead. But evolution is not dependent on chance at all, a fact Dawkins argues many times throughout his collection. There is nothing random about the body parts that make up modern humans, or any other living thing - they have been passed down from generation to generation because they enhanced our ancestors’ survival. The underlying logic is unrivalled, including by religion. But that doesn’t mean Dawkins is not a man of belief. Dawkins believes in the existence of intelligent extraterrestrial life, and for one reason above all: given the billions upon billions of planets in our universe, the chance of our own evolution would have to be exceedingly small if there was no other life out there. In other words, we believe there is life out there because we do not believe our own evolution to be so rare as to only occur once. Admittedly, it is not a new argument but it had not clicked for me before. Perhaps it was Dawkins’ poetic phrasing. At this stage it is a belief, underlined by a big ‘if’. How could we ever know if there are intelligent life forms on a planet other than Earth? Dawkins provides an answer here too. You probably won’t be surprised that the answer is science, specifically a knowledge of evolution. We do not have to discover life itself, only a sign of something that marks intelligence - a machine or language, say. Evolution remains our only plausible theory of how such a thing could be created, because it can explain the formation of an intelligent being capable of designing such things. We become the supporting evidence of life somewhere else in the universe. That’s satisfying enough for me. Previous article Next article alien back to

< Back to Issue 2 Hidden Worlds: a peek into the nanoscale using helium ion microscopy How do scientists know what happens at scales smaller than you can see using an optical microscope? One exciting method is the helium ion microscope which can be used to view cells, crystals and specially engineered materials with extreme detail, revealing the beauty that exists at scales too small to imagine! by Erin Grant 10 December 2021 Edited by Jessica Nguy and Hamish Payne Illustrated by Erin Grant The room is white, with three smooth walls and a fourth containing a small sample prep bench and high shelves. In the centre is a desk with three monitors. Next to it, occupying most of the space, is the microscope. Eight feet tall, a few feet wide, resting on an isolated floor surrounded by caution tape; “NO STEP” written in big block letters. Wires protrude from its tiered shape in orderly chaos. It is a clean, technological space; we are ready to explore science. A colleague and I are at the Materials Characterisation and Fabrication Platform of the University of Melbourne to finish off the last steps of a scientific paper I’ve been working on for many years. What I need, as the icing on the cake, is an image. What does my sample look like way down there, at the nanometre scale? Objects that are only nanometres in size are very hard to imagine when we’re used to thinking about metres, centimetres, or maybe even millimetres. We can see those length scales; they are part of our everyday. So, if you’re told that proteins have a diameter of a few nanometres, what does that mean? Well, to be precise, a nanometre is one-billionth of a metre. A human hair, the go-to yardstick for describing small things, has a width between 0.05-0.1 millimetres, which means that if you wanted to slice a hair into nanometre-wide strands you’d end up with nearly 100,000 pieces. Unfortunately, that’s still hard to visualise, but I’ve found that when working with and thinking about scales like this every day, you gain a sort of mental landscape that small things occupy, perhaps not entirely in context, but a space that contains an overall ‘vibe’ of smallness. I first noticed this when I worked in a laboratory that studies the tiny nematode worm C. elegans. These creatures are half a millimetre long, so although they are clearly visible to the naked eye, you need a microscope if you want to use them for science. After looking at these tiny creatures under magnification for many weeks, I came to recognise a feeling almost like being underwater. Upon putting my eyes to the lens, my focus would change from the macroscopic world around me, to one of minutiae. This change in perspective was quite immersive, I almost felt like I was inhabiting that small petri dish too. Working with samples even smaller than that now, I have carried some of that mental landscape with me. It now feels commonplace to imagine tiny systems, such as crystals or molecules which were once foreign. Much of this ability to visualise small things comes from the fact that in many cases, we can actually see them too. Physics has given us many tools with