Discovery, Biology Magazine 2023

Page 15

Zombie apocalypse

The Cordyceps fungus

Personalised cancer treatment

Can our T-cells be supercharged?

Searching for extraterrestrial life

Is there more life out there?

Surviving the unsurvivable

How extremophiles endure

magazine 2023
DISCOVERY Biology

About Discovery Magazine

We are A Level Biologists at Cheltenham College who came together to write a Biology magazine about topics that we found of particular interest and that we think are prominent issues in our world today.

The name of this magazine, Discovery, comes from the name of one of the expeditions E. A. Wilson took to Antarctica with Scott and Shackleton. Dr Edward Adrian Wilson (1872-1912) was an Old Cheltonian, and he was the junior surgeon, zoologist and expedition artist on the expedition. We think that this makes excellent links with the content of this magazine as well as with us personally, as he walked the same corridors we do.

About us

I’m Emily Ng and currently taking Biology, Chemistry, Mathematics and Psychology at A Level. I aspire to study Medicine at university with the hope of becoming a doctor and researcher to improve the well-being of vulnerable patients. As I was intrigued by the idea of life and death, I utilised this opportunity to explore about medical advancements that may possibly prolong our lives and their implications in today’s world.

I’m Ella Carnegie-Brown. I was first introduced to extremophiles when I attended a lecture at Warwick University by an astrobiologist. I was immediately hooked on this fascinating

This year’s edition includes an article by Luciana Jaramillo-Ruiz, the winner of the inaugural Cheltenham Muscat Biology article contest. With thanks to our colleagues in Oman, Miss Clare Blain and Mr Daniel Moss, for guiding the pupils in that competition. Once again this edition boasts some magnificent student biological drawings.

With thanks to Mr Thomas, for his guidance and support in producing this magazine. With thanks also to Luke Richardson for his photograph “Paeonia lactiflora open for lunch” which is used on the contents page.

survive in a such hostile conditions fascinating. Looking into the future of astrobiology was also intriguing, all of this guided me to write this article. I would like to study something in the field of Biology after leaving College.

I’m Kimmy Kwok. My A Levels are Biology, Chemistry, and Maths. I am hoping to study Medicine at university, specifically Cardiology. I chose CRISPR as my topic because I find it fascinating how humans have found a way to alter DNA using technology. It has given me the opportunity to research into the ethics and experiments that have been done. It has always been an interest of mine and I truly believe it is the future of medicine and science.

I’m Eleanor Langley and I am currently studying Biology, Maths and Psychology at A Level. When I leave College I hope to study Cognitive Neuroscience at university. I thought of my topic choice after attending a biology lecture at Warwick University. Here John James spoke to us about using our immune system as a personalised cancer cure. This piqued my interest and caused me to want to look into the topic further.

I’m Jude Richardson and I’m studying Biology, Psychology and French. I am fascinated by the natural environment and our human relationship with it. This essay gave me the chance to develop my knowledge; to explore the biochemical interactions between animals and plants for medicinal purposes. I was amazed to discover just how intrinsic plants have always been to treating ailments and how understanding them better can potentially provide treatments for even complex conditions like cancer.

I’m PB Tanawattanakul and I am a Lower Sixth student studying Biology, Chemistry, Maths and Art at A Level. I find Biology intriguing, and I decided to do further research into finding whether there is potential for life in outer space. Investigating this topic has expanded my knowledge outside the school curriculum and it has fascinated me to learn more about biochemistry and ways to sustain life. After I leave College, I hope to study Medicine at university.

Dr Edward Adrian Wilson (1872-1912)
3 Discovery 2022-23 CONTENTS Elixir of Immortality - Emily Ng 4 The Future of Personalised Medicine - Eleanor Langley 8 Surviving the Unsurvivable - Ella Carnegie-Brown 11 Nancy Rothwell Biological Drawings 14 Zombie Apocalypse Now - Luciana Jaramillo-Ruiz 15 To Kill or to Cure? - Jude Richardson 17 Searching for Extraterrestrial Life - PB Tanawattanakul 21 Changing DNA - Kimmy Kwok 24 Book Reviews 27

Elixir of Immortality

Is it possible to prolong our life and reverse aging?

Does the elixir of immortality exist in the world? Is it a potion concocted by mercury and sulphur? Or the water from the fountain of life? For centuries, people have been seeking ways to prolong their lives — from spiritual rituals to making potions from different combinations of ingredients. Witches in the western culture were believed to harness their magical power to make the mythical potion whereas in ancient China, alchemists spent day and night to concoct the elixir of immortality using cinnabar, gold, mercury, and sulphur (Winterhalter, 2018). Ironically, many of the elixir seekers died after drinking the mythical potion when elixirs were meant to extend their lifespan and grant them eternal life. They did not realise they had made a deadly poison that shortened people’s lifespan and made them age faster due to harmful chemicals present in the potion. As technology advanced, people started to look for scientific methods to prolong our lives by understanding how and why we age. This led to the emergence of modern innovations such as epigenetic engineering to stop us from aging rather than hunting for the elixir blindly.

to dysregulation of our body maintenance, repair and defence system (b) Error theory hypothesises that random cellular changes mean our body loses the ability to repair DNA damage and the accumulation of cross-linked proteins destroy cells and slow down biological functions (c) Genetic theory proposes our lifespan is determined by the genes inherited from our parents as telomeres located at the end of chromosomes determine the lifespan of a cell (Healthline, 2021). These DNA shorten as we grow up, and eventually the cell ceases to divide without losing the important parts of the DNA. There are also other theories proposed such as programmed senescence theory which involves the cell cycle and stem cell theory that suggests body stem cells lose their cell differentiation ability to replace old and damaged cells. It has always been believed that aging is caused by a combination of biological and environmental factors but until recently, a leading scientist and professor in the genetics field from Harvard Medical School, Dr David. A. Sinclair, stated that aging is a treatable disease that can be cured by epigenetic engineering, so reverse aging may no longer be a dream (Deac, 2022).

Epigenetic engineering and regenerative medicine

Understanding how and why we age

Aging is an inevitable part of human life due to declining of the normal functioning of our cells over time. We experience two types of aging — intrinsic and extrinsic aging. Intrinsic aging refers to ‘a genetically predetermined process that naturally occurs’ (Healthline, 2021) which is determined by an individual’s genetic clock that varies from one another. On the other hand, extrinsic aging refers to environmental stressors (surroundings and lifestyle) such as air pollution, radiation, stress level, smoking and malnutrition affecting cellular functions that cause aging. There are lots of prominent theories to explain the biological factors that lead to aging: (a) Programmed theory suggests everyone has a predetermined lifespan as specific genes are turned on and off over time that may lead

Epigenetic engineering is a type of genetic engineering that manipulates and modifies the epigenome (the operating system of a cell which consists of chemical compounds that modify or mark the genome to instruct gene expression) without causing any permanent changes in the DNA sequence (Genome.gov, 2019). Dr Sinclair analogised human body as the hardware and epigenome as the software: if the software breaks down, we can simply reboot the whole system (hardware) using a backup copy of the software that contains all the original information so that the cell can function normally again with a restored ability to read instructions correctly (LaMotte, 2023). To illustrate the existence of the rejuvenation switch, Dr Sinclair and his team used ICE (inducible

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Fig 1 - Mythical Chinese white rabbit making the Elixir of Immortality on the Moon (Wikipedia, 2021) Fig 2 - Normal mouse (left hand side) and ICE mouse (right hand side) (hms.harvard.edu, 2023)
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changes to the epigenome) to mimic the natural process of epigenetic modification experienced in everyday life such as exposure to sunlight and chemical substances (The Scientist Magazine, n.d.). ICE involves introducing temporary breaks in DNA non-coding regions to alter the way DNA folds without altering DNA coding regions that may trigger mutation. Initially, epigenetic factors (proteins that help regulate gene expression) moved to the breaks to repair DNA and returned to their original positions afterwards.Yet, after some time, the factors became distracted and did not find their way back to their original positions, ending up with the epigenome becoming jumbled up and led to cellular malfunction as the genes could not be expressed accurately anymore. As the team compared ICE mice and controlled mice after 6 months, it was found that ICE mice had much more biomarkers that indicate aging and appear to be older in phenotype such as grey hair and muscle weakness which resembled old wild mice that made them look and act old. Many methyl groups were lost across the genome in ICE mice, indicating their biological age was older than the controlled mice of the same chronological age. Then, the team tried to reverse aging in mice by gene therapy — insertion of three (Oct4, Sox2, and Klf4) of the four Yamanaka factors (a group of transcription factors capable of turning adult cells back to induced pluripotent stem cells) (Yamanaka factors, n.d.) into ICE mice to activate the genes responsible for the development of embryonic stem cells to rewind mature, old cells back to their earlier youthful stage. As a result, the ICE mice’s tissues and organs became young and healthy again (about 50-75% of the original age).

Implications of epigenetic engineering

Dr Sinclair’s study supports the idea that epigenome plays an important role in aging and that epigenetic engineering is a possible way to reverse aging. It works by installing an epigenetic program in the body to reboot the corrupted system that can stimulate body cells to restore all the information lost in order to return to their youthful state. It also employs regenerative medicine which utilises Yamanaka genes to create induced stem cells which can be de-differentiated into young pluripotent stem cells and differentiate into specific cells again. Despite the success in lab mice, will it be the same when applying epigenetic technology to humans? There are also other issues regarding epigenome engineering: how long can the reprogrammed cells sustain at the young age? Can the body epigenetic system be rebooted again and again without any side effects? Further experiments are required to answer these questions to support epigenetic treatment application on humans.

Anti-aging drug

A pill that can extend our lifespan? It may sound absurd as it only exists in fairy tale or myth, but recent studies suggest it may actually exist — Rapamycin, an immunosuppressant and cell growth inhibitor used in cancer therapy and organ transplantation. Dr Paula Juricic, who works at the Max Planck Institute for Biology of Aging, conducted a study to find out the anti-aging property of rapamycin by testing on fruit flies and mice (www.medicalnewstoday.com, 2022). The drug was given to fruit flies for two weeks that appeared to protect them from age-related pathogens in the intestine that helped extend their lifespan. A group of three-month-old mice were also given the drug treatment for three months and they experienced similar benefits of increased pathogenic resistance in the intestine, especially when they reached middle age. To investigate the optimum dosage and period of time the drug should be prescribed, scientists tested the effect of small doses of rapamycin on a group of twentymonth-old mice (equivalent to sixty-year-old humans) for three months.

Interestingly, the mice lived on average for an extra two months and some even lived up to nearly four years more (equivalent to 140-year-old humans) rather than dying at about thirty months old. Scientists then searched for the operating system of rapamycin and came up with two possible explanations — autophagy and improving DNA storage. Rapamycin can trigger autophagy, which is a recycling system of the cell that breaks down dysfunctional and misbehaving organelles and proteins to save energy in order to keep the cell alive and assemble new cellular components (www.lifespan.io, n.d.). The research also shows that rapamycin can increase the number of histone proteins wrapped around DNA in gut cells, leading to less exposure of DNA to outside environment. This reduces the number of genes contributed to aging to be expressed and thus increases lifespan. The reverse of age-related loss can also be done by inhibiting mTOR pathway (a regulator of anabolic metabolism) by rapamycin as lower activity of mTOR can lengthen lifespan based on the test results on mice, yeast and flies (www.lifespan.io, n.d.).

