The Oxford Scientist: Change (#5)

TRINITY TERM 2019 - ISSUE 5

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Oxford Scientist

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TRINITY 2019 • CHANGE

CONTENTS

CHAIRMAN

EDITOR-IN-CHIEF

Sam Sussmes NEWS EDITOR

Arlene Lo

4 5 6 8 10 12

Ketones: a newly discovered fourth fuel for the human body AZRUL BIN ABDUL KADIR

PRINT EDITOR

Classifying phase changes with unchanging topology ARLENE LO

CREATIVE DIRECTOR

Could bacteria be worth a medal for Oxford?

THE OXFORD IGEM TEAM SCHOOLS COMPETITION WINNER

Science can change the world if it is given the chance to Making research fly: the use of Drosophila Melanogaster as a model organism DANI EDMUNDS Putting the precision in medicine CARLA V. FUENTESLOPEZ

OSPL STAFF

Olivia Shovlin BUSINESS MANAGER

Atreyi Chakrabarty

Daanial Chaudhry STRATEGIC DIRECTOR

Harry Gosling

FINANCE DIRECTOR

Marina Smith

COMPANY SECRETARY

Serena Parekh LEGAL DIRECTOR

Oscar Baker

Kimberly Glassman Copyright © The Oxford Scientist 2018

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Women in STEM - a centuriesold journey RAVEN LIRIO The new silk road: how China is spinning threads of scientific collaboration NICOLE HASLER Pop culture - our changing relationship with soft drinks HANNAH CORNWALL Breaking the Mirror: how a female Chinese physicist proved that nature is left-handed IAN FOO

AZRUL BIN ADBUL KADIR

Ketones: a newly discovered fourth fuel for the human body

As any diabetic person will know, the detection of ketone bodies in a person’s urine is a danger signal. The presence of acidic ketones can lower blood pH, causing dangerous ketoacidosis. However, it is now realized that, during starvation, the brain uses the ketone bodies as a fuel in addition to its usual fuel, glucose.

Normally, the body breaks down carbohydrates, fat, and proteins to provide energy. The liver stores carbohydrate as glycogen. The brain is dependent on carbohydrates as fats cannot easily cross the blood-brain barrier. If blood glucose levels fall too low, brain function declines. Once glycogen is depleted, a cascade of hormonal signals causes the body to increase the release of stored fats (from adipose tissue) for ketone production (ketogenesis). Unlike fats, ketones are readily used as a fuel in the brain. During starvation, fatty acids are converted into ketone bodies in the liver,

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and ketones can provide up to 60% of energy for the brain.

Ketosis is the physiological state in which the concentration of ketone bodies in the blood is higher than normal (0.5 mM). Ketosis occurs as a result of the breakdown of fat, for example whilst fasting or undergoing very strenuous exercise. Although they occur naturally in the body, ketone bodies are not found in meaningful quantities in any existing food or diet. But thye are in fact nature’s super-fuel. When the body is pushed to its limit, we convert stored body fat into ketones for energy. In an award-winning scientific study conducted at Oxford University, elite cyclists rode 400+ meters further in a 30-minute trial when they were given a ketone ester sports drink. The project was initially intended to create an efficient food for the US Army and was funded by the Defence Advanced Research Projects Agency (DARPA). We now

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know that ketones provide a fuel source that’s 28% more efficient per unit oxygen than carbohydrate, and this has raised important questions about the role they might play in medicine.

Heart failure is associated with a huge economic impact as it is the most common cause of hospital admission in many Western countries. Recent research showed that ketone bodies act as a significant source for energy production in the failing heart, which is “starved” due to perturbations in energy production and utilisation. Although fats and carbohydrates remain the most important fuels for healthy hearts, the importance of ketones in heart health is becoming increasingly apparent. In one study on athletes, it was shown burning exogenous ketones and carbohydrates simultaneously allowed the performance benefits of ketosis to be obtained without employing a ketogenic diet. It was also shown that addition of ketones to glucose in food increased efficiency of the heart. Scientists have also raised another important question about whether availability of amino acids can facilitate increases in the the utilisation of ketones.

This is because some of the amino acids that are used for protein production can be converted into glucose. The role of these amino acids on ketone body utilisation remains to be elucidated, but has major therapeutic implications, as it may provide a therapeutic milieu to treat heart disease and other disorders like neurological conditions and cancer.

ARLENE LO

Classifying phase changes with unchanging topology Solid. Liquid. Gas. We are all familiar with phases of matter from everyday experience.

When the temperature drops to 0K, an exotic zoo of new phases of matter is unearthed. Ensembles of electrons split into fractions of particles. Lattices of spinning particles melt into a fluid of swirling loops. Insulators morph into conductors. Discovering these ever-changing collectives of fundamental particles, condensed matter physicists are going to catch them all.

Before zero-temperature phases were found, physicists associated phase transitions with the breaking of a symmetry. All was well until the phase fractional quantum Hall states were discovered in an ultracold 2D gas of electrons. Particles in fractional quantum Hall states have fractions of an electron’s charge and take fractions of steps around the system’s perimeter in one direction.

