Quantum Ultimatum 2021-2022

Foreword

When the prospect of conducting the Annual Moncrieff Jones Christmas Lecture was proposed to me earlier in 2021, I was excited to share with the community here the latest innovative advancements and collaborations at the forefront of medical imaging technology. I introduced several projects my colleagues and I are working on at Canon Medical, including the application of artificial intelligence to improve the accuracy of imaging technology, and bringing such capability to various parts of the country to improve the speed and accuracy of, for example, cancer diagnosis in CT and MRI scans. This technology can be applied anywhere once implemented and lends itself well to community outreach in the context of local health screening clinics in the near future. I was pleasantly surprised and actually inspired by the range and depth of questions that followed, covering areas from the physics behind MRI scanners and neural networks, to the ethical responsibilities of commercial and social enterprises applying it. I was inspired especially because of the enthusiasm and curiosity shown by the students among them, who came up after the lecture had ended to continue asking and learning about the coordination of such futuristic technology behind the scenes and various applications of it within the healthcare setting.

It was evident that students here are passionate about their learning, and well-supported by the science department to achieve that. The MoncrieffJones Society continues to provide students with amazing opportunities to push their academic literacy to new heights at this key stage of their education. This edition of Quantum Ultimatum in your hands (or on your screen) is a collection of articles distilled from the arduous work pupils have done throughout a demanding year, a product

of endless reading, writing, and learning. I am delighted to endorse this magazine and proud to support the Society in this way. It comes with relief that, with the issues we have faced in recent years, our younger generation of scientists are so well equipped to flourish and face up to the challenge.

Lastly, I’d like to express my gratitude to Mr Quinton for his commitment towards the Moncrieff Jones society that makes it as spectacular as it is today, and the administrative and ancillary staff, without whom the lecture could not have gone smoothly. A big thank you to the teachers who have lent their hand in contributing to this magazine despite their packed time, and whose passion for science is ever so contagious. And to dear readers, happy reading to you all.

Mr Mark Hitchman Managing Director, Canon Medical Systems Europe

President’s Introduction

Dear Reader,

Welcome to the 15th edition of Quantum Ultimatum. This year as well as the 54 years before it, the Moncrieff-Jones Society continues to provide a platform for students to share their enthusiasm for science, to inspire and enlighten others of the theory that makes up the world that surround us. This year, 10 pupils shared their knowledge in a specific area of interest to the society. Giving a talk in front of a crowd is a daunting prospect, but most speakers find it rewarding and amongst the most memorable experience from their time in Caterham. The autumn term saw 5 Upper Sixth students giving talks ranging from the little-known world of the microbiome to the mind-bending theory of special relativity. They demonstrated great understanding in their respective fields of research, being able to endure the grueling questions from the audience. The 5 brave Lower Sixth pupils who volunteered covered topics such as quantum computing, catecholamines, and aerodynamics, with their articles showing extensive research and fluent academic literacy, which will undoubtedly be useful in their studies beyond secondary education. I would like to thank all the speakers for their hard work and contribution.

This year, we are honored to have Mr. Mark Hitchman, the Managing Director of Canon Medical

Systems to be our guest speaker for the Annual Christmas Lecture. During this, he shared with us his insights into the development of machine learning and its integration into medical imaging and cancer diagnosis. The mesmerizing talk was followed by an enthusiastic flow of questions from the audience, eager to learn more. The appearance of the head of a nationwide technological giant is a testament to how Moncrieff-Jones Society has become more than just an ordinary school science society, and a great learning experience for our current members.

The growth of the Society was only possible thanks to the efforts of many people. In particular, I would like to extend my gratitude to Vice President Rainis Cheng, for doing so much work behind the scenes and always being supportive. A huge thank-you to Mr. Evans for co-hosting all the MoncrieffJones talks, and Mr. Keyworth for aiding in the publicity for the events. It is with greater ease we complete our work with your immense support in the administrative aspect. I am immensely grateful to Mr. Quinton for trusting me with this position, guiding us in the right direction over the last year, and giving us free reign to express our scientific interests. Last but certainly not least, to every pupil, teacher, and staff who attended the talks this year, thank you for your curiosity and enthusiasm. I believe in Moncrieff, it is each of our passion for learning and science that completes the society. I leave this position relieved, knowing that the Society is in the safe hands of the succeeding president Isabel Singleton and vice president O-Teen Kwok, with your leadership and sound judgment, I am sure the society will continue to grow. I wish you both the best of luck. Enjoy reading! With kind regards, Jason Cho

Annual Christmas Lecture: Machine Learning, Artificial Intelligence and the Future of Diagnostics in Healthcare Jason Cho ...................... 5

Upper Sixth Talks 8

Terraforming Mars Ivan Liu 10

The Microbiome Fleur Masters ............................................ 13

Genetics of Asthma Michelle Wong 16

Modeling Infectious Disease Isabelle Oliver ............................. 19

Special Relativity William Pye 23

Lower Sixth Talks .......................................................... 26

The Catecholamines Isabel Singleton 28

The Invisible Forces – Aerodynamics O-Teen Kwok ..................... 31

Brain-Computer Interface Chelsea Chen 35

Quantum Computing Alex Mylet ........................................ 40

Tumour Dynamics Ryan Li 44

Physics Extension Marc Scott 48

The Radcliffe Punt Richard Evans & Suzana Zizek 49

Science Olympiads 50

Nobel Prizes 2021 .......................................................... 52

The Wright Society Rosie Home 54 Book Recommendations ................................................... 56

Concluding Remarks Dan Quinton 58

Annual Christmas Lecture

Machine Learning, Artificial Intelligence, and the Future of Diagnostics in Healthcare

Jason Cho

The Moncrieff-Jones Society’s Annual Christmas Lecture is and has always been the climactic event of the academic year. In December 2021, the Wilberforce Hall was once again filled with a buzzing audience - students, teachers, and parents alike - all with the same goal to learn more about the current hot topic in the science community, artificial intelligence.

The brilliant talk was given by our guest speaker Mr Mark Hitchman, the Managing Director of Canon Medical Systems. Canon is one of four companies in the UK that supplies the latest cutting-edge imaging technology to all hospitals. Having been a CT clinical specialist, a General Manager for CT, MRI, X-Ray and a Managing director for a robotic radiotherapy company, Mr Hitchman is no doubt at the forefront of developing medical imaging technology. Canon has joined hands with prestigious universities across the UK in PanScreen, a data platform to implement and experiment with innovative cancer screening approaches. The work he and his team are doing is bringing us a new generation of medical equipment that implements artificial intelligence to shorten diagnosis time and improve accuracy.

The night began with Mr Hitchman outlining the different types of medical imaging techniques such as MRI and CT, pointing out the ongoing problem of limited access to this equipment, and that a mobile scanning centre in the form of a truck can help speed up the diagnostic process and give the patients what they need most. Community Diagnostic Centres could also be set up to reduce health inequalities by accurate and fast diagnosis and provision of a more personalized diagnostic experience. These services could include imaging, physiological measurement (e.g. blood pressure and ECGs), pathology (e.g. urine tests), and endoscopy. The importance of outreach and widespread provision of imaging technology could also be seen in the installation of CT relocatables in response to COVID-19. The sector is becoming more adaptive, prepared to provide emergency support when the situation calls for such.

The social significance of advancing medical technology was followed by the highlight of the talk, where Mr Hitchman explained to us how artificial intelligence can be used to revolutionize image interpretation. An image can be broken down into component pixels, they will then be inputted into the neural network, different layers of the network each identify a specific feature of the image, such as colour, shape and texture, combinations of specific values of different features will ultimately produce an evaluation of the image. Mr Hitchman then went on to explain how machine learning can be incorporated into this technology to help pinpoint the types of cancer a patient has, by pulling information from genomics data, imaging analysis and past diagnoses done by surgeons around the globe. Leaving most of the hard work to the computer greatly increases work flow efficiency and reduce the burden of doctors, as they can just interpret the analysis data from the AI and make the judgement.

Towards the end of the evening, Mr Hitchman touched on the social responsibility of enterprises

as large as Canon, reminding us that as scientists, our work and words can have a massive impact on greater society. Alongside scientific progress, we should be mindful of the needs of the community around us. Canon has provided clean water for children in need and is a sponsor in training support dogs that assist individuals living with epilepsy, autism, or diabetes.

On the whole, the Christmas Lecture was a total success, with great questions from the audience and curiosity that overspilled even after the talk had ended, as some stayed behind just to ask more questions and dive deeper into the world of AI.

A word of thanks to the student helpers who helped with preparing and ensuring a well-organised lecture, and a massive thank you to Mr Hitchman and his team for giving us so much insight into the field of imaging and the unlimited potential of artificial intelligence.

Introducing Our Speakers

After a year of online talks, interruptions from lockdown and covid restrictions, our speakers have returned to the live Moncrieff stage for the 2021-2022 season:

Upper Sixth Speakers

Lower Sixth Speakers

Ivan Liu

Isabel Singleton

Alex Mylet

Isabelle Oliver

Michelle Wong

Chelsea Chen

Fleur Masters

O-Teen Kwok

Ryan Li William Pye

Upper Sixth Talks

Terraforming Mars

Human activities are destroying the earth and there will soon come a point where saving the earth will become impossible. Terraforming Mars may provide humans with a way out if we ever need to abandon earth in search of a better home. Moreover, this far-fetched goal can also motivate us to innovate and create more which would benefit everyone in the process too.

The Microbiome

I chose the microbiome as my topic after watching a video about the organisms that live within others. I became fascinated by the importance of balance between the microbes within the gut and the diseases that can result from an imbalance. One of these is known as Clostridium difficile, which is notoriously hard to treat. I heard about a novel treatment known as faecal microbiota transplant, which helps to restore the balance of microbes within the gut.

Ivan Liu

Fleur Masters

Genetics of Asthma

Asthma is a major non-communicable disease, the inflammation and narrowing of the small airways in the lungs cause asthma symptoms, which can be any combination of cough, wheeze, shortness of breath, and chest tightness. In the UK, approximately 5.4 million people are receiving treatment for asthma, of which 4.5 million individuals are residents of England. Being such a common condition, the causes behind this disease have been fascinating as research on the genetics of asthma continues.

Modelling Infectious Disease

I chose to base my Moncrieff-Jones talk on a topic combining my two primary interests - mathematics and biology. Although initially seemingly the least related of all sciences, the applications of mathematics in biology are endless. I specifically chose to talk about mathematical modelling of infectious disease, one of the most interesting and typical examples of mathematical biology. Living through the COVID-19 pandemic, I wanted to deepen my understanding of how we model the spread of the SARS-CoV-2 virus and how this has been used to help combat the pandemic.

Special Relativity

When I first heard that space and time were not fixed quantities, I couldn’t really believe it. I began to conduct more extensive research into the topic which uncovered even more real phenomena that seemed like pure science fiction. I decided to choose Special Relativity for my Moncreiff-Jones talk because of how incredibly interesting and accessible the content is. From observers ageing less to observers having different concepts of what the present is, Special Relativity truly challenges your intuition.

Isabelle Oliver

Michelle Wong

William Pye

Terraforming

Ivan Liu

THE PROBLEM WITH MARS

Mars is a red planet and one of our neighbouring planets and is the fourth planet from the sun. It is located around 1.5 astronomical units away from the Sun and is on the edge of the habitable zone which spans 0.9 to 1.5 astronomical units from the sun. The surface temperature on a summer day near the equator can reach up to 20 degrees Celsius while near the pole temperatures can get down to -125 degrees Celsius. The atmosphere on Mars is extremely thin at approximately 6 millibars at sea level compared to the 1013 millibars on earth. It consists of 95% carbon dioxide, 3% nitrogen, 1.6% argon and has a small trace of oxygen, carbon monoxide, water, methane, and other gases. Due to the low pressure on mars of around 0.006 atm and low temperature, water can only exist as a solid or gas.

Mars does not have a global magnetic field, but rather a strong crustal field on its surface which creates local magnetic shields. When different local magnetic fields align, it creates a weak magnetosphere across the planet’s surface.