which we can peer into the smallest systems that exist. Helium ion microscopy, which I have come here to carry out, is one such technique. Dr Anders Barlow runs the helium ion microscope (HIM) at this facility. He warmly welcomes me and my colleague into the quiet room and jumps straight into an enthusiastic explanation of the machine – he can tell we’re not just here for some pictures, we want to know the inner workings of the microscope too. The HIM is a bit like the more mature surveyor of minuscule worlds: the electron microscope. While a regular optical microscope uses light to illuminate a sample, the electron microscope uses electrons. When they collide with the sample these electrons can bounce off or lose energy through several mechanisms. The lost energy can go into heat or light, but more usefully, the energy might be transferred to other electrons in the sample, called secondary electrons, ejecting them like a drill removing rocks from a quarry. The secondary electrons can be detected at each point across the sample as the beam is scanned over its surface. If more electrons are detected, then the pixel at that point is brighter compared to areas where there are fewer electrons. This tells you about the topography or composition of the sample at that point on its surface and provides a grayscale image. The HIM works in the same way, but it can generate sharper images because helium ions are heavier than electrons. This is important because the increased resolution of electron and helium ion microscopes is enabled by their quantum mechanical properties - namely the particle’s wavelength. You may have heard about the wave-like nature of light, which is a basic property of quantum mechanics. Particles also have a wavelength, called the de Broglie wavelength, which is inversely proportional to their mass - the heavier the particle, the shorter the wavelength. Having a shorter wavelength allows smaller details to be resolved because of a pesky phenomenon called diffraction. Diffraction occurs when a wave encounters a gap that is of the same or smaller width to its wavelength. When this happens, the wave that emerges on the other side will be spread out. You can think of the features that you want to image as being similar to gaps, so when light, or a particle, interacts with features that are very close together it will spread out, making those features blurry or even invisible. But if you can ensure that the wavelength is smaller than whatever feature you want to see, diffraction will not occur. Interestingly, physicists can actually take advantage of diffraction, and another phenomenon called interference, when they study periodic structures like crystals, but that’s a different article! So, because the de Broglie wavelength is very short for particles with mass, like electrons, an electron microscope can generate images of higher resolution than an optical microscope. Likewise, helium ions are even heavier than electrons because they are composed of one electron, two protons, and two neutrons. This makes them about 7,000 times heavier than a single electron (electrons are very light compared to protons and neutrons!) and consequently the images they can make are very sharp. With our samples ready, lab manager Anders loads my sample into the microscope and begins lowering the pressure in its internal chamber. Having a high vacuum – approximately a billion times lower than atmospheric pressure – is essential because it prevents air from interfering with the helium beam. Making the beam is perhaps the most miraculous part of this technological feat. At the very top of the microscope’s column, there’s a tiny filament shaped like a needle. Not like a needle, in fact, it is the sharpest needle we humans can make. To achieve this, the point is shaped by first extreme heat, and then some extreme voltages until the very tip is composed of only three atoms, reverently referred to as the trimer. Once the trimer has been formed, a high voltage is applied to the needle, resulting in an extreme electric field around the tip. Next, helium gas is introduced into the chamber and individual helium atoms are attracted towards the region of the high electric field. The field is so strong that it strips each helium atom of one electron, ionising it, and these now positively charged ions are repelled from each of the three atoms in the trimer as three corresponding beams. Using sophisticated focusing fields down the length of the column allows Anders to choose only one of the beams for imaging; we are creating a picture using a beam only one atom wide! Generating such a precise beam requires constant maintenance, but once Anders is satisfied with how it looks today, he begins scanning over a large area for what we’ve come to find: tiny