Wrapping our heads around quantum phases With the downfall of the symmetry method, MIT physicist Xiao-Gang Wen came up with a new way to distinguish these phases. Instead of visioning these states arising on a flat surface, Wen considered using different topological manifolds as the playing field. Looking into different topological settings, Wen revealed novel properties of zero-temperature phases. He described the essence of these

phases by coining the term topological order.

It is only near absolute zero, where the system is in its ground state, that topological phases show up. Particles are linked up in global patterns of quantum entanglement that is described by string patterns. Quantum spin liquid is the simplest topological phase in a system. The 2D lattice of spinning atoms develops strings of spins that all point down and close to form loops. Patterns of loops fluctuate quantum-mechanically with directions of spins. Loops of down spins may merge or divide into different-sized loops. The quantum superposition of all possible loop patterns is encapsulated in the ground state.

Wrapping the zero-temperature system around a torus has the spin liquid exist in one of four distinct topologically invariant ground states. Each ground state is in one-to-one correspondence to four different superpositions of loop patterns, with an even or odd number of loops winding around and through the torus’ hole. Even if the number and pattern of loops fluctuate and combine, topological order is always preserved.

The grand classification programme Topology now joined hands with symmetry in the hunt of quantum phases of matter.

Short-range entangled quantum particles have their global topological order only emerging from local symmetry. Long-range en-

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tangled quantum particles have their global properties defined by topological order. After categorising the topology, we further differentiate phases by if there is symmetry breaking. Using this organising schema, known classes of 1D and 2D topological phases are mathematically proven to be complete. 2016 physics Nobel prize winner Duncan Haldane discovered there is only one gapped topological phase for a 1D chain of bosons (e.g. photons).

The wilderness of quantum phases in 3D matter presents mystery and excitement to the research community. In particular, the strange particle-like faction that lock together in fractal patterns. Xie Chen, a condensed matter theorist at Caltech, discovered many examples of a class of such phases in 2015. The wild excitations in the 3D realm give rise to patterns of quantum entanglement that struck Chen as profoundly weird. There is a long way to go in the 3D forest till the complete grand classification.

“You need a new type of theory, new thinking,” Chen commented. New classifying concepts, or even whole new networks might be needed to capture the fractal nature and open the door to the full scope of exotic possibilities.

Through constructing a periodic table for phases, we can also understand the underlying patterns in collective behaviours.

Condensed matter theorists are not after some law of physics.

They are after the space of all possibilities, enumerating and classifying all possible phases of matter.

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Could bacteria be worth a medal for Oxford?

While most of you probably cannot wait to go home over the summer, travel to foreign countries, or start summer vac schemes, 10 students on the Oxford iGEM team will be stationed on the front lines, commanding bacterial warfare.

Every year, undergrads from across various disciplines are given the opportunity to represent the university at the iGEM (international Genetically Engineered Machine) synthetic biology competition. Thousands of students across the world compete to engineer organisms to perform novel tasks by modifying their DNA. This culminates in a conference in Boston in late October to present the summer’s research to over 3000 people and get assessed on their performance. This year, more than 300 teams from over 40 different countries will combine experimental work, mathematical modelling, and human practices to research their project and engage with its impact on society.

The iGEM competition gives interdisciplinary teams of students the opportunity to push the boundaries of synthetic biology whilst tackling everyday issues facing the world.

The field of synthetic biology is focused around engineering artificial biological systems for various applications, mainly by manipulating DNA. DNA stores all the information required for cell function--it makes you, you.

Sections of DNA, called genes, store the information to make millions of specific proteins that 6

carry out the functions of every cell on Earth.

If you think of a Lego kit, with an instruction set and many pieces, you can make any object if you have the right instructions.

DNA is analogous to the instruction booklet, while the protein is the desired object; amino acids are the bricks, while the cell is the assembler.

Specific proteins can be made to be produced by inserting its gene into a bacterial host. Bacteria are single-cell organisms, already used as mini-factories to mass-produce drugs such as insulin or the Hepatitis B vaccine.

The proteins produced by bacteria can also interact in countless ways to form circuits of sorts.

Cells use these biological circuits as a basis of responding to specific stimuli from the outside

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world. Whenever the cell receives an input, like the presence of food, the circuit is designed to generate an appropriate output, such as growth and division to create more bacteria.

The Oxford 2019 team will be using these principles to engineer beneficial bacteria to combat gut infection caused by pathogenic bacteria. Specifically, we’re targeting Clostridium difficile- a nasty bacterial pathogen on the CDC’s (Centre for Disease Control and prevention) list of Healthcare Associated Infections. C. difficile infection (CDI) causes symptoms including diarrhoea, bowel perforation, and death especially since it commonly infects individuals over the age of 65. It triples the cumulative death toll of the Ebola virus each year in the US alone.

OXFORD IGEM TEAM

The bacteria we are engineering, which we’ve decided to call ProQuorum, are commensal Lactobacillus bacteria, often found in yoghurts. We want to introduce these super-probiotics into the gut via yogurts to eradicate unwanted bacteria through bacteria-to-bacteria combat.

Your gut contains billions of bacteria which mainly aid in digestion but can even inhibit pathogen growth and treat central nervous system disorders.

Today, the only way to treat bacterial infections is with antibiotics. These drugs are very effective at killing bacteria, but are non-specific, often severely disrupting one’s gut flora. Moreover, antibiotics give rise to resistance and often allows dormant antibiotic-resistant C.difficile to become active. This is precisely why a ‘bacteria vs. bacteria’ approach is so promising: - you target C.difficile but only C.difficile--no other native gut bacteria.

