The Chelt Scientist ISSUE 2 by The Chelt Scientist

The first pig heart transplant The implications and ethics of xenotransplantation

The James Webb Telescope An overview of the telescope's journey since its launch

The Tongan eruption How the eruption is strengthening our understanding of Mars

the

Chelt Scientist SPRING TERM 2022

The Big Bang Theory references explained Biochemistry, Cancer and research

An interview with Dr Anscombe

Where did life come from? The different theories for the origins of life, explained

The successes of AI and the company that's building them Q&A | Staff and Student Photography | The cost of technology | The father of modern surgery

Ch Sci

Contents

Team

On the Cover

Editors-in-Chief

38 Feature: A deep dive into deep mind

Lily Pfaffenzeller Vanessa Yip

Lily Pfaffenzeller

19 Feature: The origins of life

News

Vanessa Tsui

Noelle Lee Margaret Liu Ludmila Neil Lily Pfaffenzeller Vanessa Yip

27 Interview: A conversation on cancer research with Dr Anscombe

35 Feature: The Big Bang Theory references, explained Vanessa Yip

Writers Azra Bakrie Chloe Ching Freya Dixon Rosie Evans Mr Gill Maia Kantaria Noelle Lee Lily Pfaffenzeller Vanessa Tsui Louisa Willan Vanessa Yip

Editors Muse Da Freya Dixon Sophia Joeng Justine Kwek Lucia Lee Vanessa Tsui Pippa de Wilde Louisa Willan

Graphic Designers Cheryl Luo Lily Pfaffenzeller

Illustrators Charmaine Lai Noelle Lee Regina Lo Amelie Neal Karolina Sliz Lily Pfaffenzeller Rosalind Wignall-Tory

Q&A Lily Christopherson Nell Darby Joanna Guan Mr Mallin Ludmila Neil Valerie Ostapchenko Vanessa Tsui Vanessa Yip

31 Feature: The Chemistry of colours Noelle Lee

44 Q&A: your questions, answered 15 Art: Staff and student photography

Articles 17 Epigenetics Louisa Willan

21 Why is Euclid’s fifth postulate unproven and invalid? Chloe Ching

23 An exeat weekend to Japan Azra Bakrie

25 The father of modern surgery: a biography in Spanish

Rosie Evans

News 3 The James Webb Telescope 5 January News in brief 6 The Tongan volcano eruption 7 The first pig heart transplant 9 February News in brief 11 March News in brief 13 The Russian invasion of Ukraine

26 For what it's worth Mr Gill

30 The science behind the Sunny D scandal Freya Dixon

34 The Monkeysphere Maia Kantaria

General Enquiries thecheltscientist@gmail.com Articles and Editing (Submissions & Enquiries) yipva@cheltladiescollege.org Graphics & Illustration (Submissions & Enquiries) pfaffenzellerl@cheltladiescollege.org Feedback & Suggestions thecheltscientist@gmail.com

We Want YOU! Want to take part in the next issue of the Chelt Sci? Look no further! We welcome anything and anyone, whether you're STAFF or STUDENT (of any department or year group), spanning from writing or editing articles to artwork. Message the above contacts (via teams or email) with anything from an article submission, signing up for a role to just expressing general interest. Article submissions can cover any remotely science-related topic, from AI to psychology, or even book reviews!

Editor's Note Being a scientist encompasses countless skills, one of them being the precise attention to detail. As meticulous as we thought we were, the most eagle-eyed of our readers might have picked up on a rather comical slip of the keyboard in our last issue (clue: read the caption). Although CRISPR-Cas9 was a real testament to our ever-changing technological landscape, society certainly still has a long, long way to go before seeing the first fruit develop its own agricultural industry! Mrs Jackson on the other hand, is apparently no stranger to meticulously spotting details. We’d like to congratulate her on submitting her set of answers to Mr Todd’s crossword from last issue which was spot on! In the making of this issue, we somehow ended up in Manchester one exeat weekend, which happened to be the location hosting "NewScientist Live" (an event packed full of science talks and exhibits over one weekend). It was there that we met Jim Al-Khalili, a theoretical physicist and popular science communicator. Following his talk, we ambushed him during a book signing where he was promoting his new book, "The Joy of Science" (which we very strongly recommend). On behalf of you, the reader of the CheltSci, we asked Al-Khalili “Do you have any advice for young, aspiring scientists?" to which Jim replied:

“If you’re curious about the world, then you’re already a scientist. Stay curious.”