The Mars Reconnaissance Orbiter (MRO), after years of collecting data, suggests that mars used to be a habitable planet like earth, which has a large body of liquid water. Riverbanks and dried-up deltas are common on the surface, they are created by the running water that is used to fill them.

Furthermore, by determining the enrichment of water in the polar ice caps on Mars, scientists estimated that Mars used to have 7 times more water than the current volume of the permanent ice caps. The ocean would have covered mainly the northern hemisphere of the planet as it has relatively low elevations and would have covered around 19% of the planet’s surface.

The young energetic sun around 3-5 billion years ago sent out powerful solar wind towards Mars which contain charged particles such as electrons and atomic nuclei such as carbon, nitrogen, oxygen, etc. These solar winds stripped away mars’ ancient atmosphere by ionizing gases in the atmosphere and releasing these highly energetic ions into space, combining the fact that the low-pressure sublimates liquid water which slowly left the Martian atmosphere over millions of years. In total, at least 20 million cubic kilometers of water had already left Mars during the wet Noachian period which ended around 3.7 billion years ago.

If humans are ever to terraform mars, an artificial magnetosphere will need to be used in order to protect the artificial atmosphere from the solar wind. Moreover, with an artificial magnetosphere, gases released from volcanic activities are allowed to build up and increase the pressure and temperature which can trigger a positive feedback loop where the greenhouse gas is produced, increasing the surface temperature and hence releasing even more greenhouse gases.

ARTIFICIAL MAGNETIC SHIELD

Superconducting magnets

Superconducting magnets are chosen to perform such tasks as it can store a magnetic field indefinitely. This mode of operation is usually referred to persistent mode.

At first a heating element is turned on to heat the switch wire until it is resistive. Then a burst of current is supplied by the switch wire to the conducting winding until a desired magnetic field is achieved. No energy is required to sustain the current flowing through the shorted

superconducting winding, so the heating elements are turned off and the power supply is switched off.

At this point, the only energy required is the cooling contraption which keeps the winding in a superconducting state. Over a period, the superconducting magnet will still need to be charged again as the magnetic field will slowly decay due to small residual resistance in the superconducting.

(R is the residual resistance)

Surface magnetic shield

This proposal suggests a superconducting electromagnet that encircles Mars with a loop radius of around 3400km, a length of around 21000km, and a wire diameter of around 5cm. Because most high-temperature superconductors are constructed of rare elements, 109 kg of material is needed just to create the shield and 1015kg of material will have to be mined to obtain the rare elements. This is only around 0.1% of Olympus Mons’ mass (largest volcano in the solar system which is located on mars).

Orbital magnetic shield

A spacecraft can be placed at the L1 Lagrange point (The point the gravitational pull between the sun and Mars matches the centripetal force) so that it will always be the same distance from Mars. This spacecraft will also operate with superconducting magnets and the magnetic field will be increased until the magnetotail encompasses the entirety of mars.

With this method the spacecraft can also orient itself to minimize the mass and momentum of solar winds, hence reducing energy flow into the craft.

INCREASING THE ATMOSPHERIC PRESSURE

Increasing the air pressure on mars can be achieved by deploying nuclear bombs on the poles of Mars to release the frozen CO2 into the atmosphere. The following calculations show the number of Tsar bombs (the world’s most powerful hydrogen bomb created, which has a theoretical yield of 100 megatons) that will be needed :

Heat enthalpy of sublimation of dry ice: 591 KJ/kg

Density of dry ice at 194.5K 1atm: 1562 kg/m^3

Volume of dry ice on both poles: 3.2x10^15 m^3

Temperature of Mars polar caps: 120K

Boiling point of dry ice: 194.5K

Specific heat capacity of dry ice: 0.658kJ/kg K

The energy required to sublimate all the dry ice on both poles will be:

(3.2x1015)(1562)(591)(1000) = 2.95x1024 J

The energy required to increase the temperature of the dry ice from 120K to 194.5K: (3.2x1015)(1562)(0.658)(194.5-120)(1000) = 2.45x1023 J

Total energy: 2.95x1024 + 2.45x1023 = 3.20x1024 J

Numbers of Tsar bombs required: 3.195x1024/4.18x1017 = 7643605

With around 7600000 Tsar bombs the atmospheric pressure will increase by 6 millibars which is already for liquid water to exist and will be a good start in the long journey of terraforming mars.

The Microbiome

Fleur Masters

CLOSTRIDIUM DIFFICILE

Clostridium difficile (CD) is a rod-shaped bacterium, it was first discovered in 1935 by Hall and O’Toole in the faeces of healthy infants. It was not until 1978 that CD was found to be a cause of disease in the majority of antibiotic-induced diarrhoea cases. CD is more common in older patients with weaker immunity and most common in care homes as there is a higher chance of becoming infected. CD releases 2 toxins, A and B; Toxin A is an enterotoxin and toxin B is a cytotoxin responsible for CD’s virulence. A hypervirulent strain known as Ribotype 027 has increased massively in prevalence: in 1984-1993, it accounted for less than 0.1% of the samples, but by 2000-2003, it has already increased to around 50%. This is due to the increase in the toxin that this strain can produce.

Bacteria enter the host via the faecal-oral route, yet unless the microbiome is imbalanced, it remains within the gut. CD is acid resistant, so it can survive the low pH environment in the stomach, and it has resistance to some common broad-spectrum antibiotics. CD is present in 2-5% of healthy individuals. Alterations in the gut microbiome can cause CD infection. When the normal gut flora is disturbed, CD faces less competition so they can multiply rapidly and release toxins. The disturbance in the gut can be caused by antibiotics (especially fluoroquinolone), laxatives and recent food poisoning (a lot of the microbiota is lost).

with oral antibiotics such as vancomycin. In many cases, patients experience recurring episodes of this infection. The bacteria can form spores that are spread in diarrhoea, which are alcohol resistant. Spores can be spread if a doctor goes from patient to patient without washing their hands, or if they use alcohol-based hand sanitiser. The CDC recommends killing the spores using diluted bleach. Unless the spores are killed, they can result in re-infection or colonisation of another host. Reoccurrences are treated with the same antibiotic that treated the first infection, however, on subsequent infection, the doses are higher.

Table 1. The possible course of treatment.

Symptoms are fever, abdominal cramps, nausea, appetite loss and diarrhoea. This is primarily treated

Figure 2. the massive increased rates of CDI in children in the US over time.

TREATMENT

Although antibiotics are effective in most CD cases, the addition of more antibiotics increases the chance of antibiotic resistance due to horizontal gene transfer. Treatments alternative to antibiotics may be considered. Faecal microbiota transplant (FMT) has shown promising results in clinical trials with an 80-95% cure rate. It is when stool, from healthy donors, is transplanted into patients with C. difficile infection. The introduction of other bacteria can compete with CD and increases the resistance to future colonisation.

This treatment has shown much promise, however, the gut microbiome is linked to increased risk of metabolic disease and cardiovascular disease. If a

Figure 1. Electron microscopic image of C. difficile

transplant could help a patient to recover from CDI, it could also give the recipient a type of microbe that alters their risk of having other diseases. By transplanting faeces, the bacteria could unwittingly pass on alterations in their microbiome, leading to disease susceptibility later in life. Before the transplant, the patients should be aware of the possible consequences and should only be used to treat CDI after antibiotic approaches have failed. Donors have to complete many questionaries, be screened for recent antibiotic use, intestinal infection, irritable bowel disease and other infectious diseases before consideration. In addition, related stool

donors are preferred as they have a greater chance of success. The stool is collected from the donor and sent to a lab as soon as possible, it is then mixed with saline water and screened for pathogens, the sample is then stored at -80 degrees Celsius. There are two delivery methods, to the upper and lower GI tract, these methods were compared and results showed that lower GI tract delivery by colonoscope was the most efficacious. Some side effects include diarrhoea, abdominal cramps and nausea. However not all FMTs are successful, this may be due to not making any lifestyle changes after FMT, or rejection similar to when an organ transplant occurs.

Figure 3. The process of infection and possible consequences

Figure 4. The principals of faecal microbiota transplant

Genetics of Asthma

Michelle Wong

Asthma is a common lung condition that causes occasional breathing difficulties. Asthma causes chronic inflammation in the airways making them narrow and more difficult to breathe through. People with asthma can have asthma exacerbation, or asthma attacks, which are triggered by something in the environment and causes immune cells to generate inflammation in the lungs, thus can make them even narrower and potentially be life-threatening.

WHAT CAUSES IT?

In the lungs, there are typically lots of eosinophils below the epithelium in the lamina propria. The eosinophils are white blood cells that carry a cargo of granules, soluble chemical mediators like histamines, leukotriene, prostaglandin, and platelet-activating factor. When eosinophils sense an environmental trigger, such as cigarette smoke in the airway, they release their granules. The chemical mediators are spilled out and start degrading lipids, proteins, and nucleic acids, destroying all major cell components. This creates a strong inflammatory reaction in the bronchial wall. Smooth muscles around the bronchioles spasm, which narrows the airway. This action is exacerbated by the increased mucus secretion in the narrow airways.

family history of asthma seems to increase risk as well. For environmental factors, there is the hygiene hypothesis which suggests that reduced early immune system exposure to bacteria and viruses might increase the risk of later developing asthma, possibly by altering the overall proportion of immune cell subtype. Research has shown that asthma has an important genetic component, but no clear pattern of inheritance has been observed. The heritability estimates of asthma vary between 36% to 79% as there are parts that are still unknown.

WHAT IS KNOWN?

There is a Familial Association of Asthma and Allergy that has a Genetic Component

Familial concordance of a disorder can be because of shared environment and genes. Twin studies can help to determine the relative contribution of a shared environment and genes to a phenotype. Concordance of asthma in monozygotic twins and dizygotic twins can be compared and when possible, the concordance is also compared in twins who were reared together or apart. Another type of experimental design that can identify a genetic component to the trait of interest is segregation analysis where the transmission of a trait is examined in families to see if it conforms to a genetic or environmental pattern. All these studies have shown that familial concordance is at least partly due to shared genes and most authors concluded that genetic contribution is more important than environmental influences.

Asthma and Allergy Show Polygenic Inheritance and Genetic Heterogeneity

WHY IS IT CAUSED?

Although the specific causes of asthma are ultimately unknown, it is thought to be caused by a combination of genetic and environmental factors. Certain genes have been identified to increase the risk of redeveloping asthma, and having a

Segregation analysis of phenotypes has not identified a consistent Mendelian pattern such as dominant recessive or sex-linked. A nonMendelian pattern of inheritance is characteristic of complex genetic disorders such as asthma and allergy. Genetic heterogeneity such as different combinations of gene variants contributes to the phenotype in different families.

Inheritance of Atopic Disorder is End organ Specific

The specific end organ manifestation in the airway, the nose, or the skin for asthma allergic rhinitis and atopic dermatitis are in part familial. On top of the inheritance of an exaggerated IgE response as the basis for all these conditions, individual genes may also lead to specific clinical manifestations of the allergic phenotype.

Specific Regions of the Human Genome Harbor Susceptibility Genes for Asthma and Allergy

Six loci have been implicated by independent investigations, and linkage has been replicated in chromosomes 5, 6, 11, 12, and 13, and multiple candidate genes have been suggested as the reason for the linkage. Additionally, there are no DNA sequence variations that alter protein expression or function that have been incriminated as “asthma mutations”.

WHAT IS PARTLY KNOWN?

In asthma genetic research, several replicated linked loci have been identified while fine mapping, gene identification, and polymorphism localization are in progress in laboratories.

A few specific polymorphisms have been associated with asthma and allergy phenotypes.

β2-Adrenergic Receptor Gene

These genes are on chromosome 5q within the region that had been linked to asthma and

allergy phenotypes. Several variants in the gene have been identified that alter receptor function, which influences the down regulation in response to an agonist. These polymorphisms have been associated with several phenotypes including measures of asthma severity and bronchial responsiveness.