Microscopic combat isn’t a new idea. A constant war has been waging for millennia between viruses, known as bacteriophages, and bacteria. Although viral treatment—or phage therapy— has been trialled to treat bacterial infections, it hasn’t made it to the clinic as of yet.

Our superProQuorum bacteria will be engineered to har-

ness a key weapon in its arsenal aimed at specifically killing C. difficile bacteria. The weapon, known scientifically as an endolysin, has been previously used by bacteriophage viruses against bacteria. This endolysin chewsup cells from the outside, causing these cells to die. The ProQuorum bacteria won’t always produce this endolysin, though. By using biological circuitry, ProQuorum bacteria will be able to detect a specific biomarker from virulent C. difficile, and respond by secreting the endolysin, killing the bacteria only when it poses a threat to the body.

A key advantage to this system is that it circumvents the circulatory system. This way, the bacteria-killing agent will not cause harmful side effects effects on all tissues in the body. Because the endolysin is localised to the gut, its production will be largely targeted towards virulent C. difficile. iGEM, however, isn’t just a straightforward scientific research competition, and we won’t be spending all our time in the lab. We plan on speaking to patients about their experiences with CDI and physicians who treat the infections to see if our therapeutic idea can make a measurable impact in hospitals.

We’ll also raise awareness and discuss the ethics of synthet CHANGE

ic biology by hosting talks and workshops at schools and museums across Oxford. And finally, we hope to engage with you--the public--to help shape our project into something that you think is safe, convenient, and viable.

For five consecutive years the Oxford iGEM team has returned from the conference with a gold medal, and we plan to make it six. We would like to encourage anybody who is interested to reach out to us and to apply for the next competition of iGEM when applications open in November.

For more information, please contact us at: oxfordigem@bioch. ox.ac.uk. Or visit https://2019. igem.org/Team:Oxford Acknowledgments to all our supporters: BBSRC, Wellcome Trust, Department of Biochemistry, Department of Engineering Science, Department of Plant Sciences, Department of Zoology, Sir William Dunn School of Pathology, IDT, and SnapGene.

By David Schramm, Jonathan Chan & Katharina Novikov

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SCHOOLS WRITING COMPETITION We are pleased to announce the results of our Trinity Term 2019 school science writing competition. We received 63 entries from school students across the UK in Years 10-13. The topic of the competition was “how science can change the world”. The winning article, selected by our panel of judges, was “Science Can Change the World – If it is Given the Chance to”, by Ben Bradley, Year 12, Reigate College, Surrey. Ben will receive a £50 Amazon voucher, from our sponsors Oxford Sparks. Five runner-up articles were also selected by our judges, and will be published alongside the winning article on our website www.oxsci.org .

WINNER Science Can Change the World – If it is Given the Chance to

by Ben Bradley, Year 12, Reigate College, Surrey.

RUNNERS-UP Diagnosing Cancer? There’s an App for that

by Isabella Kwiecinski, Year 12, Lady Margaret School, London.

Revolutionary Rice

by Juliet Anderson, Year 12 Reigate Grammar School, Surrey.

Can YOU Cure Cancer?

by Patrick Brown, Year 12, Merchant Taylors’ School Northwood, Middlesex.

Man and Machine

by Aaliah Dhorat, Year 10, Batley Grammar School, West Yorkshire.

JUDGES DR JACK ROWBOTHAM is a researcher in inorganic chemistry at Oxford University, and is a Junior Research Fellow at Linacre College. He is interested in catalysis, and exploring new methods for making valuable chemicals in a greener and more sustainable manner. Jack is also keen to promote chemistry to audiences beyond the lab, and has twice been a regional finalist in the Famelab competition.

DR NIKITA VED is a Novo Nordisk Research Fellow at the department of Physiology, Anatomy and Genetics, and also a EPA Cephalosporin Junior Research Fellow at Linacre College. She researches into why diabetes during pregnancy causes congenital birth defects.

THOMAS HORNIGOLD is an atmospheric physics DPhil student, where he studies climate models run on climatepredicton.net, a huge set of volunteers’ computers. In his free time, he hosts a podcast about physics (Physical Attraction) and writes popular science articles for Singularity Hub. JACQUELINE GILL is a DPhil student in Evolutionary Microbiology. She was a co-founder of The Oxford Scientist magazine, established the first national Oxford Scientist school science writing competition, and has continued running the competition ever since.

A Smile can Change the World

by Larissa Chan, Year 10, Cheltenham Ladies’ College, Gloucestershire.

Interested in being the next winner of our Schools Writing Competition?

Pease email competition@oxsci.org for more information.

If your school, sixth form or college would like to subscribe to The Oxford Scientist for just £15 a year, please contact editor@oxsci.org.

BEN BRADLEY, YEAR 12, REIGATE COLLEGE, SURREY.

