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< Back to Issue 5 Three-Parent Babies? The Future of Mitochondrial Donation in Australia Kara Miwa-Dale 24 October 2023 Edited by Yasmin Potts Illustrated by Aisyah Mohammad Sulhanuddin Mitochondria are the ‘powerhouse of the cell’. Sound familiar? This fact was likely drilled into you during high school biology classes (or by looking at memes). Beyond this, you may not have given mitochondria a second thought - but you should! This organelle has been at the centre of some heated parliamentary debates relating to mitochondrial donation. This new IVF technology, which aims to prevent women from passing on mitochondrial disease, will reshape Australia’s approach to genetic and reproductive technologies. Mitochondrial donation was legalised in Australia last year when ‘Maeve’s Law’ was passed in the Senate. This law reform has generated a minefield of social and ethical questions that are yet to be fully answered. What is mitochondrial disease? Mitochondria are the small but mighty structures found in all our cells (except red blood cells) that produce more than 90% of the energy used by our bodies (Cleveland Clinic, 2023). This organelle is vital for the functioning of important organs such as the heart, brain and liver (Cleveland Clinic, 2023). Mitochondria also have their own DNA, with a relatively small genome size of 37 genes (Garcia et al., 2017), compared to the 20,000 genes in our nuclear DNA (Nurk et al., 2022). Mitochondrial disease refers to a group of disorders in which ‘faulty’ mitochondria results in a range of symptoms such as poor motor control, developmental delay, seizures and cardiac disease (Mito Foundation, 2023). Half of the cases of mitochondrial disease are caused by mutations in mitochondrial DNA. These mutations are transmitted through maternal inheritance, which means that all the mitochondria in your cells are passed on from your biological mother (Mito Foundation, 2023). It is believed that about 1 in 200 people have a mutation in their mitochondrial DNA, with 1 in 5000 people having some form of mitochondrial disease (Mito Foundation, 2023). There is currently no cure for this group of conditions. How does mitochondrial donation work? Mitochondrial donation, also known as Mitochondrial Replacement Therapy (MRT), is an IVF technology which aims to prevent women from passing on mitochondrial disease to their children. For individuals with mitochondrial disease, this technology is currently the only way to have biological children without the risk of passing on their disease. MRT is used to create an embryo containing the nuclear DNA from two parents, in addition to mitochondrial DNA from an egg donor. This process involves taking the nuclear DNA from an embryo (created using the mother’s egg and father’s sperm) and inserting it into a donor egg which contains healthy mitochondria (NHMRC, 2023). The child will still inherit all of their unique characteristics, such as hair colour, through the nuclear DNA of their prospective parents. Therefore, it would be impossible to tell that an individual had been conceived through MRT simply by looking at them. Challenges in defining parenthood. Children conceived through MRT have been popularly referred to in the media as ‘three-parent babies’ since the technique creates an embryo containing DNA from three different individuals. However, this label is inaccurate and misleading. It suggests that all three parents make an equal contribution to the identity of the child, when in fact mitochondrial donors contribute only 0.1% of the child’s total genetic material. So, technically the term ‘2.002-parent babies’ would be more accurate! Under Australian law, mitochondrial donors will not have legal status as parents since their genetic contribution is not thought to influence the unique characteristics of the child. However, there are some concerns about the potential psychological impacts on children conceived through MRT, as the definition of parenthood is becoming increasingly blurry. It is possible that children conceived through mitochondrial donation will regard their mitochondrial donor as significant to their identity, considering how different their life may have looked without them. As researchers learn more about the function of mitochondria, we may indeed find that mitochondrial DNA has a greater influence on a person’s characteristics than we once thought. More recent studies have linked mitochondrial DNA to athletic performance (Maruszak et al., 2014), psychiatric disorders (Sequeira et al., 2012), and ageing (Wallace, 2010). Should mitochondrial donors remain anonymous? If mitochondrial donors contribute such a tiny amount of DNA to a child, and do not influence any of their personal characteristics, should they be obligated to disclose their identity to the recipient? Australia no longer allows egg or sperm donors to remain anonymous in order to protect the rights of individuals to know their biological origins. Yet, in the case of mitochondrial donation, there is a much smaller proportion of DNA involved. Some experts have compared mitochondrial donation to organ donation, in the sense that the donation also provides someone with the organ (or organelle) that enables them to live a healthy life, without altering their unique characteristics. It has therefore been argued that mitochondrial donation should be treated in a similar way to organ donation, allowing donors to remain anonymous. Considering that donated eggs are often in low supply, permitting anonymous donors may provide a way of improving the availability of donor eggs. It is likely that Australia will follow the lead of the UK by permitting anonymous donation. Are we ‘playing God’ by altering the genome? By making heritable changes to an individual’s genome, we are heading into new and potentially dangerous territory. Opponents of mitochondrial donation have voiced fears about the ‘slippery slope’ between trying to eradicate mitochondrial disease and taking this technology too far into the realm of ‘designer babies’. Considering that mitochondrial donation does not involve making any changes to nuclear DNA, and can only be used for medical reasons, these statements seem a bit sensationalist. However, there are some genuine reasons to be concerned about the safety of this technology and its implications for the future of humankind. While MRT is generally considered to be safe based on clinical research, there are still some uncertainties about its efficacy in clinical practice. For example, clinical research has found that there is a chance of ‘carry-over’ of unhealthy mitochondria during the MRT process (Klopstock, Klopstock & Prokisch, 2016). If this carry-over occurs, there is a potential for the numbers of unhealthy mitochondria to gradually increase as the embryo develops, essentially undoing all the hard work of creating an embryo free from mitochondrial disease. However, the percentage of carry-over is usually less than 2% and is likely to become lower as the technology advances (Klopstock, Klopstock & Prokisch, 2016). Unfortunately, we won’t know about any negative long-term impacts of MRT until we are able to observe the development of children conceived through this technology. However, adults over the age of 18 cannot be forced to participate in a study, which makes it more challenging to track long-term outcomes. An important consideration is the privacy and autonomy of these individuals - that they are not over-medicalised or viewed as some sort of ‘spectacle’ to the public. The future of mitochondrial donation in Australia. ‘Maeve’s Law’ was named in honour of Maeve Hood, a cheerful 7-year-old who was diagnosed with a rare mitochondrial disease at 18 months old. The law was passed with the aim of preventing the transmission of mitochondrial disease in Australia, which affects around fifty families each year. This revolutionary law permits the creation of a human embryo containing genetic material from three people and allows heritable changes to be made to the genome (although under strict guidelines). Such practices were previously illegal in Australia due to understandable concern that these technologies could be destructive in the wrong hands. Maeve’s Law introduces an exception to these prohibitions solely for the purpose of preventing serious mitochondrial disease. While MRT is no longer illegal in Australia, Maeve’s Law does not authorise the immediate use of MRT in clinical practice. The law outlines a two-stage approach in which the technology will be implemented, provided that clinical trials are successful. This initiative will be conducted by Monash University through the mitoHOPE (Healthy Outcomes Pilot and Evaluation) program, for which they received $15 million in funding (Monash University, 2023). Stage 1, which is expected to last around ten years, will involve clinical research aimed at improving MRT techniques and validating its safety. After an initial review, mitochondrial donation may become available in a clinical practice setting in Stage 2. Mitochondrial donation is an exciting technology which provides hope to the many Australians touched by the devastating effects of mitochondrial disease. However, it is important that more research is conducted into its safety and efficacy, as well as the long-term implications of its use. As is often the case with groundbreaking technologies such as this, the laws and policies lag behind the science. The passing of Maeve’s Law is only the start of what will be a long journey to the successful implementation of mitochondrial donation in Australia. The next ten years will be crucial in setting a precedent for how our society approaches the use of other novel genetic technologies in healthcare. The question is no longer ‘should we use mitochondrial donation?’ but ‘how can we implement this technology in a safe and ethical way?’ References Cleveland Clinic. (2023). Mitochondrial Diseases . https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases Garcia, I., Jones, E., Ramos, M., Innis-Whitehouse, W., & Gilkerson, R. (2017). The little big genome: The organization of mitochondrial DNA . Frontiers in Bioscience (Landmark Edition), 22, 710. Klopstock, T., Klopstock, B., & Prokisch, H. (2016). Mitochondrial replacement approaches: Challenges for clinical implementation . Genome Medicine, 8(1), 1-3. Maruszak, A., Adamczyk, J. G., Siewierski, M., Sozański, H., Gajewski, A., & Żekanowski, C. (2014). Mitochondrial DNA variation is associated with elite athletic status in the Polish population. Scandinavian Journal of Medicine & Science in Sports, 24(2), 311-318. Mito Foundation. (2023). Maybe Mito Patient Factsheet. https://www.mito.org.au/wp-content/uploads/2019/01/Maybe-Mito-Patient-Factsheet1.pdf Mito Foundation. (2023). Mitochondrial Disease: The Need For Mitochondrial Donation . https://www.mito.org.au/wp-content/uploads/2019/01/Brief-mitochondrial-donation-2.pdf Monash University. (2023). Introducing Mitochondrial Donation into Australia. The mitoHOPE Program. https://www.monash.edu/medicine/mitohope National Health and Medical Research Council. (2023). Mitochondrial Donation. https://www.nhmrc.gov.au/mitochondrial-donation Nurk, S., Koren, S., Rhie, A., Rautiainen, M., Bzikadze, A. V., Mikheenko, A., & Phillippy, A. M. (2022). The complete sequence of a human genome . Science, 376(6588), 44-53. Sequeira, A., Martin, M. V., Rollins, B., Moon, E. A., Bunney, W. E., Macciardi, F., & Vawter, M. P. (2012). Mitochondrial mutations and polymorphisms in psychiatric disorders. Frontiers in Genetics, 3, 103. Wallace, D. C. (2010). Mitochondrial DNA mutations in disease and aging. Environmental and Molecular Mutagenesis, 51(5), 440-450. Wicked back to