IL-4 Gene

The IL-4 receptor gene is another candidate gene that is in a linked region of chromosome 5q region and is important in contributing to the elevated blood level of IgE that is characteristic of asthma and allergy. The polymorphism has been identified in a region of the gene that binds transcription factors, influencing gene expression. Evidence shows that it may be associated with increased gene expression.

CD14 Gene

The CD14 gene in the 5q region is the major receptor that mediates the cellular response to endotoxin. A prevalent polymorphism has been identified in the CD14 gene and studies have shown that this gene is associated with an

increased level of IgE. The binding of the CD14 receptor by endotoxin during infections in infancy may stimulate the expression of Th1 cytokines, steering the immune system away from the Th2 predominance that exists in utero and during the immediate neonatal period.

WHAT IS REMAINED TO BE ANSWERED?

As research continues, there are still several epidemiological issues that remain to be answered. There are four genome screens published for asthma and allergy phenotypes, and which linkages of the presence of susceptibility genes are still unknown. Replication of linkage study is a difficult task in complex diseases like asthma. This leads to an extended question of which genes are responsible for the linkages. If a linked region contains no obvious candidates, it is difficult to identify the causal gene. Another important question is whether the enormous expense committed by major pharmaceutical companies to find asthma genes will lead to diagnostic or therapeutic innovation.

Modelling Infectious Disease

Isabelle Oliver

Mathematical models are used as tools to predict the spread of infectious diseases in a population. These models can inform research for the eradication and containment of the disease, through various restrictive measures and medical interventions.

THE SIR MODEL

The simplest way to model diseases is by using the SIR model. There are three groups within this model- susceptibles, infectives, and removed, all of which make up the total population:

To explain in further detail. Susceptibles are individuals who could potentially catch the disease. Infectives are people who currently have the disease and can infect others. The removed individuals are those who have already caught the disease and have either recovered or died as a result.

In order to simplify the complexities of how diseases spread, some assumptions are made:

1. The epidemic is sufficiently short- the total population remains constant.

2. The rate of increase in infectives is proportional to the increase in contacts between susceptibles and infectives and occurs at a constant rate.

3. Infectives recover or die at a constant rate.

We can calculate the rate of change of the number of susceptibles in the population over time:

We can also calculate the rate of change of the number of infectives over time: calculates the rate at which susceptibles move into the infective group, so the rate at which infectives are increasing. However, we must also take into account that infectives will recover/die so we subtract , which calculates the number of individuals that recover/die over time, by multiplying the rate at which this occurs by the number of infectives. The rate at which infectives recover or die ( ) is constant, according to assumption 3.

To calculate the rate of change of the number of removed individuals over time:

We can expect that as people become infective, the number of susceptibles is going to decrease proportionally, according to assumption 2. Therefore, individuals are moving from the susceptible group into the infective group, leading to a decrease in the number of susceptibles, so is negative.

As I previously explained, calculates the number of individuals that recover or die over time, which is the rate at which individuals move into the removed group.

Figure 1. Plotting the values of the three groups at each time gives this classic epidemic curve produced by the SIR model.

WILL THE DISEASE SPREAD?

To phrase the question differently, will grow?

is always negative, as , and are all positive, so their product is a positive number, which becomes negative when multiplied by -1. Therefore, because the rate of increase of the number of susceptibles is negative, there must be a decrease in over time, so is always smaller than (the initial value): Substituting into

BASIC REPRODUCTIVE RATIO

If we take , and multiply both sides

by , then divide by , we get:

Factorise:

If the constant is positive then there will be spread of the disease, because the rate of increase of infectives over time will be positive, so there will be an increase in the number of infectives - there will be spread of the disease.

The disease will spread if:

is the basic reproductive ratio. This is the number of secondary infections in a population that will be caused by one initial primary infection.

If only one person has the disease, tells us the mean number of infections that person will cause. This helps scientists to see and describe the intensity of an infectious disease outbreak.

An epidemic is defined when:

Examples of some basic reproductive ratios:

1. The influenza virus - ranges from 0.9-2.1.

2. Measles - from 12-18 (extremely infectious).

3. Ebola - about 1.51-2.53.

4. SARS-CoV-2 - between 1.5 and 3.5.

There is a range for each reproductive ratio as they can vary due to factors such as population density and life expectancy.

Figure 2. Graph showing the accuracy of a mathematical model of the spread of COVID-19 in comparison with the observed data

the effects of various restrictive measures to inform governmental policies.

Figure 3. Graph showing a model and the effects of different restrictive measures on the spread of COVID-19

COVID-19

As COVID-19 is a novel disease, mathematical models are difficult to produce due to little data and understanding about the mechanisms of the virus. In addition, the intricacies of COVID-19 result in a more complicated version of the SIR model, including symptomatic and asymptomatic infectives, as well as exposed and quarantined groups.

Numerous parameters must also be taken into consideration, such as the proportion of individuals who use a face mask, the efficacy of face masks, the effectiveness of social distancing, the isolation rate of individuals, to name a few.

I shall not delve too deeply into these complex models due to the intense detail. However, this application of mathematics to such a current situation, allows us to see how useful mathematical models are in aiding to predict various outcomes of disease spread. Including the possibility to see

MALARIA

Malaria is a disease caused by Plasmodium parasites, transmitted through female Anopheles mosquitos. This vector-borne transmission causes complexities to the modelling of malaria, as the compartments of the SIR model are applied to both the human host and mosquito vector.

Figure 4. A compartmental model of malaria parasite transmission between humans and mosquitos.

•

Special Relativity

William Pye

The Special Theory of Relativity was first put forwards in 1905 when Albert Einstein published his work describing ground-breaking ideas of time, energy and light. The theory was built upon two fundamental postulates:

• The laws of physics are the same in all inertial (non-accelerating) frames of reference.

The speed of light in a vacuum is constant between all observers

The first postulate is one that seems quite intuitive. The only interesting idea it challenges is that if the rules of physics are the same for all inertial observers, then all inertial frames are as relevant as each other. However, the second postulate is a bizarre claim. If we were to pretend that this result was the same for all particles, then if a stationary observer measured the velocity of a car to be 50mph, an observer travelling at 20mph would also measure the exact same car to be travelling at 50mph. Of course, in reality, this moving observer would measure the car’s velocity as 30mph.

Yet this second postulate has been experimentally proven countless times. Perhaps unsurprisingly this causes some bizarre phenomena.

LENGTH CONTRACTION & TIME DILATION

These two effects arise because of the constancy of c, the speed of light. Einstein carried out a series of thought experiments when composing his theory. One of which described a photon clock being seen by two observers moving relative to one another. The clock consisted of a photon being reflected off two mirrors. Each time the photon hit a mirror the clock ticked.

The primed values are used to show measurements taken from the stationary observer. For example, d’ is the distance travelled by the photon measured by the stationary observer. v is the relative velocity of the photon clock and t’ is the time taken for the photon to hit the photon clock. Using Pythagoras:

Now suppose the clock begins to move at a constant velocity. To a stationary observer, we may see that the photon appears to take a path like:

is known as the Lorentz gamma and is the main tool in special relativity that shows how to convert time and distances between observers. Not only is time dilated by this factor, but lengths are also contracted by this factor in the direction of motion to maintain the spacetime interval.

THE TWIN PARADOX

The most famous paradox of Special Relativity is the twin paradox. In this paradox there are two twins, one travels to a star 3 light-years away at near lightspeeds whilst the other remains at the earth. Both twins see each other’s clocks run slowly compared to their local clocks, so when they reunite, who is older?

The answer can be seen clearly using a spacetime diagram. On this diagram, the twin on earth has coordinate axes x’ and t’ and because the x’ axis is in light-years, a photon beam will always sit at 45° to the horizontal. To represent the twin moving away from us we can draw a line at an angle to the vertical.

We can see that the stationary observer sees the clock tick slower than an observer who would be travelling with the clock or relative to a local clock. If we wanted to calculate the exact difference in time, we can say that for one tick:

Here, the twin reaches the planet after 3 earth years and heads back to earth. Due to the twin on earth being stationary their worldline is straight up. The stationary twin’s worldline is just the same as its time axis and we can say the same for the moving twin. The twin’s position axis is hence at the same angle to the horizontal because the photon worldline must run at the same angle to both t and x axes.

THE LADDER PARADOX

This paradox states that there is a barn that is just too small to fit a ladder into it. The ladder is then sent through the barn at a fraction of the speed of light so that it is length contracted just enough to close the barn doors with the ladder inside. From a stationary observer, the ladder is completely locked in the barn, yet from the perspective of the ladder, the ladder is still unable to fit into the barn. How can the ladder be both in and out of the barn at the same time? The answer can once again be found in the form of a spacetime diagram. Firstly, a spacetime diagram from the stationary perspective. The gaps in the barn worldline represent the times the doors of the barn are open.

Much like how the x’ axis represents the stationary twin’s present time, the x axis shows the moving twin’s present. However, after reaching the star and turning back towards earth, the frame of reference of the twin changes and so does his x axis. If we were to see how many of the stationary twin’s birthdays the moving twin experiences we see that he doesn’t experience some birthdays as he returns home.

Yet we can add present time lines from the perspective of the ladder or the ladder’s x axis. We see the ladder views itself as far longer than the stationary person does as we would excpect and we also see that the ladder doesn’t even view the gates shutting as simultaneous events.

So does the ladder fit in the barn? Well, yes and no. Its all a matter of perspective. This also shows how simultaneity, and even sometimes orders of events, is relative.

The twin that travels to the star experiences less time than the stationary twin. Or in more conventional terms, accelerating frames of reference age less than stationary frames of reference.

Lower Sixth Talks

The Catecholamines

I first came across the catecholamines when researching the body’s response to threats. Here, I discovered this group of monoamine neurotransmitters’ role in the fight-or-flight response. It has always amazed me how something so seemingly small accounts for such urgent responses, and I found myself instantly drawn to their biosynthesis and functions. Further reading brought me to pheochromocytoma, a fascinating catecholamine-secreting tumour, which, in turn, led me to metanephrine and catecholamine degradation.

The Invisible ForcesAerodynamics

Before the stride of the Wright Brothers in the early 1900s, flying had seemed to be an impossible task, only coming true in fairy tales. Who could have anticipated thousands of airliners, each carrying hundreds of passengers across the globe daily only a century later? Like many others, I have been fascinated by the science of flight and to put it in academic terms, aerodynamics, which explains not only the theory of flight but is also applied to wind turbines, race cars, sailboats, buildings (and the list goes on!)

Isabel Singleton

O-Teen Kwok

Brain-Computer Interface

I have always been fascinated by neuroscience and its application in medicine. Inspired by one of the MIT neuroscience open courses which discusses brain-computer interface (BCI), I gained interest in what connecting the brain and computer can achieve. For paralysed patients with an interrupted brain-spinal cord-muscle pathway, BCI can act as an external conductor of their brain signals, thereby enabling movement and communication just by the thought of it. My journey of research was eye-opening as it is incredibly exciting to see the bright future of neurotechnology through BCI..

Quantum Computing

I chose to talk about quantum computing because I had seen articles announcing new milestones and developments in quantum computers, both advances in qubit numbers and error correction techniques. However, I found that many of these articles required a deep understanding of quantum mechanics and quantum computing to properly understand, so I decided to gain a basic understanding of quantum computing and then continue to read deeper.

Tumour Dynamics

Cancer is complicated, making it that much more challenging to cure, despite advances in medical technology. Science’s persistent attempt to shut off what is otherwise arguably the most successful DNA reproducing machinery in evolutionary history is ongoing. The reasons for cancer recurrence are numerous, which led me down a surprising route in investigating one of the most likely and intriguing aspects of cancer tumours - heterogeneity.

Alex Mylet

Chelsea Chen

Ryan Li

The

Catecholamines

Isabel Singleton

As the name suggests, the catecholamines are made up of a catechol (C6H4(OH)2) and an amine group (-NH2), making them monamine neurotransmitters. They include dopamine, norepinephrine and epinephrine. Dopamine is produced by neurones in the midbrain. Both norepinephrine and epinephrine are produced by chromaffin cells in the adrenal glands and in the sympathetic nervous system.