The curiosity across CLC cannot be better demonstrated by the tantalising questions students across College have sent in, some to which students and staff have tried to answer (see p44). And what better a way to exercise your curiosity by exploring what this issue has in store! If there is one thing you can count on in science, it is that there is always something new to discover. Last term, the world learnt about the awe-inspiring work of the 2021 Nobel laureates. Since then, long-awaited telescopes have been launched, xenotransplantation has taken large leaps forwards, and results that threaten to upend the fundamentals of physics have been reported (see Science News p3-12). The quick succession of advances truly reflect how dynamic science is, much like the flexibility of our genes, as Louisa explores in her article on epigenetics. Once thought final and unalterable, Louisa shows that the fundamental language of our cells that make us who we are no exception to such variability, and demonstrates how this knowledge has been applied to cancer research. Dr Anscombe is no stranger to the realms of cancer research, which we discovered in our interview with her on p27. There’s something to learn for everyone from Dr Anscombe’s experiences in academia, particularly if you’re an aspiring researcher. Any piece of research is fuelled by the pursuit of answers. The question of where life originated from is one that fascinates biologists and beyond, and Vanessa Tsui explores the different theories that address this dilemma, which remain unsolved... for now (see p19).

In the pursuit of answers, we may often find ourselves faced with things that defy our expectations. It seems foolish to refute the concept that parallel lines will never cross, right? In Chloe’s article, she explains how such an instinctive mathematical concept turns out to be unprovable in the light of Non-Euclidean geometry (see p21). Aside from redefining the domains of current knowledge, artificial intelligence is beginning to take this even further, from solving the 50 year old problem of protein folding to beating world champions at board games after teaching itself! Take a deep dive into the company fuelling all of this, DeepMind, on p38. Even outside the world of maths, expectations are constantly being defied - one would not expect a TV show to turn out educational, but the Big Bang Theory disproves this! A classic favourite of many, scientist or not, this sitcom is jam-packed with physics references dealing with notoriously difficult topics in theoretical physics, with allusions to supersymmetry, string theory, Schrödinger and more woven into its plot. Learn more about supersymmetry and topological insulators on p35 as Vanessa Yip explains the references you may have picked up on in the show. Each discipline in science has its set of (currently) unanswerable questions that, despite seeming independent of each other, ultimately are integral pieces to the larger puzzle of understanding our universe. Thanks to the plethora of contributions, we feel that this issue truly reflects this ethos, and we hope that you enjoy reading the diverse stories CLC's scientists have to offer in this issue.

The Editors, Lily & Vanessa

Thank you Following the launch of our first issue that was published last term, we were blown away by waves of support and appreciation. Suddenly all momentary sessions of second-guessing whether anyone would even pick up a magazine prior to its release seemed so trivial. To know that such a community exists within the CLC student body, staff, parents, guild and beyond has filled us with an overwhelming sense of gratitude that words cannot even express - but hopefully these words suffice! So thank you to everyone who picked up our previous issue, and to those who were brave enough to return and venture into this second one. Among these chimes of support, one voice has never wavered. Mr Gill's support and dedication has remained steadfast throughout the thick and thin of the magazine, and he even wrote an article for this issue (see p26)! We also appreciate the constructive feedback from Jim Griffin - the magazine really benefited from your expertise (and of course another thank you to Mr Gill for the opportunity to meet with Jim). Another massive thank you to Mrs Thomson, who has been at the forefront of getting the CheltSci printed, on issuu and has guided us through the process of making a magazine. Full bibliographies are on a separate document which can be accessed here (via Issuu): https://docs.google.com/document/d/1C6_nLV1ucyJPiiMsy3EnGn-WSmPQ-pxSIKqItugdT_w/edit?usp=sharing 2

