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Introduction With a new editorial team taking over, we have brought some fresh ideas with us. We really hope you enjoy the new font, the new Maths section, the book reviews and the “Intrigued?” page in addition to the articles, which span from superhero science to quantum tunnelling. The team of writers and editors is very proud to welcome you to the fifth issue of the Wilson’s Intrigue STEM, written for students by students. Our Mission • Expand your knowledge • Contribute to the Wilson’s community • Make complicated parts of science more accessible • Popularise science and make it more interesting • Inspire creativity through wider research Acknowledgements The magazine simply could not be produced with such finesse without the inquiring journalism of the writers and the multiple zoom calls the new editors have attended to learn and master formatting in Publisher. A massive thank you to all students involved for their contributions! A special thanks must go to Mr Benn, Mr Carew-Robinson, Dr Cooper, Mr Jackson, Mr Lissimore, Miss Roberts and Dr Whiting for proofreading and verifying the accuracy of our articles and the magazine as a whole. If you would like to write in the sixth issue of the STEM magazine to research and discover a new aspect to the subjects, please email me (Divy) at DAYALD@wilsonsschool.sutton.sch.uk for more information. Founded by Devanandh Murugesan and his team of editors in September 2019 Front Cover: This majestic deep sea creature is known as a siphonophore. It is estimated that there are 175 different species of this class, and although it appears to be one large organism, it is in fact a colonial organism composed of two specialised zooids. 2
The Wilson’s Intrigue Team Editors Divy Dayal (Chief Editor) Y12 Nabeel Abdul Rasheed Y12 Aditya Chougule Y12 Aditya Jain Y12 Atharva Narkhede Y12 Mann Patira Y12 Writers Adam Ali Y12 Kinshuk Jain Y12 Sanuka Arya Narang Y11 Karun Kirubananthan Gunawardena Y12 Dulain Gamage Y12 Y12 Shinujan Folaju George Y11 Matteo Cascini Y11 Saravanamuthu Y12 Syed Shah Y12 Jonathan Peter-Rajan Mohamed Ahmed Y11 Y12 Tathushan Moksh Sachdeva Y12 Subenthiran Y12 Junaid Ali Y12 Junayd Soobratty Y12 Prabhas Vedagiri Y12 3
Contents If you are viewing this digitally, you can click on the titles of the articles or sections. BIO-CHEMISTRY MATHS RNA Vaccines: The Copycats 6 Accuracy of Modelling 39 Inside the Cytokine Storm 8 Wonders of Euler’s Number 41 Curing Acute Lymphoblastic Leukaemia 10 Doomsday Argument 43 A Vaccine and a Virus 12 Prime Tuples 45 The Heart that Never Beats 14 Infinite Series and the Real World 47 Growing New Teeth 16 New: Intrigued? - Organ Donation 17 Can Chloroquine Treat Malaria? 19 How to Use Antibodies to Treat Asthma 21 COMPUTING PHYSICS Neuromorphic Computing 25 Quantum Tunnelling 50 Quantum Computing: The Future? 27 Startling Subatomic Particles 52 Volumetric Displays 54 ENGINEERING The Flying V 30 It’s Nanotech, You Like It? 32 Autonomous Vehicles 34 Hydrogen or Electric Cars? 35 How Accurate is the Flash? 36 REFERENCES 56 4
DID YOU KNOW? Dragonflies were one of the first flying winged insects (almost 320 million years ago). Today the biggest dragonflies have a wingspan of 14 cm, however, fossil records suggest ancient dragonflies had wingspans of up to two feet! 5
Bio-Chemistry Section Inside the Cytokine Lymphoblastic Heart that Never Growing New Teeth Storm Leukaemia Beats What has The immune system Cancer in the blood Artificial Hearts in translational dentistry in action p8 p10 action p14 discovered? p16 One vial (0.45ml) contains 5 doses of 30 micrograms of BNT162b2 RNA entire complex in place while a peptide bond forms between the two amino acids through a condensation reaction. The ribosome then moves along the mRNA molecule, repeating this process until a stop codon (UAA, UAG or UGA) is reached. At this point, the polypeptide chain stops growing and detaches from the ribosome [5]. The polypeptide later folds into its precise three-dimensional shape, specifically an antigen of the infectious agent that the vaccine is tailored towards. In the case of Covid-19, this antigen comes in the form of the crown-like spike protein which gives the coronavirus its name. As is typical RNA Vaccines: The Copycats during a primary immune response, the antigen is displayed on the surfaces of specific cells known as antigen-presenting cells or APCs How RNA vaccines are the key to future pandemics (which include macrophages, dendritic By Nabeel Abdul Rasheed (Y12) cells and B cells). Here, it acts as a M signal to trigger an immune response any a GCSE biologist is well- enclosed within a special coating to which eventually leads to acquainted with the protect the mRNA from extracellular immunological memory (through the traditional vaccine – RNA-degrading enzymes in the body production of B memory cells and T memorised religiously and (which detect and eliminate aberrant – memory cells). In effect, the immune reproduced on exam paper as ‘a dead meaning atypical or deviant – mRNAs system can now respond much more or weakened form of a disease- as part of cellular homeostasis) [2,3]. quickly and on a larger scale if the causing pathogen’. But more recently, Once the mRNA reaches the target actual pathogen were to enter the indeed in the last few weeks, scientific cells, it is thought to settle into small body [1,6]. discussion has shifted away from cup-like depressions in the plasma Benefits and Drawbacks these classical live-attenuated or membrane known as caveolae (Latin inactivated versions and instead for ‘little caves’), before entering the As you might imagine, a novel towards a newer, altogether more cell through caveolar endocytosis in technology like the RNA vaccine comes exciting prospect: the RNA vaccine. membrane-bound sacs called vesicles with more than its fair share of risks [4] . and rewards. Chief among the Details & Mechanism advantages are: Having entered the cell, the mRNA can As is the case in all other types, the then bind to a ribosome floating in the Safety: Despite the government’s best purpose of the RNA vaccine is to train cytoplasm or one attached to the efforts, the issue of vaccine safety is your immune system to respond rough endoplasmic reticulum, ready one of continued public concern, as rapidly to a specific infection by for the familiar process of protein illustrated by the ever-growing anti- mimicking the infectious agent. What translation. Two transfer RNA (tRNA) vaccine campaign. In the case of the distinguishes it from more established molecules, each carrying a specific RNA vaccine, there is no chance of counterparts is the mechanism by amino acid, align themselves next to infection because it is entirely free of which this agent is introduced into the mRNA codons which are pathogen particles. Once the antigen is body: rather than injecting the complementary to their own ‘memorised’ by B and T memory cells, pathogen itself, the RNA vaccine anticodons – the start codon being the mRNA is degraded by intracellular comprises a messenger RNA (mRNA) AUG, which codes for the amino acid ribosome-degrading enzymes – a strand that codes for a disease- methionine. The ribosome holds the process likened quite aptly by specific antigen [1]. This sequence is 6