proteins stuck to a diamond. In an experimental PhD, you often find yourself answering small incremental questions and today I want to know how well I’ve attached these proteins to my diamond and what the coverage looks like. Other measures have told me that I probably have a lot of them, but the best way to know is to have a look! That’s what Anders does for researchers at the university; he helps us find out whether we have done a good job putting things together or coming up with new techniques. This is something he loves about his job. “I love the exposure I get to many areas of science,” he says, “Imaging of all forms is ubiquitous in research, and the HIM is applicable to most fields, so we see samples from materials science, polymers, nanomaterials, and biomaterials, through to medical technologies and devices, to cell and tissue biology of human, plant and animal origin. I never get tired of seeing what new specimens may come through the lab door.” Unfortunately, the first images we see are very dark and washed out, like a photograph taken in low-light; not many secondary electrons are making it to the detector. To combat this, Anders uses a flood gun to stop charge build up on the surface of the diamond. When the helium ions create secondary electrons, they are ejected from the surface at low speeds. As electrons are negatively charged, the bombarded surface, which now lacks electrons, will become positive and the low energy secondary electrons will be attracted back to the surface instead of making it to the detector. In an electron microscope this is avoided by coating insulators, such as my diamond, with a conductive material like gold. If the surface is conductive, the positive charge that is left behind by the secondary electrons will be offset by electrons from the metallic coating that can flow towards the sudden appearance of positive charges. In this case, the ejected electrons can escape and be detected. However, a coating like this would reduce the resolution of the image; if you want to measure proteins that are twelve nanometres high, but you put a three-nanometre coating over them, you’ll lose a lot of the resolution! To get around this, the HIM uses the flood gun, which lightly sprays the surface with electrons of low energy as the helium beam passes over. This neutralises the surface and lets the secondary electrons escape in the same way as having a conductive layer. Once Anders turns on the flood gun, the contrast increases, allowing us to zoom in on a small region of the diamond, and there they are! Thousands of spherical proteins arranged neatly across the surface, only twelve nanometres in diameter. The sight is spectacular, only one try and we got what we came for. I am three years into a PhD and I’ve become very used to the feeling of disappointment that can accompany new experimental techniques. Things rarely work out the first time around, so to see those little spheres straight away was magical. Dotted across the diamond surface is another, extra, gem. To keep protein nice and happy, you must prepare it in a salty solution. So, when the protein was deposited, some regular table salt, NaCl, came too. We can see this salt in our images as crystals in two distinctive and very beautiful patterns which you can see in the images below. Protein on the surface of my diamond. Each small pale circle is one of these spherical proteins. The first image shows a large creeping pattern, reminiscent of snowflakes or tree roots, which spreads its soft fingers across several hundred nanometres. These crystals have taken on an amorphous pattern, where the crystal structure is broken up rather than being one continuous arrangement of the atoms. The second pattern however, shown in the right image, is what a continuous NaCl crystal looks like. When large enough crystals can form without becoming amorphous they look like precise cubes of various sizes all strewn about. One of my favourite aspects about looking at very small things, is how the patterns you see often mirror those at much larger scales. Look at a fingerprint and you’ll find mountains and valleys, or the roots of a tree and you’ll see a river system. Salt (NaCl) can take on a highly ordered structure shown by the cubic crystals (left) or an amorphous pattern similar in shape to tree roots (right). The astonishing images we get from this single session are all in a day’s work for Anders. He has imaged numerous kinds of cells on all manner of interesting substrates, patterned surfaces covered in needle-like protrusions, and many kinds of man-made materials. Today, there are vials on his prep-bench which, at first glance, look much like jars of hair. However, they are not hair, in fact they are strands of carbon fibre covered in various coatings, awaiting examination. ‘What are your favourite types of samples to look at?’ I want to know. “Cell biology is fascinating,” he says. “We’ve imaged red blood cells, pancreatic cells, stem cells, and various bacterial cells in this microscope. Most often researchers are interested in cell life and death, and the HIM assists by providing high resolution images of the structure and surface topography of the cell membrane.” Recently however, Anders has been helping researchers look at polymer materials for water filtration. “These are hierarchical porous structures, meaning they’re engineered to have pore sizes that vary through the membrane. It is stunning to see the materials at low magnification with large pores, and as we zoom in and in and in, to see new pore sizes become visible at each level, like a material engineered with a fractal quality.” One of the unique things about the HIM, Anders reminds me, is that it’s not just for imaging. Since helium ions are heavy, they carry a higher momentum than electrons. “We leverage the momentum of the ions to actually modify structures too. We can create new surface properties, new devices, new technologies, on a scale that is often too small for any other fabrication technique. This is some of the most exciting work.” If you know anyone who needs some nanoscale drilling done, then the HIM is your instrument! Today’s excursion across the university campus has been thrilling. I got what I came for and I’m excited to find other projects that could benefit from the insight and beautiful images the HIM can provide. Imaging instruments have always fascinated me and I’m looking forward to witnessing how far we will be able to delve into the nanoscale world in the years to come, thanks to the fast pace of engineering and physics research. Previous article back to DISORDER Next article

< Back to Issue 8 Functional Neurological Disorder by Esme MacGillivray 3 June 2025 Edited by Steph Liang Illustrated by Esme MacGillivray Content warning: Please be aware that this article includes discussion of mental illness, medical malpractice, and ableism. Functional Neurological Disorder (FND) is very simple to explain. It is a problem with how the brain functions. More specifically, it is a problem with how the brain sends and receives messages, resulting in diverse motor, sensory, and cognitive symptoms. But unlike other neurological conditions, FND does not appear to be caused by any identifiable structural damage to the nervous system. As a catchy metaphor: the brain is a computer, and FND is a ‘software’ problem as opposed to a ‘hardware’ problem. If that all feels frustratingly vague, I’m afraid you are out of luck — but in good company. Since developing FND a year and a half ago, I’ve become closely acquainted with confusion. My own body has felt alien sometimes, and the way others have reacted to my disability has been equally disorientating. Instead of accepting that neuroscience is yet to make sense of FND, many people — including medical professionals — rush to dismiss symptoms, or question their very existence. Understanding this condition is not just a matter of advancing scientific knowledge. Judgement and shame must be replaced with compassion. Turns out FND is far from simple to explain. Symptoms often develop rapidly and ‘out of nowhere’, most typically in adolescence or adulthood (1). These can include functional tics, non-epileptic seizures, limb weakness, paralysis, gait disorders, and speech difficulties (2). The list goes on. From the array of possible symptoms alone, it is clear that FND encompasses a broad range of presentations. Fluctuation and inconsistency can exist even within an individual’s experience. Most days, I appear completely ‘normal’. Sometimes, my disability is glaringly obvious. My FND is confusing and isolating; because there is so little information available, it is difficult to get the support I need. It doesn’t help that myths about this condition are rife within both medical and everyday settings, despite it being one of the most common diagnoses made by neurologists (3). I would like to dispel the idea that FND is just a fancy way of saying that doctors have ruled out ‘real’ neurological conditions. Neurologists can observe positive signs, or patterns of sensation and movement, that indicate functional symptoms, such as a Hoover’s sign for functional weakness (1). Therefore, although the cause of symptoms remains unknown, FND is a meaningful diagnosis. The very label itself represents progression away from the harmful beliefs that defined this condition in earlier centuries. Sometimes I joke about how I might have been treated if I was living in the past. Would people try to exorcise me, or burn me at the stake? Or would I perhaps be sent away to a charming seaside