DOPAMINE

Dopamine’s role in the body changes depending on the dopaminergic pathway. In the nigrostriatal pathway, dopamine affects the basal ganglia’s regulation of movement. Too little dopamine in this pathway establishes the link to Parkinson’s disease. The mesocorticolimbic pathway joins the mesocortical pathway (VMA in the midbrain to the prefrontal cortex) and the mesolimbic pathway (prefrontal cortex to nucleus accumbens). It is this pathway that has been nicknamed ‘the reward pathway’ as it has an effect on mood, with an increase in dopamine leading to a sense of euphoria or even hallucinations.  The final pathway is tuberoinfundibular, which is dopamine’s endocrine pathway. When there is less dopamine here, the periventricular nucleus in the hypothalamus signals the pituitary gland to secrete prolactin. This is why dopamine is sometimes referred to as the prolactin inhibiting factor.

NOREPINEPHRINE & EPINEPHRINE

the vasoconstriction that occurs during the stress response. Epinephrine increases blood sugar levels (by stimulating glycogenolysis in the liver) and heart rate. It also relaxes the smooth muscles of the bronchiole, making it easier to breathe (this is why epinephrine is the preferred treatment for anaphylaxis).

BIOSYNTHESIS

The catecholamines are derived from the amino acid tyrosine. The initial step of catecholamine biosynthesis is when tyrosine is hydroxylated to dihydroxyphenylalanine (DOPA) via an aromatic amino acid hydroxylase (AAAH) called tyrosine hydroxylase. In turn, DOPA is decarboxylated (via aromatic amino acid decarboxylase) to form dopamine. In neurones that use dopamine as a neurotransmitter, this is the final stage of enzymatic modifications.

For neurones that use norepinephrine, dopamine is hydroxylated by dopamine-beta-hydroxylase (DBH). Norepinephrine is then methylated by phenylethanolamine-N-methyltransferase (PNMT) in neurones that use epinephrine as a neurotransmitter. This uses the cofactor s-adenosyl methionine (SAM), which donates a methyl group.

Norepinephrine and epinephrine work together to carry out the fight or flight response. Their main difference is that epinephrine works on both alpha- and beta-receptors, whereas norepinephrine only works on alpha-receptors. Alpha-receptors are only found in the arteries and have a particular affinity for norepinephrine, which accounts for

A pheochromocytoma is a catecholamine-secreting tumour, formed by chromaffin cells within the adrenal medulla. 90% are idiopathic, and the other 10% are related to other genetic disorders. The increase in epinephrine leads to alpha receptor activation, causing vasoconstriction, which increases blood pressure. The increase in norepinephrine activates beta-1 receptors (found in the heart) and beta-2 receptors (found in airway smooth muscles). The activation of beta-1 receptors leads to increased heart rate and stroke volume, putting one at risk of tachycardia. Beta-2 receptor activation leads to smooth muscle relaxation in the respiratory system.

The Classic Triad of symptoms includes an episodic headache, palpitations and tachycardia, and diaphoresis. There are also other, less common, symptoms: orthostatic hypotension, weight loss, polyuria, often in conjunction with polydipsia, as well as paroxysmal hypertension. The onset of symptoms is often triggered by stress, anaesthesia, or labour.

DEGRADATION OF THE CATECHOLAMINES

Dopamine is produced mostly in dopaminergic neurones, so degradation mostly occurs in the extracellular space. The initial step of this degradation is deamination by monoamine oxidase. The product here is DOPAL, a deaminated aldehyde

intermediate. DOPAL lacks a beta-hydroxyl group, so binds more to aldehyde dehydrogenase (AD) than aldehyde reductase (AR), to form DOPAC. However, there is a pathway to DHMA via AR. The end product of dopamine degradation is Homovanillic Acid (HVA), which is produced when DOPAC undergoes o-methylation by catechol-o-methyltransferase (COMT).

Epinephrine and norepinephrine are primarily synthesised in chromaffin cells in the adrenal medulla, or in sympathetic neurones. They are stored in vesicles and only released on activation of the neurone. However, some can leak, passively, into the neuronal cytoplasm. The initial degradation step of deamination can then occur by intracellular monoamine oxidase. The remaining steps of epinephrine and norepinephrine occur in the extracellular space. DOPEGAl (the product of this deamination) has a beta-hydroxyl group, and therefore binds more readily to AR than AD, to produce DHPG. As with dopamine, there is another pathway in this step, forming DOPET via AD. COMT is then used to form MHPG, which then forms MOPEGAL via AD. MOPEGAL is a shortlived intermediate in the degradation, so soon, via AD, becomes the end product: Vanillylmandelic acid (VMA). Norepinephrine also has an additional degradation pathway when it is first o-methylated by COMT to form normetanephrine, which, in turn, forms MOPEGAL via monoamine oxidase. The final step is the same: the formation of VMA via AD.

MRI of abdomen. The arrow points to a tumour in the right

The Invisible Forces Aerodynamics

O-Teen Kwok

Aerodynamics is a branch of fluid mechanics concerned with predicting the forces and moments when an object interacts with moving air. Generally, aerodynamicists are interested in flows around airfoils - the cross-section of a wing, as well as the lift and drag produced.

HOW IS LIFT GENERATED?

The most popular ‘explanation’ of lift is Bernoulli’s principle. It states that if the pressure drops along a streamline, the velocity increases and vice versa, which is described mathematically by Bernoulli’s equation, one of the most well-known equations in fluid mechanics. Its most common form is written as:

The variables P is the static pressure, is the velocity, is the density, g is the acceleration due to gravity and h is the relative height. Bernoulli’s equation can be described as the conservation of energy for a flowing fluid, assuming a steady, incompressible and inviscid flow along a streamline. These assumptions are reasonable because air is considered to be incompressible in aerodynamics when they are flowing with the Mach number being less than 0.3 (~100m/s); whereas the effect of viscosity is only confined in a thin boundary layer around the surface of an airfoil, so it is largely negligible. Besides, the small change in height is negligible, so this can be simplified as:

Bernoulli’s principle tells us that as the velocity of air increases when it moves over the top of an airfoil, the pressure drops. As a result, the pressure gradient between the upper surface and the lower surface causes lift. However, the explanation overlooks the fact that Bernoulli’s equation applies only along a streamline and it is based on the initial assumption that air travels faster on top of an airfoil without explaining why this is so. Although Bernoulli’s principle is a fallacy, it is important to note that Bernoulli’s equation is used extensively by aerodynamicists, for instance, when calculating the freestream velocity in wind tunnels.

A common misconception is the equal transit time theory which suggests that since an airfoil has a

longer upper surface than the bottom, air molecules have a greater distance to travel compared to those that move under the airfoil. In order to meet up with other air molecules that started at the leading edge when t = 0, the air molecules going over the

top surface must move faster. Similarly, by using Bernoulli’s equation, the lift can be explained by the pressure gradient.

What’s wrong? Apart from the misuse of Bernoulli’s equation, another fundamental flaw of this theory is that the air travelling above does not get to the trailing edge at the same time as the air travelling below. If this were true, aerobatics aircrafts would not be able to fly upside down since they have symmetrical wings. In reality, the air above reaches the trailing edge before the air below as it has a significantly higher velocity. This can be observed at ease when pulses of streamlines consisting of smoke particles are fired at an airfoil shown in Figure 1. There are simply no physical laws that support the theory but frustratingly, this misleading idea is so widespread that it has even been taught in textbooks!

Among all the different theories, the explanation using Newton’s third law is most applicable. Since air has mass and is redirected downwards by the airfoil, there must be an equal and opposite force acting on the airfoil. Therefore, no matter what shape the wings are, lift can be generated as long as there is a suitable angle of attack (how steep a wing is tilted) which turns the flow down. Nevertheless, this theory still fails to elucidate the lower pressure atop the wing.

So, what is the correct theory? Surprisingly, there is no universal consensus on the theory of lift. Academics have been attempting to explain lift for

years but they either fail to fully address the problem or lack statistical evidence. John D. Anderson, a leading authority in this field, gave a disappointing conclusion in an interview: “There is no simple oneliner answer to this”.

While the absence of a theory might seem scary, the technical side of this field has reached maturity and aerodynamicists are able to accurately predict flow behaviours using both numerical and analytical methods, leading to an array of complex applications.

DRAG AND SEPARATION

Compared to lift, drag seems to be more intuitive as one could easily imagine the resistive force when walking in a pool. Drag forces are caused by two different sources, pressure and shear stress. Pressure p always acts normal to the body surface, whereas shear stress τ is the stress distribution that is tangential to the body surface. The drag force is the resultant of these two sources in the direction of the flow.

When air flows through an airfoil, a boundary layer is formed around the surface, where air travels slower as it gets closer to the surface due to friction forces. In addition, only above the boundary layer can the flow be regarded as inviscid. As fluid elements separate at the stagnation point, those which flow over the top accelerate. This acceleration must be caused by a pressure gradient known as the favourable pressure gradient. Beyond a certain point, the flow starts to retard and so the pressure in the flow direction

Figure 2. Boundary layer separation over the top surface of an airfoil

increases, pushing the fluid back. This increase in pressure is called the adverse pressure gradient. If it acts over an extended distance, the deceleration will eventually be great enough to reverse the direction of flow. Since the flow cannot travel backwards because of the oncoming air, the flow detaches from the boundary layer and a turbulent flow is produced around the surface instead, resulting in a flow separation as shown in figure 2. The turbulent flow produced increases the pressure and thus reduces the pressure gradient. This could lead to a significant loss of lift and a gain of drag when having a large angle of attack (wings are tilted up too much). In aviation, this is known as stall and could lead to catastrophic consequences; for example, causing plane crashes.

In aerodynamics, laminar flow is the airflow in parallel layers, with no disruption between them. In contrast, turbulent flow is a flow regime characterised by chaotic property changes in which the airflow mixes across. To delay flow separation, we could promote turbulence since the turbulent boundary layer has a more rapid increase in velocity along the y-direction than that in a laminar boundary layer as shown in figure 3. The resulting higher kinetic energy of the turbulent boundary makes it less susceptible to the adverse pressure gradient and therefore, shifts the separation point downstream.

For example, the dimples on a golf ball are designed to cause vortices which result in a turbulent flow. This delays flow separation and reduces the pressure drag so that the golf ball can travel farther.

Figure 3. Velocity profiles in a laminar and turbulent boundary layer

Brain-Computer Interface

Chelsea Chen

PARALYSIS

Paralysis affects millions of people in the world, leading to the loss of motor function to different extents. Tetraplegia is the most severe form of paralysis, not only involving the loss of movement but also sensation in all four limbs and torso. Multiple diseases lead to paralysis: traumatic stroke that damages the sensorimotor area, amyotrophiclateral sclerosis (ALS) which is resulted from the degeneration of motor neurones, spinal cord injury (SCI), and other types of severe central nervous system (CNS) injuries.

As conventional therapeutic or assistive approaches exhibit limited efficacy in restoring movement in paralysed patients, researchers are developing new methods to improve their life quality. A promising direction is using a brain-computer interface (BCI).

BRAIN-COMPUTER INTERFACE (BCI)

A BCI is a computer-based system that directly acquires brain signals, analyses them, and translates them into commands that are sent to an output device to carry out the desired action. Its working mechanism involves 4 sequential components.

1. Signal Acquisition: measuring brain signals using a sensor when the user is imagining themselves or perceiving a virtualisation of themselves administering a task. Equipment used to record brain signals could range in invasiveness.

Overall, non-invasive sensors are the most widely used because they are cheap, safe, and easy to manipulate. More invasive sensors have a higher

resolution as signals are not distorted after passing layers of tissue surrounding the brain, making it hard to accurately distinguish or locate them. However, invasive sensors suffer from low long-term stability as scars form around the implantation, interfering with signal transmission. Additionally, they pose higher risks to users due to the need for surgery.