SCIENCE NEWS SPOTLIGHT

The James Webb Space Telescope is finally here! Well, it’s actually 1.5 million km away from us

NASA engineer Ernie Wright looks on as the James Webb Space Telescope's primary mirror segments are prepped to begin final cryogenic testing at NASA's Marshall Space Flight Centre.

Astronomy was given the best Christmas present this year: the successful launch of the James Webb Space Telescope (JWST). From the birth of such a concept in 1996, the project suffered multiple technical problems and delays, with its budget soaring from $500 million to a whopping $10 billion. Criticisms aside, there is no doubt its highly-anticipated launch on 25th December came as a relief to those at NASA, ESA and the Canadian Space Agency who collaborated on the project. In 1996, the Hubble Space Telescope, predecessor of JWST, viewed a seemingly empty region of the sky. Upon closer inspection, the Hubble Deep Field image showed the opposite. Turns out, that region housed 3000 galaxies,

some of which were the oldest ever observed. The astronomers subsequently worked on building the Next Generation Space Telescope to probe this further, which later evolved into the JWST. The idea was revolutionary, but was met with several obstacles. Technical problems with the sun shield and thrusters meant its planned launch in 2018 was pushed back. When COVID-19 hit, pandemic protocols delayed the launch date even further, from March 2021 to December 25th, the day JWST finally took its leap into the cosmos. Launched on the ESA’s Ariane 5 rocket from French Guiana, JWST reached the moon’s orbit in 3 days. On 4th January, JWST unfolded and tensioned its sunshield, a meticulous manoeuvre comprising a total of over 140 release mechanisms. Once this was

deployed successfully between the telescope and the Sun, Earth and moon, its secondary and primary mirrors were unfolded. 27 days after its launch, JWST then reached the second Lagrange point (L2), 1.5 million km from Earth (in the direction opposite to the Sun). L2 is one of the five Lagrange points established in the 18th century. It is the point where the gravitational forces of the Earth and the Sun are equal, meaning JWST would orbit steadily around the Sun along with the Earth, only needing rocket thrust every three weeks to keep it in orbit. At L2, it would not be precisely stationary; instead, it would orbit around L2 in a “halo orbit”. The instruments were then turned on and astronomers began calibrating them, a key step to ensure images captured by the observatory were

perfectly aligned. JWST took its first picture of its mirrors (a “mirror selfie”, some may even call it), and astronomers have proceeded to align the 18 hexagonal mirrors. After all of this, JWST will be ready to capture images of everything from exoplanets and stars, to the most distant galaxies. (Update: as of April 2022, JWST has sent back an image of a star - our highest resolution yet! The alignment process is nearly completed, and its instruments and mirrors are nearly fullycooled.) The advanced design of the JWST caters to the primary function of the observatory: to look at infrared radiation. As our universe continues to expand, light travelling from distant galaxies to us stretches in wavelength towards the infrared side of the electromagnetic spectrum, resulting in a phenomenon termed “red shift”.

Josef Aschbacher and Thomas Zurbuchen celebrate after hearing confirmation that the James Webb Space Telescope successfully separated from the Ariane 5 rocket. Lagrange Points 1-5 of the Sun-Earth system