retreat? A mental asylum may have been more likely. Indeed, symptoms of FND once would have awarded me a diagnosis of ‘hysteria’. This label originates from ancient beliefs about the uterus punishing the female body with illness if left infertile, representing an ideological burden forced on suffering women for centuries (4). In the words of Eliot Slater in 1965, the term was “a disguise for ignorance and a fertile source of clinical error” (5). As theories of psychology and neurology were reworked, clinicians began using the term ‘Conversion Disorder’ (4). FND symptoms were misunderstood as manifestations of psychological trauma being ‘converted’ into physical distress (4). It’s an interesting idea, but an inaccurate one. Many people with FND have not experienced significant trauma prior to developing symptoms (5). It is now understood that mental and physical harm, such as a severe illness or injury, may increase the risk of an individual developing FND (1,7). However, this is not a requirement, and certainly not the cause of this condition. Unfortunately, the medical field has not unanimously moved on from the misunderstandings of the past. Since my episodes of collapse, unresponsiveness, and uncontrollable movements were not typical of epilepsy, they didn’t seem to concern the first, second, or even third medical professional who saw me. I am glad that my condition is not inherently life-threatening — but declaring that there is nothing wrong with someone is a far cry from reassuring them that their brain isn’t in danger. The attitudes I encountered leant strongly towards the former. Doctors seemed eager to attribute my symptoms to ‘stress’, and prove that I could directly control what was happening to me, while some even tried to convince my mum that I was faking everything for attention. These experiences are not an anomaly. In fact, being dismissed or disbelieved is an almost characteristic part of having FND (8,9). It often takes years for people to be correctly diagnosed (8), let alone be offered any semblance of support. After a month, I was privileged enough to receive a diagnosis — and compassion — from a neurologist who took me seriously. Despite this, there are lingering impressions from that first month without any understanding or guidance. It urges me to ignore what I know to be true about FND, and about my own body, to entertain the idea that my thoughts are secretly orchestrating everything. I am crazy, or too weak minded to stop choosing thoughts that make me have FND. Don’t ask me how one can subconsciously do something on purpose. I didn’t put this idea in my own head, just like I didn’t put FND in my own head. Nevertheless, these things exist. People with FND are tasked with navigating not only frightening symptoms, but also ignorance, stigma, and shame. Sometimes science doesn’t give us a satisfying answer. Future research can hopefully provide people with FND more concrete answers, including ways of understanding ourselves and possibilities for symptom management and recovery. Health and disability are complex, and we can never fully understand what someone else is going through. When it comes to FND, I barely understand my own body half of the time. Fortunately, I now understand that I deserve to be treated with respect. Compassion doesn’t need to be confusing. It shouldn’t take a breakthrough in neuroscience for people with FND to be listened to and cared for. References 1. Bennett K, Diamond C, Hoeritzauer I, et al. A practical review of functional neurological disorder (FND) for the general physician. Clinical Medicine . 2021;21(1):28-36. doi: 10.7861/clinmed.2020-0987 2. FND Hope. Symptoms. 2012. Accessed May 11, 2025. https://fndhope.org/fnd-guide/symptoms/ 3. Stone J, Carson A, Duncan R, et al. Who is referred to neurology clinics?--the diagnoses made in 3781 new patients. Clinical Neurology Neurosurgery . 2010;112(9):747-51. doi: 10.1016/j.clineuro.2010.05.011 4. Raynor G, Baslet G. A historical review of functional neurological disorder and comparison to contemporary models. Epilepsy & behavior reports . 2021;16:100489. 10.1016/j.ebr.2021.100489 5. Slater E. Diagnosis of “Hysteria”. Br Med J . 1965;1:1395–1399. doi: 10.1136/bmj.1.5447.1395 6. Ludwig L, Pasman JA, Nicholson T, et al. Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies. Lancet Psychiatry . 2018;5(4):307-320. doi: 10.1016/S2215-0366(18)30051-8 7. Espay AJ, Aybek S, Carson A, et al. Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders. JAMA neurology , 2020;75(9):1132–1141. Doi: 10.1001/jamaneurol.2018.1264 8. Robson C, Lian OS. “Blaming, shaming, humiliation": Stigmatising medical interactions among people with non-epileptic seizures. Wellcome Open Research , 2017:2, 55. Doi: 10.12688/wellcomeopenres.12133.2 9. FND Australia Support Services Inc. Experiences of Functional Neurological Disorder - Summary Report. Canberra (AU): Australian Government National Mental Health Commision; 2019. 13p. Previous article Next article Enigma back to