Non-invasive No surgery

Externally or on the scalp

2. Feature Extraction: distinguishing signals relevant to the desired action. Environmental artefacts such as waves produced by powerlines or magnetic field of the earth are distinguished and extracted, and the elimination of biophysiological artefacts requires machine learning. The user needs to imagine themselves conducting an action repeatedly while their brain activity is being recorded. The computer looks for similar patterns and finds the exact neural activity that relates to an action. Such a process may require repeated calibration to adapt to temporal changes in the user’s neural activity.

Electroencephalogram (EEG), functional magnetic resonance imaging (fMRI)

Electrical or metabolic

Invasive

Craniotomy Sitting on or embedded in the brain cortex

Electrocorticography (ECoG), microelectrode array Electrical

Type of BCI Surgery Placement Example Signal measured

3. Feature Translation: using calibration acquired from machine learning, decode processed signals into appropriate commands for output devices. E.g., increased oscillation frequency produced by a certain group of neurons indicates a forward movement of the left arm.

4. Device Output: administering instructions such as robotic arm movement, cursor control, and letter selection. Feedback (usually visual) is given to the user for them to adjust movement if needed. Achieving successful movement control over a BCI can require months of practice.

THE MOTOR CORTEX

In humans, the control of voluntary movements involves the brain sending signals to muscles via the spinal cord. While multiple cortices coordinate to command a movement, the motor cortex in the frontal lobe is the most predominantly engaged region. It can be divided into three areas: the premotor cortex which plans for the movement, the supplementary motor area (SMA) which rehearses the movement, and the primary motor cortex (M1) which calculates exact vectors of the motion and sends out instructions to the spinal cord. Any disruption in this pathway, such as spinal cord injury or brain damage caused by stroke, could result in compromised movement function such as paralysis.

As shown by the cortical homunculus, areas on the motor cortex are specialised in controlling the movement of individual body parts. This allows BCI sensors to be implanted or placed specifically on the desired region to acquire neural commands for moving a particular body part. Moreover, as the direction of movement changes, different groups of neurones fire (known as population coding) in synchronisation; as the strength of movement varies, neurones fire at different frequencies. The exact indication of neural activity is understood through repetitive sampling of the same movement for the machine to ‘learn’, as mentioned before.

In the motor cortex locate mirror neurones. They fire not only when executing a movement, but also when imagining a movement, known as motor imagery. Seeing or hearing someone else conducting a specific action would also trigger a mirror neurone to light up. This allows BCIs to record neural activity for a specific movement from paralyzed patients without them moving.

MOVEMENT RESTORATION

BCIs can assist movement of paralysed patients by either stimulating muscles according to acquired brain signals or using them to move a neuroprosthetic (e.g., robotic arm, exoskeleton). In a clinical trial in 2014-2016, a patient with tetraplegia received implants of intracortical microelectrodes in his brain and electrodes in his muscles. Together with another neurotechnology called functional electrical stimulus (FES), which stimulates peripheral muscles and nerves, the patient commanded functional

multi-joint movements with a success rate of 80-100%. This patient practiced target upper-limb movement by first controlling a virtual arm with brain signals, and then his own arms with a mobile arm support to overcome gravity. Eventually, he was able to reach and grasp a cup of coffee to drink after being paralysed for 8 years.

MOVEMENT REHABILITATION

Stroke is a leading cause of paralysis. Movement rehabilitation in stroke patients could be accomplished by stimulating more use of the ipsilesional (affected) brain region to increase excitatory neural activity in said region, a process known as cortical reorganisation, which could be done by FES of muscles.

A controlled study involving a BCI-FES group and a pure FES group suggested that BCI is effective in patients with hemiparesis (compromised motor function on one side of the body). Usual FES gives the patient’s paretic limb an electric stimulation whenever they are instructed to move, thus stimulating the muscles to contract, attempting to reconnect motor pathways involving the ipsilesional region by this reward. However, in the BCI-FES group patients were specifically given electric stimulations when their attempt to execute a movement is

recorded by the EEG, therefore providing a much more accurate reward, preventing false-positive results (when the patient didn’t attempt to move but FES is given). It was observed that the BCI-FES patients made significantly better motor recovery compared to the FES group, which is associated with increased connectivity between the premotor and primary motor cortex in the ipsilesional brain areas of BCI patients. Furthermore, the BCI group exhibit maintained functional recovery in follow-up evaluations 6-12 months after the study.

COMMUNICATION RESTORATION

In severe forms of paralysis such as tetraplegia and locked-in syndrome (LIS, where all muscles are paralysed, except for eye muscles), patients lose the ability to communicate. A study published in May 2021 demonstrated a possible assistive communication approach for these patients---brain-to-text communication via handwriting. Participant T5 had tetraplegia resulting from cervical SCI. With the implantation of 2 microelectrode arrays in his premotor area, T5 was instructed to imagine himself handwriting 26 letters and 5 punctuations with a pen for 27 repetitions in each trial, while the microelectrodes recorded his neural activity. The computer then reconstructed these characters by linearly decoding the pentip velocity from trial-averaged neural activity. During the trials, T5 ‘attempted’ to write sentences

given by the researchers as the BCI decoded his handwriting in real-time and output sentences on a screen. Eventually, T5 reached a writing speed of 90 characters per minute (close to the average smartphone typing rate in his age group) with a 94.1% success rate. With the application of a language model that simulates an autocorrect mechanism retrospectively, the accuracy was increased to 99%.

This study has exceeded any past BCI studies in both the speed and accuracy of communication. However, it did not enable text editing or deletion, and daily retraining of BCI was required. More studies should work on the practicality of this communication method.

THE FUTURE

BCI is still in its infancy. Only 5% of the studies in this field involve end users, and even those with one tend to be uncontrolled or case studies. Recruiting participants is particularly difficult for studies using invasive BCI due to the risks induced by surgery. Therefore, it is difficult to gain a large

sample size, which is crucial for investigating the effect of variability between individual brains on the control of BCI. Although there is evidence supporting BCI’s competency in helping paralysed patients to complete functional movement or communication tasks, they are still way too basic for daily use. Moreover, the use of most BCI requires professional assistance in a lab setting, therefore more improvements should be done to the design of BCIs suitable for home use. For a user, learning to control a BCI requires good vision and cognitive function to understand instruction and receive feedback, which limits its use in some paralysed patients.

In conclusion, BCI is a neurotechnology with a remarkable potential in reconnecting paralysed patients to the world through assistive and rehabilitative approaches in movement or communication restoration. However, it still lacks applicational value at the current stage. More investigations need to be conducted to generalise the long-term home-use of BCI to satisfy the large population of patients living with paralysis.

Quantum Computing

Alex Mylet

Quantum computing extends the idea of a classical computer to use quantum mechanics to its advantage, manipulating quantum bits through quantum logic gates. Richard Feynman first proposed quantum computers to simulate quantum mechanics, but it is also possible to perform mathematical calculations on them much faster than on any classical computer.

MATHEMATICS

Classical bits can either be 0 or 1 (represented as and ) but quantum bits (qubits) can be in a superposition of these two states. Superposition is often described as being in both states at once, but a better description is that when in superposition, qubits are in a combination of the states and , with a probability of being found as when measured, and a probability of being found as . In superposition, each of and (referred to as basis states) are multiplied by a complex number (a number in the form , where ) and added together, so a general qubit state . The probability of measuring is and the probability of measuring is ( means take the ‘size,’ or amplitude, of the complex number then ). Therefore . The state of the qubit is not decided in advance, and the process of measurement collapses the superposition to a single state.

Alternatively, qubits can be represented using vectors, and gates by matrices, meaning linear algebra (which focuses on manipulating vectors and matrices) can be used to design quantum circuits. Doing this, is equivalent to and is equivalent to and the general state is

One of the simplest classical logic gates is the NOT gate, which turns a 0 into a 1 and vice versa. This has been extended into the quantum NOT, or X, gate, which flips the numbers in the vector of the qubit (known as a ‘bit-flip’), so . The matrix representation of the X gate is

The Hadamard gate (H) takes qubits from the basis states into and out of superposition. Applying it to gives ,

which has a 50% chance of being when measured and a 50% chance of being . The amplitude for each state is

therefore , and so

The Hadamard gate takes a qubit into a superposition with the same probabilities, but there is a minus sign instead of a plus sign, hence the state is called .

The Hadamard gate is also reversible, so and

Hadamard gate matrix

To represent multiple qubits in a system, you can combine the qubits together to make a single vector in an operation called tensoring. The amplitude squared for each element is the probability of the whole system being measured in a particular state.

Tensoring of two qubits

To make a universal quantum computer, you must have a set of enough one-qubit gates, as well as a twoqubit gate, such as the Controlled NOT gate (CNOT). CNOT applies NOT to one of the qubits (the target qubit), but only if the other qubit is (control qubit). CNOT can be represented as a 4x4 matrix, acting on the tensor product of the two qubits. In this form, CNOT swaps the amplitudes of and : if you have going into the gate (the first qubit being the control), the control is and so the target gets flipped, becoming (and likewise for ).

Matrix-vector multiplication

CNOT matrix

ENTANGLEMENT

Fig. 1 Diagram of quantum circuit of making, then applying CNOT using this as the control qubit. tensored with In a two-qubit system, if you start with two qubits, apply H to the first one (getting ) and then apply CNOT with the qubit as the control and the qubit as the target, the qubits will either both be 0 or both be 1 when measured. Thus, the qubits are correlated, or entangled. The qubits will also still be correlated if you take them far apart before measuring.

See the diagram for the mathematics of applying H then CNOT. Intuitively, you can understand this based on the result of the first qubit (the one that went through the H gate) retroactively determining what had to have happened to the other qubit. If the first qubit is measured in the state, then the CNOT will not have fired, so the other qubit remains in the state. However, if it is measured in the state, then the CNOT will have fired, so the other qubit is flipped to the state.

ARCHITECTURE

There are three main ways of implementing qubits: using the polarisation of light, using the energy levels of charged particles (ions or electrons) trapped in magnetic fields, and using the state of a superconducting circuit, along with others still in development. In both trapped ion and superconducting architectures, different energy levels are used as the basis states of the qubit, meaning there is the potential for the system to decay back to the ground state, causing loss of the quantum superposition and causing errors.

Applying CNOT: The result is a chance of being measured in each of the and the states.

A superconductor is a material where a current can keep flowing when there is no voltage and has no resistance. Electrons collect into pairs (called Cooper pairs) and a macroscopic quantum state is formed, which can be controlled with and measured by conventional electronic equipment. The qubits can be fabricated with processes adapted from integrated circuit manufacturing. However, to achieve the superconducting effect, and make a reliable qubit, metals must be cooled down below 20 mK (milli-Kelvin).

Fig. 2 The Sycamore processor. a, layout of processor b, Photograph of the Sycamore chip. (Image: Springer nature)

SUPREMACY

In 2019, researchers at Google AI Quantum created a 53-superconducting-qubit chip called Sycamore, which they used to achieve quantum supremacy – the completion of a task on a quantum computer that is infeasible to compute on a classical computer; in this case simulating the outputs from a random collection of quantum logic gates. Although the task has little practical application, it is still an important milestone to quantum advantage, where a quantum computer can perform a useful task that is not feasible on a classical computer.

The processor uses a type of superconducting qubits called transmon qubits, which act as resonators at 5-7 GHz, where and are encoded as the lowest two energy states. Two-qubit gates are performed using coupling between neighbouring qubits, while single-qubit gates are performed by using microwave pulses while the coupling is turned off. Measurement is performed using a read-out resonator, which changes state depending on the state of the qubit.

faster than a classical computer. This can be used to break much of modern internet cryptography, which mostly relies on the fact that factorising integers using currently known algorithms is classically ‘hard’.

Another interesting quantum algorithm is Grover’s algorithm, which can be used for searching unstructured datasets. Classically, if you have items, you must check on average of them to get the item you want, and at worst all of them. However, Grover’s algorithm offers a quadratic speed-up, allowing you to find the desired item in roughly steps. The algorithm is generic, so can provide a speed-up for other classical problems, to select a single input from the domain of a function where the output is different.