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Fig 3 - Regenerative medicine (SanBio - Official Site, n.d.) Fig 4 - The epigenome (Genome.gov, 2016)
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Implications of the anti-aging drug

Conclusion

Rapamycin is a successful example of anti-aging drug which seems to bring positive impact on lifespan extension. Scientists are still considering the best way to maximise its benefits with a lowest dosage without serious side effects that has an outcome equivalent to a lifelong treatment. The fruit fly and mice study shows that rapamycin treatment had the best effect when the drug was given at a young age compared to no effects when given at an older age (ScienceDaily, n.d.). This suggests that early adulthood is a critical period of rapamycin consumption as it increases the survival rate of memory and effector T cells (developed from bone marrow stem cells that protect the body from infection in the immune system) during contraction phase when majority of effector T cells die by apoptosis. Higher number of T cells survived implies better immune system to fight against pathogenic invasion, leading to stronger body and thus longer lifespan.

Nevertheless, there are still questions raised about this antiaging drug, such as the right dosage of rapamycin as it varies in situations — low dosage required in the mTOR pathway but high dosage required in the IIS pathway (for insulin and insulin-like peptide cell signalling). Is it possible to strike a balance of dosage to maximise the positive effects with the least side effects?

On the other hand, a recent study (UCL, 2019) conducted by UCL researchers suggested that effectiveness of rapamycin depends on the biological gender. They gave rapamycin to both male and female fruit flies and surprisingly, only female fruit flies had an extended lifespan and decelerated emergence of age-related intestinal diseases. Female fruit flies were found to have increased autophagy in gut cells but not in male gut cells that already had a high autophagy activity from the start of experiment which could not further rise up after the drug treatment. Understanding the sex-specific nature of rapamycin allows us to explore alternatives that can work on both sexes: maybe a combination of drug treatment such as a mixture of lithium, trametinib and rapamycin can extend the lifespan more than using rapamycin alone. This is supported by the latest UCL study that fruit flies which received a combination of drug treatment lived 48% longer than those without any drug treatment. The combination of drugs may compensate the side effects of each other and eliminate our concerns over undesirable side effects of rapamycin such as anaemia, high blood pressure and elevated potassium level in the blood.

All the technological innovations are fascinating and recent studies mentioned above have demonstrated encouraging results in finding ways for longevity that can inspire other scientists to join this new age-related exploration field. By conducting more research on some long-lived species such as the bowhead whale, which are warm-blooded mammals that can live up to 200 years with similar genetic makeup as humans, we may find more evidence to support the idea of how epigenetic clocks may affect our lifespan and apply the knowledge to modify the current proposal of epigenetic engineering. Yet, humans are a complex system that requires different components interact and work together. Should the root cause of aging be solely reduced to the loss of DNA information and critical instructions in epigenome? There may be other factors involved that have not been discovered which may allow or prevent anti-aging to be possible. In addition, there are social implications of reverse aging technology as it might eventually lead to overpopulation if everyone’s lifespan was extended (Farnam Street, n.d.). Though it may become a burden on society due to resource scarcity, it may also be an advantage if the increasing population is productive and more people with wisdom and knowledge can survive longer and contribute more to the society.

To conclude, I believe that seeking for technological advancement to extend lifespan is beneficial, but at the same time, we should also put more focus on the quality of life — how we can live out a meaningful and fruitful life by incorporating healthy habits such as balanced diet and exercising rather than extending the lifespan without living well. Maybe in a few years or decades, we can witness the first person who lives for more than 120 years utilising epigenetic engineering or anti-aging drugs, turning the ‘Elixir of Immortality’ into reality.

Discussion questions

1. Do you think epigenetic engineering is applicable on humans after several animal trials?

2. Should the government put more funding into epigenetic research and bulk production of rapamycin to increase people’s lifespan? Why do you think so?

3. How do you think anti-aging research will impact our lives and why?

Interested in learning more?

Here’s a video you may enjoy:

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Fig 5 - Studying about the effect of rapamycin on fruit flies (UCL, 2019)
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References

Araki, K., Youngblood, B. and Ahmed, R. (2010). The role of mTOR in memory CD8+ T-cell differentiation. Immunological Reviews, 235(1), pp.234–243. doi:https://doi.org/10.1111/j.0105-2896.2010.00898.x. [Accessed: 27/2/23]

BBC Science Focus Magazine. (n.d.). Anti-ageing pills are real, and some of us are taking them without knowing it. [online] Available at: https://www. sciencefocus.com/the-human-body/anti-ageing-medication-health/

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Blagosklonny, M.V. (2019). Rapamycin for longevity: opinion article. Aging, [online] 11(19), pp.8048–8067. doi:https://doi.org/10.18632/aging.102355.

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Deac, M. (2022). Lifespan Summary. [online] Four Minute Books. Available at: https://fourminutebooks.com/lifespan-summary/ [Accessed: 27/2/23]

Dissecting T Cell Contraction In Vivo Using a Genetically Encoded Reporter of Apoptosis. (2012). Cell Reports, [online] 2(5), pp.1438–1447. doi:https://doi. org/10.1016/j.celrep.2012.10.015. [Accessed: 27/2/23]

Farnam Street. (n.d.). Dr. David Sinclair: Reversing the Aging Process [The Knowledge Project Ep. #136]. [online] Available at: https://fs.blog/knowledgeproject-podcast/david-sinclair/ [Accessed: 27/2/23]

Genome.gov. (2019). Epigenome. [online] Available at: https://www.genome. gov/genetics-glossary/Epigenome [Accessed: 27/2/23]

Glasner, J. (2022). For 2022, Here’s What Startups Are Doing To Extend Our Lifespans. [online] Crunchbase News. Available at: https://news.crunchbase. com/startups/health-care-longevity-investors-gene-editing-startupsforecast/ [Accessed: 27/2/23]

Healthline. (2021). Why Do We Age, and Can Anything Be Done to Stop or Slow it? [online] Available at: https://www.healthline.com/health/why-do-weage#can-aging-be-slowed. [Accessed: 27/2/23] hms.harvard.edu. (n.d.). Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It. [online] Available at: https://hms.harvard.edu/ news/loss-epigenetic-information-can-drive-aging-restoration-can-reverse. [Accessed: 27/2/23]

LaMotte, S. (2023). Old mice grow young again in study. Can people do the same? [online] CNN. Available at: https://edition.cnn.com/2023/01/12/health/ reversing-aging-scn-wellness/index.html [Accessed: 27/2/23]

Lang, P.O., Govind, S. and Aspinall, R. (2012). Reversing T cell immunosenescence: why, who, and how. AGE, 35(3), pp.609–620. doi:https:// doi.org/10.1007/s11357-012-9393-y. [Accessed: 27/2/23]

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New Atlas. (2023). Epigenetic ‘reboot’ reverses aging in mice and could extend lifespan. [online] Available at: https://newatlas.com/biology/epigeneticreboot-reverse-aging-extend-lifespan/ [Accessed: 27/2/23]

Park, A. (2023). Scientists Have Reached a Key Milestone in Learning How to Reverse Aging. [online] Time. Available at: https://time.com/6246864/reverseaging-scientists-discover-milestone/ [Accessed: 27/2/23]

ScienceDaily. (n.d.). Brief exposure to rapamycin has the same anti-aging effects as lifelong treatment, shows study in fruit flies and mice. [online] Available at: https://www.sciencedaily.com/releases/2022/08/220829112829.htm

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Simpson, D.J., Olova, N.N. and Chandra, T. (2021). Cellular reprogramming and epigenetic rejuvenation. Clinical Epigenetics. [online] BMC. Available at: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/ s13148-021-01158-7 [Accessed: 27/2/23]

Stibich, M. (2019). Are Your Genes Making You Age? [online] Verywell Health. Available at: https://www.verywellhealth.com/the-genetic-theory-ofaging-2224222. [Accessed: 27/2/23]

The Scientist Magazine®. (n.d.). Epigenetic Manipulations Can Accelerate or Reverse Aging in Mice. [online] Available at: https://www.the-scientist.com/ news-opinion/epigenetic-manipulations-can-accelerate-or-reverse-agingin-mice-70888 [Accessed: 27/2/23]

UCL (2019). Fruit flies live longer with combination drug treatment. [online] UCL News. Available at: https://www.ucl.ac.uk/news/2019/sep/fruit-flies-livelonger-combination-drug-treatment. [Accessed: 27/2/23]

Ullah, M. and Sun, Z. (2018). Stem cells and anti-aging genes: doubleedged sword—do the same job of life extension. Stem Cell Research & Therapy, [online] BMC. Available at: https://stemcellres.biomedcentral.com/

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Willingham, E. (2021). Humans Could Live up to 150 Years, New Research Suggests. [online] Scientific American. Available at: https://www. scientificamerican.com/article/humans-could-live-up-to-150-years-newresearch-suggests/ [Accessed: 27/2/23]

Winterhalter, B. (2018). Elixirs of Immortal Life Were a Deadly Obsession. [online] JSTOR Daily. Available at: https://daily.jstor.org/elixir-immortal-life-deadlyobsessions/. [Accessed: 27/2/23]

www.babraham.ac.uk. (n.d.). A jump through time – new technique rewinds the age of skin cells by 30 years | Babraham Institute. [online] Available at: https:// www.babraham.ac.uk/news/2022/04/new-technique-rewinds-age-skincells-30-years. [Accessed: 27/2/23]

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www.lifespan.io. (n.d.). Why we Age: Deregulated Nutrient Sensing | Lifespan. io. [online] Available at: https://www.lifespan.io/topic/deregulated-nutrientsensing/ [Accessed: 27/2/23]

www.medicalnewstoday.com. (2023). Scientists reversed aging in mice: Is it possible in humans? [online] Available at: https://www.medicalnewstoday. com/articles/harvard-scientists-reverse-aging-in-mice-is-it-possible-inhumans#What-might-these-mean-for-humans [Accessed: 27/2/23] www.medicalnewstoday.com. (2022). Rapamycin: The next anti-aging drug? [online] Available at: https://www.medicalnewstoday.com/articles/ could-rapamycin-be-our-next-weapon-in-the-fight-for-longevity#Dosingrapamycin-for-protective-effects [Accessed: 27/2/23]

www.science.org. (n.d.). Two research teams reverse signs of aging in mice [online] Available at: https://www.science.org/content/article/two-researchteams-reverse-signs-aging-mice [Accessed: 27/2/23]

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Yoga, H. (2015). The Elixir of Life: Across History and World Cultures. [online] Hridaya Yoga. Available at: https://hridaya-yoga.com/blog/the-elixir-of-lifeacross-history-and-world-cultures/. [Accessed: 27/2/23]

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The Future of Personalised Medicine

Can T-cells be supercharged to fight cancer?

The term ‘cancer’ refers to more than 100 forms of the disease. Nearly all tissues and cells in the body have the ability to form malignant tumours. There were 17 million new cases of cancer in the world in 2017, and this is due to grow to 27.5m by 2040 (Cancer Research UK, 2019). The way that these tumours are formed are all quite similar, cancer is “a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body” (Weinberg, 1996). The formation of cancer is due to a mutation that occurs during cell division. During division, cells grow old or become damaged, they then die, and new cells take their place. If this order breaks down, meaning damaged or abnormal cells are able to continue growing and multiplying, a tumour can form. These tumours will either be malignant (cancerous) or benign (non- cancerous). The cancerous cells tend to spread uncontrollably, causing the tumours to invade tissues and other part of the body in order to form new tumours. This process is called metastasis.

in the treatment of cancer. Unfortunately, cancer treatments, such as chemotherapy, radiotherapy, targeted drugs and high doses of steroids, can also weaken the immune system. The balance between treatment and maintaining a healthy immune system is key in the fight against cancer (Cancer Research Institute, 2018).

As a result of this balancing act, recent technological and biological advancements in cancer treatments have focused on supporting a patient’s own immune system in its fight against cancer. These treatments are at the centre of hope in reducing death caused by cancer. This article explores these recent advancements and the impact they may have on healthcare for generations to come.