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 ScienceNews to “a Mission Impossible message that self- Delivery: As mentioned previously, the RNA-degrading destructs once it has been played” [2,7]. enzymes in the body make delivery of the vaccine to body cells quite challenging. The most common drug delivery Efficacy: The most striking example of an effective RNA system used to combat this are lipid nanoparticles, tiny vaccine is undoubtedly the most recent one of them all. spherical molecules which can carry lipid-soluble drugs in BNT162b2, as it is fondly named, was developed by their cell membrane bilayer. They contain protruding biotechnology giants Pfizer and BioNTech and consists of surface proteins known as homing peptides which allow a modified mRNA encoding a mutated form of the SARS- for specific, targeted drug delivery. What’s more, lipid CoV-2 spike protein. Large-scale clinical trials involving nanoparticles ensure high encapsulation efficiency of more than 43,000 participants demonstrated a vaccine mRNA, ease of transport and reduced risk to body cells efficacy rate of 95%, measured from seven days after the and immune system compared to alternative methods second of two doses [8]. This was consistent across most [12] . demographics, so much so that in early December 2020, the UK became the first country in the world to approve Storage: Many RNA vaccines need to be frozen or the coronavirus vaccine – ordering over 800,000 within refrigerated, owing to the instability of the RNA molecule the first few days [9]. Up to now, the largely successful itself and the temperature-sensitive nature of the lipid results of this project serves as testament to the nanoparticles. The Pfizer-BioNTech vaccine must be potential of the RNA vaccine. Even so, in the context of stored at -70°C, almost four times colder than the vaccine trials, a sample size of 43,000 may not represent average household freezer [7]! Such demanding all demographics to the degree of validity associated with requirements may be difficult to reach for countries with other, non-emergency use vaccines – thus paving the way limited or no refrigeration facilities; even for those for more extensive research in the near future. privileged with this infrastructure, the cost of procurement and transportation acts as yet another Production: RNA vaccines have the added advantage of barrier to large-scale vaccine distribution [2]. being produced much more rapidly and easily in standardised laboratory procedures than traditional The Future vaccines. In fact, the German biopharmaceutical company Unsurprisingly, a strong focus of current RNA vaccine CureVac (which specialises in mRNA technology) believes research is aimed at developing and improving the that it would only take two months to produce an RNA current mRNA sequences used in the COVID-19 vaccines – vaccine for influenza. Perhaps more importantly, the particularly minimising side-effects and making the drastically lowered production period would enable swift molecule more suitable to everyday conditions. However, rollout of vaccines during pandemics, once again this looks likely to be overshadowed by the even more illustrated by the invaluable efforts of Pfizer and daunting prospect of new, emerging variants of the virus BioNTech [1,2]. – growing areas of concern for governments and Equally, however, the problems associated with any biotechnological companies alike. medical treatment cannot simply be ignored. Just as Looking further ahead, RNA vaccines may well hold the there have been major reasons to celebrate, we are also key to further advances in multi-purpose treatment, faced with numerous challenges when it comes to RNA providing protection for more than one disease at a time vaccines: (as has already been achieved in conventional vaccines Side-effects: While the RNA vaccine may be free of for a select few diseases – most notably the MMR vaccine pathogenic material, it can on rare occasion induce which protects against measles, mumps and rubella) [3]. adverse effects on users, the most recent of which Research and clinical trials are also being carried out on involved two NHS workers suffering allergic reactions to RNA vaccines that could be used to encode cancer the Pfizer-BioNTech vaccine just one week after it was antigens and stimulate immune responses against approved for use in the UK. Both suffered an malignant tumours [3]. This may even become a form of anaphylactoid reaction (not to be confused with immune- personalised treatment by tailoring the mRNA to the mediated and life-threatening anaphylaxis), but were unique properties of the tumour cells of that particular later treated and soon restored to full health. Some individual [1]. allergists and immunologists believe this type of reaction Whatever the future holds, it seems increasingly likely to BNT162b2 could be linked to the compound that RNA technology will play a major part in it, making it polyethylene glycol (PEG) contained in lipid nanoparticles of greater interest to us than ever before. Our role both used to package the mRNA [10]. They believe that a small as students and members of the public is to continue number of people previously exposed to PEG may have educating ourselves of the advances and the shortfalls high levels of antibodies against it, putting them at risk – encountered along the meanders of its development. however small – of an anaphylactic reaction to the Only then can we hope to leave behind a society rife with vaccine [11]. Nevertheless, this theory is supported by uncertainty and scepticism into one which offers hope limited evidence as of yet, and the general consensus is and remedy for all. that initial side-effects are “common with new vaccines” (the words of Professor Stephen Powis, medical Edited by Aditya Chougule director for the NHS in England) [10]. 7
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 Inside the Cytokine Storm By Aditya Chougule (Y12) O ur immune system is both a blessing and a curse. Its intricacies allow for a phenomenal structured defence against invaders but these intricacies also mean a great deal more places for mistakes to be made. As such many diseases arise from malfunctioning of the immune system, the very organ that swore to protect us. One poignant example of this is the cytokine storm. Particularly relevant at the moment, the cytokine storm is a terrifying condition whereby an overabundance of cytokines can cause hyperinflammation and can lead to multi-system organ failure and eventually death. cellular apoptosis- programmed cell death- and inhibit carcinogenesis and viral replication [3]. Essentially, all these cytokines play a wide variety of roles and communicate with a multitude of organ systems, making their betrayal even more frightening. Those reading this will likely have heard of cytokine storm from the news in relation to COVID-19 but in fact there are quite a few triggers for cytokine storm besides a viral pathogen. Indeed, there are three Cytokine distribution [1] types of cytokine storm: iatrogenic, pathogen- induced and monogenic. Pathogen-induced cytokine Key to the disease process of cytokine storms is (you storm probably sounds more familiar than the other guessed it) the role of cytokines; these tiny proteins two since it is the most common cause for the are tremendously important in