SCHOOLS COMPETITION WINNER

Science Can Change the World – If it is Given the Chance to “The good thing about science is that it’s true, whether or not you believe in it”- Neil deGrasse Tyson, Astrophysicist and science communicator. But in the age of fake news, since when has the truth been important? Despite consensus throughout the scientific community on the threat of climate change, and an international treaty signed by 195 countries that attempts to limit global warming to 1.5 degrees, carbon dioxide emissions are still rising and forest coverage is still shrinking. According to the Intergovernmental Panel on Climate Change (IPCC) “Limiting global warming to 1.5°C would require rapid, far-reaching and unprecedented changes in all aspects of society”.

Those rapid, far-reaching and unprecedented actions are finally starting to emerge, but as unhurried, vague and limited promises – the environmental equivalent of “thoughts and prayers”.

And all the while, violent storms and flooding sweep across the coasts, and wildfires rage on every major continent.

Both harsh droughts and unprecedented polar vortexes have be seen simultaneously on opposite sides of the globe, and naturalist Sir David Attenborough has asserted that “we are in the midst of the Earth’s sixth mass extinction, one every bit as profound and far-reaching as that which wiped out the dinosaurs.”

Yet much of the technology to combat climate change already exists- where the science, the innovation and the number crunching have already been done. An

assessment from 12 leading environmental institutions has identified 18 potential methods that - if implemented widely - could cut global carbon dioxide emissions by approximately 12 gigatonnes. If countries stick to the commitments laid out by the Paris climate deal, that’s 25% of projected emissions that can be cut by solutions that are currently technologically viable. These actions range from rolling out widespread renewable energy generation, to improving industrial efficiency, to reducing deforestation, and could provide a much needed curb to a continuing growth in global emissions. Nevertheless, the UK continues to provide more subsidies for fossil fuels than for renewable energies- €3.7 billion more as of 2016. The science is there. The money is not. As Greta Thunberg, the teenage environmental activist, has said: “Listen to the science. Listen to the scientists. Invite them to talk. They have many things, a lot of solutions you can do.”

The UK government is quick to point out that UK greenhouse gas emissions have fallen by 42% compared to 1990 levels: a figure that, on the face of it, seems substantial. But this reduction is primarily due to the switch away from coal in energy production and the outsourcing of industry to the developing world (such as China). When factoring in non-territorial “consumption emissions”, this figure falls to a 10% reduction since 1997. There are reasons that these consumption figures aren’t used

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officially, such as the possibility of double counting and the difficulty of accurate tracing.

However, we need to remember that we are all in the same boat, and making other countries drill holes in its side won’t prevent that boat from sinking.

Recent environmental strikes and protests are a cause for hope, as the concerns scientists have been voicing are finally being listened to. But they also show the extent of the neglect of this climate science, for decades met with half-promises and limited action from the people in power. If it takes a worldwide campaign and over 1000 UK protesters to be arrested, just for politicians to vaguely listen to pleas to consult with scientists, then something is fundamentally wrong. The science is showing that focused and extreme action is urgently needed to combat the potentially crippling effects of climate change. Effects that the world is only beginning to feel.

Persistent and exhaustive effort must be put into climate policy now to avert catastrophe in the coming decades, and the only way to do this is to have the voice of science heard, loud and clear, in every corridor of government and power.

Science is continuously changing the world: from the biggest breakthroughs to the smallest refinements. But to keep the world, people need to wake up to the science that already exists.

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Making Research Fly – The Use of Drosophila Melanogaster as a Model Organism to fruit fly research. Here, by focusing on the work of the Wigby and Perry research group at the University of Oxford, I’ll present just a snippet of why Drosophila melanogaster is such an important and fascinating animal in biology.

Life in a Flash

Tell people you work with animals, and they will immediately be interested. Everyone loves animals. Tell people these animals are in fact fruit flies, and their excitement often turns to disgust. People think flies are pests. But this is where they’re wrong. Fruit flies, or Drosophila melanogaster, are one of the most important species studied by biologists, contributing to an extensive range of research including genetics, behaviour, evolution, ecology, neurobiology, medicine, and many more. Indeed, it would be impossible to summarise all the thousands of scientific discoveries that we owe 10

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One of the most common questions people ask about fly research is ‘but don’t they only live for a day?’. Now, any fruit fly biologist who has had to record data on fly lifespan will have wished this was true when their experiments have been running for over two months and the flies are still alive… In a laboratory environment, a fruit fly can typically live for about 5 weeks. However, it takes just under two weeks for a fly to develop from an egg to a reproductively mature adult, and this very short generation time makes Drosophila amenable to lab-based studies of important biological topics such as evolution and ageing. As fly populations can pass through many generations in a very short time scale, it’s possible to observe how both natural selection and sexual selection influence the evolution of many traits.

Similarly, as a fly goes from being very young to very old in a matter of weeks, it is also possible to observe the effects of ageing. For example, the Wigby and Perry research group has investigated how various selection pressures can influence the evolution of mating strategies and social interactions, and how reproductive abilities can change with age.

Imagine trying to answer such questions using organisms with longer life-cycles – experiments would take decades!

DANI EDMUNDS

On Your Best Behaviour

For such a small organism, fruit flies have incredibly complex and well-documented social behaviours, including lengthy courtship routines and elaborate aggressive encounters. Take courtship for example – a male fly will begin by orientating himself towards the female, tap her with his forelimbs to ‘taste’ her, then extend and vibrate a wing to produce a ‘courtship song’. He will then attempt to copulate, and, if she is receptive, mating and sperm transfer will occur.