Recent advancements

In the early 2000s targeted drug therapies like Imatinib (Gleevec) and Trastuxumab (Herceptin) first emerged. These drugs kill cells that display the specific molecular changes that are first seen as cancer emerges. This treatment is a form of immunotherapy and has become more commonly used over the last decade due to their ability to shrink, and even remove, tumours in some patients with advanced cancer. These treatments can be effective for many years in a small percentage of patients.

Cancer is a genetic disease, this means that it is caused by a change in the genetic coding that controls how our cells function, grow and divide. These genetic changes can be caused by many things such as errors in cell division, damage to DNA due to environmental factors (e.g. smoking or UV radiation), as well as being inherited from parents. All these factors make you more vulnerable to getting cancer (National Cancer Institute, 2021).

One way in which cancer can be treated is by the immune system. The immune system protects the body against illness and infection caused by bacteria, viruses, fungi or parasites. This system is a collection of reactions and responses that the body makes in order to damage cells or infection and is pivotal

More recently, CAR T-cell therapy has become very prominent. Although T-cell therapies aren’t very widely used, they have shown the same ability to eradicate and prevent the return of cancer as other immune checkpoint inhibitors. Since 2017, six CAR T-cell therapies have been approved by the Food and Drug Administration (FDA) in the US. These forms of therapy are all able to treat various forms of blood cancer (National Cancer Institute, 2019). In the last 3 years, 130 U.S. based clinics have been authorised to provide this treatment, although these centres have treated fewer than 2,000 people to date. The cost of these treatments is also very high, with the newest costing more than $450,000. However, despite the cost and low success rate, CAR T-cell therapies have become part of the mainstream of cancer treatments (National Cancer Institute, 2019).

The Biology

Renier J. Brentjens, M.D., Ph.D., explained that CAR T-cells are the equivalent of ‘giving patients a living drug’. T-cells are the backbone of CAR T-cell therapy. T cells are a type of white blood cell, an important component of the immune system, and develop from stem cells in the bone marrow. They help to

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Fig 1 - Comparison between cancer cells and healthy cells (Verywell, 2017).
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protect the body from infection and can help to fight cancer (Cancer Research, 2021).

will help with the treatment. This will allow for a vast reduction in the time, materials and labour required to generate CAR T-cells, this will be extremely beneficial for patients with rapidly progressive diseases and those in poorly resourced healthcare environments (Penn Medicine News, 2022). If the researchers are able to do this, it will cut down on production time and allow for the treatment to become much more readily available. Therefore, allowing personalised medicine to be taken to the global market of healthcare.

Efficacy

In order for the FDA to approve these types of therapy in the US, the clinical trials have to show significant success in treating cancer; however, they don’t always work. Of the six CAR T-cell treatments that have been approved, the long-term success rate is less than 50% (National Cancer Institute, 2019).

At this stage in the research, it appears that CAR T-cell therapy may have limited efficacy because:

• CAR T-cells are T-cells with different genetic instructions. These T-cells are now able to create chimeric antigen receptors (CAR) and molecules. These new receptors need to be active for T-cells to find and kill the cancer cells. If this doesn’t happen T-cells cannot work and are unable to destroy the cancer.

T-cells are firstly collected by a cannula, one in each arm. One tube removes the blood and passes it into an apheresis machine, separating different parts of the blood. The T-cells are removed, and the rest of the blood cells and fluid go back into your body through the other tube. This process usually takes between 4 to 5 hours. The T-cells are then sent to a laboratory to make CAR T-cells. This process can take several weeks. While in the laboratory the patients’ T-cells are re-engineered to produce proteins on their surface. These proteins are called chimeric antigen receptors (CARs). The CARs recognise and bind to specific proteins or antigens on the surface of cancer cells. These receptors are synthetic molecules and do not exist naturally (National Cancer Institute, 2019).

Before undergoing CAR T-cell therapy patients undergo chemotherapy. This lowers the number of T-cells and prepares your body for the CAR T-cells. Once the specialised nurse has received your CAR T-cells, they are introduced back into the bloodstream through a drip. This process takes less than 30 minutes. You are then monitored for 2 weeks after CAR T-cell therapy (Cancer Research, 2021). The CAR T-cells will continue to multiply in the patient’s body and will recognise and kill cancer cells that have the target antigen on their surface.

Scaling up to commercial manufacturing of CAR T-cells presents one major challenge: the process needs to be simplified to help the transition from lab manufacturing to mass production (Eder. M, 2021). Due to T-cell therapy being unique to each individual patient, the ability to upgrade numbers of people being able to access it is very difficult.

Researchers at Penn Medicine are currently trying to manufacture shorter wait time to produce CAR T-cells, from the standard two-week-time to less than 24 hours. CAR T-cell therapy typically takes 9 to 14 days. A faster engineering time

• Once in your body, CAR T-cells are supposed to multiply. When they don’t, they aren’t able to find and kill enough cancer cells to stop them from spreading.

• Sometimes CAR T-cells cannot kill cancer cells. This is known as T-cell exhaustion. Scientists believe that transcription factors (proteins that help turn genes on and off) are linked to this.

• Cancer cells are able to change or mutate. This can lead to the antigen, that the CAR T-cells were created to find, changing. If this happens, the T-cells are unable to locate the cancer cells (Cleveland Clinic, 2022).

The future

Personalised medicine is a type of medical care in which treatment is customised for an individual patient. Personalised medicine classifies tumours according to their genetic makeup instead of where they grow. People with the ‘same’ cancer can have different forms of the disease, meaning that their response to the treatment can vary. Using treatment that are specially tailored allows for more successful treatments. It gives patients a range of new, more effective treatments (Cancer Research, 2013).

At the moment, CAR T-cell therapy has been approved by the FDA and other institutions in the US, Europe, China, Australia and a few other countries. All of these countries are wealthy, developed countries. While there have been around 10,000 patients worldwide that have received this treatment in a clinical trial, only a small number of participants were from middle- and low-income countries. Africa, South America and India didn’t have a single registered member during this trial (Eder. M, 2021). This shows the need for this treatment to be more accessible as to allow people in lower-income countries to benefit from this treatment.

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Fig 2 - The process of creating CAR T-cells (National Cancer Institute, 2022).
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As more longitudinal and diverse sources of research emerge, the healthcare sector will be able to understand the long-term benefits of personalised medicine. Doctors will be able to use patients’ genetic and molecular information as part of routine medical care, which have the improved ability to predict which treatment will work better considering a deeper understanding of the underlying mechanisms by which various diseases occur. This will deliver improved approaches to preventing, diagnosing and treating a wide range of diseases (Medline Plus, 2022).

Conclusion

Personalised medicine will have a large impact on healthcare, but there are a number of influences which will impact patient health outcomes. Significant infrastructure investments are required to expediate the production process. The treatment will then have to reach at least 1 million patients – with all of their data collected and monitored – so that treatment plans are informed by historical case studies. This large amount of genomic data will have to be collected and stored securely. There is also the possibility of missing out certain groups of the population. This can lead to an over or under-representation of certain groups thereby limiting the validity of the data in the treatment of all. Finally, this treatment is very expensive. Although CAR T-cell therapy should reduce the cost of alternative long-term treatment plans, including surgery, chemotherapy and hormone therapy, for a patient, the upfront investment in this immunotherapy is beyond the budget of most public healthcare systems (Hospital Admin, 2016).

However, as Edward Wolton, Technical Consultant to Genomics England (a company of the Department of Health

References

Cancer Research Uk (2021). CAR T-cell therapy. [online] Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/treatment/ immunotherapy/types/CAR-T-cell-therapy [Accessed 9/5/23]

Cancer Research UK (2013). Personalised medicine. [online] Cancer Research UK. Available at: https://www.cancerresearchuk.org/get-involved/donate/ become-a-major-donor/how-you-can-give/the-catalyst-club/personalisedmedicine [Accessed 9/5/23]

Cancer Research UK (2018). The immune system and cancer. [online] Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/ what-is-cancer/body-systems-and-cancer/the-immune-system-and-cancer [Accessed 9/5/23]

Cancer Research UK (2019). Worldwide cancer statistics. [online] Cancer Research UK. Available at: https://www.cancerresearchuk.org/healthprofessional/cancer-statistics/worldwide-cancer [Accessed 9/5/23]

Cleveland Clinic (2022). CAR T-cell therapy. [online] Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/treatments/17726-car-t-cell-therapy [Accessed 9/5/23]

Eder,M. (2021). Availability of CAR T-cell therapy: list of all countries. [online] Available at: https://www.support.com/knowledge/cell-gene-therapy/ which-countries-cell-therapy-available [Accessed 9/5/23]

Eder,M. (2021) Standardizing CAR-T therapy – Getting it scaled up! [online] Single Use Support. Available at: https://susupport.com/company/news/cellgene-therapy/car-t-therapy-getting-it-scaled-up [Accessed 9/5/23]

Eldridge, L. (2013) Cancer Cells vs. Normal Cells: How Are They Different? [online] Verywell Health. Available at: https://www.verywellhealth.com/cancer-cellsvs-normal-cells-2248794 [Accessed 9/5/23]

& Social Care) said “The difference between conventional and genetic medicine is like the difference between blood-letting medieval barbers and modern sterile surgery. Personalised medicines tailored to the patient’s genome is the future of targeted treatment for many diseases and is already saving countless lives; over time the cost per treatment will reduce to be far more affordable as the cost of genetic sequencing has already reduced 99.94% in 15 years!”

There are also exciting developments in the use of AI and machine learning in personalising medicine, as featured in a recent MIT Technology Review (Heaven. W, 2023). This research, published in 2022, illustrates that personalised drug treatment can also include the use of AI to select the most appropriate suite of drugs from those currently on the market, to provide the best patient outcome.  As a result, technology may have its own answer on some of the problems it creates around cost and time – when many cancer patients have neither to spare.

Discussion questions

1. Will this treatment be accessible to lower income countries?

2. Is it worth investing in if only 50% of treatments have shown long term success?

3. Will life hacking or the editing of our unborn embryos be the natural next step in personalised medicine?

Interested in learning more?

Here is a TED talk on CAR T-cell therapy:

Heaven,W. (2023). AI is dreaming up drugs that no one has ever seen. How we’ve got to see if they work. [online] MIT Technology Review. Available at: https://www.technologyreview.com/2023/02/15/1067904/aiautomation-drug-development/?utm_source=engagement_email&utm_ medium=email&utm_campaign=wklysun&utm_content=02.26.23.subs_ eng&mc_cid=f5646a922c&mc_eid=18316ba0ad [Accessed 9/5/23]

Hospital Admin (2016). Advantages and Disadvantages of Precision Medicine [online] Health view X. Available at: https://www.healthviewx.com/ advantages-disadvantages-precision-medicine/ [Accessed 9/5/23]

Medline Plus (2022). What are some potential benefits of precision medicine and the Precision Medicine Initiative? [online] Medline Plus Genetics. Available at: https://medlineplus.gov/genetics/understanding/ precisionmedicine/potentialbenefits/ [Accessed 9/5/23]

National Cancer Institute (2022). CAR T Cells: Engineering Immune Cells to Treat Cancer. [online] National cancer Institute. Available at: https://www.cancer. gov/about-cancer/treatment/research/car-t-cells [Accessed 9/5/23]

National Cancer Institute (2019). NCI Dictionary of Cancer Terms. [online] National Cancer Institute. Available at: https://www.cancer.gov/publications/ dictionaries/cancer-terms/def/t-cell [Accessed 9/5/23]

National Cancer Institute (2021). What is Cancer? [online] National Cancer Institute. Available at: https://www.cancer.gov/about-cancer/understanding/ what-is-cancer [Accessed 9/5/23]

Penn Medicine News (2022). Penn Researchers Shorten Manufacturing Time for CAR T Cell Therapy. [online] Penn Medicine. Available at: https://www. pennmedicine.org/news/news-releases/2022/march/penn-researchersshorten-manufacturing-time-for-car-t-cell-therapy [Accessed 9/5/23]

Weinberg, Robert A. “How Cancer Arises.” Scientific American 275, no.3 (1996): 62-70.