About 13.6 billion years ago, the first stars and galaxies were born, and light emitted from them has now redshifted. Hope therefore remains high that the JWST will be our modern way of looking back in time, that peering into the infrared spectrum will yield interesting findings about the young universe. Because

planned, the mission of the JWST falls under 4 main pillars. They aim to elucidate how the first stars and galaxies were formed 100-250 million years after the Big Bang, which occurred 13.6 billion years ago. Another long-standing mystery in astronomy is dark matter content. Our universe is made up of five times as much dark

infrared radiation is given out by warm objects, heat must be

matter as “normal” (baryonic) matter, but scientists cannot

reflected from the observatory to ensure clear images are

measure this directly as dark matter does not interact with

captured. A sunshield made of five layers of Kapton, a

baryonic matter. Equipped with gravitational lensing

lightweight thermal material, is designed to cater to this need. Spanning the width of a tennis court, it keeps the side facing away from the Sun at -233°C, while the other side is exposed to 85°C. At L2, the large distance from the Sun further ensures scientific instruments aboard are kept sufficiently cool. Furthermore, the JWST also has 18 hexagonal mirrors arranged in a honeycomb pattern that are gold-plated to reflect and focus infrared light onto the ISIM (Integrated Science Instrument module), which subsequently produces images. All of this means the JWST, when compared to the Hubble Space Telescope, is capable of viewing objects that are 10-100 times fainter, 10 times more precisely! With

techniques, astronomers at JWST will indirectly investigate dark matter content through studying faraway galaxies, and also gain insight into the formation and evolution of

300 observing programmes

background shows other stars and galaxies. It is the highest resolution infrared image ever taken from space. Credit: (NASA/STScI)

18th century mathematician Joseph-Louis Lagrange found 5 solutions to the “three-body problem”, which asked if there were any stable configurations where three bodies could orbit each other while staying in the same position relative to each other. These 5 solutions then became the 5 Lagrange points (see diagram), locations where the gravitational forces of two large masses and the centripetal force needed for a small mass to move between them are equal.

galaxies over time. JWST will also investigate the formation of stars and planetary systems whilst studying exoplanets in search of signs of alien life. TRAPPIST-1 is a star of particular interest as 3 of the 7 planets orbiting it are in the habitable zone, and one of them may even contain liquid water!

The long-awaited launch of the JWST was undoubtedly a significant event in space exploration. As we follow the news of JWST making its ambitious way through the cosmos, who knows what kind of new information about our universe will be discovered! Vanessa Yip

This image is JWST's first image of a star which is called 2MASS J17554042+6551277, and uses a red filter to optimize visual contrast. The

SCIENCE NEWS IN BRIEF

January BIOTECH

CRISPR used to produce all female or all male litters of mice

GENETICS

Genetic variant linked to longevity could reveal underlying mechanisms of ageing With ageing being such a multifactorial phenomenon, a particular area of interest is the role of genetics. To probe the existence of an ageing-associated genetic variant, Vera Gorbunova at the University of Rochester in New York led a study comparing the DNA sequence of 500 Ashkenazi Jewish centenarians with 500 from less long-lived families. 1% of the centenarians carried the centSIRT6 variant while 0.5% of the others did, which proved statistically insignificant. However, a larger study into 150,000 subjects from diverse ethnic backgrounds later demonstrated those with a longer lifespan had a higher chance of having the centSIRT6 variant. Through

Scientists at the Francis Crick Institute and the University of Kent have used CRISPR technology to produce allfemale or all-male litters of mice with 100% accuracy with no adverse effects on surviving offspring. The researchers targeted a gene called TOP1; when altered via CRISPR, embryos fail in early development. The CRISPR technology edits this gene by wielding two molecular tools: an enzyme called Cas9 which cuts the region of DNA where TOP1 resides, and a molecule named 'guide RNA', which guides the Cas9 enzyme to the gene. The two parts are split between gametes, with the Cas9 enzyme being placed on the father's X or Y chromosome, and the guide RNA on one of the mother's X chromosomes. The geneediting process is activated upon fertilisation when these two parts meet. For example, if the Cas9 enzyme was placed on the Father's Y chromosome and the guide 5