< Back to Issue 6 Cosmic Carbon Vs Artificial Intelligence by Gaurika Loomba 28 May 2024 Edited by Rita Fortune Illustrated by Semko van de Wolfshaar “There are many peculiar aspects of the laws of nature that, had they been slightly different, would have precluded the existence of life” - Paul Davies, 2003 Almost four billion years ago, there was nothing but an incredibly hot, dense speck of matter. This speck exploded, and the universe was born. Within the first hundredth of a billionth of a trillionth of a trillionth second, the universe began expanding at an astronomical rate. For the next 400 million years, the universe was made of hydrogen, helium, and a dash of lithium – until I was born. And thus began all life as you know it. So how did I, the element of life, the fuel of industries, and the constituent of important materials, originate? Stars. Those shiny, mystical dots in the night sky are giant balls of hot hydrogen and helium gas. Only in their centres are temperatures high enough to facilitate the collision of three helium-4 nuclei within a tiny fraction of a second. I am carbon-12, the element born out of this extraordinary reaction. My astronomical powers come from my atomic structure; I have six electrons, six protons, and six neutrons. The electrons form teardrop shaped clouds, spread tetrahedrally around my core, my nucleus, where the protons and neutrons reside. My petite size and my outer electrons allow my nucleus to exert a balanced force on other atoms that I bond with. This ability to make stable bonds makes me a major component of proteins, lipids, nucleic acids, and carbohydrates, the building blocks of life. The outer electrons also allow me to form chains, sheets, and blocks of matter, such as diamond, with other carbon-12 atoms. Over the years of evolution, organic matter buried in Earth formed fossil fuels, so I am also the fuel that runs the modern world. As if science wasn’t enough, my spiritual significance reiterates my importance for the existence of life. According to the Hindu philosophy, the divine symbol, ‘Aum’ is the primordial sound of the Cosmos and ‘Swastika’, its visual embodiment. ‘Alpha’ and ‘Omega’, the first and last letters of the Greek alphabet, represent the beginning and ending, that is the ‘Eternal’ according to Christian spirituality. When scientists photographed my atomic structure, spiritual leaders saw the ‘Aum’ in my three-dimensional view and the ‘Swastika’ in my two-dimensional view. Through other angles, the ‘Alpha’ and ‘Omega’ have also been visualised (Knowledge of Reality, 2001). I am the element of life, and within me is the divine consciousness. I am the beginning and I am the end. My greatness has been agreed upon by science and spirituality. In my absence, there would be no life, an idea humans call carbon chauvinism. This ideology and my greatness remained unquestioned for billions of years, until the birth of Artificial Intelligence. I shaped the course of evolution for humans to be self-conscious and intelligent life forms. With the awareness of self, I aspired for humans to connect back to the Cosmos. But now my intelligent toolmakers, aka humans, are building intelligent tools. Intelligence and self-consciousness, which took nature millions of years to generate, is losing its uniqueness. Unfortunately, if software can be intelligent, there is nothing to stop it becoming conscious in the future. Soon, the earth will be populated by silicon-based entities that can compete with my best creation. Does this possibility compromise my superiority? A lot of you may justifiably think so. The truth is that I am the beginning. Historically, visionaries foresaw asteroid attacks as the end to human life. These days, climate change, which is an imbalance of carbon in the environment, is another prospective end. Now, people believe that conscious AI will outlive humans. Suggesting that I will not be the end; that my powers and superiority will be snatched by AI. So the remaining question is, who will be the end? I could tell you the truth, but I want to see who is with me at the end. The choice is yours. References Davies, P. (2003). Is anyone out there? https://www.theguardian.com/education/2003/jan/22/highereducation .uk Knowledge of Reality (2001). Spiritual Secrets in the Carbon Atom . https://www.sol.com.au/kor/11_02.htm Previous article Next article Elemental back to