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Surviving the Unsurvivable

How extremophiles endure the most hostile habitats on Earth by Ella

Earth is peppered with harsh environments. From deadly pressures to extreme temperatures, lack of oxygen to high acidity, one might assume that life could not survive in these conditions. In spite of this presumption, there are organisms that thrive in these environments called extremophiles (NOAA, 2019). This name comes from the Latin extremus and Greek philia meaning “extreme-lovers” (Schröder, Burkhardt, Antranikian, 2020). Life as we know it needs two instruments for it to thrive; food and water. Every living organism needs to acquire energy and no matter what biome you examine on Earth, all of them share the same requirements for energy and water (NOAA, 2022). However, the bizarre and unique discovery of these organisms can tell scientists all about the range of conditions in which life can be possible.

About extremophiles

Extremophiles are of biotechnological interest as they are predominantly prokaryotic (archaea or eubacteria) but possess a fascinating adaptation allowing them to produce enzymes called extremozymes. These remarkable catalysts can convert substrates under harsh conditions. There are a vast variety of different extremophiles depending on their environment. Some are called hyperthermophiles which grow at temperatures from 80°C all the way up to 110°C. These special organisms can be found thriving in deep water where the mantle of the Earth’s core escapes from the seabed. These vents can reach up to an astounding 400°C. Additionally, the variety includes alkaliphiles (pH 9-12) and acidophiles (pH 0.5-4) (see Fig.1), (Schröder et al, 2020). Moreover, within the deepest parts of the ocean, piezophiles can be found. These unique organisms can withstand intense pressures. Expanding into more detail, we can delve into how extremophiles are adapted to their extreme environments.

Hyperthermophiles

Hyperthermophiles cannot be protected by insulation against their environment. Therefore every single cell component has to be resistant to heat to maintain survival. The molecular

basis for this case is unknown and still under investigation. Lipids, proteins and nucleic acids all react to heat and are fairly sensitive. Therefore the lipid membrane they have contains a novel glycerol ether lipid. This can stabilise and maintain the membrane against hydrolysis at very high temperatures. For archaeal hyperthermophiles, to protect their DNA (which is usually very sensitive to heat), they use a special histone which changes the shape of the chromosomes and thus increases the DNA’s melting temperature (Rogers, 2023). When reaching 100°C, ATP begins to hydrolyse very fast and amino acids will begin to decompose. Any hyperthermophiles that can withstand a higher temperature than this could only do this by rapidly re-synthesising compounds. Therefore, the highest temperature hyperthermophiles could survive would be at 113-150°C (O. Stetter, 2019).

Acidophiles

Acidophiles are microorganisms that grow in extremely acidic environments. Many fungi and bacteria are acidtolerant; however, microbes can withstand extreme acidity. The Picrophilus is an archaebacteria which is one of the most acidophilic microorganisms ever known. It can fascinatingly grow at a pH below 0. The way acidophiles can survive their hostile conditions is due to their durable cytoplasmic membranes. To maintain the stability of the membrane they require a very high concentration of hydrogen ions. The structure of their membranes are obviously different to other microorganisms as they have evolved to contain many glycoproteins which make the cytoplasmic membrane durable within a hot and acidic condition. Many of these acidophiles have unusual arrangements of lipids which form a strong membrane that can help the organism survive in an extremely acidic habitat (Garg, 2016).

On the opposite side of the pH scale, we find a complete contrast of extremophiles called alkaliphiles which are microorganisms that thrive and grow at pH values above 9. These microorganisms have been discovered to have incredible adaptations which has benefited industrial purposes as they can produce alkali enzymes such as alkaline proteases and alkaline celluloses which is used in the laundry detergent market (Horikoshi, 1999). Alkaliphiles can be found in highly acidic soils and faeces, whereas haloalkaliphiles (alkaliphiles requiring a pH above 9 and a high salinity) can be found within Serbian lates such as Rift Valley Lakes of east Africa. For these extremophiles, their survival relies on maintaining homeostasis and the intake of H+ ions. They protect themselves from the alkaline surroundings using acidic substances like amino acids. Some alkaliphiles increase their hydrophobic interactions and negatively charged amino acids at the interface for stability in their environment (Salwan et al, 2020).

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Fig 1 – pH scale
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Psychrophiles

In contrary to hyperthermophiles, we can delve into the harsh freezing environment where psychrophiles are found. They must overcome reduced enzyme reactivity, a decreased membrane fluidity, different transport of nutrients and waste products, slower rates of cell division, protein denaturing and proteins folding differently. Which all these challenges, psychrophiles have evolved to overcome every single one and can successfully thrive in extremely cold and icy conditions. The lowest temperature life can survive is −24 °C, at these temperatures both aerobic and anaerobic organisms can be found such as the lichen Xanthoria elegans (see Fig.2). To overcome membrane fluidity, psychrophiles has an altered lipid composition, there is a higher amount of unsaturated fatty acids, there is an increased number of lipid head groups which result is a decreased number of interactions in the membranes. As for cell division, protein synthesis occurs at a reduced rate. The enzymes that are used for translation and transcription are adapted to function at low temperatures, an example of this is their RNA polymerase which has evolved to be optimally active. Psychrophiles contain antifreeze proteins which are a remarkable and significant feature as they have the ability to bind to ice crystals and thus they can create the ram hysteresis and lower the temperature which the organism can grow. Therefore the psychrophile is an incredible form of life that can withstand its hostile environments (D’Amico 2006).

New research

These remarkable organisms give a new insight into a world of research with is beneficial to humans. We can use our knowledge of extremophiles for biotechnology all research. All the extremophiles previously discussed can go through cell division and multiply in their environments. Due to these fascinating adaptations, scientists can use them to produce significant biomolecules which can withstand extremely hot or cold temperatures and acidic or alkaline environments. There are of course many different types of extremophiles which are also undergoing research. These biomolecules can perform different abilities at industrial levels. An example of these abilities is biodegradation, sources of biofuel and bio energy. For biodegradation, many

extremophiles microorganism contain enzymes which are robust and versatile; an example of an extremozyme is Bacillus safensis which contains the enzyme oxidoreductase which can degrade aromatic compounds. Furthermore, many enzymes have an important role in chemical, food, paper and waste-treatment industries (Shukla et al, 2020). Therefore, extremophiles can play a predominant role within the future of a sustainable earth benefitting humans across the globe.

Astro biology

Due to their robust structure, extremophiles push the boundaries of life on Earth. They are therefore of interest to astrobiologists curious about exploring life beyond earth. Planets with harsh environments similar to those in which extremophiles can survive may be home to organisms with similar extreme physiological and biochemical adaptations. Scientists have found an extremophile called the Haloarchaea These are anaerobes that can grow with or without the presence of oxygen. Furthermore, they can tolerate many extremes and is the key microorganisms in which astrobiologists believe could expand our knowledge on life in space. To begin with the study of life on other planets, we must understand evolution and habitability as this allows organisms to adapt and survive. Evolution is caused by a random mutation that occurs in the DNA sequence. The mutation could be beneficial and increases survival chances making the organism more likely to pass on its alleles which could include the survival benefactor. The perfect case for this is the Haloarchaea as it represents the perfect model for astrobiology as it has evolved to survive in many different extreme conditions, therefore they possibly evolved very early on Earth. Due to the ancient microorganisms, they could possible survive on Mars as they can survive exposure to radiation, sub-zero temperatures and remarkably, they have been discovered to survive the process of launching them into the stratosphere with high exposures to the conditions of space. Further research includes the proof that Haloarchaea constrain highly acidic proteins. With these proteins, they can maintain an osmotic equilibrium within very salty concentrations. Lastly, with future modelling studies there are plans for astrobiological observations which could lead to new discoveries and potentially answer the question of the existence of life in space and if it is possible (DasSarma et al, 2021).

Extremophiles are an incredible life form that can give scientists further understandings into pushing the boundaries of life. With this knowledge on extremophiles, we can produce biodegrading enzymes and medicine, extremophiles serve a purpose in industrial levels and help benefit society. They also give scientists hope for new life as certain extremophiles could possibly be adapted for another planet. Therefore, with the continuous research produced everyday, we could possibly answer some very important questions about humanity and life based off these incredible organisms.

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Fig 2 – The cold tolerant lichen Xanthoria elegans
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Discussion questions

1. What is the most hostile environment an extremophile can be found in?

2. What are the challenges of studying extremophiles as a career?

References

A, A. (2016). Acidophiles: Meaning, Molecular Adaptations and Applications. [online] Biology Discussion. Available at: https://www.biologydiscussion. com/micro-biology/microbial-growth/acidophiles-meaning-molecularadaptations-and-applications/55119. [Accessed 25/02/23]

Arora, N.K. and Panosyan, H. (2019). Extremophiles: applications and roles in environmental sustainability. Environmental Sustainability, 1(1). doi:https://doi. org/10.1007/s42398-019-00082-0. [Accessed 12/02/23]

Brittanica, E. (2019). Thermoplasma | prokaryote genus. [online] Encyclopedia Britannica. Available at: https://www.britannica.com/science/Thermoplasma. [Accessed 24/02/23]

D’Amico, S., Collins, T., Marx, J.-C., Feller, G. and Gerday, C. (2006). Psychrophilic microorganisms: challenges for life. EMBO reports, [online] 7(4), pp.385–389. doi:https://doi.org/10.1038/sj.embor.7400662. [Accessed 16/02/23]

DasSarma, S., DasSarma, P., Laye, V.J. and Schwieterman, E.W. (2019). Extremophilic models for astrobiology: haloarchaeal survival strategies and pigments for remote sensing. Extremophiles, 1(1). doi:https://doi.org/10.1007/ s00792-019-01126-3. [Accessed 01/02/23]

Direct, S. (2019). Alkaliphile - an overview | ScienceDirect Topics. [online] www. sciencedirect.com. Available at: https://www.sciencedirect.com/topics/ immunology-and-microbiology/alkaliphile. [Accessed 17/02/23]

Interested in learning more?

Here is a short video from National Geographic:

Horikoshi, K. (1999). Alkaliphiles: some applications of their products for biotechnology. Microbiology and molecular biology reviews : MMBR, [online] 63(4), pp.735–50, table of contents. Available at: https://www.ncbi.nlm.nih. gov/pmc/articles/PMC98975/.[Accessed 14/02/23]

NOAA (2019a). What is an extremophile? [online] Noaa.gov. Available at: https://oceanservice.noaa.gov/facts/extremophile.html. [Accessed 22/02/23]

NOAA, N. (2019b). NASA Astrobiology. [online] astrobiology.nasa.gov. Available at: https://astrobiology.nasa.gov/education/alp/what-does-life-need-forsurvival/.[Accessed 24/02/23]

Schröder, C., Burkhardt, C. and Antranikian, G. (2020). What we learn from extremophiles. ChemTexts, 6(1). doi:https://doi.org/10.1007/s40828-020-01036. [Accessed 23/02/23]

Shukla, A.K. and Singh, A.K. (2020). Exploitation of potential extremophiles for bioremediation of xenobiotics compounds: a biotechnological approach. Current Genomics, 21(1). doi:https://doi.org/10.2174/1389202921999 200422122253. [Accessed 11/02/23]

Stetter, K.O. (1999). Extremophiles and their adaptation to hot environments. FEBS Letters, [online] 452(1-2), pp.22–25. doi:https://doi. org/10.1016/s0014-5793(99)00663-8. [Accessed 12/02/23]

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Nancy Rothwell Biological Drawings

Each year a number of College students submit entries to the Nancy Rothwell Award, which challenges young people to draw, paint, sketch or digitally create artwork capturing plant or animal anatomy. The competition is organised by the Royal Society of Biology, supported by the Royal Veterinary College, and is named after the Society’s first President, Professor Dame Nancy Rothwell, who is a strong advocate for bringing art and science together. The award encourages and celebrates biological specimen drawing, promoting the value of observation, creativity and artistry in science learning and discovery.