RNA on the mother's X chromosome, any XY chromosomes formed would activate the CRISPR process. In uniting these two components, the guide RNA on the X chromosome can guide the Cas9 enzyme on the Y chromosome to the TOP1 gene to edit it, in turn disrupting the development of male embryos. Hence, an all-female litter would be born. Conversely, to produce an all-male litter, the formation of an XX pair would have to be prevented, so the Cas9 enzyme would have to be placed on the father's X chromosome instead (the CRISPR process only targets the chromosome the enzyme is placed on).The implications are far-reaching: farming yields for one, would increase. Consider male chickens, for example, who cannot produce eggs. By producing all-female chickens, more eggs could be produced. It's good news for lab animals used in research too, since culling would no longer be necessary. Lily Pfaffenzeller

conducting experiments in vitro, Gorbunova and her team elucidated that the variant maintains the efficient packaging of DNA, which naturally deteriorates as we age. The variant also suppresses the activity of transposons, also known as “jumping genes”, which can move from one location to another on the genome. This can lead to mutations, triggering inflammatory responses which, if sustained long-term, is strongly linked to ageing. Each gene codes for a particular protein in our body, and the corresponding protein produced (SIRT6) from centSIRT6 has a dual function. It catalyses the removal of the acetyl group from some proteins, and the addition of ribose to others.

“We see some evidence that SIRT6 can rejuvenate .” The variant achieves these observed effects due to an improved ability to add ribose, which suggests drug development could be directed onto focusing on ribose, rather than acetyl activity. Although other genetic variants have been linked to ageing, such as one that affects cholesterol, Gorbunova believes that her team is uncovering an “underlying mechanism” that “drives ageing”, rather than an “associated symptom” of ageing. If they can be created, such drugs might even be able to “reverse ageing to some extent”, Gorbunova says. “We see some evidence that SIRT6 can rejuvenate.” Vanessa Yip

SCIENCE NEWS SPOTLIGHT

The Tongan eruption was out of this world (Quite literally; here's how the eruption is helping us understand Mars)

Satellite imagery shows the Hunga Tonga-Hunga Ha'apai volcano on Jan. 6, 2022, before the eruption on Jan. 14th, 2022 in Hunga Tonga-Hunga Ha'apai Islands, Tonga. Photo credit: Maxar via Getty Images

On January 15th we all spectated from our screens the plumes of ash that engulfed Tonga as a volcanic eruption devastated the unsuspecting archipelago. Half-submerged underwater, the volcano named 'Hunga Tonga-Hunga Ha'apai' has not only changed the lives of 100,000 Tongan citizens, but also the frontiers of Volcanology as we know it. The explosion was calculated to be 500 times the force of the Hiroshima atomic bomb, and for the 11 hours that the eruption lasted, a tsunami was further triggered and reverberations from the eruption circled the globe several times.

500 times the force of the Hiroshima atomic bomb These reverberations have further shaken the foundations of volcanology, questioning our true understanding of seismic activity. Imaging says the eruption is one of the largest ever in satellite era, with a diameter of 650km (that's almost the size of Spain!), yet researchers are scratching their heads over the amount of ash emitted, which was much lower than the expected amount for an eruption of this magnitude. While the eruption itself has rendered volcanologists clueless, it could pave the way to certainty beyond Earth when it comes to other planets that also have volcanoes.

Prior to the explosion, the volcanic island of Hunga Tonga-Hunga Ha'apai had already attracted the eager eyes of chief scientist James Garvin and his team of researchers at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. It is rare to observe the real-time formation of islands, so when an underwater volcano in 2015 began to expel ash and lava, Garvin's team had a front row seat in watching the formation of the island. Unlike most volcanic islands which erode away months after formation, Hunga Tonga Hunga Ha'apai persisted for years, allowing Garvin and his team to analyse its changes using satellite imaging and seafloor surveys. Following its eruption however, the vast majority of the island disappeared, with teams now monitoring the island using optical, radar and laser satellites to measure what is left. This all contributes to a greater understanding of the formation of volcanoes in Mars, which are suspected to have formed in the presence of water. Scientists aren't quite sure if or when volcanoes on Mars erupted, nor what the nature of these eruptions are like, but Hunga Tonga-Hunga Ha'apai reduces this level of speculation. Take the marine environment surrounding Hunga Tonga-Hunga Ha'apai for example, which also mirrors the low-gravity settings found on Mars and thus “can shed unique light on Martian features that formed in lower gravity", according to planetary scientist Joseph Michalski at the University of Hong Kong. Lily Pfaffenzeller 6