Have you ever wondered if trees talk to each other? Happily, many scientists across time have had the same thought. So much fascinating knowledge has arisen from their research about the intricacies of trees and the different ways they converse with one another. Chatter Silent Conversations: How Trees Talk to One Another By Lily McCann There are so many conversations that go on beyond our hearing. This column explores communication between trees and how it might change the way we perceive them. Edited by Ethan Newnham, Irene Lee & Niesha Baker Issue 1: September 24, 2021 Illustration by Rachel Ko It’s getting brighter. A long, long winter is receding and warm days are flooding in. I’m not one for sunbathing, but I love to lie in the backyard in the shade of the gums and gaze up into the branches. They seem to revel in the weather as much as I do, waving arms languidly in the light or holding still as if afraid to lose a single ray of sun. If there’s a breeze, you might just be able to hear them whispering to one another. There’s a whole family of these gums in my backyard and each one is different. I can picture them as distinctly as the faces of people I love. One wears a thick, red coat of shaggy bark; another has pale, smooth skin; a third sheds its outer layer in long, stringy filaments that droop like scarves from its limbs. These different forms express distinct personalities. Gum trees make you feel there is more to them than just wood and leaves. There’s a red gum in Central Victoria called the ‘Maternity Tree’. It’s incredible to look at. The huge trunk is hollowed out and forms a sort of alcove or belly, open to the sky. Generations of Dja Dja Wurrung women have sought shelter here when in labour. An arson attack recently blackened the trunk and lower branches, but the tree survived (1). Such trees have incredibly long, rich lives. Imagine all the things they would say, if they could only tell us their stories. Whilst the ‘whispering’ of foliage in the wind may not have significance beyond its symbolism, there are other kinds of communication trees can harness. All we see when a breeze blows are branches and leaves swaying before it, but all the time a plethora of tiny molecules are pouring out from trees into the air. These compounds act like tiny, encrypted messages riding the wind, to be decoded by neighbours. They can carry warnings about unwanted visitors, or even coordinate group projects like flowering, so that trees can bloom in synchrony. If we turn our gaze lower we can see that more dialogue spreads below ground. Trees have their own telephone cable system (7), linking up members of the same and even different species. This system takes the form of fungal networks, which transfer nutrients and signals between trees (3). Unfortunately, subscription to this network isn’t free: fungi demand a sugar supply for their services. Overall, though, the relationship is beneficial to both parties and allows for an effective form of underground communication in forests. These conversations are not restricted to deep-rooted, leaf-bearing beings: trees are multilingual. A whole web of inter-species dialogue murmurs amongst the branches beyond the grasp of our deaf ears. Through the language of scent, trees entice pollinators such as bees and birds to feed on their nectar and spread their pollen (4). They warn predators against attacking by releasing certain chemicals (5). They can even manipulate other species for their own defence: when attacked by wax scale insects, a Persimmon tree calls up its own personal army by alerting ladybugs, who feed on the scales, averting the threat to the tree (6). Such relationships demonstrate the crucial role trees play in local ecosystems and their essentially cooperative natures. Trees can be very altruistic, especially when it comes to family members. Mother trees foster the growth of young ones by providing nutrients, and descendants support their elderly relatives - even corpses of hewn-down trees - through their underground cable systems. These intimate, extensive connections between trees are not so different from our own societal networks. Do trees, too, have communities, family loyalties, friends? Can they express the qualities of love and trust required, in the human world, for such relationships? This thought begs the question: Can trees feel? They certainly have an emotional impact on us. I can sense it as I lie under the gums. Think about the last time you went hiking, sat in a tree’s shade, walked through a local park. There’s something about being amongst trees that calms and inspires. Science agrees: one study has shown that walking in forests is more beneficial to our health than walking through the city. How do trees manage to have such a strong effect on us? Peter Wohlleben, German forester and author of The Hidden Life of Trees, suggests that happy trees may impart their mood to us (9). He compares the atmosphere around ‘unhappy’ trees in