ISSUES

Quantum computers have several issues that need to be solved before they will be useful at a large scale in the real world. Qubits are highly sensitive to noise from the environment (e.g., cosmic rays or random photons), and they can also randomly decay from the higher energy state ( ) to the lower energy state ( ). Therefore, robust error detection and correction are needed so that calculations can be performed at a large scale, requiring multiple physical qubits to implement one logical qubit. Some of these qubits are used to store data and others are used to detect errors in the data qubits.

APPLICATIONS

Richard Feynman first proposed quantum computation to simulate quantum mechanics, as the time taken on a classical computer grows exponentially as you add more particles. This would have uses in areas such as materials science, chemistry, and physics. Quantum computers also may be useful for optimisation, machine learning, and other mathematical problems.

One of these problems is factorising integers, which can be solved using Shor’s algorithm. Shor’s algorithm factorises integers using a related problem, that can be solved easily on a quantum computer (but not on a classical computer) – finding the period of the modular exponential function. Quantum computers allow us to easily measure this period, meaning it is possible to factorise numbers on a quantum computer much

Another issue is the scalability of quantum computers. Currently, the largest quantum computer has 127 physical qubits, but implementing simulations of largescale quantum algorithms will require thousands of logical qubits to allow for full error correction, and tens of thousands of physical qubits. Research is ongoing into how best to scale up architectures to the desired levels, focusing on making modular designs that scale easily, and can be manufactured at scale.

Quantum computers will not replace classical computers as most people use them. Instead, they will be available via the cloud, like how most large-scale computing is down currently. This is because of the need for most quantum computers to be at extremely low temperatures so that they can operate properly, which makes them unfeasible to have outside of largescale facilities.

Fig. 3 A 4-transmon-qubit circuit fabricated by IBM (Image: npj quantum information)

Tumour Dynamics

Ryan Li

A cancer tumour is a group of aberrant cells whose uncontrolled expansion harms the surrounding host tissue, often leading to patient death. It is also a population of genetically and phenotypically varied cells that compete, multiply, and contribute to the cellular society. Tools from population biology are therefore increasingly used to study cancer dynamics. Cancer’s genetic instability and high mutation rate, along with strict spatial limits, a lack of resources, and immune surveillance, result in fast selection for the fittest tumour cells’ survival.

SOMATIC EVOLUTION THEORY

The nature of life is the arrangement and management of genetic information recorded in DNA, powered by energy obtained from solar and chemical sources and polished via mutation, selection, sex, and recombination. To preserve previous evolutionary achievements, biological organisms spend extensively in a wide range of DNA repair systems that ensure correct DNA replication during cell division and the removal of DNA damage. However, random mutations nevertheless accumulate in genomes and contribute to diminished fitness with age.

According to the somatic mutation hypothesis of ageing, the accumulation of mutations in the genetic material of somatic cells over time leads to a reduction in cellular function.

Cells (blue) are constantly exposed to DNA damaging events throughout normal organismal ageing, which eventually results in cells containing numerous mutations (red). Some mutations develop in genomic areas, resulting in uncontrolled cell growth. Adopting a mutator phenotype allows for faster somatic evolution, which constantly acts to select for cells capable of bypassing many defensive systems that prevent uncontrolled cell growth.

Proto-oncogenes are genes that ordinarily aid in the growth of cells. When a proto-oncogene mutates or has excessive copies, it can permanently activate. When this happens, the cell proliferates uncontrollably, resulting in cancer. This mutant gene is referred to as an oncogene.

Tumour suppressor genes (TSGs) are normal genes that regulate cell division, correct DNA errors, or induce apoptosis. When TSGs fail to function properly, cells can multiply uncontrollably, leading to cancer. For example, tumour suppressor p53 mutates in almost half of all malignancies, and its expression and mutational status drastically influence cellular competitiveness.

Oncogenes result from the activation of protooncogenes, but TSGs cause cancer when they are inactivated.

CLONAL COOPERATION INDUCES METASTASIS

Tumours are made up of numerous subclones with varied genetic and phenotypic traits as a result of genetic and epigenetic modifications, as well as variable tumour microenvironments. Intratumor heterogeneity promotes clonal collaboration through cell-cell contact or factor secretion, resulting in faster tumour development.

Subpopulations originating from the same tumour might have varying metastatic potentials. Furthermore, there is a link between tumour heterogeneity and metastasis. Despite the apparent relevance of distinct inherent properties of different subpopulations, collaborative interactions across subpopulations can also help the metastatic cascade. Subpopulations may obtain a selective advantage throughout the metastatic phase if interclonal cooperation exists.

PROTO-ONCOGENES AND TSGs

Cancer progression involves multiple genetic events, which can activate oncogenes and disrupt the function of specific tumour suppressor genes.

Metastatic subclones can increase the metastatic potential of non-metastatic subclones. For example, the rat mammary cancer cell line has two stable subtypes: epithelioid cells (E-cells) and myoepithelioid cells (M-cells). Surprisingly,

collagenase, enzymes that break down the native collagen that holds animal tissues together, could only be secreted enough when both cellular types were present.

In brief, a soluble component produced by M-cells stimulates collagenase production by E-cells, demonstrating that interclonal cooperation may increase at least local invasiveness. The presence of a metastatic subpopulation in the circulation can enhance the metastatic potential of non-metastatic subpopulations located in either subcutaneous sites or circulation.

CLONAL COOPERATION INDUCES TUMOR GROWTH

Human cancers have a high genetic and phenotypic variability, partly due to the chromosomal instability in cancer cells. Tumorigenesis, the gain of malignant properties in normal cells, are aided by complex signalling connections between cancer cells and their surroundings and collaboration or competition amongst diverse cancer clones.

CC is a homeostatic process in which cells detect and remove less-fit cells by initiating apoptosis of the less-fit cells. This is followed by compensatory proliferation, in which surrounding normal cells revive proliferation and thereby restore tissue size in response to the less-fit cell’s death. The idea of “super-competition” is identified as another cell behaviour in which mutant cells proliferate much more aggressively as they actively induce apoptosis to their neighbour normal cells. In all of these interactions, apoptosis promotes the cell proliferation of surviving cells, and if these events are stopped, tissue homeostasis is compromised.

Stabilisation of a cancer tumour’s heterogenic nature occurs because of evolution; tumour heterogeneity is desirable, as a positive growth effect on subclones can confer a fitness advantage to them, and because multiple subclones with high fitness will then interfere with each other, inhibiting expansion of individual subclones.

Tumour cells use cell competition to promote tumour development. For example, CC between wild-type (WT) and mutant (MT) p53 progenitor cells, where MT p53 progenitors have a competitive advantage over WT counterparts, eliminates WT p53 cells from the progenitor pool via differentiation. Because p53 mutations are important cancer drivers, WT and MT p53 cells often engage in CC. CC selects MT p53 cells with higher neoplastic potential at the expense of WT cells, allowing cancer to spread aggressively.

Cell-cell interactions rely heavily on pathways that control cell growth and death. Normal cells in a tissue respond to irradiation by promoting cell proliferation to restore tissue homeostasis following cytotoxic insults. This adopts the mechanism of cell competition (CC).

On the same principle, radiation-induced apoptosis triggers similar compensatory type signalling interactions. The cells that die due to radiotherapy encourage the compensatory proliferation of the surviving, and thereby radiation-resistant, cancer cells. Furthermore, referring to the cancer stem cell (CSC) theory, dying non-CSCs may stimulate compensatory proliferation of CSCs, which contributes to the aggressiveness of recurrent tumours, at least in part.

This demonstrates that CC is active in cancer cell

selection and may potentially drive the progression of oncogenic events and consequently tumour growth.

HYPERTUMOURS

Despite the benefits of subpopulation cooperation, it can result in tumour collapse if the driving subclone, which induces other subclones to grow non-cell autonomously, is outcompeted by fast-growing exploitive subclones. This may result in tumour collapse because it promotes homogeneity within the tumour, rendering it incapable of reacting to unfavourable circumstances such as hypoxia if “incompetent communicators” become prevalent; tumour homogeneity is undesirable.

Competition between different clones of a cancer line reduces the ability and effects of cancer metastasis. Even if metastatic subclones arise through mutation, interclonal competition may hinder its proliferation, providing a potential explanation for recent surprising findings that most metastases are derived from early mutants in primary tumours.

A phenotypic feature that is nearly always favoured in nascent tumours is angiogenesis, or the formation of new blood vessels within the neoplasm, as this delivers nutrients needed for tumour proliferation. Tumour cells induce angiogenesis when exposed to hypoxia by secreting tumour angiogenic factors (TAF). Competing tumour cells differ in growth potential and sensitivity to changes in local oxygen pressure, which influences birth and death rates and their ability to release TAF.

Under realistic conditions, tumours anticipate the emergence of “hypertumours,” which are aggressive cells that fail to release enough TAF to promote tumour growth. In essence, hypertumours are “cheaters” who take advantage of the vascular infrastructure that other tumour cells have developed. This cheater population grows parasitically on the tumour, potentially harming it to the point of unviability. Hypertumours represent the primary mechanism by which tumours develop ischemic necrosis, a loss of blood flow.

THERAPEUTIC IMPLICATIONS

Intratumor heterogeneity positively correlates with a shorter time to relapse and increased multidrug resistance in different types of cancers.

Almost all cancer patients die of recurrent malignancies rather than newly-diagnosed, naive tumours. Some patients respond relatively well to first-line therapy regimens but do not survive subsequent recurrences due to the recurrent tumours’ lack of therapeutic response to medicines.

Patients returning to clinics frequently encounter cancer relapse during or immediately after treatment due to quickly regrowing therapy-refractory tumours. Treatment of heterogeneous tumours with targeted therapies leads to the elimination of therapy-sensitive subclones, leaving behind intrinsically drug-resistant as well as death-resistant subclones. The bulk of the tumour will thereafter be repopulated by drugresistant subclones. Therefore, recurrent tumour samples include more of said resistant cells than naive, making treatment challenging. Furthermore, numerous additional cooperative processes may play a role in therapeutic resistance. For example, subclones expressing large quantities of immune-inhibitory molecules may help other subclones avoid immunological treatments like chimeric antigen receptor T-cell therapy by generating an immune-suppressive TME. Thus, reducing intratumor heterogeneity or disrupting existing clonal cooperation may be critical to overcoming resistance and postponing relapse.

Physics Extension

Dr Marc Scott

The Sun is not the first star to sit in our portion of the Milky Way. You weigh a fraction less travelling west in the northern hemisphere than you do travelling east. There are just as many numbers on the number line between 0 and 1 as there are in total. Science and the mathematics which supports its many theories is a marvellous and wonderful subject, enabling us to detail, predict and change the world around us, as well as astound us with bizarre and beautiful claims.

Over the last two years, Physics Extension has been an opportunity for any keen Sixth Formers to embark on getting to grips with the rules of the Universe from an undergraduate perspective. Open to all, not only our physicists, the weekly sessions have delved into topics such as classical mechanics (avalanche theory, rocket motion, gyroscopic motion), cosmology (FRW metric, shape and expansion of the Universe), thermodynamics

(heat engines, the laws of thermodynamics, the derivation of the Boltzmann factor, microstates and macrostates) and the beginnings quantum mechanics (UV catastrophe, Planck distribution, Bohr model, Schrodinger’s equation).

An outlet for those eager to push beyond the confines of the A Level specification, the class allows our future physicists and engineers to grapple with the mathematically abstract ideas which underpin the structure of bridges or the interactions between atoms. With Extension Physics there is no endgame, no exam to pass, no concrete syllabus to rigidly adhere to; our only stipulation is curiosity and a willingness to questions everything (especially the typos and frequent minus sign errors!). It is 90 minutes in the week, where people get together to discuss and learn about physics, what could be more fantastic than that?!