In 2021, Serena Zhang was awarded ‘Best in College’ for her beautiful hand drawn anatomy of Przewalski’s horse, also called the Mongolian wild horse (Equus ferus przewalski ). In 2022, the ‘Best in College’ award went to Vivien Li for her colourful Koala (Phascolarctos cinereus).

Also shown here is the fabulous cuttlefish by Ava Grimshaw, whose depiction of the anatomical features is outstanding. Pupils are in fine company as Old Cheltonian Edward Wilson was himself an ornithologist, natural historian and artist. Some of his exquisite work is displayed alongside the work of current pupils in the Biology corridor at College.

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Zombie Apocalypse Now –the Cordyceps Fungus

Winner of the 2023 Cheltenham Muscat Biology article contest

‘Frankenstein’...fiction. ‘World War Z’...fiction. ‘The Girl with All the Gifts’...fiction.

One thing that all these texts have in common is that they include gruesome, undead, corporeal revenants, otherwise known as zombies. But of course, these aren’t real.... or are they? We all love horror books, movies, and tales; especially ones that include zombies, but the question is, are zombies really real?

Well, technically...yes.

How the fungus turns its prey into ‘zombies’

The Cordyceps fungus, better known as the zombie ant fungus, infects insects such as ants or spiders. The fungus is found in southeast Asia, and it has over 400 variations that can be found worldwide. Like any other parasite, the Cordyceps fungi clears out the host’s nutrients before filling its body with spores that later allow it to reproduce. Noticeable actions prove that the fungi are infiltrating the host such as twitching, behaving erratically and irregular timed full body convulsions.

The fungi then compel its host to quest for an area of height where the temperature, humidity and sunlight is ideal. This process is called summiting. The fungi force its prey to perform a ‘death grip’ or a ‘death pose’ which causes the host to stay in a certain fixed position for an extended period. When the fungus is ready to reproduce, the fungi takes in its real form and ‘sprouts’ out of the hosts head revealing a tendril shooting its spores out, after some time infecting other insects matching the hosts species. This process takes about 4-10 days (about one and a half weeks).

When these spores are shot out, they are likely to land on a new host or prey, which become the next generation of killer fungi. Think of them as being terrorists (albeit without a political agenda – hopefully) because that’s exactly what they do to the ants’ population, terrorise them! The process of spores being shot out continues for hours. If the Cordyceps succeeds but lands on the insect’s wing (where it can’t bore into) it will shoot out secondary spores to increase the risk or chance of the Cordyceps brain washing its next prey. The Cordyceps deadly spores are very fragile and this oppressive puppet master only does what it needs for its own survival.

Can the ‘zombie fungus’ threaten humans?

Now the moment we’ve all waited for, can this parasitic fungus take over the human body? No. I bet that’s what you wanted to hear before you went to sleep. The Cordyceps fungi can’t infect human beings due to our high body temperatures and our complex immune systems which are harder to take over compared to those of an ant or an insect. Due to this, our immune system is highly efficient at destroying spores. In this case, the Cordyceps fungi, as one gets infected when the Cordyceps spores enter the hosts body. Our innate immune system plays a key role in keeping pathogens (bacteria, virus fungi or other harmful microorganisms) out of our body by identifying the infected cells with pattern recognition receptors (PRRs) and destroying them through specialised cells. There are thousands of Cordyceps species each designed to infect a particular species, thankfully we aren’t on their hit-list.

A Cordyceps infected ant

Although our human bodies are more resistant to Cordyceps than those of an ant or spider, that does not mean we are free from fungi assailing our bodies. One of these examples

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Zombie from Last of Us and insect infected by the Cordyceps
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is ergot poisoning otherwise known as ‘St. Anthonys fire’ or ‘Holy fire’. Ergot poisoning, or ergotism, is caused by eating food (typically rye) contaminated with a fungus called C. purpurea. The popular show: ‘The Last of Us’, took inspiration from the Cordyceps fungi. In the show the Cordyceps can infect both humans and animals, it is also transmitted through food supplies which is somewhat like what the ergot poisoning does.

What use does the Cordyceps have?

The Cordyceps fungi plays a particularly vital role in the jungle’s diversity (where the Cordyceps fungi is mostly found). In most ecosystems, top predators are important in controlling their prey diversity, regulating lower species in the food chain. This is similar to what the Cordyceps does in the insect population. The parasite stops any group of insects from getting the upper hand, in this case, gaining an advantage via overpopulation. If any insect species overpopulates in the jungle or its habitat, they have a higher chance of becoming this puppeteer’s next marionette.

Unbelievably, the Cordyceps fungi has been used as traditional Chinese medicine for a long time. Although the Cordyceps is a fungus, the type of Cordyceps grown in labs, later produced transformed into medicine, isn’t a mushroom. People often

References

David Attenborough, 3 Nov 2008, Cordyceps: attack of the killer fungi - Planet Earth Attenborough BBC wildlife, BBC Studios, 4/13/2023, https://youtu. be/XuKjBIBBAL8

Ed Yong, Nov 14 2017, How the zombie fungus takes over ant’s bodies to control their minds, The Atlantic, 4/12/2023, https://www.theatlantic.com/ science/archive/2017/11/how-the-zombie-fungus-takes-over-ants-bodies-tocontrol-their-minds/545864/

Youri Benadjaoud and Dr. John Brownstein, February 5, 2023, the science behind the ‘zombie fungus’ from the last of us, ABC news, 4/10/2023, https:// abcnews.go.com/Health/science-zombie-fungus-us/story?id=96819243

use the Cordyceps as a medicine for coughs, CKD (chronic kidney disease), ringing in the ears, immunosuppression after organ transplant and more. Although Cordyceps is generally safe, it may sometimes have negative side effects including an upset stomach, nausea, and dry mouth in some people.

Wildlife can be cruel, grotesque and fascinating. Humans have barely scraped the surface in understanding what the cohabitors of our planet can do. Despite the advances that science has made over the past century, our understanding of nature is still far from complete. Afterall, who knew a parasitic puppet master hijacks insects that live among us? We like to believe that our mind is of our own and that we dominate our thoughts and actions, but is this always true? These infamous parasites’ methods of mind controlling are more complex and sinister than anyone could have reckoned. Next time you feel eccentric, or start twitching, who knows, you might be next...

Interested in learning more?

Here’s a video you may enjoy:

Mike Hume, January 15 2023, ‘The Last of Us’ zombie fungus is real and its found in health supplements, The Washington Post, 4/09/2023, https://www. washingtonpost.com/video-games/2023/01/15/last-of-us-hbo- cordyceps/ Jennifer Lu, April 18 2019, How does the parasitic fungus turn ants’ into ‘zombies’, National Geographic, 4/10/2023, https://www.nationalgeographic. com/animals/article/cordyceps-zombie-fungus-takes-over-ants

16 Discovery 2022-23
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To Kill or to Cure?

How plant poisons can surprisingly save life

One of my earliest memories is helping my mother water the plants in the garden. I had my own mini watering can and would stand beneath a bank of beautiful, tall, white, pink and purple foxgloves in awe and fascination as I knew they were the one plant I was on no condition allowed to touch.

the sodium potassium ion pump causes the cells to depolarize and the negative internal charge of the nerve cell becomes temporarily positive due to increased intercellular sodium and calcium ion concentrations. This stimulates the nerve cell causing the heart to contract. The sodiumpotassium ion pump then readjusts the balance of ions and the cells repolarize as the positive potassium ions leave the cell. As they repolarize the heart relaxes (Fig 3).

By inhibiting the pump, the cells become more depolarized and the intercellular sodium levels increase, causing the strength with which the heart contracts to increase but also decreasing the pressure that the blood flows into the heart. In addition, the cells no longer have the ability to repolarize and the heart cannot relax as quickly. If it cannot relax as quickly, it cannot contract again so the rate at which it beats also slows down.

Foxglove or Digitalis (relating to the fingers) from the family Plantaginaceae is a plant that can grow up to six-feet-tall, with spires of tubular shaped flowers generally in shades from purple through to white. The bottom petal of the 5 fused petals has a delicate mottled effect, that folklore says are fairy handprints. Folklore also claims that foxes wear the flowers on their paws to keep dew off their fingers. Widespread throughout Europe, Asia and North America it was brought to the UK in 1694. Although beautiful, it is also highly toxic.

Foxglove poisoning

Foxgloves contain toxic cardiac glycosides, an organic compound that inhibits the cellular sodium-potassium ion pump in our bodies. This pump creates and maintains the electrochemical gradient of the neurones (or nerve cells) in the membrane around your heart.

The maintenance of this electrochemical balance (Fig 2) makes your heart beat (Klabunde, 2022). A nerve signal does not fire when the inside of the cell has a negative charge relative to the outside of the cell. This is called polarization, and consequently in this state the heart is at rest. However,

Ingesting just 140mg of any part of the foxglove plant is enough to stop a healthy person of average weight’s heart beating altogether. Foxglove will also kill the cells and poison the tissues of a foetus and is used by doctors in medicine used for abortion before the second trimester (John, 2022).

It is advisable not to grow foxgloves in allotments or the same soil as edible plants because even the roots are poisonous. Whilst simply touching it should not cause a problem, absorbing the digitoxin, digoxin and digitonin compounds contained within the plant via cuts or by transferring them to your eyes or mouth could be enough to slow your heart or cause arrythmia. Fortunately, perhaps, severe nausea, vomiting and diarrhoea are the more usual symptoms of poisoning.

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Fig 1 - Growing Foxglove flowers Fig 2 - The Sodium Potassium Pump Fig 3 - Basic Heart structure
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For foxglove poisoning it is vital to seek urgent medical help. Activated charcoal is likely to be given in order to help absorb the poisons in the stomach. The porous nature of this type of charcoal trap the toxins enabling them to pass safely through the gut without being absorbed into the bloodstream. In addition, anti-digoxin immunoglobin will be administered which binds to the digoxin preventing it binding to the active site of the target cells within the body. It then accumulates in the blood and is filtered out as waste by the kidneys (Purohit, 2018).

Even deer and rabbit will avoid munching on its broad green leaves and columns of flowers as it is just as fatal eaten by wild animals or domestic ones like dogs and horses. However, this successful defence mechanism deterring herbivory and ensuring continuation of the species does not mean that humans have left it alone, instead we harvest it for its medicinal properties.

Foxglove in medicine

But foxglove also has an established history as a life saver and has been used in herbal medicine through the ages precisely for the characteristics that make it so deadly. Foxglove was first used by William Withering to treat 163 individuals suffering with Dropsy (a swelling under the skin often caused by heart failure) in 1775. Dramatically slowing a healthy heartbeat rate, or decreasing blood pressure significantly is not usually a great idea. However, if your heart is beating too fast or irregularly (tachycardia or arrythmia) or is not pumping effectively causing a high risk of a heart attack, then a very small dose of Digitalis to slow down and regulate the rhythm as well increasing the efficacy of its pumping action, might just save your life.