< Back to Issue 4 Interviewing Dr Karen Freilich by Rachel Ko 1 July 2023 Edited by Caitlin Kane Illustrated by Pia Barraza Science in the real world is never straight-forward. The realm of medicine and health is particularly intricate, riddled with myths and marvels. This makes the healthcare journey a difficult one to navigate, both for the patient, and for the provider. It is undeniably a field where an ever-evolving myriad of factors makes the bedside experience vastly different to the textbooks. In my first year studying medicine, I am constantly realising that a strong understanding of the fundamentals is often a saving grace, while learning to dispel the mirage of medicine as a simple science. Enter Humerus Hacks , a podcast recommended to me in the first week of medical school by peers who had walked the treacherous road before. A guiding light in the murky waters of medical education, Karen and Sarah’s playful banter lays out high-yield medical content with catchy mnemonics and gracious advice. In this interview, we had the special opportunity to talk to Dr Karen Freilich, one of the hosts of Humerus Hacks , about her journey in medicine so far as a young GP, and the story of how she created a podcast that masters the art of science communication in a perfect marriage of education and entertainment. Tell us about your journey with science, and your career so far. I’ve just completed my GP Fellowship training after about 12 years of study. It’s a relief to be done —medicine is a long slog! I’ve had a brilliant time and been fortunate to take part in exciting studies. I took some time off clinical medicine to complete a Masters of Reproductive and Sexual Health Research in London (LSHTM) as well as completing a Diploma of Obstetrics (DRANZCOG). I currently teach at the University of Melbourne’s Medical School as a tutor in Sexual Health, and write and train high school sexual health educators through Elephant Ed. I work as a GP most days of the week, in a clinic with a focus on sexual and reproductive health and I’m a proud medical abortion and contraception provider. I’m also fortunate to work at Monash in the Sexual Medicine and Therapy Clinic, and work together with the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). It’s a tricky balance wearing a number of hats, but I love the diversity. Unsurprisingly everything I do is focused in sexual and reproductive health through clinical work, education, advising and science communication. My career is certainly tailor-made to my interests and passion, and took quite some time to get to this point! I love being able to educate on both a one-on-one and broader level on sexual and reproductive health care, particularly through a reproductive justice lens. What was the inspiration behind Humerus Hacks ? In the early years of medical school, my mate Sarah and I used to spend hours and hours trying to memorise different antibiotics and the differences between them. It felt incomprehensible to have to learn not only a new science, but an entirely new language behind it. It felt like a Duolingo course! So in order to scrape through exams, we made silly little stories to try and remember the differences between gentamicin, amoxicillin etc.. Fast forward a few years and Sarah and I ended up running a weekly study group for the year below us, filled with our mnemonics and silly stories. We developed a bit of a cult following (if I say so myself!). It seemed there was a real appetite for otherwise tedious and dry medical education made fun and entertaining. In final year, we both ended up on placements requiring huge drives. We turned to podcasts for ‘edutainment’ — and found there simply were none. So we did what everyone in 2016 was doing, bought a microphone and recorded our own. We were a bit mortified at the start and convinced we wouldn’t get internships if our future employers heard us swearing and being inappropriate online, so we hid our faces and were anonymous with our names. Fortunately it turned out we had nothing to be nervous about, and Humerus Hacks was a hit. Sarah is a musical genius and recorded the intro song with her band. It’s now been over 50 episodes and over 150,000 downloads. We’re often in the iTunes Medical Podcasts Top 10! The inspiration has and always will be pure study laziness — trying to make studying more interesting, fun and accessible and ultimately, more memorable. What is the process of developing and recording an episode? Me, Sarah, or another co-host or friend (Callum, Bridget, Robbie and Dan to name a few!) sitting on a couch with a microphone and chinwagging about a topic. If we’re lucky, maybe some prep. I’d love to suggest it’s more fancy than that! I have brilliant colleagues who play an integral role. Alex edits our episodes and does a brilliant job. And Bella creates fantastic art for the episodes. Sometimes I play around on Canva too for some social media. Shout out as well to our friends who helped with some graphic design and audio. It’s definitely a team effort, and so many people to thank for their ongoing contributions and support. What is your relationship with your audience like? Our audience sends us messages and emails all the time — even if we haven’t made an episode in months! It’s a joy to receive any messages and warms our hearts every time. We get the most delightful and lovely messages. We also get a lot of requests which I wish we could keep up with more, the irony of doing our own exams over the past few years! We try to respond to all messages and keep up with requests. Knowing that our silly little mnemonics has helped anyone with exams is a huge joy. How has science communication evolved since you began? Mnemonics have been a huge part of medicine for a very long time. In fact, I have my uncle’s Medical Mnemonic book from 1958! Some of them have aged terribly, unsurprisingly, but many we still use to this day. So, we are far from inventing the wheel. In saying that, the boom of social media and podcasts over the past few years has lent itself to subspecialised Instagram pages, YouTube channels and more podcasts than I could have ever imagined. Making medical education (and science communication) fun has become much more mainstream and accepted as a genuine study tool. Who knew, making dry education entertaining actually works…! What has been the biggest challenge in your science communication journey? Hands down, time. I run Humerus Hacks with a group of excellent friends and colleagues, but we all happen to be medical students or doctors. Unsurprisingly, it means we are all always bogged down with shift work, exams, and burn out. Humerus Hacks is a labour of love. So we make an effort if and when we can, without any time pressure. I wish we had more time! What role would you say science communication plays in your daily practice? I’m a GP with a special interest in sexual medicine as well as a sexual health tutor for medical students. I also write and train individuals to run high school sexual health education. I’ve also been fortunate to be a guest host on ABC Breakfast Radio under ‘Doctor Breakfast’ providing science communication for a number of medical topics. So, it plays a huge role in my daily practice! I particularly enjoy the interplay of small scale science communication through one-on-one patient interactions compared with larger scale communication through radio, teaching and podcasts. They balance each other really well, and I enjoy the individualised, tailored approach whilst simultaneously thinking of the broader public health messaging. What role would you say science communication plays in society generally? There is so much misinformation floating around. As a huge fan of social media and TikTok myself, I can see how these avenues can be both a wonderful source of information but simultaneously promote unnuanced, oversimplified and often blatantly incorrect health messaging. Social media (including podcasts) provides a really accessible, often free avenue for science information that is otherwise inaccessible. However, we have a responsibility to ensure the information is correct, up to date, and safe. Social media loves a quick snap messaging, but science is almost always more nuanced and complex. A 30 second TikTok often unsurprisingly misses the mark! So, accurate and accessible science communication is the key — the hard thing is making it fun and interesting. What are your immediate goals in science communication this year, and what do you hope to achieve in science communication in the long-term? Great question! I am thoroughly enjoying my career balance at the moment. It’s a great mix of GP clinic, sexual medicine and therapy clinical work, sexual health teaching, and radio/podcasting. I’d love to make more Humerus Hacks episodes now that I’ve finished my own training and have (hopefully) both more knowledge and time! I’ve put together a SPHERE Sexual and Reproductive Health podcast focusing on upskilling clinicians to provide medical abortion and contraception in primary care. I am also loving radio work and would love to keep going with this. I may or may not delve into the TikTok world… watch this space! Long term, hopefully ongoing science communication in the field of sexual and reproductive healthcare. What advice would you give to students exploring the world of science communication? Social media is a game changer that had only just begun when I was a student. TikTok, Instagram etc all provide a free and accessibly way to both gain knowledge and skills, and to educate others. Science students in all disciplines have such incredibly knowledge and insight, and if you’re interested, there’s a willing and enthusiastic audience out there. The phrase ‘see one, do one, teach one’ forever rings true. Teaching and providing science communication helps your own education, and has always been my favourite learning tool. Finally, and I cannot emphasise this enough, being a student is long, tedious, and exhausting. Enjoy the process and look after yourself and your colleagues as a priority! ------------------- It is undeniable that Humerus Hacks is a project succeeding on its steadfast mission to uncover the mirage of medicine. Through a blend of education and entertainment, it reveals the intricate realities of science in health, as a complex and ever-changing landscape that demands a strong foundation of knowledge and willingness to adapt. We extend our heartfelt gratitude to Dr Karen Frielich, for not only agreeing to talk to us, but also for all of her work to demystify the healthcare journey, both for the professional, and for the patient. You can check out 'Humerus Hacks' on Spotify , on Apple Music , or online! Previous article Next article back to MIRAGE