The Radcliffe Punt

Mr Richard Evans & Dr Suzana Zizek

On a Wednesday evening in September 2020, seven aspirational Upper Sixth science students headed up to the biology lab B1. They subsequently participated in the first session of our Radcliffe Punt enrichment programme, designed to encourage Caterham’s Sixth Form science community to broaden their reading, presentation, and problemsolving skills beyond the limits of our A-Level syllabi. Originally envisioned as an Oxbridge preparation programme, and originally named Trinity Merton (after two Oxbridge colleges), the Radcliffe Punt settled into its new name and form in February 2021, when that year’s Lower Sixth picked up the gauntlet. Despite the Oxbridge-inspired current name, Radcliffe Punt has a much wider scope than just preparing attendees – the Punters – with interview skills. Our doors are open to all keen scientists. We launched our 2021 programme by handing out a couple of prestigious journal articles (past and present) from chemistry and biology, and the challenge for the Punters was simply to read them and prepare for an open-ended discussion at the next session. From the versatility of oxygen in biology to the sophistication of organic chemistry lab work, we went off on many tangents, all of which allowed the Punters to demonstrate the breadth of their reading and on-the-spot thinking.

Since then, our biology and chemistry challenges have taken many enriching forms. We have debated the merits of mandatory COVID vaccinations and “designer babies” (albeit not at the same time). We have displayed various graphs and images on the screen and asked the Punters to “say what they see” and “explain what they see.” We have tested the Punters’ public speaking skills through presentations on grisly diseases and by playing the Radio 4 favourite Just a Minute (with topics ranging from “peer review” to “the chemistry of the amino acids”). We have, from a supposedly innocuous opening question, dived into a half-hour discussion about the insidious impact of Andrew Wakefield’s fraudulent claims about MMR vaccinations.

In all of these, our focus has been on developing the Punters as all-round scientists. The world-leading scientist of the 21st century is not just capable of conducting high-quality experimental work; we must also be able to sell a compelling, evidence-based written or spoken argument, without resorting to the uncivil ad hominem attacks that have sadly become so common in today’s political world. The health of our planet and the organisms that inhabit it will continue to depend on our ability to be “the very model of a modern world-leading scientist.” Join us at the Radcliffe Punt to evolve into the best thinker that you can be.

Physics Olympiad

This year nineteen budding Caterham students across fifth year and the sixth form put themselves forward to take part in the fiendishly difficult British Physics Olympiad Round One paper organised by the University of Oxford. With questions ranging from the physics of liquids being transported in accelerating railway trucks and vibrating drum skins to physics favourites probing the mechanics of pendulums and springs, the three-hour long experience was certainly very challenging. Nevertheless the group more than rose to the challenge, securing a total of seventeen medals! Ruby in Upper Sixth achieved a ‘Gold’, as did Thomas in Lower Sixth – an extremely impressive achievement considering the competition is aimed at those in their final year of studies and requires knowledge thereof. Achieving a ‘Gold’ ranks Ruby and Thomas among the top 16% of those 2300+ students across the country who took part. Special mention goes out to Helen in fifth year who secured a ‘Bronze’ medal! Think you might be able to answer a couple of questions from this year’s paper? Have a go for yourself:

1. A railway carriage for transporting liquids is carrying a viscous liquid and it is only half full. The carriage is attached to an engine which pulls away with a constant acceleration, so that the fluid in the carriage forms a steady sloping surface. If the acceleration of the train is 0.84 m/s2, what is the angle of the liquid surface to the horizontal?

2. Water flows at a steady rate of 1.0 litre/min through a pipe in which there is an electrical heater connected to a 230 V supply. The rise in temperature of the water after passing through the heater is 60˚C. Calculate the resistance of the heater. Assume no heat loss to the surroundings.

Gold

Thomas Chang and Ruby Chan Silver William Pye, Alex Mylet, Kelly Hou and Cameron Hudson

Bronze

O-Teen Kwok, Ellen Cross, Anson Cheng, Nagim Ibragimov, Helen Yip, Josh Benjamin, Catherine Chao, Luke Yuan and Artem Streltsov

Biology Olympiad

Based on the A-level syllabus and built to push budding Biologists even further, the Biology Olympiad challenges students with an interest in biology to extend their talents. It consists of two 45-minute online multiple-choice papers, with questions ranging from the evolution of mammals and gel electrophoresis to the Krebs Cycle and the Hardy-Weinberg Principle.

The 24 students who took part in the competition this year consist of the top Biologists of our Upper Sixth cohort and passionate scientists alike. There were a record-breaking 18 medals, with 3 bronzes, 7 silvers and 8 golds - the most gold medals a year group has ever achieved in the history of Caterham Biology. Our Gold medallists are amongst the top 8% of all candidates who took part in the Olympiad nationwide, commendations to Alex M in particular, who achieved gold without formally approaching most of the theories in a classroom environment as he is in Lower Sixth, and congratulations to the biologists who participated in the event for successfully completing.

Gold

Gleb Iagelskii, Ruby Chan, Rainis Cheng, Brandon Kim, Jason Cho, Michael Wong, Alex Mylet and Rosie Home

Silver

Isabelle Oliver, Bobby Benford, Fleur Masters, Perlie Tse, Ivan Liu, Ollie Van As and Mariella Atterbury

Bronze

Katie Tudor, Jeremy Chan and Sharon George-Kalu

Chemistry Olympiad

The UK Chemistry Olympiad is an opportunity for students to push themselves further and excel in the chemistry field. Run by the Royal Society of Chemistry, the immensely hard 2-hour paper include questions on the theme of: A platonic solid called cubane and its synthesis; E10 petrol and its combustion; nitrous oxides; equilibria in lateral flow tests; synthesis of the smallest Chinese knot; and some physical chemistry related to storing vaccines. All of which are based on, but beyond the scope of the A Level syllabus.

This year, 30 students participated in the competition, achieving 24 medals in total. Achieving the Gold medal puts the 8 students amongst the top 9% of all candidates in the UK. Congratulations to Gleb, who has gotten the top score for 2 consecutive years, as well as to Alex, Luke and Kelly, who received the Gold medal despite being in the L6! The 6 Silver medallists, including Lisa who is a 5th year student, did very well and are ranked amongst the top 32% of all students. Getting a Bronze medal in this extremely discriminating exam is in itself a huge achievement, well done. It was great to see so many students from different year groups participate and show interest in Chemistry.

Gold

Gleb Iagelskii, Jason Cho, Alex Mylet, Ruby Chan, Brandon Kim, Maestro Yan, Luke Yuan and Kelly Hou Silver

Rainis Cheng, Lisa Hu, Ella Bryn, Avery Chen, Michael Wong and Holly-Heather Cook Bronze

Thomas Chang, Sophia Liu, Nigel Chan, Marcus Cheng, O-Teen Kwok, Sophie Hobbs, Joshua Ko, Elliot Major, Daniel Qi and Harry Jude

Nobel Prizes 2021

Inherited from the fortune and last will of Alfred Nobel, the Nobel Prizes are among the most prominent awards one could receive for their contributions to scientific discovery, literature, or peace movements. For 2021, 13 individuals were awarded Nobel Prizes, of which 7 were from the scientific domain. Their work span from climate change to organocatalysts and sensory receptors, and remind us of the efforts researchers pay to push breakthroughs in science.

PHYSICS

Nobel Prize of Physics was awarded to three excep tional physicists by the Royal Swedish Academy of Sciences “for groundbreaking contributions to our understanding of complex physical systems”. Syukuro Manabe studied the relationship between radiation and movement of air particles due to con vection, while incorporating the contribution of the water cycle, showing that the increased atmospheric carbon dioxide caused an increase in the Earth’s surface temperature. Klaus Hasselmann created a model which reliably predicts climate change,

taking into consideration of the chaotic nature of weather. He also developed ways to identify the impacts of natural phenomena and human activities on the climate. Both were awarded “for the physical modelling of Earth’s climate, quantifying variability and reliably predicting global warming”. While the third winner, Giorgio Parisi, discovered patterns in disordered complex systems, making it possible to describe and understand seemingly random phenomena. He was awarded “for the discovery of the interplay of disorder and fluctuations in physical systems from atomic to planetary scales”.

CHEMISTRY

The Chemistry Prize was awarded to Benjamin List and David MacMillan “for the development of asymmetric organocatalysis”. Catalysts are sub stances that increase the rate of chemical reactions and are regenerated when the reaction is complete. Before the development of asymmetric organocatal ysis, there were just 2 types of catalysts, metals, and enzymes. The two laureates, independently of each other, discovered that small organic molecules can speed up the production of a compound, with one particular stereoisomer favoured. List thought that only a small number of amino acids in an enzyme participates in the catalytic reaction, hence an entire enzyme was unnecessary. He successfully showed that the amino acid proline could act as a catalyst in an aldol reaction as the nitrogen atom can act as an electron acceptor, while MacMillan demonstrated that the nitrogen atom in an iminium ion can speed up the Diels-Alder reaction, a reaction that forms rings of carbon atoms, with one stereoisomer being formed predominantly. Organocatalysis is very im portant to the molecular construction of drugs and pharmaceutical research, as only certain stereoiso mers of a compound are biologically active.

PHYSIOLOGY or MEDICINE

David Julius and Ardem Patapoutian were the recipients of the Nobel Prize in this category. With the understanding that temperature and mechanical stimuli are converted into electrical impulses, they were eager to know how. Capsaicin is a compound found in chili peppers that causes the sensation of pain, Julius used it to identify the single gene that codes for the protein capable of reacting to capsa icin, and he later found out that this ion channel protein could respond to heat. The thermoreceptor TRPV1 was discovered. Patapoutian and his team discovered the gene whose silencing caused individ ual cells to be insensitive to mechanical stimuli. This mechanosensitive ion channel was later named Pi ezo1. He soon discovered a second gene that codes for a protein similar to Piezo1, and named it Piezo2, which was found to be highly expressed in sensory neurons, essential for the sense of touch. Both pro teins are activated by the exertion of pressure on cell membranes and have been shown to regulate blood pressure. This knowledge enables the development of treatments for different disease conditions, such as chronic pain. The two were awarded “for their discoveries of receptors for temperature and touch”.

The Medical Society of Caterham School

Rosie Home

The Wright Society is Caterham School’s prestigious medics society; founded in Summer 2020, I have had the honour of being the society’s second ever president, a role that I have found incredibly rewarding and enjoyable. The society is named after our patron, Dr Richard EP Wright MB BS (Lond); MRCGP, who, as well as being the school GP, is the Clinical Director of North Tandridge Primary Care Network. Our aim is to aid aspiring medics, dentists, and vets in the difficult process of applying to their chosen course, as well as promoting interest in the subject, and preparing the members for studying it in the future.

In the Lower Sixth, the focus in the society has been widening the breadth of the medics’ knowledge, particularly by weekly presentations. Each session a member of the society presents to their peers on a subject of their choice, which so far this year have ranged from general practice to heart transplants. In the latter half of the spring term the focus for the Lower Sixth will shift towards university applications, with several sessions being dedicated to preparation for the UCAT; the clinical admissions test all medics and dentists must take before applying. Meanwhile, in the Upper Sixth, the focus has been predominately on applications, particularly preparation for interviews. We’ve had sessions going through previous interview questions, as well as some on polarising ethical cases, all of which have been incredibly useful. Both the Lower and Upper Sixth have also been lucky enough to receive some inspiring talks from outside speakers: on top of multiple great presentations from Dr Wright himself, we were also treated to a session with Dr Ramesseur, an

anaesthetist at St Thomas’ Hospital, who gave an amazing talk on his career in medicine.

Many of the Upper Sixth medics have secured multiple interviews, being able to put everything learnt in the interview sessions this year into practice.

My advice to anyone wishing to apply to medicine in the future would be to gain as much knowledge and experience within the career as possible; it is really important to demonstrate throughout the application process that you have a broad understanding of the medical profession, so it’s beneficial to start accumulating this early on. This can be done in many ways, but a good place to start is simply reading books; those such as This Is Going To Hurt and Do No Harm are great introductions to the career and really interesting reads. Work experience is also important, but this does not just have to be in a hospital; volunteering in care homes, for example, is a great experience to be able to talk about. No matter what you do to gain insight into the career, reflection is key; being able to talk about what your experience has taught you, and how it relates to being a doctor, is arguably more important than what the experience actually is. Ultimately, any activity that uses the skills required to become a good doctor, such as communication, teamwork, and empathy will be beneficial.