Since such behaviours are well documented and can be observed over a short time scale in lab conditions with a very large sample size, fruit flies are very useful tools for studying important competitive and sexual behaviours. Indeed, the Wigby and Perry lab group have investigated how factors such as nutrition, social environment, and past experience influence many aspects of courtship and aggression. Naturally, this makes behavioural studies much more efficient than trekking through the field, waiting quietly hidden in vegetation, trying to catch a glimpse of animal behaviour in the wild.

ly mapped out. Our extensive knowledge and simple manipulations of the fruit fly genome allow molecular mechanisms to be integrated into evolutionary biology to understand how genes and proteins directly influence survival and reproduction. The Wigby and Perry lab have used genetics and proteomics to add a new level of understanding to behaviour and evolution.

Why the fly?

It’s clear that the fruit fly is very well suited to biological research.

But why do we care so much about flies? Well, the fruit fly is what we call a ‘model organism’, meaning that it is amenable to research, but the findings can contribute to our understanding of broader biological principles in a wide range of species. Indeed, the many similarities between the human and fruit fly genome means fruit fly research can help us understand more about ourselves, including the genetics underpinning diseases and subsequent treatments. So, next time you see a fruit fly, remember, it’s not just a pest, it’s an essential tool in modern biological research.

Getting Down to the Genes

Fruit fly DNA contains just over 100 million base pairs. Now this may seem like a very large number, but compared to the 3 billion base pairs of humans, fruit fly DNA is relatively simple. Indeed, the 14,000 genes that make up a fruit fly, and the proteins they code for, have been largely characterised and clear-

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Putting the Precision in Medicine

Cancer treatment has attracted the interest of scientists, clinicians, investors, and the general public for years now. Despite the outstanding progress in cancer treatment, the traditional trifecta (chemotherapy, radiation, and surgery) still cannot deliver optimal results. Partly, this can be attributed to the same formula being used to treat different patients, with different cancers, and in different stages.

By better understanding genes and mutations, as well as being able to identify appropriate biomarkers, researchers could determine which specific treatment plan would work best for a particular patient and entail the fewest side effects. This is precisely what precision medicine promises.

Precision medicine takes into account individual variability in genes, environment, and lifestyle for each person and, based on these, suggests a particular treatment or prevention strategy. In essence, 12

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this would allow practitioners to predict more accurately which treatment works best for a particular group of people, as opposed to a ‘one-size-fits-all’ approach.

Although the term is relatively new, the concept has been around for a number of years. At its most basic level, blood transfusion is an example of precision medicine where blood type is matched between the donor and the recipient to reduce the risk of complications. However, examples of more advanced precision medicine in day-to-day healthcare are relatively limited.

Bearing in mind the unprecedented benefits that precision medicine hopes to deliver, several organisations have launched programmes and initiatives to further develop it.

The U.S. National Cancer Institute hopes to use an increased knowledge of genetics and cancer biology to find new and more effective treatments for this disease. As a first step, it launched the All of Us Research Program, which will look at a cohort of at least 1 million volunteers who will provide their genetic data, biological samples, and additional health information. Using this data, the objective is to be able to predict better disease risk, understand how diseases occur, and develop more accurate diagnosis and treatment strategies.

Initiatives, such as The Genome Project, focus on improving our ability to learn how tumour cells work at the molecular level. The Precision Medicine Initiative aims to determine the best approach to prevent or treat a disease by looking at a number of factors specific to an individual. Initially, it focuses on expanding precision medicine in cancer research and, ultimately, bringing it to all areas of healthcare.

While precision medicine promises to improve many aspects of health and healthcare, it faces a number of challenges: patient’s pri-

CARLA V. FUENTESLOPEZ

vacy and data confidentiality; the design of new tools for building, analysing and sharing large data sets; ensuring that the products are safe and effective while supporting innovation; and consolidating new partnerships between scientists, investors, and healthcare professionals.

In the future, healthcare professionals could use patients’ genetic and other molecular information as part of routine medical care, integrating this information into electronic health records.

Nevertheless, many of the technologies required to achieve what precision medicine promises are still in the early stages of development - or have not yet been developed! Naturally, ethical, social, and legal issues need to be addressed before precision medicine makes its way into medical care. Also, it is worth considering that the healthcare personnel will need to know more about molecular genetics in order to be able to interpret the results of genetic tests, understand how that information is relevant to treatment or prevention approaches, and successfully convey this knowledge to the patient.

One of the most pressing concerns is cost. Sequencing large amounts of DNA is expensive, although it is decreasing quickly.

Also, it is highly likely that drugs able to target a person’s genetic or molecular characteristics will be expensive and, furthermore, reimbursements from third-party payers (i.e. private insurance companies) will likely be an issue.

Precision medicine is a young and growing field. The market value is expected to reach 88.64 billion USD by 2022, an increase of roughly 50 billion since 2015.

Taking this into account, sever-

al companies and start-ups have decided to pursue this field. Pfizer Inc. and Concerto Health AI formed a partnership to develop precision medicines, particularly for the treatment of solid tumours and hematologic malignancies. The artificial intelligence-powered analytics developed by Concerto are capable of gaining better and faster insights in key cancer subpopulations.

Today, when people are diagnosed with cancer the treatment of choice is the same for people who have the same type, stage of cancer and if it has spread.