Where The Wild Things Were By Ashleigh Hallinan We may consider ourselves to be the most advanced species on the planet, but this has come at the cost of the natural world. Delve into this article to gain insight into how ecosystem restoration plays a role in nature-based solutions for biodiversity loss and climate change mitigation globally. Edited by Niesha Baker & Caitlin Kane Issue 1: September 24, 2021 Illustration by Jess Nguyen The scale of threats posed to humanity and the natural world is confronting and difficult to grasp. The natural world is being pushed towards its brink, but it’s not too late to act. Ecosystem restoration plays an important role in nature-based solutions for biodiversity loss, food insecurity, and climate change. Global discourse and action also need to continue moving towards greater acknowledgement of Traditional Owners and local communities in biodiversity conservation efforts and climate change resilience. Ecosystem degradation is an accelerating calamity of our own making. A recent study from Frontier Forest and Global Change shows that humans have altered 97 per cent of the Earth's land, meaning a mere 3 per cent of land remains untouched, or ‘ecologically intact’ (1). ‘Ecosystem degradation’ refers to the loss of natural productivity from environments as a result of human activity. Many of the world’s ecosystems have been pushed beyond the point of unassisted self-recovery due to a mix of stressors, most of which are human-induced. Ecosystems are made up of interacting organisms and the physical environment in which they are found, so disturbing the balance of an ecosystem can be disastrous for all the living things relying on it, including humans. If trends of ecosystem degradation continue, 95 per cent of the Earth’s land could become degraded by 2050 (2). In this scenario, we would face irreversible damage. But how does this affect you and me? Beyond the role ecosystem degradation plays in accelerating climate change and the loss of countless species from our planet, its impact on ecosystem services is also of great significance. Ecosystem services are the benefits humans derive from the natural environment. These range from the oxygen we breathe to aesthetic appreciation of the natural environments around us. These services are necessary for life to exist on Earth, and without them, our quality of life would decline drastically. Luckily for us, humans are capable of learning from their mistakes, and efforts are being made to address these global concerns. Ecosystem restoration is the process of reversing ecosystem degradation to regain environmental health and sustainability. This often involves re-introducing plant and animal populations that may have been lost, as well as restoring their habitats. Abandoned farmland is one example of where this can be achieved. Farmlands are one of the most vital ecosystems in sustaining humankind. Not only do they provide us with food, but they are also home to a variety of organisms within and above the soil. Many of these organisms play a critical role in soil health, which is essential for agriculture. Agriculture has transformed human societies and fuelled a global population that has grown from one billion to almost eight billion people since around 1804 (3). This has had significant consequences on natural systems worldwide, particularly as farmland has continuously expanded into surrounding landscapes. Agroecosystems now cover around 40 per cent of Earth's terrestrial surface (4). However, despite a growing demand for food due to the world’s rapidly increasing population, the amount of farmland being abandoned outweighs the amount of land being converted to farmland (5). There are an estimated 950 million to 1.1 billion acres of deserted farmland globally (6). This unproductive farmland could be converted to meet conservation goals and mitigate the impacts of climate change. For example, farmland could be regenerated with carbon-capturing forests. These would contribute to sequestering large amounts of anthropogenic CO2, water retention, soil fertility, and providing habitats for a variety of organisms. Abandoned farmland could also be re-established with native vegetation to provide habitats for animals. This was the case at the Monjebup Nature Reserves, located in south-west Western Australia (WA) on Noongar Country, established by Bush Heritage Australia between 2007 and 2014 (7). Despite being a biodiversity hotspot, animals and plants in the Monjebup Nature Reserves have faced many threats. These were mainly in the form of introduced species and land clearing for agriculture. Decades of land clearing resulted in a transition from deep-rooted woody vegetation systems to shallow-rooted annual cropping systems across the south-western Australian landscape. This caused a decrease in natural habitats and accumulation of salt in soil and water, which contributed significantly to biodiversity loss. In 2007, Bush Heritage Australia secured the Monjebup Nature Reserves in a bid to establish important conservation areas. Since then, they have restored nearly 1,000 acres of cleared land in the north of the Reserve (8). An important contributor to the success of this project was Indigenous knowledge, which reflects a long history of close connection with the land. These unique human-land relationships provide opportunities for learning in environmental research, particularly regarding land management and sustainability. The Monjebup Nature Reserves now protect a significant patch of native bushland on the land of the Noongar-Minang and Koreng people. This has been critical in restoring the heavily cleared landscape between WA's Stirling Ranges and Fitzgerald River National Parks, reconnecting remnant bush in the south with that of the Corackerup Nature Reserve further north. It has also provided habitat for vulnerable animal species such as the Malleefowl, Western Whipbird, Carnaby's Cockatoo, and Tammar Wallaby. Local knowledge plays a critical role in re-introducing plants and animals by identifying species suitable to particular environments. In the Monjebup Nature Reserves, re-introduction of native plants involved research on local plant communities and soil conditions in immediately surrounding areas. This research also involved communication with Traditional Owners who had used the area for gathering raw materials, food processing, hunting, stone tool manufacturing, and seasonal movement over millennia (9). Seeds of suitable flora were then collected in and around the site for the restoration works. It is crucial that consultation with Traditional Owners, like that seen in the Monjebup Nature Reserves project, becomes a more common practice. An estimated 37 per cent of all remaining natural lands are under Indigenous management (10). These lands protect 80 per cent of global biodiversity and the majority of intact forests, highlighting the value of Indigenous knowledge (11). We have left ourselves a challenging yet attainable goal. Raising public awareness on the importance of ecosystems and improving our knowledge on the interconnectedness of the natural world will be key to decreasing our impacts on Earth's incredible ecosystems. In March 2019, the United Nations General Assembly announced 2021 to 2030 as the Decade on Ecosystem Restoration (12). El Salvador’s Minister of Environment and Natural Resources, Lina Pohl, proposed the creation of the Decade in a speech to the General Assembly. More than 70 countries from all latitudes quickly jumped on board, committing to safeguarding and restoring ecosystems globally (13). 2030 also happens to be the deadline for the Sustainable Development Goals, which are a collection of 17 interlinked global goals designed to address the global challenges we face, and provide a ‘blueprint to achieve a better and more sustainable future for all’ (14). 2030 is also the year scientists have identified as the last chance to prevent catastrophic climate change (15). As part of the Decade on Ecosystem Restoration, the United Nations has called for countries to make the pledge to restore at least 2.5 billion acres of degraded land - an area larger than China (16). This will require international cooperation, led by the UN Environment Programme and the Food and Agriculture Organisation. Humans have an essential role in halting and reversing the damage that has been caused so far. Ecosystem restoration is not a quick or easy process. It requires deep, systematic changes to the economic, political, and social systems we currently have in place. But the natural world is finite, and it is important we continue taking steps towards a more sustainable future. References: 1. Plumptre, Andrew J., Daniele Baisero, R. Travis Belote, Ella Vázquez-Domínguez, Soren Faurby, Włodzimierz Jȩdrzejewski, Henry Kiara, Hjalmar Kühl, Ana Benítez-López, Carlos Luna-Aranguré, Maria Voigt, Serge Wich, William Wint, Juan Gallego-Zamorano, Charlotte Boyd . “Where Might We Find Ecologically Intact Communities?” Frontiers in Forests and Global Change 4 (15 April 2021): 1-13. https://doi.org/10.3389/ffgc.2021.626635. 2, 4. Scholes, Robert, L Montanarella, Anastasia Brainich, Nichole Barger. “The Assessment Report on Land Degradation and Restoration: Summary for Policymakers”. Bonn, Germany: Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), 2018. https://ipbes.net/sites/default/files/2018_ldr_full_report_book_v4_pages.pdf 3. Food and Agriculture Organisation of the United Nations,“FAOSTAT”, Accessed 8 September 2021, http://www.fao.org/faostat/en/#home . 5, 6. Yang, Yi, Sarah E. Hobbie, Rebecca R. Hernandez, Joseph Fargione, Steven M. Grodsky, David Tilman, Yong-Guan Zhu, Yu Luo, Timothy M. Smith, Jacob M. Jungers, Ming Yang, Wei-Qiang Chen. “Restoring Abandoned Farmland to Mitigate Climate Change on a Full Earth”. One Earth 3, no. 2 (August 2020): 176–86. https://doi.org/10.1016/j.oneear.2020.07.019. 7, 8, 9. Bush Heritage Australia,“Monjebup Nature Reserves (WA),” Accessed 8 September 2021, https://www.bushheritage.org.au/places-we-protect/western-australia/monjebup . 10. Garnett, Stephen T., Neil D. Burgess, Julia E. Fa, Álvaro Fernández-Llamazares, Zsolt Molnár, Cathy J. Robinson, James E. M. Watson, Kerstin K.Zander, Beau Austin, Eduardo S. Brondizio, Neil French Collier, Tom Duncan, Erle Ellis, Hayley Geyle, Micha V. Jackson, Harry Jonas, Pernilla Malmer, Ben McGowan, Amphone Sivongxay, Ian Leiper. “A Spatial Overview of the Global Importance of Indigenous Lands for Conservation‘. Nature Sustainability 1, no. 7 (July 2018): 369–74. https://doi.org/10.1038/s41893-018-0100-6 . 11. Ogar, Edwin, Gretta Pecl, and Tero Mustonen. ‘Science Must Embrace Traditional and Indigenous Knowledge to Solve Our Biodiversity Crisis’. One Earth 3, no. 2 (August 2020): 162–65. https://doi.org/10.1016/j.oneear.2020.07.006. 12, 13, 14, 15. United Nations Environment Programme and the Food and Agriculture Organization of the United Nations, “About the UN Decade,” Accessed 8 September 2021, http://www.decadeonrestoration.org/about-un-decade . 16. United Nations Environment Management Group, “The UN Sustainable Development Goals – UN Environment Management Group”, Accessed 8 September 2021, https://unemg.org/our-work/supporting-the-sdgs/the-un-sustainable-development-goals/ .