Unfortunately, it’s not as simple as just chewing on a leaf, the range within which digoxin is useful and within which it is toxic is miniscule, a difference of around 0.2 nanograms per litre of blood (Stoye, 2016). Consequently, in order for it to be measured so precisely, it has to be chemically extracted from the foxglove. Of the many glycosides within the foxglove, digoxin accounts for 90% of the world market. There are a number of ways digoxin is extracted from the plant, but essentially the foxglove leaves are first fermented, then the digoxin is percolated and further isolated and purified. It is generally sold under the name, Lanoxin and administered as either tablets, in liquid form or by injection in hospital (Novković et al, 2013).

Other plants containing cardiac glycosides

Foxglove is not the only plant in your garden that contains cardiac glycosides. Lily of the Valley, Convallaria majalis, (Fig 4) our late Queen’s favourite flower, is also capable of the same heart stopping effects as the foxglove. Fortunately, it is much less cumulative in effect as it is more commonly the cause of poisonings because it is often mistaken for wild garlic (Fig 5) and foraged. Thankfully you are more likely to suffer with dizziness, nausea and vomiting before a cardiac arrest (Lofton and Dasgupta, 2005).

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Fig 4 - Lily of the Valley Fig 5 - Wild Garlic
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Fig 6 - Oleander, Nerium oleander

Oleander, (Fig 6) from the Nerium family, is a beautiful evergreen flowering shrub, with slim grey green leaves and pink, white or red flowers. Although not native to the UK many gardeners, like my mother, have pots or boarders into which Oleander is nestled to protect it from the cold. Like the Foxglove and Lily of the Valley, Oleander is another source of cardiac glycosides and is a common suicide agent in Sri Lanka where poisonings exceed 150 per 100,000 each year.

Like the foxglove it has been used for centuries in herbal medicine to treat various cardiovascular problems, but it has also been used for the treatment of a much larger array of other conditions such as eczema, epilepsy, herpes, malaria, ringworm, abscesses and asthma to name a few, with varying degrees of success or poisoning.

Oleandrin, the most significant of five cardiac glycosides Oleander contains, unlike digoxin, has not been used by pharmaceutical companies in the development of potentially lifesaving heart medication. In fact, it has largely been ignored until very recently. This is partly due to a much more complex pharmacokinetics profile which makes it even more toxic. Ingesting even 20ng/ml is likely to be fatal. Touching the leaves or inhaling smoke from burning twigs is likely to cause any number of severe reactions from ulcerating of the skin and mouth, dizziness, headaches, nausea and vomiting to serious cardiovascular problems including heart failure (Zhai et al, 2022).

Oleander in medicine

Oleandrin obtained recent notoriety when Donald Trump’s Secretary of Housing and Urban Development, Ben Carson and Mike Lindell, an investor of a company that develops Oleandrin, suggested its use to treat COVID 19 in 2020.

Oleandrin tablets are available through various outlets as an herbal remedy, which considering the potential range of serious side effects is actually quite amazing. Consequently, the medical profession has been very quick to discredit these claims over fears of increased numbers of poisonings as people try to avoid COVID 19. However, a flurry of research was subsequently reviewed and compiled and studies later published in 2021 have shown Oleander is an excellent antioxidant (Plante et al, 2021).

Reactive species are by-products of crucial cellular processes, however they sometimes cause damage or mutations to proteins, lipids and DNA which in turn can lead to cancer. Fortunately, these reactive species and free radicals can be neutralised by natural antioxidants found not only in Oleander, but many types of plant thereby reducing their damaging effects.

References

Aronson, J.K. “Positive Inotropic Drugs and Drugs Used in Dysrhythmias.” Side Effects of Drugs Annual, 2008, pp. 209–222, www.sciencedirect.com/topics/ biochemistry-genetics-and-molecular-biology/cardiac-glycoside, https://doi. org/10.1016/s0378-6080(08)00017-2. Accessed 26 Feb. 2023.

Bueno-Orovio, Alfonso, et al. “Na/K Pump Regulation of Cardiac Repolarization: Insights from a Systems Biology Approach.” Pflügers Archiv - European Journal of Physiology, vol. 466, no. 2, 15 May 2013, pp. 183–193, https://doi.org/10.1007/s00424-013-1293-1.

In addition, Oleandrin and Anvirzel, both cardiac glycosides contained in Oleander have also been shown to induce immunogenic cell death in human cancer cells and the subsequent destruction of tumours. Even better, it seems they do this without the detrimental effects on normal somatic cells associated with traditional chemotherapy whereby healthy cells are also destroyed (Li et al, 2021).

With cancer now the leading cause of death in the UK (Whipple, 2016) it is no surprise that consequently Oleander is currently the primary focus of the pharmaceutical industry with treatments currently in phase I and II clinical trials of malignant diseases.

Back to the foxglove

Childhood memories and the magic of folklore have biased me in favour of the tough towering beauty of the foxglove over the more recent pampered purchase of my mother’s potted Oleander, so I must just point out that Digitalis was shown by Stenkvist to do very much the same to breast cancer cells 20 years earlier.

So, killing by foxglove is clearly easy, curing a lot more difficult. But understanding has moved on so much from herbal witchcraft where it was clearly often a gamble as to which the result might be. If we are careful the risks are small, if we are educated the benefits are enormous…

Discussion questions

1. According to the World Health Organisation 40% of pharmaceutical formulations in the Western world are based on ordinary plants, 11% from flowering ones, but is medicine looking hard enough at old traditional remedies for simpler solutions to our healthcare needs?

2. Paracetamol has been proven to be little more effective than a placebo, would doctors be better prescribing herbal alternatives for our aches and pains?

3. With the current trend for foraging, growing our own produce and eating less intensively farmed food, should people be educated and encouraged to use a range of plants as remedies for daily ailments rather than turning to highly processed pharmaceutical drugs?

Interested in learning more?

Here’s an article you might enjoy from the Natural History Museum:

Cheung “Cardiac Glycosides: What Are They, What Are They Used For, How Do They Work, Side Effects, and More | Osmosis.” Osmosis, 2017, www. osmosis.org/answers/cardiac-glycosides. Accessed 26 Feb. 2023.

Cummings, Earl D, and Henry D Swoboda. “Digoxin Toxicity.” Nih.gov, StatPearls Publishing, 4 July 2022, www.ncbi.nlm.nih.gov/books/NBK470568/. Accessed 26 Feb. 2023.

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Farooqui, S., and T. Tyagi. “View of NERIUM OLEANDER: IT’S APPLICATION in BASIC and APPLIED SCIENCE: A REVIEW | International Journal of Pharmacy and Pharmaceutical Sciences.” Innovareacademics.in, 2023, innovareacademics.in/journals/index.php/ijpps/article/view/22505/14014. Accessed 26 Feb. 2023.

“Fascinating Foxgloves – Jane Goodall’s Roots & Shoots: Mission Possible in the UK.” Rootsnshoots.org.uk, 22 June 2018, www.rootsnshoots.org.uk/ blog/2018/06/22/fascinating-foxgloves/. Accessed 26 Feb. 2023.

John, “How Much Foxglove Is Fatal – Superfoodly.” Superfoodly |, 16 May 2022, superfoodly.com/how-much-foxglove-is-fatal/. Accessed 26 Feb. 2023.

Keating, H. Trust, Woodland. “Foxglove and Other Poisonous Plants.” Woodland Trust, 7 Jan. 2020, www.woodlandtrust.org.uk/ blog/2020/07/uk-poisonous-plants/. Accessed 26 Feb. 2023.

Khan, Ibraheem, et al. “Acute Cardiac Toxicity of Nerium Oleander/Indicum Poisoning (Kaner) Poisoning.” Heart Views, vol. 11, no. 3, 2010, p. 115, www. ncbi.nlm.nih.gov/pmc/articles/PMC3089829/, https://doi.org/10.4103/1995705x.76803. Accessed 26 Feb. 2023.

Klabunde, R. E. “CV Pharmacology | Cardiac Glycosides (Digoxin).” Cvpharmacology.com, 2021, www.cvpharmacology.com/ cardiostimulatory/digitalis. Accessed 26 Feb. 2023.

Klabunde, R. E. “CV Physiology | Action Potentials.” Cvphysiology.com, 2021, www.cvphysiology.com/Arrhythmias/A010. Accessed 26 Feb. 2023.

Klabunde, R. E. “CV Physiology | Sodium-Potassium ATPase Pump.” Cvphysiology.com, 2021,www.cvphysiology.com/Arrhythmias/A007b. Accessed 26 Feb. 2023.

Li, X et al. “Oleandrin, a Cardiac Glycoside, Induces Immunogenic Cell Death via the PERK/ElF2α/ATF4/CHOP Pathway in Breast Cancer.” Cell Death & Disease, vol. 12, no. 4, 24 Mar. 2021, www.nature.com/articles/s41419-02103605-y, https://doi.org/10.1038/s41419-021-03605-y. Accessed 26 Feb. 2023.

Lofton, A and Dasgupta, A. (2020). Toxic herbals and plants in the United States. Toxicology Cases for the Clinical and Forensic Laboratory, [online] pp.359–368. doi:https://doi.org/10.1016/b978-0-12-815846-3.00019-3.

NHS Choices. About Digoxin - Brand Name: Lanoxin. 2023, www.nhs.uk/ medicines/digoxin/about-digoxin/. Accessed 26 Feb. 2023. Nicole, Marie, and Mrin Shetty. “Digoxin.” Nih.gov, StatPearls Publishing, 5 Sept. 2022, www.ncbi.nlm.nih.gov/books/NBK556025/. Accessed 26 Feb. 2023.

Novković, V.M “Extraction of Digoxin from Fermented Woolly Foxglove Foliage by Percolation.” Separation Science and Technology, 2014, www. tandfonline.com/doi/abs/10.1080/01496395.2013.864679. Accessed 26 Feb. 2023.

Pathak, Sen, Multani, Asha, Newman, Robert, Narayan, Satya, Kumar, Virendra. “Oleander Extract Induces Cell Death in Human but Not Murine ... : Anti-Cancer Drugs.” LWW, 2023, Plante, K.S., Dwivedi, V., Plante, J.A., Fernandez, D., Mirchandani, D., Bopp, N., Aguilar, P.V., Park, J.-G., Tamayo, P.P., Delgado, J., Shivanna, V., Torrelles, J.B., Martinez-Sobrido, L., Matos, R., Weaver, S.C., Sastry, K.J. and Newman, R.A. (2021). Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2. Biomedicine & Pharmacotherapy, [online] 138, p.111457. doi:https://doi.org/10.1016/j.biopha.2021.111457.

Panzer, Oliver, and Tricia Brentjens. “Wolff-Parkinson-White (WPW) Syndrome.” Essence of Anesthesia Practice, 2011, p. 388, www.sciencedirect. com/topics/medicine-and-dentistry/heart-depolarization, https://doi. org/10.1016/b978-1-4377-1720-4.00340-x. Accessed 26 Feb. 2023.

Pathak, Sen, Multani, Asha, Newman, Robert, Narayan, Satya, Kumar, Virendra .journals.lww.com/anticancerdrugs/Citation/2001/08000/Oleander_extract_ induces_cell_death_in_human_but.13.aspx. Accessed 26 Feb. 2023.

Purohit, M.P. “First Aid for Foxglove Poisoning.” DoveMed, 2018, www. dovemed.com/healthy-living/first-aid/first-aid-foxglove-poisoning/. Accessed 26 Feb. 2023.

Stoye, E. “The Chemistry of Foxgloves – Poison & Medicine.” Compound Interest, 21 June 2016, www.compoundchem.com/2016/06/21/foxgloves/. Accessed 26 Feb. 2023.

Wawer, I. “Solid-State Measurements of Drugs and Drug Formulations.” NMR Spectroscopy in Pharmaceutical Analysis, 2008, pp. 201–231, www. sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceuticalscience/digitalis-lanata, https://doi.org/10.1016/b978-0-444-53173-5.00009-3. Accessed 26 Feb. 2023.