coordinating the condition; it results from naturally occurring immune response since they act as regulatory microbial infections and viral invaders. In sepsis- signals that activate effector cells and also help to associated cytokine storm (sepsis being a life- resolve the immune response. There are a few threatening reaction to an infection), very often the cytokines that have a higher significance over others collateral damage caused by the immune response in the context of a cytokine storm- specifically interferon-γ, interleukin-1, interleukin-6, and TNF- and as such they are usually found in elevated levels in the midst of a cytokine storm. Interferon-γ is primarily secreted by activated T cells (Th1 and cytotoxic T lymphocytes) and natural killer cells and is a potent activator of macrophages, which engulf pathogens and cells by phagocytosis [1]. The interleukin-1 cytokines are a family of 11 cytokines that have a wide range of biological functions, including acting as a leukocytic pyrogen (mediator of fever) and activating macrophages and Th17 cells, the latter acting as helper cells that coordinate the immune response [2]. Interleukin-6 Cytokine storm pathway [1] is one of the more complex cytokines since it is produced by and acts on immune and nonimmune cells across multiple organ systems- it is an important mediator of the acute inflammatory response and in increasing antibody production. And last but not least, TNF (tumour necrosis factor) is a proinflammatory cytokine with a vast array of functions; although its primary role is to induce fever, augment inflammation, and activate antimicrobial responses through interleukin-1 and interleukin-6 producing cells, TNF can also induce 8
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 as it attempts to clear the pathogen can be more (sensitivity measuring the proportion of positives deadly than the pathogen itself, which is why that are correctly identified) and specificity of 0.73 sepsis has such a high mortality rate [4]. Iatrogenic (specificity measuring the proportion of negatives and monogenic cytokine storms are quite different that are correctly identified) in patient trials- very but equally as terrible. An iatrogenic trigger is that encouraging figures [6]. caused by medical treatment, for example, As for treatment, very often it simply involves infusion of CAR T cells (T cells which have been supportive care to maintain critical organ function genetically engineered to target cancer cells) has as well as control of the underlying disease- in the been shown to induce cytokine storm with excess case of a bacterial trigger this would include levels of interferon-γ and interleukin-6 [1]. antibiotics, for example- and immunosuppression, Additional iatrogenic causes of cytokine storm such as with the use of corticosteroids like include gene therapies, immune checkpoint dexamethasone, to limit collateral damage inhibitors, cardiac-bypass surgery and allogeneic induced alongside the cytokine storm. Eliminating stem-cell transplantation. Furthermore, a particular cytokine that is elevated in the blood monogenic disorders- genetic disorders caused by using treatments such as anti-interleukin-6, anti- a single gene mutation- can also trigger cytokine TNF, anti-interferon-γ, or anti-interleukin-1β storm, although this is rare, along with antibody therapies may be effective in some autoimmune and neoplastic diseases. For instances. However, it may also propagate the example, in patients with primary HLH autosomal underlying disease if given too soon, especially if recessive monogenic abnormalities this leads to the cytokine storm has been caused by a defects in effector and regulatory mechanisms in pathogenic invader. Hundreds of the immune system, which results in overactive immunomodulatory drugs are currently under histiocytes and lymphocytes without a pathogenic investigation for treatment of COVID-related trigger [5]. In patients with secondary HLH, viral, cytokine storm; successful examples include the autoimmune or neoplastic disorders lead to a interleukin-6 receptor antagonists tocilizumab and cytokine storm. For example, patients lacking sarilumab- drugs used to treat rheumatoid functional perforin, which is critical for resolving arthritis which have showed to reduce mortality infections and inflammation, have prolonged T-cell from 35.8% to 27.3% when compared with production of interferon-γ and TNF, so when they standard care and found to significantly improve are infected with a viral pathogen, secondary HLH- survival as well as cutting time spent in hospital by associated cytokine storm develops and it a week to ten days in patients with severe COVID- becomes very difficult to shut off the immune 19 (REMAP-CAP trial) [7]. response; a self-reinforcing inflammatory spiral ensues, leading to multi-organ failure and likely I’d like to finish by lauding the work of healthcare death [1]. professionals and scientists in helping the world get a grip on this pandemic. While there are many In the COVID-19 sphere, a distinct positive lessons to be learned from the past year, we must correlation between the nasopharyngeal viral load stop to appreciate the selfless work that these and cytokine levels in ICU patients suggests that people carry out and what they are willing to risk those with high viral loads are more susceptible to to help others. So, THANK YOU! cytokine storm [1]. Also, comorbidities such as hypertension, diabetes and obesity are associated Edited by Mann Patira with more severe cases of COVID-19, possibly because of the pre-existing chronic inflammatory state or a lower threshold for the development of organ dysfunction, thereby increasing susceptibility to cytokine storm in these patients. Surprisingly, it has been found that classic cytokine storm identification methods, such as the 2004 HLH criteria and the 2016 macrophage activation syndrome criteria, each missed at least 75% of COVID-associated cytokine storm patients, while classifying many others as false positives. Lacking an acceptable scale, scientists at Temple University in Philadelphia created their own Temple Criteria using patient data to determine whether a patient had cytokine storm from COVID- 19; the method had a sensitivity of 0.84 9