< Back to Issue 8 Mental Time Travel: How Far Can I Remember? by Sophie Potvin 3 June 2025 Edited by Kara Miwa-Dale Illustrated by Elena Pilo Boyl Trigger warning: This article mentions mental illness and trauma... If at any point the content is distressing, please contact any of the support services listed at the end of the article. Mental Time Travel: How Far Can I Remember? I like to go back in time. Travel to places I have been to. See faces I have not seen in a while. Meet my younger self. See the world as new. As every memory slips through my fingers, I write the pages hoping not to forget anymore. How far can I remember? She opens her eyes, her head hammering as she puts her glasses on to ease the pain. The room is uncommonly empty; it almost echoes her thoughts. In the centre of the room is a teal box in the shape of a seahorse with the label “Recreate your favorite scenes!” This box is the hippocampus — the seahorse shaped structure that is found in the medial temporal lobe (MTL) of the brain — that encodes the space and context of a memory. It is essential for associating information from sensory cortices, binding it to the context and sending the information to the rest of the brain. Confusion makes its way through her mind as a sheet appears on top of the box like magic. It says “Pick a book, read the recipe, and put the right items in the teal seahorse box.” Did you know that every memory is a reconstruction — that a scene is made up every time you remember an event? She does not know it yet, but she will certainly learn that when these fragile pieces are brought back together in the hippocampus, she can relive a moment. Endless shelves of books and objects suddenly appear in rows and columns just like a grid, a playground. She notices that the shelf in front of her, the one wearing the tag “2025”, is half empty. The one next to it, with the sticker “2024”, is full. She walks through a few rows, imagining what secrets are held in the books and between their lines. Her hand chooses the blue book “Costa Rica: Camaronal” and flips through the pages. These words are written in her handwriting: “starry sky, moonlight, high tide, sunburn, hammocks, turtles, beach, sunrise, sand, meetings, deck of cards”. She finds the objects at the end of the shelf and runs to the teal box. She can feel the air sticking to her skin, and hear the waves crashing on the shore. It is the power of mental time-travelling; recollecting episodes of her life. The objects disappear from the box, the feeling goes away, but she wants more. She runs like a child and stops in front of the “2019” shelf to experience a Dungeons & Dragons Friday night with her high school friends. She seems surprised to see that the list of objects for that memory is so short. She brings back the objects, but the hippocampus can only make her travel to a blurry place. Moments from six years ago are already a faint memory. Her curiosity takes over when she wonders how far she can remember. She finds the recipe of her last night of summer camp in 2013: “‘I Love It (feat. Charli XCX)’, dance, lights”. She sighs when looking at the short list because she hates to forget, she really does. Her heart starts beating fast, is her memory failing her? How bad can it be? She continues to wander down the alleys, but her eyes are tearing up as she thinks how she might be nothing without her memories; only a few objects are left, most of them did not stand the test of time. As she reaches her early years, she notices the label “cognitive self” and the floor colour changes under her feet. The cognitive self is a knowledge structure that helps to integrate and bind memories from personal experiences. These experiences are added to the evolving self-consciousness. Along with neurobiological changes in brain structures and the acquisition of language, this can help to make them last longer and shape a sense of being. At least she knows that she is someone. Intrigued, she brings all the objects she can find in the “2004” shelf, but there is no recipe to guide her, no story to be made. All the pieces are in the box, but nothing happened; no feelings, no breeze, no music. The memories that were made in the first two years of her life, were taking the form of beliefs, habits or procedures. There is nothing she can consciously recollect. The inability to consciously recollect memories from one’s own early years of life is also known as infantile amnesia. While waiting for the hippocampus box to make its magic, she loses patience, hits the box a few times begging it to give her back her memories. She does not know that it is universal: cognitively healthy adults and nonhuman species like mice or birds experience infantile amnesia. During infantile neurodevelopment, humans and other species like birds and rats undergo a critical period of learning for memory. Throughout critical periods, different functions like language, sensory functions or memory—in this case, the hippocampal memory system—mature with experience. The presence of specific stimuli are essential for functional development because without it, its competence will forever be impaired. Her hippocampal system must have been responsive to a great amount of experiences to ensure its maturation. It is working as it should. Inside of her, a void of hopelessness sits in her chest because she feels like her brain is failing her; it is her against biology. She looks for clues in the fuller shelves wondering where the memories could be hidden. Were memories ever stored or created? They were created, but any information was stored in latent form due to the immature mechanisms of the young hippocampus. They can get activated under particular circumstances, but not recollected consciously. It is a failure in memory retrieval, not a failure in memory storage. She finds a trap on the green floor thinking pieces might be hidden in the basement. Events leave traces—whether they are full-fledged memories or only remnants—and during the critical period, deleterious experiences can have lifelong consequences on behaviour, affection and the development of psychopathologies. The trap is too small for her to enter, warning her she should not enter this road. She understands that some things are not meant to be found. These moments she cannot recollect are hiding in plain sight; they are embedded in her. Somehow, she learned from them. For a second, she hates the teal seahorse box. Then, she looks at it in awe, terrified and amazed at peace with herself. The hippocampus box starts to turn and Joe Dassin plays. Threads of lights bind items and books together. It takes her back as far as she can go. Feelings. Moments. People. Episodes. Magic. Her. She opens her eyes, teal ink pen in her hand as she is writing these words. Some things I will never remember; My first steps on my two feet. The first time I met my sisters. Just old stories or memories handpicked from a field of photos; And in the end, I would be a stranger. Support resources Grief Australia: counselling services, support groups https://www.grief.org.au/ga/ga/Get-Support.aspx?hkey=2876868e-8666-4ed2-a6a5-3d0ee6e86c30 Griefline: free telephone support, community forum and support groups https://griefline.org.au/ Better Health Channel: coping strategies, list of support services, education on grief https://www.betterhealth.vic.gov.au/health/servicesandsupport/grief Beyond Blue: understanding grief, resources, support, counselling https://www.beyondblue.org.au/mental-health/grief-and-loss Lifeline: real stories, techniques & strategies, apps & tools, support guides, interactive https://toolkit.lifeline.org.au/topics/grief-loss/what-is-grief?gclid=CjwKCAjw-KipBhBtEiwAWjgwrE1pJaaBabh3pT_UR0PlVBZTFMEA26NVJe2ue8sqCF0BLg2rMI4i2xoCp5IQAvD_BwE Reach Out Australia: coping strategies https://au.reachout.com/articles/working-through-grief?gclid=CjwKCAjw-KipBhBtEiwAWjgwrKXLb9w-wXXVLIbhZDkPumIF6ebe-0Pk77Hv7-cK4dLDrHJxCRkyRBoC2B4QAvD_BwE Find a Helpline: for international/country-specific helplines https://findahelpline.com/ References 1. Li S, Callaghan BL, Richardson R. Infantile amnesia: forgotten but not gone. Learn Mem [Internet]. 2014, March [cited 2025 Mar 27]; 21(3):135–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929851/ 2. Donato F, Alberini CM, Amso D, Dragoi G, Dranovsky A, Newcombe NS. The Ontogeny of Hippocampus-Dependent Memories. J Neurosci [Internet] . 2021, Feb 3 [cited 2025 Mar 27]; 41(5):920–6. Available from: https://doi.org/10.1523/JNEUROSCI.1651-20.2020 3. Howe, ML. Early Childhood Memories Are not Repressed: Either They Were Never Formed or Were Quickly Forgotten. Topics in Cognitive Science [Internet]. 2022, July 11 [cited 2025 Mar 27]; 16(4): 707–717. Available from: https://onlinelibrary.wiley.com/doi/10.1111/tops.12636 4. Bauer PJ, Amnesia, Infantile☆. In: Benson JB, editor. Encyclopedia of Infant and Early Childhood Development (Second Edition) [Internet]. Oxford: Elsevier; 2020. p. 45–55 [cited 2025 Mar 27]. Available from: https://www.sciencedirect.com/science/article/pii/B9780128093245212078 5. Stoencheva B, Stoyanova K, Stoyanov D. Infantile Amnesia can be Operationalized as a Psychological Meta Norm in the Development of Memory. JIN [Internet]. 2025, Feb 10 [cited 2025 Mar 27]; 24(2):1–11. Available from: https://www.imrpress.com/journal/JIN/24/2/10.31083/JIN25889 Previous article Next article Enigma back to