However, people in these groups can respond very differently to treatment. Tumours have distinct patterns of genetic changes that cause them to grow and spread. The same changes do not always occur in everyone with the same type of cancer and the same changes may be found in individuals with different types of cancer.

By tailoring treatments to the specific genetic changes present in each person’s cancer, genetic tests will help decide which treatments an individual is most likely to respond to, sparing them from receiving treatments that are not likely to help. Currently, there is ongoing research into treatments that target the cancer-causing genetic changes in tumours, regardless of their location within the body.

People with melanoma, some leukemias, breast, lung, colon, and rectal cancers are usually tested for certain genetic changes when they are diagnosed. The process is quite simple - once a biopsy is taken, a DNA sequencer is used to detect the genetic changes that may be causing the cancer to grow. However, it is worth remembering that not all the genetic changes driving cancer development, growth and CHANGE

spread have been identified, and that additional changes may occur over time.

Targeted therapies, the cornerstone of precision medicine, act on specific molecular targets associated with cancer, while chemotherapy acts on all rapidly dividing cells (normal and cancerous). Examples of these therapies are hormone therapies, signal transduction inhibitors, gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapies, and toxin delivery molecules.

Many targeted cancer therapies have been approved by the Food & Drug Administration (FDA) to treat specific types of cancer, while several more are in clinical or pre-clinical testing.

Even so, cancer cells can become resistant to targeted therapies. This occurs when the target itself changes through mutation (targeted therapy no longer interacts well with it) or the tumour finds a new pathway (that does not depend on the target) to achieve growth. As such, the best results are obtained when combining targeted therapies.

Precision medicine hopes to deliver more accurate treatments and diagnosis, ultimately shifting from a trial-and-error approach to ‘the right drug, for the right patient, at the right time’. However, this is not as straightforward as it might seem, as identifying how to develop a medicine with the right biomarker is a significant challenge. With the rising prevalence of genetic diseases, a greater involvement in personal healthcare, and the integration of wireless technologies with portable healthcare devices, precision medicine is gaining traction in the public discussion. Could this become the new golden standard for disease prevention, diagnosis and treatment?

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RAVEN LIRIO

Women in STEM – a centuries-old journey Beginning in the ancient civilizations of Egypt and Greece, women have played a powerful and influential role in the field of science. Initially recognized for their contribution to medicine, women have since branched into all other areas of scientific study. Much of today’s scientific progress has been the result of a long journey undertaken by women throughout the ages, battling against stereotypes and prejudices for scholastic respect.

According to the UNESCO Institute for Statistics, less than 30% of the word’s researchers are women. This percentage is even smaller for more specific fields, but this shows significant improvement compared to the early 1960s where, for example, less than 1% of engineers were women. Women of the time were encouraged to enter into more “feminine” careers and areas of study like education, English, or the humanities. It wasn’t even until 1920 that Oxford allowed women to fully matriculate into the university despite women having attended lectures and taken examinations since the 1870s. Higher education was just not a viable option for women, limiting the number of female scientists in the field until the 1900s.

Despite this, however, women have long cooperated with male scientists and helped to shape the various fields of science today. Caroline Herschel was a German astronomer in the 1700s who assisted her brother in recording the night sky. Another female scientist, Mary Anning, collected fossils, initially under her father’s tutelage, and soon discovered the first full skeleton of a dinosaur, later classified ichthyosaurus. Some of her findings can be seen in the Natural History Museum in London. Marie Anne Paulze, who was only 14, worked alongside her husband Antoine Lavoisier, contributing to the discov-

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ery that oxygen was the key to combustion. She translated works for him as she was fluent in English and worked with him on experiments to make the discovery possible. Other famous figures like Marie Curie, Rosalind Franklin, and Ada Lovelace made huge impacts in the scientific community, challenging the widely held belief that women were incapable of contributing to the STEM field.

Throughout the 1900s, steadily more women applied to university to obtain degrees in scientific fields. In the United states, 43% of scientists and engineers in the work force are women. In Central and South America, nearly half of PhD degrees were earned by women. Central Asia had around 46% female researchers in comparison to the world average of 30%. As of 2018, women make up 25% of the STEM workforce in the UK. According to the Women into Science and Engineering (WISE) organization, there are over 900,000 women in core STEM occupations in the UK, with numbers expecting to rise this year.

While the disparity still exists for women in STEM, programs continue to sprout which encourage young women to enter STEM related subjects. More and more young girls are seeing women playing a core part in scientific research.

The belief that women were unable to work as well as men in STEM has dramatically changed throughout the centuries, allowing women to stand equal to men in scientific fields. There is still a long way to go, but it is thanks to the struggles of women throughout the ages that future female scientists can now make a decisive impact on the world.

TRINITY 2019

The new silk road: How China is spinning

NICOLE HASLER

threads of scientific collaboration

Last year, the scientific community was surprised by the announcement that Pakistan was the fastest-growing country for scientific research. This is unexpected news for a country that was nearly completely destroyed by the international war on terror and is still considered dangerous by many governments. The explanation for the rise of Pakistani research output lies in the Chinese funding that has recently flowed in under the heading of the “Belt and Road Initiative”.