Overall, it’s been a great year for The Wright Society. Many of the Upper Sixth medics have secured multiple interviews, being able to put everything learnt in the interview sessions this year into practice. In addition, it’s been such a pleasure to welcome in the brilliant Lower Sixth, and watch their confidence and knowledge grow enormously over the past few months; I have every confidence the society will be in incredibly capable hands next year.

Book Recommendations

The books in the following list, from our science department teachers, provide a good introduction to different fields of science. Biology

The Ancestor’s Tale: A Pilgrimage to the Dawn of Life –Richard Dawkins

The book follows the path of humans backwards through evolutionary history, describing some of humanity’s cousins as they converge on their “concestor”, the most common ancestor between species.

A Brief History of Everyone Who Ever Lived – Adam Rutherford

This book explains the Out of Africa hypothesis: Homo sapiens originated from Africa and migrated to Europe and further. The author discusses genes for human traits, arguing that racial classification is a scientifically invalid concept.

Your Inner Fish – Neil Shubin

This book explores the evolutionary ancestry of vertebrates by an author with expertise in palaeontology, genetics and embryo development.

On the Origin of Species –

Charles Darwin

A fundamental text in the life sciences. The book presents a body of evidence that the diversity of life arose by descent through a branching pattern of evolution, with natural selection as the chief agent of change.

The Greatest Show on Earth –Richard Dawkins

Oxygen: The Molecule that Made the World – Nick Lane

Sapiens – Yuval Harari

Homo Deus – Yuval Harari

Medicine

Do No Harm: Stories of Life, Death, and Brain Surgery –Henry Marsh (Specialty: neurosurgery)

A very informative book on the delicate work of a neurosurgeon and the struggles against bureaucratic limitations in healthcare. The documentation of outreach in Ukraine is particularly insightful to the role of professionals on a global scale.

Breaking and Mending –Joanna Cannon (Specialty: psychiatry) Follow a late medical student’s path to becoming a doctor, lined with emotionally charged and deeply reflective stories she encounters. It is a beautifully written short collection which will leave you relishing the hardships of a doctor-intraining, and in awe of the beauty hidden in everyday happenings.

This is Going to Hurt – Adam Kay (Specialty: obstetrics and gynaecology)

A humorously-told account of a junior doctor’s struggles, which eventually led to him leaving the medical profession. It reveals the dilemma of duty of work versus insufficient compensation a doctor in the UK faces.

Twas the Nightshift Before Christmas

– Adam Kay

War Doctor: Surgery on the Front Line – David Nott (Specialty: trauma surgery)

Being Mortal: Medicine and What Matters in the End – Atul Gawande (Specialty: general & endocrine surgery)

Biochemistry

The Selfish Gene – Richard Dawkins

Named the most influential science book of all time by the Royal Society, the book illustrates the gene-centred view of evolution. Arguing that the genes that are passed on are the ones whose evolutionary consequences serve their own implicit interest in being replicated, not necessarily those of the organism.

The Vital Question – Nick Lane

Why is life the way it is? Cells rely on the electrochemical gradient set up across a membrane to power ATP synthase, producing ATP. Lane argues that such a gradient could not have arisen in ordinary conditions such as the open sea. Instead, life began in deep-sea hydrothermal vents.

Foundations of Chemical Biology –C. M. Dobson, J. A. Gerrard & A. J. Pratt

Have you ever questioned how much of the text in a biology textbook is completely true? Why do hydrogen bonds between amino acids form an alpha helix? This book delves into the intrinsic properties of biomolecules such as amino acids, sugar-phosphate derivatives, and phospholipids, explaining how their chemical structures allow them to perform the function. A great introduction to biochemistry.

The Chemistry of Life – Steven Rose

Foundations of Organic Chemistry –Michael Hornby & Josephine Peach

Principles and Problems in Physical Chemistry for Biochemists

–N. C. Price, R. A. Dwek, R. G. Ratcliffe & M. R. Wormald

Bringing Chemistry To Life: from matter to man – R. J. P. Williams & J. J. R. Frausto da Silva

Nature via Nurture – Matt Ridley

Understanding Biochemistry: Essays in Biochemistry –The Biochemical Society

Molecules of Murder – John Emsley

This book deals with naturally occurring and man-made molecules that are notorious murder weapons, looking at their chemistry, toxicology and effects on the human body. It also explains the techniques used by forensic chemists.

H2O: A biography of Water –

Phillip Ball

A book that explains what we do and don’t know about the strange character of one of the most essential and ubiquitous substances, water. Explaining its origin, where it can be found on other planets, and the different kinds of ice and liquid water.

The Disappearing Spoon... and other true tales from the Periodic Table –Sam Kean

Periodic Tales: The Curious Lives of the Elements –Hugh Aldersey-Williams

Why Chemical Reactions Happen –James Keeler & Peter Wothers

A Guidebook to Mechanism in Organic Chemistry – Peter Sykes

Nature’s Building Blocks –John Emsley

Engineering

Physics

The Making of the Atomic Bomb –

Richard Rhodes

An informative account on early nuclear weapons history and the development of modern physics in general, praised by both historians and weapon engineers and scientists alike. Written in simple language, it covers immense detail of the discovery of modern physics and multiple prominent events and projects of its application.

Chernobyl: History of a Tragedy –Serhii Plokhy

On 26 April, 1986, the reactor at the Chernobyl nuclear power plant in Soviet Ukraine exploded. A mere 5% of the reactor’s fuel escaped, but half of Europe was swallowed in radioactive contamination. This book traces a flawed nuclear industry, political pressures, and human errors that led up to the tragedy, and the humanitarian turmoil that was left in its wake.

Understanding Flight –

David Anderson & Scott Eberhardt

How to Build a Car – Adrian Newey

Mr Tompkins in Paperback –George Gamow

A delightful explanation of the central concepts in modern physics, from atomic structure to relativity, and quantum theory to nuclear fusion. Recommended to both scientific and general readers.

The Character of Physical Law –

Richard Feynman

A series of seven lectures by Nobel laureate Richard Feynman on the natures of the laws of physics, including gravity, the conservation principles, symmetry in physical laws, relation of maths and physics, distinction of past and future, and quantum mechanics.

Quantum Theory Cannot Hurt You – Marcus Chown

A great read for those who want to become interested in the foundation understanding of quantum theory, or who already know a bit about it but want to know how to explain it. Easily understood and a good starting point with many simple analogies used.

Six Easy Pieces – Richard Feynman

Six Not So Easy Pieces –

Richard Feynman

Relativity for the Layman –

James A. Coleman

QED - The Strange Theory of Light and Matter - Richard Feynman

Concluding Remarks

Mr Dan Quinton

The Moncrieff Society started over 50 years ago here at Caterham School to showcase the best in science above and beyond the curriculum, and today the Society is still flying high with those same founding principles. I took over the reins over 20 years ago and renamed it “The Moncrieff-Jones Society” to acknowledge the massive contribution of its founder John Jones. The MJS has been a big part of my life here at Caterham and is therefore very dear to my heart. I have heard many times the foolish argument that some people in this world are scientific and others are creative. There is no one more creative than some of the pioneers in science who must devise ways and design equipment to test the hypotheses they are investigating. I would argue that scientists are amongst the most creative people on the planet. Lockdown and Covid were not able to stop our lecture series - we just adapted and went online which provided opportunities for pupils from our partner state schools to attend –from Oxted, Warlingham and the London Academic of Excellence in Newham. It has been wonderful though this year to return to what MJS does bestlive lectures by outstanding students.

Thanks to science we live in an extraordinary technological age, but also a dreadful world of Twitter sound bites, where ill-formed, selfappointed armchair gurus give their opinion about anything and everything, without really knowing or understanding the facts, or only having superficial knowledge having read the first article that appears in Google. The brave students giving lectures at the MJS meetings not only make me very proud, but also give me hope for the future. They receive no help from staff in their research and normally must present a 30-minute talk before then being grilled by a large audience for another 40 minutes. They teach themselves a vast array of material outside any A level specification and then have to understand it all if they are to survive a MJS lecture. The trendy buzz phrase ‘Independent Learning’ has crept into education in recent years. Although as scientists we loath trendy jargon, the MJS has been doing just this for the last 50 years – a Moncrieff-Jones lecture surely must be the ultimate in ‘Independent Learning’. In delivering an MJS talk pupils are showing a skill the top universities around the world are looking for in their undergraduates. We live in an age of science.

There has never been a better time to study science and I am jealous of all our students leaving to go to university to study science degrees at this time. How I would love to sit in on their lectures. Finally, I must thank Jason (President) and Rainis (Vice President) for the incredible job they have done leading the society over the last 12 months and taking it to new heights. The quality of talks this year has been truly exceptional. I look forward to welcoming them back here anytime. They will always be a part of the Moncrieff-Jones Society.

Past Moncrieff-Jones Society Presidents & Vice Presidents

2007-2008

President: Luke Bashford (University College London)

Vice President: Edd Simpson (University of Leeds)

2008-2009

President: Tonya Semyachkova (Balliol College, Oxford)

Vice President: Raphael Zimmermann (University of East Anglia)

2009-2010

President: Alex Hinkson (St Catherine’s College, Oxford)

Vice President: Alexander Clark (Robinson College, Cambridge)

2010-2011

President: Oliver Claydon (Gonville and Caius College, Cambridge)

Vice President: Sally Ko (Imperial College, London)

2011-2012

President: Glen-Oliver Gowers (University College, Oxford)

Vice President: Ross-William Hendron (St Peter’s College, Oxford)

2012-2013

President: Rachel Wright (St Peter’s College, Oxford)

Vice President: David Gardner (University of Nottingham)

2013-2014

President: Holly Hendron (St Peter’s College, Oxford)

Vice President: Annie-Marie Baston (Magdalen College, Oxford)

2014-2015

President: Ollie Hull (Merton College, Oxford)

Vice President: Cesci Adams (University of Durham)

2015-2016

President: Thomas Land (University of Southampton)

Vice President: Emily Yates (University of Birmingham)

2016-2017

President: Hannah Pook (St John’s College, Oxford)

Vice President: Vladimir Kalinovsky (University College London)

2017-2018

President: Kamen Kyutchukov (University College London)

Vice President: Natalie Bishop (University College London)

2018-2019

President: Daniel Farris (University of Exeter)

Vice President: Rowan Bradbury (University of York)

2019-2020

President: Michael Land (University of Warwick)

Vice President: Ben Brown (Bristol University)

2020-2021

President: Alex Richings (Imperial College London)

Vice President: Max Fogelman (University of St Andrews)

2021-2022

President: Jason Cho (University College London)

Vice President: Rainis Cheng (University of Hong Kong)

Past Endorsers of the Moncrieff-Jones Society

Dr Jan Schnupp

Lecturer in the Department of Physiology, Anatomy and Genetics at the University of Oxford

Dr Bruce Griffin

Professor at Surrey University, specialising in lipid metabolism, nutritional biochemistry and cardiovascular disease

Dr Simon Singh

Popular author and science writer including the book “Trick or Treatment”

Dr Mark Wormald Tutor of Biochemistry at the University of Oxford

Dr Alexis Bailey Surrey University, Department of Biochemistry and Physiology Leader of the Drug Addiction Research Team

Dr Nick Lane

Reader in Evolutionary Biochemistry at University College London

Mike Bonsall

Professor of Mathematical Biology at St Peter’s College, Oxford

Dr Max Bodmer

Marine Biologist and lecturer at Lincoln and Nottingham University

Dr Jansen Zhao

Senior Researcher in the Computer Science Department at ETH Zürich

Mr Shahnawaz Rasheed Consultant Surgeon at The Royal Marsden and Senior Lecturer at Imperial College London

Mr Mark Hitchman Managing Director at Canon Medical Systems