< Back to Issue 8 The Lost Link: A Mystery in Evolution by Eymi Gladys Carcamo Rodriguez 3 June 2025 Edited by Ciara Dahl Illustrated by Anabelle Dewi Saraswati The Enigma of Evolutionary Gaps Few scientific mysteries have captured the public imagination as deeply as the search for the “missing link”, a hypothetical species that bridges the evolutionary gap between ancient primates and modern humans. For generations, scientists and the public alike imagined that a single fossil discovery would neatly connect our distant ancestors to Homo sapiens . Yet as our understanding of evolution has grown, it has become clear that the story is far more complex. Rather than a single missing puzzle piece, human evolution is now regarded as a tangled web of interconnected species, with many branches and dead ends (1). The Myth of the Missing Link Historical Context The term “missing link” surged in popularity during the 19th century, following Charles Darwin’s ground-breaking work on the theory of evolution. Early evolutionary theorists envisioned a linear process: one species evolving directly into another, with the “missing link” as the crucial fossil that would clearly show how humans evolved from apes. This view persisted in popular culture; even as scientific evidence began to suggest otherwise. In Victorian England, the idea of a missing link became a cultural phenomenon. Fossil discoveries–like the first Neanderthal skulls–were hailed as evidence of humanity’s ascent from apes. However, modern evolutionary biology has revealed that evolution is not linear, but a branching tree, filled with dead ends and interwoven paths (2). The Fossils: Pieces of a Complex Puzzle Despite a shift in scientific thinking, fossil discoveries remain central to our understanding of human origins. Iconic finds such as Australopithecus afarensis (“Lucy”), Homo habilis , and Homo naledi have each provided snapshots of different stages in human evolution. Yet, none of these fossils fit the mould of the elusive “missing link” (3, 4). Australopithecus afarensis (c. 3.9–2.9 million years ago) walked upright and had both human-like and ape-like features. Lucy’s skeleton suggests a close connection to the human lineage, but her brain size and cranial features remain distinctly primitive. Homo habilis , one of the earliest members of our genus, shows evidence of tool use and increased brain size, but still differs significantly from modern humans. These fossils demonstrate that human evolution was not a simple progression from one species to the next. Many early hominins coexisted for millions of years, and some, like Homo habilis , may have lived alongside more primitive ancestors such as Australopithecus . The idea of a singular “missing link” is now viewed as a historical artifact, replaced by the recognition that human evolution is a mosaic, with branches and offshoots that defy easy classification. The Persistent Gaps Despite advances in palaeontology and genetics, many questions about human evolution remain unanswered: Why did early human brains grow so rapidly? Around 2 million years ago, our ancestors experienced a dramatic increase in brain size. The causes-whether tool use, diet, or social complexity-are still debated. How much did early humans interbreed with other hominins? Ancient DNA reveals that Homo sapiens interbred with Neanderthals and Denisovans, raising questions about the scale and impact of these interactions. Why did Homo sapiens spread so quickly across the globe? Our species began migrating out of Africa roughly 60,000 years ago, adapting rapidly to new environments. The role of culture, technology, and innovation in this expansion is still being explored (5). These questions highlight the complexity and dynamism of human evolution, suggesting that the process was shaped by a mix of biological and environmental factors. DNA: The New Frontier in the Search for the Missing Link While fossils have provided crucial insights, the latest breakthroughs come from genetic research. Advances in DNA sequencing allow scientists to peer into the ancient past in unprecedented ways. One of the most surprising findings is the discovery of a “ghost population” – an ancient group whose DNA is present in modern humans, but whose fossils have never been found. These genetic traces suggest that entire populations once co-existed and interbred with Homo sapiens , yet left no physical evidence behind. This challenges the traditional fossil-focused search for the missing link and highlights the importance of genetic inheritance in understanding our origins (6). “The idea that entire populations could have existed and disappeared without leaving any fossil evidence challenges our traditional search for the missing link. It suggests that the story of human evolution is not just about the fossils we find, but also about the genetic material we carry with us today” (7). The Real Missing Link: A Paradigm Shift The quest for a single missing link is now seen as outdated. Evolution is not a straight line but a complex web, with species branching, merging, and sometimes vanishing without a trace. Rather than a specific fossil, the “missing link” has become a symbol of our evolving understanding of what it means to be human. Each new discovery-whether in the fossil record or in our DNA-forces us to rethink our place in nature and the forces that shaped our evolution. Conclusion: The Journey of Discovery Continues The story of human evolution remains incomplete. Each new fossil and genetic breakthrough bring us closer to understanding our origins, but the mystery endures. The search for the missing link may never be resolved, and perhaps it is not meant to be. Instead, it is the ongoing process of discovery that enriches our understanding of who we are and where we came from. References Veldhuis D, Kjærgaard PC, Maslin M. Human Evolution: Theory and Progress. In: Smith C, editor. Encyclopedia of Global Archaeology. Cham: Springer International Publishing; 2020. p. 5317-30. Kjaergaard PC. 'Hurrah for the missing link!': a history of apes, ancestors and a crucial piece of evidence. Notes Rec R Soc Lond. 2011;65(1):83-98. Martinón-Torres M, Garate D, Herries AIR, Petraglia MD. No scientific evidence that Homo naledi buried their dead and produced rock art. J Hum Evol. 2024;195:103464. Schrein CM. Lucy: A marvelous specimen. Nature Education Knowledge. 2015;6(2). Chagi S. The Mosaic of Human Evolution: Challenging the Concept of a Singular ‘Missing Link’ World of Paleoanthropology2024 [Available from: https://worldofpaleoanthropology.org/2024/08/27/the-mosaic-of-human-evolution-challenging-the-concept-of-a-singular-missing-link/ . Sample I. Scientists find evidence of 'ghost population' of ancient humans: The Guardian Australia; 2020 [Available from: https://www.theguardian.com/science/2020/feb/12/scientists-find-evidence-of-ghost-population-of-ancient-humans . Banich MT. The Missing Link: The Role of Interhemispheric Interaction in Attentional Processing. Brain and Cognition. 1998;36(2):128-57. Previous article Next article Enigma back to

< Back to Issue 6 Editorial by Ingrid Sefton & Rachel Ko 28 May 2024 Edited by Committee Illustrated by Louise Cen Science craves fundamentals. Without a true appreciation of the basics, the most complex and elaborate theories will crumble. Both the natural and manmade worlds are meticulously crafted, full to the brim with nuances and modulations, from the laws of physics to the laws of democracy. There is, in our minds, an inextricable desire for classification, organisation, rationalisation. We are in a ruthless pursuit of understanding, striving to decompose the elemental origins of the world around us into fathomable pieces. What drives this urge to discern the building blocks of life? Perhaps, it is the belief that a bottom-up understanding of the laws governing the universe will afford us the ability to reconstruct and create. To know how to defy these laws, rebelling against constraints of the natural world. It is also conceivable that this desire stems from overwhelm. We may never truly understand the expanse of natural forces, cosmological phenomena and ubiquitous elemental power operating beyond any level of mortal control. By examining the microscopic, science becomes tangible. But in isolation, these atoms, elements, fragments of knowledge are just that: fragmented. Scientific understanding exists on a continuum, where the microscopic informs the macroscopic and is contextualised by time, place and culture. It leads one to wonder how exactly “science” should be conceptualised. There is no doubt many people conceive a certain rationality and procedure inherent to scientific progress. Yet, the idea of a specific methodology with the aim to uncover a particular truth is a relatively modern perception of science. Our yearning for understanding and knowledge, on the other hand, is anything but new. Knowledge systems adapt. We observe, we learn, we ask questions. Scientific method and controlled experimentation inform our understanding. But we are also human; inextricably driven by passion and curiosity and irrationality. Should science seek to exclude these values and forces guiding our intrigue? Elemental asks of its contributors to transform their perspective on scientific exploration and consider these different scales of understanding. Creation, destruction, classification and investigation are united in this issue, through the elements of Science. Join us as we dissect our world, from the most natural senses of the human state, to the most mysterious artificial elements of technological intelligence, and beyond. Come explore! Let us see what we can create. Previous article Next article Elemental back to