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 Can Stem Cells Help Cure Acute Lymphoblastic Leukaemia? By Aditya Jain (Y12) What is leukaemia? into a different type of cell, for example, a skin L cell cannot create a neuron. Our body does, eukaemia is a cancer caused by the however, have some multipotent stem cells left. uncontrolled division of white blood They are stored in the bone marrow, brain and cells. There are two categories of some other organs. There are three types of leukaemia: fast spreading acute stem cells: totipotent stem cells – the best leukaemia and slow spreading chronic example of which is the zygote and can leukaemia [1]. Acute leukaemia further splits into differentiate into any cell and create a whole two categories: acute myeloid leukaemia and organism; pluripotent stem cells – the ones in acute lymphoblastic leukaemia. In this article I the embryo four days after fertilisation which will focus on acute lymphoblastic leukaemia can also differentiate into any cell in the body which, unfortunately, is one of the most but not a whole organism; multipotent stem common cancers in children. cells – found in the foetus and in specific tissues How does acute lymphoblastic leukaemia in the body and can only differentiate into those occur? tissues [4]. Acute lymphoblastic leukaemia is a condition that affects the bone marrow. The cells of the bone marrow have a mutation in which portions of two non-homologous chromosomes are switched. As a result, the cells are stuck in the early stages of development and are immature. This means that they do not function effectively, so lose their ability to properly produce mature blood cells and uncontrollably divide, overcrowding the bone marrow and causing cytopenia. These faulty chromosomes also cause the intracellular proteins of the cell to fold incorrectly and so the cells cannot function and divide as they normally would be able to. Acute lymphoblastic leukaemia leads to the release of large volumes of premature white blood cells. Stem cell potency hierarchy As a result, this means that the number of red blood cells and platelets are reduced (cytopenia) Why are stem cells vital? which can cause tiredness and breathlessness. Being premature, the white blood cells are The stem cells in our body help promote normal ineffective in fighting off viruses and other function and allow the body to produce new infections, allowing the viruses to proliferate to cells to repair minor damage, for example. The other places like the brain and liver [2]. adult blood stem cell in our bone marrow can differentiate into different types of cells that are What are stem cells? vital to normal body function as displayed in the Stem cells are undifferentiated human cells that diagram. Without the adult bone marrow stem are able to develop into many different cell cell, we would not have any white blood cells types. This can range from muscle cells to brain that protect us from pathogens or the red blood cells. In some cases, they can also fix damaged cells that are essential to allow aerobic tissues [3]. Most of the cells in our body are not respiration and not even the platelets that help stem cells, they can only replicate through stop bleeding. Therefore, stem cells are mitosis, creating copies of themselves. These extremely necessary & vital to the body. When therefore are very specialised and adapted to stem cells stop functioning properly, the their function; they cannot just suddenly turn patient’s immune system is likely to be 10
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 compromised; the likelihood of catching with either healthy stem cells from a donor infections, therefore, increases. (allogenic) or the patient’s own stem cells (autologous), which are purged and frozen for Blood stem cell differentiation preservation, removing any leukaemia cells from the sample, and then infused back into the blood, after chemotherapy [6]. This treatment can significantly improve the survival chances of cancer patients. In a study of 508 patients the eight-year survival average was 65% in patients less than 30 and 38% in patients less than 60 [7]. This treatment provides many How does stem cell therapy help cure acute benefits and forms of the treatment are already lymphoblastic leukaemia? in use. For example, in Europe, more than 26,000 patients are treated with blood stem Stem cells are extraordinary in our body cells and this is only going to grow with time [8]. considering their ability to develop into different cell types. They can, therefore, help to prevent Drawbacks of therapy or cure diseases such as heart disease, spinal There are many potential concerns with stem cord injuries and diabetes, as well as cancer. As cell therapy: part of multipotent stem cell therapy, the cells used here form a specific germ layer after the • Risk of cancer: the stem cells could divide differentiation of pluripotent stem cells, and can uncontrollably and cause cancer once give rise to one or two specialised cells. This again; this means that it could actually type of therapy is proven to be effective and has harm the person even further, affecting been used for decades in haematopoietic stem their normal function and not actually cell transplantation. Haematopoietic stem cell helping them. transplantation uses either allogeneic stem cells • Rejection: the immune system attacks and (stem cells from another individual) to replace destroys these stem cells since they are the defective ones found in the bone marrow or foreign; to reduce risk of this the patient autologous cells from the patient’s own body could take immunosuppressants and also that have the leukaemia cells removed. These take cells from a blood relative to help cells will now produce the correct lymphocytes reduce the chance of rejection. that function properly and do not uncontrollably divide. • Graft vs Host disease: transplanted stem cells or bone marrow contains cells from This type of stem cell therapy involves the use of the donor’s immune system; these cells bone marrow as a treatment to haematologic can sometimes recognise your own tissues and lymphoid cancers – mainly acute as being foreign and attack them. lymphoblastic leukaemia. The underlying cause of the cancer may be that the patient has faulty Although stem cell therapy is still in its infancy, genes producing defective cells which can cause its benefits and widespread uses mean that it is problems like the uncontrollable division of T- likely going to flourish in the future. With further cells. The way this treatment works is that bone research and development, I believe stem cell marrow from a healthy individual with matching therapy will be at the forefront of our fight antigens (to help avoid rejection) is transplanted against cancer, and will be the next major into the bone marrow of the patient. Replacing revolution in patient healthcare, just like the bone marrow means that healthy antibiotics and vaccines were before it. intracellular proteins are produced which yield Edited by Aditya Chougule and Atharva healthy precursors, thereby, reducing the Narkhede production of unhealthy and defective lymphocytes [5]. The old cancerous cells are either already killed due to previous chemotherapy or surgery. These are replaced 11
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 A Vaccine and a Virus By Moksh Sachdeva (Y12) W hat is a virus? A virus is an obligate parasite made of proteins and sometimes a membrane made of lipids containing single stranded or double stranded DNA or RNA. Viruses cannot replicate on their own however they can replicate in living cells. A spherical with themselves into a virus can also affect the icosahedral symmetry. modified form of a cell behaviour of the host Prolate – this is a membrane where either cell. It is estimated that common arrangement an internal membrane over one million different for bacteriophage (a (such as the nuclear viruses infect virus that infects membrane) or the outer invertebrates on earth. bacteria) heads and membrane (that Viruses can be argued to consists of an surrounds the infected be alive since they can icosahedron elongated host cell) allows them to persist independently, along one axis. gain a viral envelope. however some may Helical – this shape may Complex – this shape argue viruses are not consist of a central cavity possesses a capsid that alive since they are or hollow tube and tend is unlike the other unable to replicate to form a helical shapes and may also independently [1]. structure since they tend possess other structures to be stacked a central such as a complex outer What is the structure of axis. wall or a tail of protein. a virus? Envelope – these types Viruses don’t have a of viruses envelop specific shape since they display a variety of sizes and shapes otherwise known as morphologies. In general, they can be summarised into five main morphological virus types [1]: Icosahedral - these are most animal viruses however some animal viruses may be near 12