Wei, Xingyu, et al. “Physiology, Cardiac Repolarization Dispersion and Reserve.” Nih.gov, StatPearls Publishing, 21 Apr. 2022, www.ncbi.nlm.nih.gov/ books/NBK537194/. Accessed 26 Feb. 2023.

Whipple, Tom. “Cancer Kills More People than Heart Disease.” Thetimes.co.uk, The Times, 14 Aug. 2016, www.thetimes.co.uk/article/cancer-kills-morepeople-than-heart-disease-vk65zgzt0. Accessed 26 Feb. 2023.

Zhai, Jinxiao, et al. “Oleandrin: A Systematic Review of Its Natural Sources, Structural Properties, Detection Methods, Pharmacokinetics and Toxicology.” Frontiers in Pharmacology, vol. 13, 21 Feb. 2022, www. ncbi.nlm.nih.gov/pmc/articles/PMC8902680/, https://doi.org/10.3389/ fphar.2022.822726. Accessed 26 Feb. 2023.

Images

Figure 1

Burnett, J. (2018). Growing Foxglove Flowers. [online] Flower Magazine. Available at: https://flowermag.com/growing-foxglove-plant-and-foxgloveflowers/ [Accessed 30 Apr. 2023].

Figure 2

Gsu.edu. (2023). The Sodium-Potassium Pump. [online] Available at: http:// hyperphysics.phy-astr.gsu.edu/hbase/Biology/nakpump.html [Accessed 30 Apr. 2023].

Figure 3

Twinkl. (2023). Twinkl Bahrain - Educational Resources across all School levels [online] Available at: https://www.twinkl.com.bh/ [Accessed 30 Apr. 2023].

Figure 4

Hartsnursery.co.uk. (2022). Product reviews: Convallaria Majalis ‘Lily of the valley ’ (Pack of 10). [online] Available at: https://www.hartsnursery.co.uk/reviews. php?productid=18066 [Accessed 30 Apr. 2023].

Figure 5

james (2018). Wild Garlic (Allium Ursinum) Identification -. [online] Totallywilduk.co.uk. Available at: https://totallywilduk.co.uk/2018/11/10/wildgarlic-identification-allium-ursinum/ [Accessed 30 Apr. 2023].

Figure 6

Living Color Garden Center. (2022). How To Safely Grow Oleander In Your Garden. [online] Available at: https://livingcolorgardencenter.net/gardening/ how-to-safely-grow-oleander-in-your-garden/ [Accessed 30 Apr. 2023].

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Searching for Extraterrestrial Life

Is there more life out there?

Astrobiology is the study and search for extraterrestrial life. Nasa’s Perseverance rover has found organic molecules on the dry river delta on Mars. Many molecules containing carbon, which are the fundamental building blocks of life, have also been discovered. When looking for extraterrestrial life, scientists look for biosignatures that could indicate evidence of life or former life on that planet. A biosignature could be any element, molecule, or substance that suggests the presence of organisms and provide evidence of their metabolic activities.

An example of a biosignature is methane; it has been proposed as an exoplanet biosignature. Methane can be produced by many metabolic mechanisms, such as outgassing (the release of gas) and serpentinisation (seawater releasing hydrogen that can reduce carbon dioxide to methane). Methane is an unstable gas existing in the atmosphere, therefore, if methane is found on a planet, it must be constantly replaced.

Exoplanets

Exoplanets are planets that are outside of our solar system, and orbit around other stars. They can also be free-floating and untethered to a star, and these exoplanets are called rogue planets (NASA, 2021).

To look for life outside of planet Earth, astrobiologists search for other rocky planets outside of the solar system to determine whether that planet could support life. There are many methods used by scientists to discover exoplanets. One of the many methods is direct imaging, but only a small number of exoplanets have been discovered this way, as it is difficult to see an exoplanet through a telescope. A more favourable method where most exoplanets are found is the transit method, measuring the dimming of a star while a planet passes it, and using the Doppler shift to see if there is a planet pulling on a star’s light.

The Goldilocks zone

In celestial space, very few planets ever come close to possessing Earth’s habitable conditions. The Goldilocks zone is known as a habitable zone, where temperatures are not too high or low, and just enough to sustain life (NASA, 2022). If the Earth was much closer to the Sun, like Mercury, our water on would boil and evaporate, creating a steam atmosphere. On the other hand, if Earth was much further away from the sun, like Pluto, the water would freeze. The Goldilocks zone is the range of distance close enough to the sun for water to remain in a liquid state, but not so far as to where all the water would become frozen.

Scientists are looking for planets similar to Earth, and although many show potential signs of habitability, Earth is the only one that we know of to have life on it. Some examples of planets in the Goldilocks zone include Kepler-186f and Mars. Although other planets have been found in this habitable zone, they are all larger than Earth, which makes the study of their compositions more difficult.

Kepler-186f is an exoplanet which has similar properties to Earth, such as a similar size, a rocky composition and liquid water on its surface (Culler, J, 2014). However, despite all of its ideal conditions, Kepler-186f only receives a third of the energy from its star that Earth receives from the Sun. Kepler186f is therefore placed on the outer edge of the habitable zone. It is also 500 light years away from Earth.

Another potential candidate located in the Goldilocks zone is Mars. Both Mars and Earth have valleys and mountains, weather and seasons, and one Martian day is only less than an hour longer than Earth’s (Williams, M., 2015). This makes Mars seem like an ideal place for humans to inhabit. Nevertheless, although Mars has been considered to be a ‘second Earth’

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Fig 1 - Diagram of Kepler-196 (Washington Post, 2014) Fig 2 - Earth in comparison to Mars (The Independent, 2019)
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within our solar system, there are still many differences between the two. As seen in Fig 2, the image shows Earth in comparison to Mars; Earth is larger and is at a shorter distance from the Sun. Furthermore, while Earth is covered with liquid water, any trace of water on Mars is frozen under the north and south polar ice caps. The air on Mars is also thinner than Earth’s air. The air on Earth is made up of up to 21% oxygen, which allows humans to live and breathe comfortably on Earth. In contrast, Mars’ air is made up of only 0.13% oxygen, and most of the air is composed of carbon dioxide, which makes it difficult for humans to survive on Mars’ land without any extra supply of oxygen. Mars is also an exceedingly hostile place; with a frozen and dry surface, the cosmic radiation and bombarding protons that would instantly kill any human setting foot upon it.

Despite the fact that Mars would not be able to provide an optimal environment for humans to live in, other organisms that are susceptible to living in more extreme conditions could survive on Mars. Most life on planet Earth such as humans, animals, and plants, require very specific conditions to survive. However, extremophiles, a group of microorganisms that are recognised for their ability to live in ‘extreme’ conditions, are well adapted to living in severe environments and therefore would be fit for living in such conditions of Mars.

Life in extreme environmentsextremophiles

capable of living in extreme conditions, and they thrive in the extreme environments. A thermophile, as its name suggests, would thrive in hot temperatures without their enzyme activity decreasing or their proteins becoming denatured. Psychrophiles, on the other hand, survive in extremely cold temperatures without becoming frozen or letting water expand inside of them and rupturing their bacterial cell walls. Taking into account the environment on Mars, the microorganism that would be able to survive there would need to be a psychrophile to live in the cold temperatures and be radiation-resistant extremophiles to withstand the high doses or radiation on the planet.

Conan the bacterium

Extremophiles are able to live in harsh environments of extreme temperature, pH, salinity, pressure and radiation. These microorganisms have been found deep inside the Earth’s crust, withstanding incredibly high temperatures, and they can also be found living deep inside the ocean at high pressures. Extremophiles are suggestive of the possibility of finding extraterrestrial life, and also may provide an insight into the origins of life on Earth. Since habitable conditions that could support life outside of Earth are so rare, the adaptability and simplistic needs of extremophiles seems more achievable for existence of life outside of Earth.

There are many types of extremophiles - ‘phile’ means to love and be attracted to something. These microorganisms are

In Fig 4 is Deinococcus radiodurans, a microbe known as Conan the Bacterium which was found to have qualities that would allow it to survive on Mars (Magazine, S., 2022). This microbe is one of the toughest microbes on earth, as it is capable of remaining alive even in radiation that would kill other organisms. They are considered as a polyextremophile because they are able to survive many types of extreme environments. They fulfil the requirements of being able to survive in both hot and cold temperatures, and they are also able to survive under high doses of radiation. Scientists tried exposing Conan the Bacterium to ultraviolet light and radiations such as protons and gamma rays to simulate the space-like radiation found on Mars. The bacterium was able to endure extremely high doses of radiation up to more than 100,000 grays. In comparison, humans would suffer fatal health problems after exposure of 0.3 grays of radiation.

The discovery of Conan the bacterium’s ability to withstand such radiation shows it is able to survive the environment on Mars. This suggests that the bacterium along with similar species to it could be lying dormant underneath Mars’ ground for millions of years. However, even if samples of organisms from Mars could be retrieved back to Earth, scientists need to be careful to not contaminate Earth with microbes from Mars. In addition, if humans were ever to visit Mars, they must also be careful to not bring microbes from Earth to Mars, as it could disrupt the native microbial life there.

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Fig 3 - Tardigrada, tardigrade or water bear, is an extremophile Fig 4 - Image of Conan the Bacterium (Smithsonian Magazine, 2022)
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Discussion questions

1. Should we discover a planet enriched with useful resources, are we ethically permitted to take them for use on Earth?

2. Would colonising Mars be worth the risk of potentially harming life forms that are indigenous to the planet?

References

Culler, J. (2014). Kepler Finds 1st Earth-Size Planet in ‘Habitable Zone’ of Another Star. [online] NASA. Available at: https://www.nasa.gov/ames/ kepler/nasas-kepler-discovers-first-earth-size-planet-in-the-habitable-zoneof-another-star. [Accessed on 01/05/23]

Exoplanet Exploration: Planets Beyond our Solar System. (n.d.). Goldilocks Zone. [online] Available at: https://exoplanets.nasa.gov/resources/323/ goldilocks-zone/#:~:text=The%20%27Goldilocks%20Zone%2C%27%20or.

[Accessed on 01/05/23]

Magazine, S. and Kuta, S. (n.d.). ‘Conan the Bacterium’ Has What It Takes to Survive on Mars. [online] Smithsonian Magazine. Available at: https://www. smithsonianmag.com/smart-news/conan-the-bacterium-has-what-it-takesto-survive-on-mars-180981019/. [Accessed on 01/05/23]

Interested in learning more?

Here’s a YouTube video you may enjoy:

NASA (2021). Overview | What is an Exoplanet? [online] Exoplanet Exploration: Planets Beyond our Solar System. Available at: https:// exoplanets.nasa.gov/what-is-an-exoplanet/overview/. [Accessed on 01/05/23]

Williams, M. (2015). Mars compared to Earth. [online] phys.org. Available at: https://phys.org/news/2015-12-mars-earth.html. [Accessed on 01/05/23]

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Changing DNA

Will CRISPR revolutionise genetic engineering?

From cloning to genetic engineering, humans have revolutionised genome editing technology. However, the most recent discovery in the science of gene modification is known as CRISPR; clustered regularly interspaced short palindromic repeats. This technology allows us to change genetic material in living organisms. As represented in Fig 1, the cells are being broken apart to allow natural DNA repair processes to take over. A technology that isn’t even ten years old and can already perform surgery on our genes. It is the cheaper, faster, and more accurate process of changing an organism’s DNA. It is said that ‘the future of CRISPR is now’.