By Julia Lockerd Meet the New Kid By Julia Lockerd 23 March 2022 Edited by Caitlin Kane Illustrated by Quynh Anh Nguyen ‘Machines Enrol in Art Class!’ The title of the American Scientist article (1) I’m currently reading is droll take on the process of artificial intelligence (AI) learning. I imagine the first art class I ever attended had a robot classmate. “I want everyone to be very welcoming to our new student! Class this is DALL-E.” DALL-E’s name is a clever blend of surrealist painter Salvador Dali and robot character WALL-E. It is the most popular AI art platform in the world, as well as the face of a quickly expanding industry. The purpose of DALL-E is evident in its namesakes: simply, it is a robot that creates art. Artificial intelligence is described as "the science and engineering of making intelligent machines (2).” More specifically “machines that think like humans.” AI art is an application of this wider machine learning. In short, it is art created by a “thinking” computer. In mid-2022 the world of AI art became a monster of industry, with AI art platform Midjourney reporting over 12 million users since its launch in July 2022 (4). However, as with any quick advancement in technology, there are issues that come with the new power we’ve been given; there is a question we must ask ourselves: how far is too far? Back in art class, other students and I share uneasy glances as our strange companion clicks and whirrs behind his desk. I smile at him and reach out a hand. He breaks my finger and steals my Snoopy drawing right off my desk. Ouch. This is the first impression many artists had when AI art was first introduced. For years we had been told that truck drivers, factory workers and other industry roles would be fully automated in the future. This was an issue in itself, but an inevitability as the wheels of advancement turned over. Few expected that the creative industries would so quickly slip under the control of automated technology. With AI on the rise, many artists fear for their livelihoods, job prospects and their intellectual and creative property. To both create and vet the art for our personal viewing experience, AI uses tools called Generative Adversarial Networks (5). Imagine two little robots hunched over side-by-side desks. One’s job is to create images and fool the other into believing its art is original. If the second robot is fooled half the time, the first is performing as it should, creating art the public will believe is genuine. Fool me once. The definition of “genuine” art is vague at best and still under heavy debate. I believe that “genuine” is a feeling you get when you look at the art in front of you. It’s up to you to decide, can AI art ever really be genuine? Another issue arises from AI art: usually when you go to an art class, the teacher knows they’re teaching. My robot classmate begins to shuffle through its filing cabinet of pre-existing works made by humans. It’s been fed these images, paintings, photographs and learnt to reassemble the input as AI-created art (1,6,7). I can’t help but bristle in contempt as he examines my sketch of Snoopy and adds it to the ever-growing collection of “borrowed” art. As public use of AI continues to rise, we will inevitably have more ethically grey tundra to cross. In 2018 the Portrait of Edmund Belamy, sold for 432,500 USD at Christie’s Auction house. The controversy surrounding the piece stems from the fact that it was painted by an AI that had been fed 15,000 portraits from 20th century artists (7). Edmond De Belamy is not a real person, nor is the person who painted his portrait. Both are simply amalgamations of the people who came before. Which begs the questions, who deserves to be rewarded for this artistic feat? Is this painting even original? Once upon a time it was something genuine; it is up to us to decide how many times we can take the derivative of a piece of art before it loses its emotion. Or is it simply always the case that every artist takes inspiration from those who came before? When each creation is the derivative of a piece, it’s critical to examine what it’s deriving from. It is both fascinating and alarming that social biases have even made their way into the creative and malleable minds of machines. Dark-skinned people and hijab wearers have taken to social media to report their selfies, which they had run through an AI software, had returned distorted, warped or whitewashed (8). AI learns from the dataset that its human trainers provide, and it's important that we consider who and what are represented in that training. It is a strange sort of embarrassment to know that these machines and their endless learning have picked up on our shortcomings. In a world that already rejects difference and shame people for their deviation from unachievable standards, we have taught machines to do the same. Like a child passively taking up its parents' opinions. In this way, some consequences of our technological development aren’t so much AI art issues as they are societal issues. The only fix is to work to include and recognise all people in creative spaces so that machines can learn to think like all humans. Despite criticism and philosophising, we cannot stop the march of progress. AI will continue to advance, to become better at thinking and emulating us. Perhaps our responsibility will just be to give them something good to copy. As for traditional artists left behind by the AI advance? I believe we’ll be okay. We differ from machines, and there will always be something more rewarding than just an output. The joy is in the creation, the connection, and the humanity of art. Half of my art class is robots now, churning out hundreds of creations per second. I hold up a half-finished picture to my desk mate to see their smile. That moment of connection is why it’s worth staying until the end of the class. References Elgammal A. AI Is Blurring the Definition of Artist [Internet]. American Scientist. 2019. Available from: https://www.americanscientist.org/article/ai-is-blurring-the-definition-of-artist McCarthy J. What is AI? [Internet]. Stanford.edu. 2012. Available from: http://jmc.stanford.edu/articles/whatisai.html Midjourney Discord Interface [Internet]. docs.midjourney.com. Available from: https://docs.midjourney.com/docs/midjourney-discord Hughes RT, Zhu L, Bednarz T. Generative Adversarial Networks–Enabled Human–Artificial Intelligence Collaborative Applications for Creative and Design Industries: A Systematic Review of Current Approaches and Trends. Frontiers in Artificial Intelligence. 2021 Apr 28;4. Goodyear S. Why those AI-generated portraits all over social media have artists on edge [Internet]. CBC. 2022. Available from: https://www.cbc.ca/radio/asithappens/artificial-intelligence-ai-art-ethics-greg-rutkowski-1.6679466 Christie's. Is artificial intelligence set to become art’s next medium [Internet]. Christies.com. Christies; 2018. Available from: https://www.christies.com/features/A-collaboration-between-two-artists-one-human-one-a-machine-9332-1.aspx GANs. Edmond De Belamy, From La Famille de Belamy [Internet]. Caselles-Dupré H, Fautrel P, Vernier G, editors. original gilded wood frame. 2018. Available from: https://www.christies.com/lot/lot-edmond-de-belamy-from-la-famille-de-6166184/?from=salesummery&intobjectid=6166184&sid=18abf70b-239c-41f7-bf78-99c5a4370bc7 AI selfies — and their critics — are taking the internet by storm. Washington Post [Internet]. Available from: https://www.washingtonpost.com/technology/2022/12/08/lensa-ai-portraits/ Previous article Next article

The Intellectual’s False Dilemma: Art vs Science By Natalie Cierpisz The age-old debate once again resurfaces. How do art and science truly interact? Is one dependent on the other? How does the ‘art intellectual’ embrace science, and how does the ‘science intellectual’ embrace art? Is this all a meaningless debate anyway? Edited by Andrew Lim, Mia Horsfall & Hamish Payne Issue 1: September 24, 2021 Illustration by Casey Boswell The autumnal Melbourne wind whistles through the naked plane trees lining South Lawn, the sky is flat and grey. Two individuals who regard themselves and only themselves as ‘intellectual paragons’ are seated on a somewhat uncomfortable wooden bench, a perfect perch for people-watching, yet they are rather egotistical and notice only their own presence. One carefully places down their black coffee to light a hand-rolled cigarette; they are a liberal arts intellectual. As the wind grows stronger, the other tightly wraps a lab coat around themselves, and pushes a pair of wire-rimmed spectacles up their nose for the nth time. This would be our scientist. “So, are you still fooling around with your test tubes and pretty lights?” asks the liberal arts academic, cigarette hanging out the corner of their mouth. “If you mean, am I still investigating antiprotons using laser spectroscopy, then yes, indubitably so. How’s your fooling around with Hegel going?” replies the scientist, again pushing their glasses back up to a suitable height. The liberal arts intellectual is quick to retort the scientist’s trite remarks - they are in fact composing a Hegelian analysis of The Communist Manifesto, and not ‘fooling around’ by any means. The tension between the two self-professed intellectuals is building. The two appear to be fighting for dominance in their passive attacks on ego. So goes the age-old feud between the arts and the sciences. These two shallow characters play into the false dilemma that science and art are separate, distinct, alien. Two polar opposites. A total and unequivocal dichotomy. In all fairness, it is difficult to imagine many people will take this