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 A virion, which is more the surface antigens due weakened or inactive commonly known as a to point mutations. A pathogen into the body complete virus particle, point mutation is a where white blood cells has a protective coat of genetic mutation where a then produce antibodies protein called a capsid single nucleotide base is that would be able to which surrounds the changed, inserted or combat the virus if it were nucleic acid. The virus deleted from the DNA or encountered by may also have gained a RNA sequence of an traditional infection. lipid envelope from the organism. This results in Vaccines harness the membrane of the host the wrong amino acid natural activity of the cell. Proteins encoded being produced, thus immune system to better from the viral genome altering the shape of the prepare it for the make up the capsid and protein. Often, when a exposure of a particular the shape of the capsid virus drifts a vaccine may virus [3]. allows for morphological still be effective. This is distinction. due to the change in the The different types of protein structure being vaccines [4] How does a virus work? minimal and so the virus The Oxford vaccine is Viruses work by attaching is still recognised by the composed of a weakened onto specific molecules antibodies. However, version of the common on the cell surface. A when a virus shifts the cold virus which has penetration virus will be vaccine is no longer indeed been genetically endocytosed into the cell. effective. When a virus engineered to produce The capsid will remove shifts, a major change in proteins from the the exposing nucleic acid the antigens surface coronavirus. and then the replication occurs accompanied by Nuclei acid (mRNA) host of nucleic acid and virus fusion. Virus fusion makes spike protein. synthesis of protein coats can be described as the These are safe and quick will occur allowing the process by which to develop but difficult to virus to replicate. enveloped viruses enter store and this is similar to the host cells. The shift the vaccine developed by Why is it so hard to leads to a major change in Pfizer for Covid. control viruses? the antigens and so they Whilst a vaccine may help are much less likely to be Edited by Aditya the body to produce recognised by the Chougule antibodies to combat the antibodies which were virus, the vaccine cannot produced in response to eradicate the virus from the vaccine. Thus, the the general population vaccination is not very since it is not feasible to effective [2]. have everyone vaccinated. Furthermore, What is a vaccine? over time a vaccine may A vaccine is a device that no longer be effective for helps prepare the body to preparing the body to produce antibodies for a produce the required virus so that it can fight antibodies since the virus the virus when it would have mutated. A encounters it. Vaccines virus mutates through are designed to prevent either drifting or shifting. the replication of a virus When a virus drifts, a in a cell rather than treat minor change occurs in them. A vaccine injects a 13
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 The Hearts that Never Beat By Shinujan Saravanamuthu (Y12) T he heart is the blood? Not quite. Jarvik began his work on driver of the body, However, mechanical artificial organs in 1971 with a simple hearts may be humanity’s and the Jarvik-7 was function yet with next evolution in our conceived around 1982 [3]. such complex intricacies, quest to become cyborgs; giving it the strength to a hunk of titanium The Jarvik-7 was designed channel up to 9000 litres strapped to the chest with to completely replace the of blood a day. When the a motor spinning at heart so the diseased heart fails many face the 10,000 RPM seems to be heart had to be removed only option of a heart the vital next step- for its installation. It is transplant- receiving a impractical maybe- but composed of two bell- donor heart is life lifesaving indeed, and in shaped plastic, shown to changing, a second chance the medical world that will the right and titanium at life but granted at the do. pumps that take the place expense of another. of the two ventricles (the Unfortunately, however, main chambers that this is not accessible to deliver the final flow of everyone; as of July 2020 blood to the lungs and there are 343 patients in body). It works by sewing the UK who have been on the cuff end of the placed onto a waiting list pump to portions of the for a donor heart [1]. Even atria that remained when though donor numbers the heart was originally are increasing, with removed. After attaching people now having to opt the pump the chest is out of being a donor, it is closed, leaving two still not meeting demand flexible plastic tubes with patients having to Robert Koffler Jarvik extruding from the torso, wait on average 1085 which are attached to an days for a transplant- one external air compressor in six patients do not With all great inventions, which draws and pumps receive the heart they there is a mastermind, blood to the heart. require in time [2]. Instead pioneer and successor; for of a donor heart what else artificial organs it was can be done… Robert Koffler Jarvik, with permanently have the Jarvik-7. Born in someone strapped to a Michigan, in 1946, he was cardiopulmonary bypass a curious man: always machine? As well as being either elbow deep into his impractical, this machine research or a patient does not maintain blood (quite literally) and flow, can only sustain the inventing the surgical body for 45 minutes and is stapler just as a teenager. only used as a stopgap Working under the wing of measure during surgery. Williem Johan Kloff- the Jarvik-7 Maybe implant vibranium inventor of the dialysis to magnetically control machine during WW2- 14