SCIENCE NEWS SPOTLIGHT

First pig heart transplant "Will I oink?" asks David Bennett, recipient of the pig heart transplant Seven days into the new year, a ground-breaking operation was carried out in Baltimore, Maryland: the first ever transplant of a pig heart into a human. 57-year-old David Bennett suffered from end-stage cardiac failure. Having been deemed unsuitable for both a human heart transplant and a ventricular assist device (an artificial mechanical pump), he was permitted to receive the xenotransplant under compassionate use, which allows severely ill patients to receive unauthorised medicine as a last resort. Xenotransplantation entails inserting an organ of a different species into humans, an idea that has been around since the 1920s and still remains contentious. While the ethics that come with such a procedure are highly debated, the idea may offer hope to those awaiting transplants. A longstanding concern with all transplants is the risk of rejection from the recipient’s immune system. Using CRISPR, however, the organs can be genetically modified to reduce this risk. These organs typically come from pigs, as they are favoured over primates given they achieve human size in 6 months and are easy to raise. With pigs producing around 8 piglets per litter, many believe utilising their modified organs

Surgeons at the University of Maryland Medical Center transplanted a genetically altered pig heart into David Bennett.Credit: University of Maryland School of Medicine

may solve the urgent problem of organ shortages. The heart was derived from a pig developed by the US firm Revivicor, with 10 modified genes. Alpha-gal is a sugar found on the surface of pig cells which causes an aggressive immune response to flare up in humans. Of the 4 genes scientists inactivated, one coded for the enzyme that attaches this exact sugar. They also inactivated a gene which prevents the heart from continuously growing after transplantation by hindering its response to growth hormones. To boost acceptance, 6 human genes were further inserted into the heart.

Pigs stand in a barn of the of Ludwig-Maximilians-University Munich at the Badersfeld bog test farm in Oberschleissheim, Germany. (Photo: Reuters)

On 7th January, David Bennett underwent this procedure under immunosuppressants, and the outcome seemed to be optimistic afterwards, with reports of Bennett slowly gaining strength. He was under close monitoring for signs of organ rejection, which could take weeks or longer to manifest. Albeit the low risk at the time, they were also on the lookout for signs of infections. Unfortunately, Bennett passed away in March. Recent news disclosed that a latent virus, compounded with his initial heart condition, may have been contributing factors. However, scientists have noted that the cause of his death may not fall solely on the infection.

David Bennett Sr. (centre) after his heart transplant pictured with his son, David Bennett Jr (left) (Image credit: University of Maryland Medical Center)

Despite this, he survived significantly longer than the recipient of a baboon

Nonetheless, with 100,000 on the waiting list but less than 25,000 receiving kidney

So, is experimenting with heart transplant ethical, such as in Bennett’s case?

heart in 1984, and the surgical procedure has provided "invaluable

transplants in the US, kidney xenotransplantation may offer hope to many.