polarised a stance on the relationship between art and science. And now, as we delve into the complex relationship between the two domains, it should become clear that science and art are functionally interdependent (1), and considering art and science as totally separate is simply absurd. Let’s get back to our two feuding intellectuals. There seems to be much stereotypical disjunction between the two. But how does this translate to the true relationship between art and science? If the liberal arts intellectual and scientist were not so wrapped up in their self-interested ways, perhaps their gaze would slowly drift to the grandiose arches and imposing columns of the Old Quad. The harmonious form and mathematical ratios of these monuments are an enduring reminder of the architectural leaps and bounds made in the early 14th century, a blended pursuit of art and science. Ergo, we will head to one of the greatest paradigm shifts in Western history – the Renaissance. The Renaissance roughly spanned from the 14th to the 17th century and was a period of complete intellectual revolution – for both science and the arts (2). Everyone is familiar with Leonardo da Vinci, the great Renaissance artist. Less people know that he was also an inventor and a man whose artistic practice was heavily influenced by science (3). To ensure his paintings were as realistic as possible, Da Vinci dissected cadavers to better understand human anatomy, and studied optics and astronomy to perfect his use of space and form in paintings like The Last Supper. Likewise, scientists like Nicholas Copernicus and Galileo Galilei kickstarted a revolutionary paradigm shift towards the heliocentric model, their work in optics and astronomy being heavily reflected in artworks of the same era. Both science and art challenged what was for centuries prior considered the status quo. Source: Leonardo da Vinci, The Last Supper, 1498, tempera on gesso, pitch, and mastic, 460 cm × 880 cm, Wikipedia, https://en.wikipedia.org (4). This certainly isn’t a call for readers to head to the Melbourne General Cemetery and begin digging up specimens, nor to transfer to a double degree in fine arts and biomedicine. Instead, the point is more about how fruitful interaction between the two domains can be, and how one requires the other to flourish. Returning briefly to South Lawn, the snarky liberal arts intellectual continues looking bored and takes out their copy of The Myth of Sisyphus. Sitting directly opposite them the scientist has gone back to finishing the latest New Scientist podcast and calculating a quantum theory of gravity. We have seen that science can inspire art, but how can art inspire science? “The greatest scientists are artists as well.” (5) So said perhaps the most well-known scientist of the modern century. Not only did Albert Einstein develop the special and general theory of relativity (we won’t get into the mathematical specifics for both our sakes), he was also a talented violinist and pianist. Einstein often credited his artistic side for his success in science, testifying that, "the theory of relativity occurred to me by intuition, and music is the driving force behind this intuition. My parents had me study the violin from the time I was six. My new discovery is the result of musical perception.” (6) We have already seen how science prompts art to create new visions, and Einstein was no exception. His revolutionary ideas about space and time have been acknowledged as a prime artistic influence for Picasso’s arguably infamous Cubist style, as well as for the Surrealist art movement. (7) But the arts are not just confined to visual and musical expression. How about the area of expertise of our liberal arts friends? Liberal arts as they are known today, include sociology, literature, philosophy, psychology, politics, and more. The knowledge and, most importantly, critical thinking that is learnt through humanistic education is perhaps key to the future of science. As the world changes and evolves, humans must change and evolve with it, creating innovative solutions along the way. If we shift our focus to around the 1st century BCE, we will encounter what is widely regarded as the coining of the term artes liberales, or liberal arts. Roman statesman, scholar and writer Marcus Tullius Cicero wrote extensively about a wide array of topics, from politics and education to Stoic philosophy. “Artes liberales” roughly translates to “subjects worthy of a free person” - academic study that would enable one to actively participate in society (8). This curriculum consisted of a focus on seven key disciplines of rhetoric, geometry, grammar, music, astronomy, arithmetic, and logic. Liberal arts by nature are not the antithesis of science. From the crux of the artes liberales evolved the study of mathematics, physics, philology, history, and so on. Today we have reached a point where these seven disciplines have evolved and branched out so expansively that we have lost sight of the fact that our modern-day science and arts curriculums are sown from the same seed. Both science and art stem from the real world. Simply put, science is a lens into the study of this world and the inhabitants within it. Art is another lens into this complex system, providing a different but equally valuable perspective. Life is not binary, so neither should be our approach to studying it, and by virtue studying ourselves. Now is the time to embrace such transdisciplinary thinking. We need to bridge the gap between rigorous climate science facts and currently inadequate policy making, assess the ethics of the future of gene-editing, and ultimately become better thinkers. The combined intellectual strength of analytical thinking associated with science, where we learn how to test hypotheses, interpret data and draw valid conclusions; and the arts, where we learn critical thinking, how to develop arguments, how to understand a diverse audience, is necessary to keep humanity’s head above water as our world rapidly changes. Take for example the future of the CRISPR-Cas9 editing tool. This enzyme-based tool allows scientists to remove or add sections of DNA sequence in our genome, our code for life. With this ‘hand of God’ comes great responsibility. Collaboration needs to be made between scientific thinkers and humanistic thinkers to identify what type of robust legislation needs to be implemented to ensure ethical use of this tool. It is no longer a case of scientists working in isolation in underground bunkers. Scientists are making huge strides in research that extend to and greatly impact the wider community. Cases like CRISPR-Cas9 demand a lens from science and a lens from the arts in order to see the full picture – and in this case, to ensure the ethical and safe practise of a tool that has potential to save lives and improve individuals’ quality of life – but this only happens if science and art function in harmony. So back to you, the reader. Perhaps think about enrolling in that philosophy breadth subject next semester that your liberal arts friend raves about. Pick up that popular science book you have been eyeing off at Readings on Lygon St. Listen to that science podcast that keeps popping up on your Spotify homepage (The BBC’s The Infinite Monkey Cage is excellent). Pick up that paintbrush. Go visit Science Gallery Melbourne, a recent art scene addition affiliated with University of Melbourne – how fitting! This isn’t Romeo and Juliet, where you are either a Capulet or a Montague. Rather, this is a case of wave-particle duality, where an electron is both a wave and a particle, and you are both an artist and a scientist. As the typical Melbourne wind continues to pick up and the Old Arts clocktower strikes 7:00 pm, it appears the liberal arts intellectual just swapped their copy of The Myth of Sisyphus for the scientists’ copy of Brief Answers to the Big Questions. Looks like they’re making progress. References: 1. Richmond, Sheldon. “The Interaction of Art and Science.” The MIT Press 17, no. 2 (1984): 81-86. https://www.jstor.org/stable/1574993 . 2. History.com Editors. “Renaissance.” History.com. April 4, 2018. https://www.history.com/topics/renaissance/renaissance . 3. Powers, Anna. “Why Art is Vital to the Study of Science.” Forbes. July 13, 2020. https://www.forbes.com/sites/annapowers/2020/07/31/why-art-is-vital-to-the-study-of-science/?sh=7dfd8f8942eb . 4. Da Vinci, Leonardo. The Last Supper. 1498. Tempera on gesso, pitch, and mastic. 460 cm × 880 cm. Wikipedia. https://en.wikipedia.org . 5, 6. Root-Bernstein, Michelle. “Einstein On Creative Thinking: Music and the Intuitive Art of Scientific Imagination.” Psychology Today. March 31, 2010. https://www.psychologytoday.com/au/blog/imagine/201003/einstein-creative-thinking-music-and-the-intuitive-art-scientific-imagination . 7. Muldoon, Ciara. “Did Picasso know about Einstein?” Physics World. November 1, 2002. https://physicsworld.com/a/did-picasso-know-about-einstein/ . 8. Tempest, Kathryn. “Cicero’s Artes Liberales and the Liberal Arts.” Ciceronian on Line 4, no. 2 (2020): 479-500. https://doi.org/10.13135/2532-5353/5502 . Feynman, Richard, P. The Pleasure of Finding Things Out: The Best Short Works of Richard P. Feynman. New York: Basic Books, 2005. Science Gallery Melbourne. “Inspiring and Transforming Curious Minds.” Published 2021. https://melbourne.sciencegallery.com/what-we-do . White, Fiona. “Why art and science are better together.” The University of Sydney News. September 17, 2020. https://www.sydney.edu.au/science/news-and-events/2020/09/17/arts-and-science-better-together.html .