The initiative, BRI for short, is sometimes called the “new silk road” after the silk road of ancient times, which connected Asia with Europe. The BRI consists of over $1 trillion worth of loans and investments in other nations, and currently extends to 127 countries worldwide with the aim of fostering contact with China.Though the main focus is on facilitating trade and transport via motorways, railways, and sea ports, science is also seen as an important factor in strengthening connections.

As part of the BRI, the Chinese Academy of Sciences (CAS) has invested over $268 million in research and technological development. Projects include studies on kidney disease in rural Sri Lanka, construction of research centres in Pakistan, and the building of a Chinese-Belgian science park. Additionally, the Chinese government offers fully funded scholarships for students from BRI countries to complete master’s or PhD degrees in China, an opportunity that has so far attracted around 30,000 students.

The idea of a new silk road has attracted criticism on both the scientific and infrastructural sides, mainly because investments are mostly in lower-and middle-income countries. Though the CAS maintains that the aim of the projects is to benefit both countries involved, critics say China is exploiting struggling nations by offering technological and research support in return for potentially lucrative resources, such as biological samples, readings of oceanic currents, or permission to build railways and motorways through these countries.

The criticism also extends to China’s scientific interactions with BRI countries. In Sri Lanka, private companies have been allowed access to the so-far public healthcare system, which raises concerns about the independence of researchers and healthcare administrators.

Another problem is the potential lack of inclusion and transparency, as CAS officials have a voice in deciding which research groups and institutes in other countries participate in the joint research projects.

Despite these points, Chinese collaboration with Pakistan is welcomed by BRI countries, who now have access to skilled researchers as well as more funding and increased interactions with Chinese universities, which in the last three decades have become some of the best in the world. The international scientific community as a whole has been changed over that timespan by a dramatic rise in China’s scientific output,as well as the quality of the research, with annual Chinese publications recently having exceeded those of the U.S. The rise of Chinese science also extends to more daring projects, such as the cloning of chimpanzeesand plans for the first-ever landing of a spaceship on the far side of the moon. China’s growing scientific prowessis the result of decades of changes in science and educational policy.

Now, another policy is poised to change the scientific output of other nations as well, with Pakistan being one success story.

It remains to be seen what the effects these policies will haveon the scientific community. While in the past, graduate students and researchers from other continents aimed to come to Western countries to work and complete their training, now there may be a shift towards establishing academic roots in China instead. With the “new silk road” projects aiming to foster scientific research not only in China itself, but also in other countries previously not very strong in academia, it seems like not only the physical landscapes of BRI countries will change as the new rail- and motorways cut through them. The landscape of the international scientific community will perhaps be redrawn as well.

CHANGE

15

Pop culture - our changing relationship with soft drinks

In spring 2018, the UK brought in the ‘sugar tax’, in part to reduce the impact of carbonated drinks on public health. One year on, how have British habits changed? In this article, we explore the history of carbonation, our national fizzy drink identity, and the effect of changing health values on our pop culture.

The First Fizz

In 1767, Englishman Joseph Priestley suspended a bowl of distilled water over a beer vat in a Leeds brewery, finding that he could infuse water with carbon dioxide. Priestley was later credited with creating the first artificially carbonated soft drink by agitating water over the carbon dioxide generated by mixing sulfuric acid and chalk. The drinking of this carbonated mineral water was encouraged as a healthy practice, and soda fountains became a regular sight in Georgian England.

As for the sweeteners and flavourings, the first marketed non-carbonated soft drinks appeared in 17th century France, where the Compagnie de Limonadiers of Paris gained a monopoly on the sale of honey-sweetened diluted lemon juice or ‘lemonade’. The earliest reference to a carbonated flavoured drink is a ginger beer found in a Practical Treatise on Brewing published in 1809. Coca Cola first landed in England in 1900 as five gallons of sugar and caffeine loaded syrup, but was not sold regularly until the 1920s.

By the 1940s, available cheaply and for the masses from over fifty manufacturers, fizz had outgrown its medicinal fanbase. In 1951, Schweppes was designated the official drinks supplier for the Great Exhibition, London, where they sold over one million bottles of pop to its patrons.

British Consumption

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TRINITY 2019

The popularity of pop has far from waned over the last half-century.

Brits spend £14.7bn annually on soft drinks. Cola-flavoured drinks take

HANNAH CORNWALL

the lead, accounting for 58% of the UK carbonated drinks market in 2017. According to the National Diet and Nutrition Survey 2008-12, approximately 25% of the nation’s daily dietary sugars are obtained from soft drinks, rising to 40% among adolescents.

In fact, adolescents and children are the largest consumers of soft drinks in the UK. Sugary soft drink consumption in young children is known to be a risk factor for poor diet quality, poor dental health, weight gain, and future development of type 2 diabetes, with children from lower socioeconomic classes most likely to be affected. It is thought that a child’s weight status is set by age 5 and tracks throughout childhood.

One in five children are obese or overweight on entering primary school in England, rising to one in three by the start of secondary school. Therefore, reducing sugary soft drink consumption at a young age presents itself is a keystone in national obesity reduction.