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 The first patient to receive 2000, and the birth of the implantations [6]. Finally, the Jarvik-7 was retired Jarvik 2000: a motor the ‘bridges to transplant’ dentist Barney Clark on designed to fit onto the could evolve to become December 2nd 1982. After heart with a maximum the ‘bridges to the operation Clark awoke output of up to seven destination’, where the and was able to live litres per minute [5]. It was pumps could take over another 112 days; the first implanted into a 61- the heart either giving Jarvik-7 had extended year old man with enough time for a donor Clark’s life, but it could be cardiomyopathy- an to be found or for the argued that he was not inspiring procedure… heart to recover again. truly living as he was With the leading causes of mostly bed bound during A skull pedestal, is death in the UK since 2001 this period, trapped within attached to the head as being ischaemic heart the confines of the the connecting point disease and hospital. The media between the motor on the cerebrovascular disease, documented Clark’s heart and the external complete artificial hearts condition on the road to battery. This is done demonstrate increasing recovery, however, it was because the scalp tissue is potential in treating soon clear that Clark was fixed closely to the skull today’s biggest diseases, not to get any better with so can reduces risk of and with upcoming the major problem being trauma and damage to inventions such as Total that the site where the soft tissue- maceration. Artificial there is much tubes were attached to more to look forward to [7] the chest were prone to Then a posterolateral . infection; this resulted in thoracotomy incision- just the lungs being below the shoulder blade- Edited by Aditya compromised and is made and a cruciate Chougule significantly weaker so (cross-shaped) incision is unable to support the made at the apex of the artificial heart. This was in heart, which is then cored, addition to the high removing a section of velocity blood that, due to myocardium. When this constant compression occurs, the pump is then from the pump, was being inserted to minimise damaged resulting in the bleeding. The right motor blood clotting and leading is connected at the now to a stroke which left open ventricular apex and Clark paralysed [3]. the blood is then run through a Gore-Tex sleeve This sequence of events which is connected to the led to the fall of the Jarvik descending aorta. During -7 with the media seeing implantation, the power it as doctors playing God cable is carried from the and extending life in apex up to the scapula return for one at a lower where it is then connected quality; which was also to the pedestal described presented in the second above. patient, William Schroeder. Ultimately, the This miracle procedure FDA discontinued the was performed by Dr Jarvik pumps due to Stephen Westaby as well quality control resulting in as Bud Fraizer, who the end for the ‘bridges to impressively improvised transplant’ [4]. much of the operation, Fast forward 18 years, to paving the way for future 15
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 Can We Grow New Teeth? By Mohamed Ahmed (Y12) T ranslational dentistry (a collective term for regenerative dental medicine and dental tissue engineering) has been an active frontier of research over the past 100 years and it seems that it may soon be fit for use today [1]. To understand why dentists have been looking for ways to effectively digest or obtain their the adult gum can respond to grow new teeth back, we have to food, which demonstrates that ‘tooth-inducing’ signals from ask why we cannot replace our evolution has favoured well embryonic tooth mesenchyme in teeth- like many reptiles and aligned teeth that are produced a way that is appropriate for in fish who regrow a new set of once. vitro (in a living organism) teeth every few months [2]! In growth, which would contribute fact, leopard geckos have been While the process of tooth to tooth formation. the ideal model organisms to creation is complicated, it is use when researching luckily well understood: The issue we face today is in the mechanisms of teeth growth. essentially, soft and connective ethics of obtaining embryonic tissue, nerves and blood vessels cells for tooth replacements, (all found in the pulp at the which may be considered a centre of the tooth) are bonded frivolous use of the resource to 3 types of hard tissue: when extractions and other dentine, enamel and cementum. treatments are available and Using RNA sequencing, these cells could be used for researches have deduced more critical procedures (or differentiation pathways of certainly those who are ethically stem cells to odontoblasts and opposed to the use of the ameloblasts which are cell embryo in its entirety), and a populations that give rise to lack of understanding in the cell dentine (the softer- but still dynamics- how the cell interacts In humans and other mammals, harder than bone- tissue closest with its environment- involved the relevant stem cells needed to the pulp) and enamel (a over the differentiation process. to build up the adult teeth when harder protective coating of the Research is currently being we were children die later on in tooth) [4]. conducted to induce the same our lives whereas these geckos differentiation pathways The fruits of this research have form new generations of teeth possible in embryonic stem cells expedited efforts to replace (from retained stem cells) which from adult stem cells and to missing teeth in places such as grow in size under the tissue, understand how these cell King’s College London who have until they surface and displace populations respond to a variety published their research in the the more mature tooth above of environmental factors. Journal of Dental research the tissue [3]. This is much rarer where they are able to produce Edited by Aditya Chougule in mammals due to the dentine, enamel and roots by specialization of our teeth in cultivating adult human gingival response to more specific and tissue (from the gums) evolved dietary needs. For combined with embryonic tooth example, carnivores and mesenchyme (loose multipotent omnivores have developed cells in a protein and fluid canine teeth and molar teeth mesh). The epithelial cells from respectively to allow them to 16
Intrigued? Organ Donation Here at the Wilson’s STEM Intrigue, we are very curious and this often leads to big discussions and debates of scientific news within the magazine writers. Our new “Intrigued?” section hopes to shed some light on one of our most heated debates, while hoping to inform and update news you may have missed, and tackle the big questions with STEM. We surveyed our editors and writers and below are some of the responses. Poll One : The New Law: 20th May 2020 marked a defining moment in the history of organ donation as the new opt-out system first came into effect in England. Also known as Max and Keira’s law, this system means that all adults in England will be “considered potential donors unless they choose to opt out or are excluded” (gov.uk). Those excluded from the plans include: children under 18; people who lack the mental capacity to understand the changes for a significant period before their death; people who have not lived in England for at least 12 months before their death. Great! From what I had heard, hospitals were always short on organ donors, despite the fact that so many people would happily Slightly queasy but it would help lots of donate their organs to save other people's people lives. Having sensible defaults is important William Y12 for anything, but especially where people's @Wilson’sIntrigueOrganDonation lives are involved. Michael Y13 @Wilson’sIntrigueOrganDonation The idea is there and it is a good one, however, I feel that there has been a lack of effort by the NHS that the law has changed; I believe that it was a valid decision to make, yes I have seen and heard adverts to opt out seeing as the majority will be willing to donate but I still don't believe that it it sufficient. Thus their organs. This would ultimately make life it can lead to controversies and future easier for many, whilst preserving the freedom problems for organ donation, however , it may to choose. have seen daunting for people to think about organ donation especially during the current Ishan Y11 climate. @Wilson’sIntrigueOrganDonation Shinujan Y12 @Wilson’sIntrigueOrganDonation Poll Two: As a devout Muslim, my stance on most issues of morality is motivated by my faith. In the case of organ donation, many modern Islamic scholars differ in opinion. Although the most recent fatwā (Islamic scholarly opinion) is that organ donation is permissible in Islam following circulatory arrest, I would rather in this case err on the side of caution. Nabeel Y12 @Wilson’sIntrigueOrganDonation 17