< Back to Issue 7 Peaks and Perspectives: A Word from the Editors-in-Chief by the Editors-in-Chief 22 October 2024 illustrated by Ingrid Sefton In geometry, an apex may refer to the highest point of a solid figure, such as a pyramid. Move to the fields of ecology and evolution, and we find apex predators, overseeing population dynamics atop of the food chain. We too find ourselves situated at an apex position in society – observing, experimenting with, and utilising the world at our feet for scientific innovation and headway. Common amongst these apexes in science is unsurprisingly the emphasis on reaching soaring heights and breathtaking summits. We strive to reach these peaks, endpoints that are perceived to signal scientific greatness and knowledge. We create, we innovate, we explore – all with this vision in mind. Yet, this is not, or rather, should not be the “why” for scientific endeavour. Implicit in reaching the highest point of something is the notion that there is no further to climb. That upon reaching an apex, all that remains is to precariously balance upon this peak and hope not to misstep, tumbling down from great heights. Scientific curiosity and a yearning to understand the science underpinning our existence is not about reaching the envisioned apex. It is instead defined by the steps climbed by us and our predecessors in our journey towards discovery, and in turn, the steps that remain untrod and paths that remain uncharted. The routes we are yet to take will be forever changing. Piloted by the evolving foci of our society, where and how we may next seek to innovate remains undetermined. Infinite possibilities abound. With a birds-eye view, Apex visualises the new levels of human-tech connectivity, ills of antimicrobial resistance, and the fringes of outer space that loom on the horizon; with it, encouraging readers to envisage where the next steps may lie. Yet alongside these perspectives of the expansive, limitless world, Apex invites reflection and hypotheticals. Taking time to pause from the unfaltering upward march of innovation, this issue embraces the breathtaking view of where we are now. Apex guides us to consider time-old traditions and technicalities from a new perspective, celebrating those who have paved the way to the peaks of modern science. Wandering within, across and between disciplines of Science, it is these ruminations along the way that enrich the journey. After all, what is scientific advancement without knowing what we do not know? In the words of Sir Isaac Newton, it is by standing on the shoulders of giants that we hope to see further. So come along, and revel in the expansive view. Let the heights of scientific innovation inspire you, but don’t let such peaks constrain you. Previous article Next article apex back to

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

< Back to Issue 7 Timeless Titans: Billionaires defying death by Holly McNaughton 22 October 2024 edited by Arwen Nguyen-Ngo illustrated by Esme MacGillivray Humans are destined to face an unavoidable end, but what if we weren't? What if humans could push the boundaries of death and become "un-ageable"? What would be the consequences if the world's top apex predators became immortal? The concept of anti-ageing and the quest for eternal life is not new. Cleopatra supposedly bathed in donkeys’ milk to reduce wrinkles. The first emperor of the Qin dynasty (221-206 B.C.), tried to achieve immortality by taking pills. Unfortunately for him, the key ingredient was the highly toxic substance—mercury. In 16th century France, members of the nobility would drink gold to preserve youthful looks. Much like in the past, today’s leading figures in the anti-ageing field are those with power and wealth. Today, the same obsessive quest for youth persists, but now it is backed by cutting-edge science and more importantly, staggering wealth. This article delves into the latest anti-ageing trends—pills, specialised diets, and more—championed by modern-day billionaires. We’ll explore the innovations they fund, and more provocatively, what it means for humanity when death is no longer inevitable. Anti-ageing pills The first “key” to anti-ageing is metformin, which dates to the1920s and was first discovered in the medicinal herb Galega officinalis . It lowers blood sugar levels and is taken as a popular treatment for type 2 diabetes (Bailey, 2017). Metformin works by tricking your body into thinking there is not enough energy, lowering blood glucose levels, and helping the insulin your body makes to work better. In a 2014 clinical study, patients with type 2 diabetes initiated with metformin had longer survivals than non-diabetics who did not receive the drug (Bannister et al. 2014). Although this is a correlation, not causation, some studies state Metformin has increased lifespan in mice (Martin-Montalvo et al., 2013). While we are anticipating the results of a trial on the effects on humans, and particularly the effects on non-diabetic lifespan, some are already convinced by the results from preliminary studies, such as Byran Johnson. Johnson is a self-proclaimed Professional Rejuvenation Athlete and founder of Project Blueprint. The Blueprint protocol is an extensive regimen of exercise, health tests, supplements, and a strict diet, to reverse biological age. Bryan has been following the protocol since 2021 and has successfully slowed down his rate of ageing to 0.76, meaning that for every year, Bryan is only ageing 277 days. Luckily, it only costs him 2 million a year. As part of the protocol, Bryan takes several prescription drugs daily, including metformin twice a day and rapamycin. Rapamycin is another promising “key” anti-ageing drug that works as a mTOR inhibitor. mTOR is a key component in cell growth, proliferation and survival. By inhibiting mTOR, cell growth and protein synthesis processes are slowed, thus reducing the chance of pathology (disease and/or injury) of cells and tissues. It has been shown to extend the lifespan of mice, yeast, worms and fruit flies (Harrison et al., 2009) and in 2018, elderly humans given rapamycin showed promising results with improvement in immune function and decreased infection rates (Mannick et al., 2018), which could ultimately lead to longer lifespans. Young blood transfusion Throughout history, blood has been a popular anti-ageing remedy. In the 15th century, Pope Innocent VIII drank the blood of three young boys, to heal his ailments (Scott & DeFrancesco, 2015). It did not work. The term “Young Blood transfusion” is now used to refer to the practice of transfusing blood from a young person into an older one to tackle age-related diseases. The rationale comes from parabiosis experiments. Parabiosis is the anatomical and physiological union of two organisms, and in the 1950s it was performed on two mice, surgically stitched together. A month after the procedure, the older mice showed rejuvenation (Conboy et al., 2005). In 2017, a new startup called Ambrosia emerged offering transfusion from young people at $8,000 a session. According to the U.S Food and Drug Administration, there were no clinical benefits of this treatment, and it was shortly shut down. PayPal founder Peter Thiel believes he will live to be 120 years old; a fan of young blood transfusions, he also credits his future success to taking human growth hormones daily and following a strict paleo diet. The science of which diet is best for anti-ageing is constantly changing. The paleo diet cuts out sugar, carbohydrates and highly processed food and is praised by celebs, but is not currently supported by science for having anti-aging benefits. Other diets such as intermittent fasting, keto and veganism are all praised for their anti-aging properties, but again the claims are under-researched. However, there is a growing body of evidence that a whole-food, plant-based diet can aid in the prevention, and in some cases reversal, of chronic diseases (Solway et al., 2020). For example, in Loma Linda, California, one of the world's five original blue zones (areas of the world with the healthiest, longest-living populations), the life expectancy is 10 years longer than the average American, which has been linked to the high number of Adventist vegetarians in the community. The key link between all five blue zones is a mostly whole-food, plant-based diet. Ethical and social implications – consequences of immortal humans The cure to ageing is still a while away but there is already a growing body of evidence of how we can extend our lifespans, but is that a good idea? The first argument against extending human lifespans is the risk of furthering the gaps in inequality. There is already a 30–40-year life expectancy gap between first-world and third-world countries. As highlighted in this article, it is primarily the wealthy benefiting from advancements in anti-ageing. Although, it is the responsibility of politicians and governments to remove the disparities worldwide. Thus, the question arises – should our focus and resources be directed towards addressing the health crises in developing countries instead? The second argument is overpopulation. An interesting study that looked at a 100-year projection of population size if no one aged after 60 showed that total population size only increased by 22% or 9 million to 11 million (Gavrilov & Gavrilova, 2010). They also pointed out that many members of society may choose to reject new anti-ageing technologies due to religious reasons, fear of side effects and/or costs. I would also like to point out that the world’s declining birth rates due to increased fertility issues may also mean overpopulation won’t be a near-future issue. An increasing population size does however mean increased demand for finite resources like water. Increases in water demand could cause an increase in civil and international conflicts over existing water supplies. In Australia, water scarcity is already a persistent issue, given the relatively dry and variable climate and an increased population size will see demand rise above our limits. To conclude, science has not found a cure for mortality, but with the development in age reversal or anti-ageing science, we may see the longevity of life increasing as well as quality of life. There are several ethical and social implications of an “un-ageable” race, but most importantly, developments in the anti-ageing community may allow loved ones to be healthier for longer. References AIHW, Australian Institute of Health and Welfare. (2024). Deaths in Australia. Retrieved from https://www.aihw.gov.au/reports/life-expectancy-deaths/deaths-in-australia Bannister, C. A., Holden, S. E., Jenkins-Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G.,Mukherjee, J., & Currie, C. J. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab , 16 (11), 1165-1173. https://doi.org/10.1111/dom.12354 Bailey, C. J. (2017). Metformin: historical overview. Diabetologia , 60 (9), 1566-1576. Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature , 433 (7027), 760-764. https://doi.org/10.1038/nature03260 Gavrilov, L. A., & Gavrilova, N. S. (2010). Demographic consequences of defeating aging. Rejuvenation Res , 13 (2-3), 329-334. https://doi.org/10.1089/rej.2009.0977 doi.org Metformin: historical overview - Diabetologia Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat’s rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin’s future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications. Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., Pahor, M., Javors, M. A., Fernandez, E., & Miller, R. A. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature , 460 (7253), 392-395. https://doi.org/10.1038/nature08221 Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M. J., Schwab, M., Pollak, M., Zhang, Y., Yu, Y., Becker, K. G., Bohr, V. A., Ingram, D. K., Sinclair, D. A., Wolf, N. S., . . . de Cabo, R. (2013). Metformin improves healthspan and lifespan in mice. Nat Commun , 4 , 2192. https://doi.org/10.1038/ncomms3192 Mannick, J. B., Morris, M., Hockey, H.-U. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., Glass, D. J., & Klickstein, L. B. (2018). TORC1 inhibition enhances immune function and reduces infections in the elderly. Science Translational Medicine , 10 (449), eaaq1564. https://doi.org/doi:10.1126/scitranslmed.aaq1564 Scott, C., & DeFrancesco, L. (2015). Selling Long Life. Nature Biotechnology , 33 , 28-37. Solway, J., McBride, M., Haq, F., Abdul, W., & Miller, R. (2020). Diet and Dermatology: The Role of a Whole-food, doi.org Selling long life - Nature Biotechnology A new generation of commercial entities is beginning to explore opportunities for new types of interventions and services in a graying world. Plant-based Diet in Preventing and Reversing Skin Aging-A Review. J Clin Aesthet Dermatol , 13 (5), 38-43. Poganik, J. R., Zhang, B., Baht, G. S., Tyshkovskiy, A., Deik, A., Kerepesi, C., Yim, S. H., Lu, A. T.,Haghani, A., Gong, T., Hedman, A. M., Andolf, E., Pershagen, G., Almqvist, C., Clish, C. B., Horvath, S., White, J. P., & Gladyshev, V. N. (2023). Biological age is increased by stress and restored upon recovery. Cell Metab , 35 (5), 807-820.e805. https://doi.org/10.1016/j.cmet.2023.03.015 Previous article Next article apex back to

< 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