plantations where threats abound and stress signals fill the air to old forests where ecosystem relations are more stabilised and trees healthier. We feel more relaxed and content in these latter environments. The emotive capacity of trees is yet to be proven scientifically, but is it a reasonable claim? If we define happiness as the circulation of ‘good’ molecules such as growth hormones and sugars, and the absence of ‘bad’ ones like distress signals, then we may suggest that for trees an abundance of good cues and a lack of warnings could be associated with a positive state. And this positive state - allowing trees to fulfill day-to-day functions, grow and proliferate, live in harmony with their environment - could be termed a kind of happiness in its own right. This may seem like a stretch - after all, how can you feel happiness without a brain? But Baluska et al. suggest that trees have those too, or something like them: command centres, integrative hubs in roots functioning somewhat like our own brains (10). Others compare a tree to an axon, a single nerve, conducting electrical signals along its length (11). Perhaps we could say that a forest, the aggregate of all these nerve connections, is a brain. Whilst we can draw endless analogies between the two, trees and animals parted ways 1.5 billion years ago in their evolutionary paths (12). Each developed their own ways of listening and responding to their environments. Who’s to say whether they haven’t both developed their own kinds of consciousness? If we take the time to contemplate trees, we can see that they are infinitely more complex and sensitive than we could have imagined. They have their own modes of communicating with and reacting to their environment. The fact is, trees are storytellers. They send out a constant flow of information into the air, the soil, and the root and fungal systems that join them to their community. Even if we can’t converse with trees in the same way that we converse with each other, it’s worth listening in on their chatter. They could tell us about changes in climate, threats to their environment, and how we can best help these graceful beings and the world around them. References: 1. Schubert, Shannon. “700yo Aboriginal Maternity Tree Set Alight in Victoria.” www.abc.net.au , August 8, 2021. https://www.abc.net.au/news/2021-08-08/dja-dja-wurrung-birthing-tree-set-on-fire/100359690. 2. Pichersky, Eran, and Jonathan Gershenzon. “The Formation and Function of Plant Volatiles: Perfumes for Pollinator Attraction and Defense.” Current Opinion in Plant Biology 5, no. 3 (June 2002): 237–43. https://doi.org/10.1016/s1369-5266(02)00251-0.; Falik, Omer, Ishay Hoffmann, and Ariel Novoplansky. “Say It with Flowers.” Plant Signaling & Behavior 9, no. 4 (March 5, 2014): e28258. https://doi.org/10.4161/psb.28258. 3. Simard, Suzanne W., David A. Perry, Melanie D. Jones, David D. Myrold, Daniel M. Durall, and Randy Molina. “Net Transfer of Carbon between Ectomycorrhizal Tree Species in the Field.” Nature 388, no. 6642 (August 1997): 579–82. https://doi.org/10.1038/41557. 4. Buchmann, Stephen L, and Gary Paul Nabhan. The Forgotten Pollinators. Editorial: Washington, D.C.: Island Press/Shearwater Books, 1997. 5. De Moraes, Consuelo M., Mark C. Mescher, and James H. Tumlinson. “Caterpillar-Induced Nocturnal Plant Volatiles Repel Conspecific Females.” Nature 410, no. 6828 (March 2001): 577–80. https://doi.org/10.1038/35069058. 6. Zhang, Yanfeng, Yingping Xie, Jiaoliang Xue, Guoliang Peng, and Xu Wang. “Effect of Volatile Emissions, Especially -Pinene, from Persimmon Trees Infested by Japanese Wax Scales or Treated with Methyl Jasmonate on Recruitment of Ladybeetle Predators.” Environmental Entomology 38, no. 5 (October 1, 2009): 1439–45. https://doi.org/10.1603/022.038.0512. 7, 9. Wohlleben, Peter, Jane Billinghurst, Tim F Flannery, Suzanne W Simard, and David Suzuki Institute. The Hidden Life of Trees : The Illustrated Edition. Vancouver ; Berkeley: David Suzuki Institute, 2018. 10. Baluška, František, Stefano Mancuso, Dieter Volkmann, and Peter Barlow. “The ‘Root-Brain’ Hypothesis of Charles and Francis Darwin.” Plant Signaling & Behavior 4, no. 12 (December 2009): 1121–27. https://doi.org/10.4161/psb.4.12.10574. 11. Hedrich, Rainer, Vicenta Salvador-Recatalà, and Ingo Dreyer. “Electrical Wiring and Long-Distance Plant Communication.” Trends in Plant Science 21, no. 5 (May 2016): 376–87. https://doi.org/10.1016/j.tplants.2016.01.016. 12. Wang, Daniel Y.-C., Sudhir Kumar, and S. Blair Hedges. “Divergence Time Estimates for the Early History of Animal Phyla and the Origin of Plants, Animals and Fungi.” Proceedings of the Royal Society of London. Series B: Biological Sciences 266, no. 1415 (January 22, 1999): 163–71. https://doi.org/10.1098/rspb.1999.0617.