The Sugar Tax

The Soft Drinks Industry Levy, colloquially known as the ‘sugar tax’, was announced in March 2016 and implemented in April 2018 in response to concerns over

rising child and adolescent obesity. It aimed to prompt reformulation of common beverages, reducing the availability of high-sugar soft drinks on an industry-wide scale. Despite drawing criticism for its Orwellian “nanny state” mentality, the levy seems to have had the desired effect in the UK, with Irn-Bru, Shloer and Lucosade reformulating their drinks to reduce sugar content or replace added sugars with fruit juices.

Even companies who refused to reformulate high-sugar drinks like Coca Cola’s classic Coke have seen changes in buyers’ preferences. In February 2018, Coca Cola reported £10.9m weekly UK sales of its rebranded Diet Coke, £140,000 more than classic Coke. This sales gap continued to rise to £2.3m into May, with Diet Coke sales topping £13.7m per week.

Anti-Sugar Culture

Taxation is not the only player in our changing relationship with sugared drinks. British sugar habits appear to be changing more broadly too. In a 2016 survey, 43% of adults claimed to avoid added sugars in soft drinks and 13% avoided sugar at all costs. Only 32% of adult respondents did not consciously consider the sugar content of soft drinks.

As public enemy number one, CHANGE

the culture in which we consume sugar is changing on all fronts. Recent fad diets focus on limiting simple sugars, from the Keto to the Atkins. Vitamin-enriched drinks are prevalent on grocery shelves whilst celebrities like Jamie Oliver have the power to improve the national diet with televised radical school dinner reforms. The belief that we have too much sugar in our diets has gained traction in the national psyche.

Is the end of fizz in sight? Colour coded nutrient labelling has helped to reinforce a good-choices food culture and in 2018, Public Health England introduced an aspirational 30g recommended daily sugar allowance for over11s – equivalent to just seven sugar cubes or less than one can of classic Coke. A strong history, changing formulations and reducing sugar content mean that pop culture is unlikely to leave our national identity soon. However, with bottled water overtaking fizzy pop as the world’s most popular drink, the industry may be stepping back to its health-conscious Georgian roots.

17

IAN FOO

Breaking the Mirror: How a female Chinese physicist proved that nature is left-handed Nietzsche said it best: ‘When you gaze long into a mirror, the mirror also gazes into you.’ Would you ever expect your reflection to wink out of turn, or run suddenly out of frame?

So imagine the shock of the physics community when something similar happened in 1956, in an experiment conducted by one Chien-Shiung Wu. Also known as “Madame Wu”, the “First Lady of Physics”, she was one of the most accomplished experimentalists of her time. Her revolutionary overturning of a fundamental law of nature changed the way scientists approached physics for decades to come.

Parity is a mathematical operation defined as “reflection through the origin”, which is mostly equivalent to reflection in a mirror. In quantum mechanics, states and quantities can either have negative or positive parity, which means that they either change sign, or do not, upon being flipped. Up to this point, in all processes involving changes in states (e.g. particle creation and annihilation), the overall parity of the system had been conserved. Indeed, this conservation of parity had become so ubiquitous that it was assumed to be true by default: a fundamental law of nature. Nobody ever expected it to be proven wrong.

The 1950s saw the discovery of dozens of new subatomic particles, which scientists struggled to classify satisfactorily. Two in particular, the theta and tau mesons, caused great headaches.

Although almost identical, they decayed into states of positive and negative parity respectively. This could only be resolved if they were the same particle, but with conservation of parity violated.

Although most physicists did not consider this a realistic avenue of inquiry, two theoreticians at Princeton, Tsung-Dao Lee and Chen-Ning Yang, did. In 1956, they realised that parity conservation was unproven in nuclear reactions involving beta decay. Chien-Shiung Wu was then one of the foremost experts in beta decay, and they approached her with ideas for an experiment that would either confirm or refute parity conservation in such reactions.

In beta decay, neutrons in atomic nuclei decay

18

toprotons, emitting an electron in the process.

Subatomic particles possess a property similar to angular momentum called spin. If the spins of the nuclei are all aligned in the same way (say, by a magnetic field), a parity operation can be imposed by reversing the direction of the magnetic field. This has the effect of flipping the directions in which electrons are fired from the nuclei during beta decay.

If parity were conserved, reversing the magnetic field would make no difference in the number of electrons fired in a certain direction—but if not, a difference would be detected. Wu chose a species called cobalt-60, which was particularly easy to align magnetically, and also emitted photons which were known to obey parity conservation, and could be used as a control.

Wu and her colleagues painstakingly constructed the experiment over the next six months. Their results were staggeringly clear: the electrons were preferentially emitted in a certain direction.Parity was not conserved. This greatly shook the physics community, with some calling it ‘total nonsense’—however,other groups soon reproduced Wu’s findings, and parity conservation was no more. A new paradigm had established itself.

The discovery was so monumental that the Nobel Prize was awarded for it the very next year—to Lee and Yang. In a disappointing turn of events, Wu was not included in the award.

This slight, however, did nothing to deter her from her research. A legendary workaholic, Wu went on to break experimental ground on other fundamental phenomena like charge conjugation and quantum entanglement, eventually writing the book—literally—on beta decay. In later years, Wu was outspoken about gender discrimination in science, advocating equal representation and encouraging women to pursue careers in STEM fields.

By going against common wisdom, Madame Wu showed the world that nothing in science should ever be accepted as given, and that unprecedented changes are around every corner.

TRINITY 2019

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