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 Arguments supporting this system include: 80% of people in England support organ donation but only 38% have opted in. This means that families are often left with a difficult decision when a loved one dies. Moreover, in 2019, 408 patients died in the UK on the transplant waiting list and as part of the law, the prospective donor’s family will continue to be involved prior to organ donation. Nevertheless, there are concerns that inaction in an opt-out system may lead to false positives, where individuals who do not wish to donate eventually become a donor. An opt-out system may also increase proportions of deceased donations, which are less likely to be suitable on account of possible brain inju- ry, trauma, hypoxia or cancer prior to death. In the UK, it is estimated that only around 1% of patients who die do so in circumstances that allow organ donation to proceed. On top of this, some religious be- lief systems discourage or prohibit organ donation, attaching greater ethical implications to any poten- tial false positives. More information can be found at: https://www.organdonation.nhs.uk/helping-you-to-decide/about-organ-donation/faq/what-is-the-opt -out-system/ https://www.gov.uk/government/news/opt-out-organ-donation-max-and-keira-s-bill-passed-into-law Although I am in favour of the opt-out scheme law, I believe that an opt-in donation scheme would be better, because it ensures that everyone who actually wishes to donate their organs are doing so. It eliminates the cases of uncertainty where it is unclear whether the donor actually We need more organs. Opt-in may wishes to donate their organ(s). prevent those pesky false positives, Shanjeev but there is always discussion with the donor’s family beforehand whether or not to proceed with the donation. In most cases, the family should be It saves essential time, and OPT-IN aware of the donor’s decision. therefore lives, for those who Koushikk are in need of organs, which require extensive waiting lists Control over our own bodies, dead or which can go on for years. alive, should not be superseded by a OPT-OUT Opting out increases the need for organs in a hospital. availability for organs in the Haris future. However, in the coming years use of stem cells It is not worth giving people an opt in and dying hearts are becoming system when thousands of people are increasingly promising and dying - action needs to be taken to maybe the need for organs help these people. Also, when people will decrease. die, they wouldn’t care whether they have their organs in their body or not Shinujan so it shouldn’t be a problem for them either. It’s a win-win situation. Arya What do you think: OPT-IN or OPT-OUT? 18
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 Is Chloroquine an Effective Medication for the Prevention and Treatment of Malaria? Where Malaria Occurs Across the World By Junaid Ali (Y12) M alaria is a parasitic causes the most deaths parasite must reproduce. To disease spread by worldwide [5]. do this, it requires energy for female Anopheles It is also capable of avoiding metabolic processes and mosquitoes. It is detection from the immune amino acids to create new widely spread in many tropical system. proteins. The parasite regions, mainly areas in Africa, achieves this by breaking Central/South America, Asia Whenever a red blood cell is down haemoglobin. As well as and parts of the Middle East, infected by P. falciparum, it proteins, haemoglobin is also because mosquitoes are able expresses a molecule on its made of a heme unit. The reproduce and complete their surface: P. falciparum heme molecule is toxic to the growth cycle in areas with Erythrocyte Membrane Protein parasite and soluble. To high humidity and high -1 (PfEMP1). PfEMP1 is coded protect itself, the malarial temperatures [1]. Symptoms by var genes in P.falciparum parasite crystallises heme into may begin any time from 7 to and it is this protein that acts hemozoin – a non-toxic 18 days after being bitten by a as the antigen which should be molecule that forms insoluble mosquito that carries the detected in an immune crystals. pathogen. Symptoms can vary response. However, in a P. and include a high falciparum genome, there are When chloroquine is taken temperature (>38°c), 50-60 var genes and only one into the body, it enters red headaches, vomiting, muscle gene is expressed at a time [6]. blood cells by diffusion and it pains and diarrhoea [2]. This means that the surface occupies the parasite’s antigen is able to repeatedly vacuole where the Malaria is caused by single- change so that it is not haemoglobin is digested. The celled eukaryotes known as detected by the host’s vacuole is acidic, so the Plasmodium parasites [3]. immune system. In 2018, P. chloroquine gains H+ ions Plasmodium species develop falciparum made up 99.7% of (protons) and it can no longer in blood-feeding insect hosts. estimated malaria cases in the leave the vacuole by diffusion. When the mosquito bites the World Health Organisation Chloroquine is able to limit the host’s skin, the parasite enters (WHO) African Region, 71% of amount of hemozoin their bloodstream through the cases in the Eastern molecules that the malarial mosquito’s saliva. The Mediterranean and 65% in the parasite can crystallise. parasite can then reproduce in Western Pacific [7]. Therefore, after a certain the liver asexually. The new point, the parasite can no parasites then infect red blood Chloroquine is a medicine that longer continue to crystallise cells and begin to multiply is commonly used in the heme into hemozoin, so heme asexually. This causes the cell treatment and prevention of begins to build up. Heme binds to burst, allowing the malaria. It is composed of a to chloroquine to create an FP parasites to infect more cells combination of various -chloroquine complex. FP- and the cycle repeats. antimalarials and is typically chloroquine is very toxic to the taken with another medication parasite and disturbs its usual There are 5 different species called proguanil [8]. It is able to membrane function. In the of Plasmodium: P. falciparum, prevent the spread of the end, the parasitic cells break P. malariae, P. vivax, P. ovale malarial parasite by down and undergo lysis. and P. knowlesi [4]. P. interfering with the processes falciparum is the most carried out while it is in the Chloroquine was first dangerous as it is the most host’s red blood cells. During discovered in 1934 by Hans common malarial parasite and this phase of the lifecycle, the Andersag. Only in 1947 was 19