Cas9 has revolutionised life sciences, including targeted gene editing. It was originally adapted from a naturally occurring process that bacteria use as a defence mechanism. When the bacterium detects the presence of the virus DNA, it produces two different short pieces of RNA. One containing a sequence that matches the virus. The two RNAs form an enzyme known as Cas9. Cas9 acts as a pair of ‘molecular scissors’ as its job is to cut DNA. Cas9 proteins cut out a segment of the viral DNA, disabling the virus. It will stitch the taken segment into the bacterium’s CRISPR region. The viral code is then copied to short pieces of RNA where it binds to Cas9.

CRISPR in the future?

The testing of CRISPR had started in labs, but it has slowly advanced to the testing in humans (Drillinger, 2021). Scientists discovered to replace a mutant gene with a healthy one, they had to add another piece of DNA that carries the desired sequence. The CRIPSR system will make a cut, allowing the DNA template to pair up with cut ends, which combines and replaces the original sequence with the new one. It is an exciting advancement of science and medicine where it could even be a potential cure for cancer.

Why use CRISPR?

A lot of attention has been on using CRISPR to cure sickle cell disease. Cells are extracted and treated before inserted back into patients and it happens right in front of their eyes. Unlike other genetic engineer methods, CRISPR can be used to target large areas at once. This is extremely practical for complex human diseases that are caused by many genes acting together. It accelerates research into diseases such as cancer and mental illnesses. Not only can it happen to humans, but it has also been tested on animals. CRISPR can cure mice with Duchenne muscular dystrophy – DMD (Kaiser, 2015). CRISPR will simply snip out part of the defective gene in mice, allowing the organism to make its own essential muscle protein. This approach was the first time CRISPR has been successfully delivered throughout the body to treat animals with a genetic disease.

What is CRISPR?

From living organisms to foods, CRISPR has made advanced breakthroughs, starting from its discovery in 1993 to 2005. Francisco Mojica was the first researcher to characterize this technology. The discovery of Cas9 was made in 2006, by a scientist studying at an Agricultural Research Institute. Scientists have discovered if one would like to edit genes, one would have to use the technology known as CRISPR. The technology was designed to locate a desired piece of DNA inside a cell and genetically alter it. The discovery of CRISPR-

Top breakthroughs made by CRISPR

13,000 edits in a single cell

A student at MIT known as George Church has made a breakthrough by using CRISPR. He made 13,000 edits in a single cell without killing it (Fan, 2019). Church led a study to wipe out PERV - a virus that are integrated in the genome of all pigs. CRISPR has successfully mutated every PERV gene in the pig’s cell which was roughly 62 copies. While doing this study, he found if one made too many edits, a cell could

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Fig 1 - An artist’s impression of CRISPR in action (Genotipia, n.d.)
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commit suicide. This was due to CRISPR breaking the double helix multiple times.

No hangover wines

A team of researchers at the University of Illinois have genetically modified the yeast that is used to ferment wine. They achieved no hangover wines by increasing a chemical known as resveratrol, thus decreasing your hangover. Resveratrol is found in the skin of grapes used to make wine (Patsnap, 2022). The yeast being modified is called Saccharomyces cerevisiae. It has many copies of its own gene, making it highly adaptable and difficult to genetically modify with older methods. Researchers have successfully used CRISPR to cut every copy of a desired gene in one go, increasing the amount of resveratrol. Thus, leaving those hangovers in the dust.

Faster racehorses

How far should we be allowed to go in transforming human race?

Some are suggesting using CRISPR on early embryos to change the genetics at an early stage. But due to safety, social, and ethical reasons, scientists say that’s a step too far. However, that didn’t stop He Jiankui. Jiankui was the rogue scientist behind the creation of the world’s first CRISPRmodified babies, twin girls known as Lulu and Nana (Patsnap, 2022). Said by Dr Kiran Musunuru, who studied stem cell and regenerative biology at the Harvard University, ‘No babies should be born at this point of time following the use of this technology. It’s simply too early, too premature.’ Jiankui altered a gene to protect them from HIV because their father has AIDS. But he did it while the twins were still in a petri dish. Which leads to the problem of his use of CRISPR technology. He genetically altered sperm line cells – the sperm and the egg. In this case of the twin girls, a fertilised egg at the singlecell stage. By changing the DNA at that stage, it will appear in every cell in a person’s body. One may call that effective, however, they are permanent and will be passed onto future generations. There is a real chance that an edit can cause a mutation in the genome, leading to worse case scenarios. Another problem was consent. The twin girls had no authority to say no in the changes made to their bodies.

This sort of technology would only be available for people with status or significant wealth. By encouraging them to use CRISPR, it has the potential to increase inequality in our world. To regulate it, 75 countries have banned the use of CRISPR in human reproduction. But many scientists and governments agree there should be more rules to guarantee its prohibition.

What if there was a way to make certain horses run faster or stronger? Researchers have discovered that different versions of the myostatin gene, an inhibitor of skeletal muscle growth, accounts for the speed of a horse. Argentinian KheironBiotech is using CRISPR to edit the genome of racehorses making breeds that are faster, stronger, and better jumpers (Patsnap, 2022). Thus, increasing their rate of winning. They have a success for removing the myostatin gene with 96.2% efficiency. This includes creating horse embryos with the genetically altered edit. Looking to the long term, we hope to identify more alleles that give horses a natural advantage.

Discussion questions

1. What other scientific uses can CRISPR be used for beyond genetic engineering?

2. Can embryos consent to the use of CRISPR?

3. Will CRISPR increase wealth inequality?

Interested in learning more?

Here’s a YouTube video you may enjoy:

References

Balch, B. (2021). The future of CRISPR is now. [online] AAMC. Available at: https://www.aamc.org/news-insights/future-crispr-now [Accessed 13 Feb. 2023].

Broad Institute (2018). CRISPR Timeline. [online] Broad Institute. Available at: https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/ crispr-timeline [Accessed 14 Feb. 2023].Drillinger, M. (2021). CRISPR Study Is First to Change DNA in Participants. [online] Healthline. Available at: https:// www.healthline.com/health-news/crispr-study-is-first-to-change-dna-inparticipants#How-does-retinal-dystrophy-gene-correction-work? [Accessed 13 Feb. 2023].

Fan, S. (2019). New CRISPR Method Can Edit Over 13,000 Spots in a Single Cell. [online] Singularity Hub. Available at: https://singularityhub.com/2019/04/10/ new-crispr-method-can-edit-over-13000-spots-in-a-single-cell/ [Accessed 13 Feb. 2023].

Genotipia. (n.d.). Genome Editing Image courtesy of Stephen Dixon and Feng Zhang solo apra noticias51426_web. [online] Available at: https://genotipia. com/genetica_medica_news/edicion-crispr-linfocitos-t/genomeediting-image-courtesy-of-stephen-dixon-and-feng-zhang-solo-apranoticias51426_web/ [Accessed 10 May 2023].

25 Discovery 2022-23
Fig 2 - A photo of a racehorse
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Greely, H.T. (2019). CRISPR’d babies: Human Germline Genome Editing in the ‘He Jiankui affair’*. Journal of Law and the Biosciences, 6(1). doi:https://doi. org/10.1093/jlb/lsz010. [Accessed 13 Feb. 2023].

Jazeera, A. (2021). CRISPR: What is the future of gene editing? | Start Here. [online] www.youtube.com. Available at: https://www.youtube.com/ watch?v=pVIVSpUgR44 [Accessed 15 Feb. 2023].

Kaiser, J. (2015). CRISPR helps heal mice with muscular dystrophy. [online] www.science.org. Available at: https://www.science.org/content/article/ crispr-helps-heal-mice-muscular-dystrophy#:~:text=Three%20groups%20 report%20today%20in [Accessed 13 Feb. 2023].

Kurzgesagt – In a Nutshell (2016). Genetic Engineering Will Change Everything Forever – CRISPR. YouTube. Available at: https://www.youtube. com/watch?v=jAhjPd4uNFY [Accessed 14 Feb. 2023].

Liu, A. (2021). TALEN gene editing tool more efficient than CRISPR-Cas9 in compact DNA: study. [online] Fierce Biotech. Available at: https://www. fiercebiotech.com/research/talen-gene-editing-tool-more-efficient-thancrispr-cas9-certain-dna-study#:~:text=A%20research%20team%20from%20 the [Accessed 14 Feb. 2023].

McGovern Institute (2014). Genome Editing with CRISPR-Cas9. YouTube. Available at: https://www.youtube.com/watch?v=2pp17E4E-O8 [Accessed 13 Feb. 2023].

MedlinePlus (2020). What are genome editing and CRISPR-Cas9? [online] medlineplus.gov. Available at: https://medlineplus.gov/genetics/ understanding/genomicresearch/genomeediting/ [Accessed 13 Feb. 2023]. PatSnap. (2022). 7 Innovations Driving CRISPR Technology Forward. [online] Available at: https://www.patsnap.com/resources/blog/7-innovationsdriving-crispr-technology-forward/#:~:text=The%20applications%20of%20 CRISPR%20technology [Accessed 14 Feb. 2023].

P. Zipes, D. (2019). Transcription Activator-Like Effector Nuclease - an overview | ScienceDirect Topics. [online] www.sciencedirect.com. Available at: https://www.sciencedirect.com/topics/biochemistrygenetics-and-molecular-biology/transcription-activator-like-effectornuclease#:~:text=Transcription%20activator%2Dlike%20effector%20 nucleases%20(TALENs)%20are%20synthesized%20by [Accessed 14 Feb. 2023]

26 Discovery 2022-23
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Book review

War Doctor (David Nott) is a gripping real-life story about a British doctor volunteering to work as a frontline surgeon in war zones. Nott emphasises the gruelling nature of the battlefield, and the devastating damage that soldiers have to face. He includes brutally honest and clinical descriptions of his surgeries, and a glimpse of the human experience in the midst of war. This read reminds people of the futility of life and presents the importance of compassion for those who have suffered both emotionally and physically from war.

The Language of Kindness (Christie Watson) is about the twenty-year nursing journey of the author. The book reveals the inner workings of hospitals with some little stories about patients. It is easy to follow the flow of story as she talks about her nursing experience in a chronological order, starting from maternity, young children, A&E, and palliative care at the end of life stage. It is astonishing to see how much work a nurse has to do and the kindness and compassion nurses give to the patients despite the heavy workload. From this book, you will learn the power of kindness from Christie as it makes a huge impact on one’s life, just by listening to and accompanying the patients during their most vulnerable time. I truly recommend this book to anyone, not only those who are interested in nursing and medicine, to spread the power of kindness and make a difference to someone’s life just by a simple, kind act.

Water Always Wins (Erica Gies) is a report of the many ideas and initiatives which aim to reverse the way that humans have abused and mismanaged water over many centuries. The author has visited many places around the world to investigate new ways of managing water. She looks at the effect of dams, the reintroduction of beavers and how we can allow and manage the effective development of mangrove swamps and marshes. This book will appeal to people who would like an introduction to how they can manage their water use differently.

Sapiens: A brief history of Humankind (Yuval Noah Harari) looks at the origins and development of humans from over 100,000 years ago until today, exploring the development of our social interactions and our differences in culture. Harari talks about the introduction of the human language and how our imagination has been shaped over thousands of years. The book shows that while humans have not evolved much biologically in the last 100,000 years our social interactions have advanced significantly. I would highly recommend this book to anyone interested in the science of human advancement, as well as more psychological and sociocultural changes.

27 Discovery 2022-23
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28 Discovery 2022-23 Cheltenham College Bath Road Cheltenham Gloucestershire GL53 7LD Tel: +44 (0) 1242 265 600 Email: admissions@cheltenhamcollege.org www.cheltenhamcollege.org Registered Charity No. 311720 BACK TO CONTENTS

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