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 enough learnt about its concern. For example, the malaria may arise if properties for it to be interaction between chloroquine-resistant P. incorporated into clinical chloroquine and another drug falciparum develop in a certain practice [8]. Chloroquine is now named cimetidine may lead to area, which could lead to a a part of the WHO’s Model List increased levels of chloroquine wider spread if it is not of Essential Medicines and it is in the body due to the controlled. Chloroquine should available as a general inhibition of chloroquine still be used, but I believe only medication [9]. The first metabolism [8]. Additionally, under controlled recorded resistance of the chloroquine in overdose has a circumstances for cases where parasite towards chloroquine 20% chance of death and can there is shown to be no was in the 1950s and ever cause problems with vision, resistance to it. since, chloroquine has breathing, the heart or gradually become less and less sleeping. Build-up of Edited by Aditya Jain effective against P. falciparum chloroquine deposits in the [10] . This is because the body can result in blurred parasites have evolved due to vision and blindness. natural selection and are able to channel chloroquine away Overall, it is clear that from its vacuole. This means chloroquine is an invaluable the drug is incapable of medicine as it is extremely interfering with the parasitic useful in the prevention and cell’s processes. Parasite cells treatment of malaria, that have developed particularly malaria caused by resistance can drain P. falciparum, which is a highly chloroquine at 40x the rate of deadly infection. However, it is a cell without chloroquine also clear that resistance to resistance. chloroquine is becoming more widespread across the world In places where chloroquine with many countries opting to resistance has not yet been use other treatments such as discovered amongst P. artemisinin combination falciparum, chloroquine is still therapy (ACT) as the first-line shown to be highly effective as drug for the treatment against a form of treatment. From P. falciparum. I believe that it 2008-9, a study was carried is necessary for countries (at out in the municipality of high risk especially) to be Puerto Lempira, Gracias a Dios, ready to use ACT if they are Honduras, in order to evaluate not already using it, as the the use of chloroquine. A total WHO advises ACT to be used in of 68 patients from ages 6 areas where chloroquine- months to 60 years of age resistant P. falciparum are completed the entire trial and present [12]. Small outbreaks of each patient was positive for malaria due to P. falciparum according to light microscopy. Each patient was given a dose of chloroquine of varying sizes over the first 3 days, depending on their body weight. Patients received supervised treatment until day 28. The data showed that the parasite density in most patients had dramatically decreased by day 3 and by day 7 all patients were parasite negative (shown by no detected asexual stages in the blood) [11]. Chloroquine can have several side effects on the body, including nausea, vomiting, headaches and diarrhea. It also has several interactions with other drugs, which may be of 20
THE WILSON’S INTRIGUE | BIO-CHEMISTRY Issue 5 | April 2021 What is the Effectiveness of the Use Of Antibodies when Treating Paediatrics Patients with Mild/Severe, Acute/Chronic Asthma Exacerbation? By Junayd Soobratty (Y12) A n asthma exacerbation is distinguished part of the immune system produced in the bone by the swelling or inflammation of the marrow. However, high levels of eosinophils can airway [1]. Respiratory difficulties are cause inflammation in the airways, affecting the caused due to the narrowed bronchial sinuses and nasal passages as well as the lower tubes. The word exacerbation (more commonly airways [5]. The majority of asthmatic conditions referred to as an attack) denotes the event can be controlled with conventional treatment caused by a trigger such as an allergen leading such as inhaled corticosteroids (ICS) appropriate to the airways constricting. Triggers may for their severity. However, some types of include, animal fur, pollen, dust or exercise asthma, known as ‘refractory asthma’ which is where the trachealis muscles contract, when the patient experiences persistent producing more than standard levels of mucus. symptoms, frequent asthma attacks or low lung Asthma is the most common obstructive function despite taking asthma medications as pulmonary disease in children affecting one in they do not respond to high doses of this eleven in the UK [2]. conventional treatment. Some refractory An asthma exacerbation can be categorised in asthma patients have to take oral steroids such two main ways which can further be subdivided as prednisone to manage their asthma. into six classifications [3]: In general: A) Intermittent asthma Short-term treatments [6]: 1) Mild intermittent asthma: where the • Short-acting beta-agonists; first choice for paediatric patient will only experience quick relief of asthma symptoms as they slight tightness of the airways on rare are used as muscle relaxants so decrease occasions the contraction on the trachea by the 2) Moderate Intermittent asthma: where the Musculus trachealis asthmatic will feel some respiratory • Anticholinergic agents; acts swiftly to distress in exceptional cases instantly relax airways 3) Severe intermittent asthma: where the • Oral and intravenous corticosteroids; person would feel significant tightness of relieve airway inflammation but can cause the chest and pain sporadically serious side effects when used long term B) Persistent asthma Treatment used in long-term: 1. Mild persistent asthma: where the person • Inhaled corticosteroids; the most effective would be wheezing or whistling when long-term control medicine usually breathing, with slight swollen airways; • Inhaled long-acting beta-agonists; open symptoms occur more than twice a week the airways by relaxing the smooth but less than once a day muscles around them 2. Moderate persistent asthma: wheezing to • Combination inhaled medicines; an inhaled an extent of murmured speech, coughing, corticosteroid along with a long-acting swollen airways, development of mucus in beta-agonist the airways, some chest tightness or pain; • Biologics; target a cell or protein in the experience asthma symptoms every day body to prevent airway inflammation 3. Severe persistent asthma: where the • Long-acting bronchodilators; possibly paediatric patient will feel significant tiotropium (Spiriva) along with respiratory distress. There may be a corticosteroids even though daily inhaled display of nasal flaring and paradoxical steroid is taken. Long-acting thoraco-abdominal movement; experience bronchodilators alone as a long-term asthma symptoms every day and at least asthma treatment is ineffective as it does one night per week [4]. not prevent and has short term effect for a Key characteristics of an asthmatic paediatric long-term use patient is the reversible airway obstruction, airway hyper-responsiveness and chronic airway inflammation typically with eosinophil infiltration. Eosinophilic asthma involves abnormally high levels of a particular type of white blood cell called eosinophils which are 21
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