Scientists are eager to start larger trials testing similar heart transplants which

insight", in the researchers' words. Prior to this, late 2021 additionally saw several successful transplants of modified pig kidneys into brain-dead humans. In one such experiment, the

Even if pig organs do not last as long as human organs might, a xenotransplant could be used while waiting for a compatible human organ to be available in the meantime. Reasonably, hesitancy remains. Worries are not least due

can prove useful as attempts at understanding how humans would respond to xenotransplants are limited by animal models. However, some argue such experiments should be done

recipient of the kidney was Jim Parsons, a registered organ donor whose family gave permission for the experiment to be carried out. The kidney came from the same line of pigs that Bennett obtained the transplanted organ from. They found that the transplanted kidney managed to produce urine for 77 hours.

to the viral genes that lurk in the genomes of all pigs (porcine endogenous retroviruses). However, fears may have been assuaged by evidence of successful transplants of pig pancreas cells into humans, and efforts to delete viral genes through genetic modification. Concern has also been raised over animal rights and welfare, especially given pigs will have to be reared in strictly-

incrementally with kidney transplants rather than heart transplants while others are adamant that the chances of surgical success greatly outweigh the risk of waiting for an available human organ. How would attitudes towards xenotransplantation change if we consider the usage of other animal parts in medicine that has been established for

However, kidney function was not perfectly restored: it was unclear why

monitored pathogen-free environments to ensure organs are free of disease. And, of

decades, such as that of pig heart valves, or insulin produced by pigs and cattle?

the kidneys did not remove creatinine from the blood, which is an indicator

course, there is the everlasting question of what effects a xenotransplant may have on a

Equipped with recent apparent successes in xenotransplantation, this poses many

of normal kidney function.

recipient’s sense of identity. Clearly, the technology is not without ethical debate. If a

questions to consider when deciding the ethics, regulations and policies of such a

kidney transplant does not go to plan, surgeons can remove the organ and put the

technology, and how best to move forward.

The kidney produced urine for 77 hours

patient back on dialysis. If the same happens for a heart transplant, the outlook does not bode so well.

Vanessa Yip

The surgical team examines the pig kidney for any signs of hyperacute rejection, during the 54-hour study period Joe Carrotta for NYU Langone Health / via Reuters

SCIENCE NEWS IN BRIEF

February BIOTECH

MEDICINE

Switching blood types - a step towards creating universal donor organs? Each individual has a particular blood type, which corresponds to the type of antigen presented on the surface of red blood cells. For example, type A blood contains A antigens (AAg) and anti-B antibodies, while type O lack antigens but has both anti-A and anti-B antibodies. Before patients undergo organ transplantation,

which removed nearly all A-Ag. Fluids were then supplied to the lungs in preparation for the transplantation via ex-vivo lung perfusion, where they tested the tolerance of the treated lungs. To simulate an incompatible transplant, type O blood containing high amounts of anti-A antibodies was added to the fluid. Minimal antibody

doctors must ensure the ABO blood groups of the donor and

response was recorded, suggesting a low chance of

patient are compatible. This is because our immune systems

antibody-mediated injuries if done in vivo. How long the lack

are not infallible - if the body detects foreign antigens from

of antigens will be maintained is not clear, and the team has

an incompatible blood type, hyperacute rejection could be launched, bearing deleterious consequences for the organ recipient. Given the lack of antigens in type O organs, an immune response will not be provoked, heralding type O as the “universal donor”. Dr Marcelo Cypel and his team at the University of Toronto, Canada performed a proof-ofconcept study into switching a type A organ into a type O, effectively making it a universal donor. They treated lungs with sugar-digesting-enzymes

plans to test the novel technique further in mice. With wait times for type O patients averaging twice as long as type A patients, “switching” blood types to create type O organs has massive implications for eliminating the “bloodmatching barrier” and allows doctors to “prioiritise patients by medical urgency, saving more lives and wasting less organs”, says Dr Cypel.

Vanessa Yip

Biohybrid fish powered by human cardiac muscle cells swims for 100 days

The first fully autonomous biohybrid fish from human stem-cell derived cardiac muscle cells. Credit: Michael Rosnach, Keel Yong Lee, Sung-Jin Park, Kevin Kit Parker

Harvard University researchers, in collaboration with colleagues from Emory University, have developed the first fully autonomous biohybrid fish from human cardiac muscle cells, in pursuit of building an artificial heart. The biohybrid fish is engineered with two cardiac muscle cells, one of each side of the tail fin. Whenever one of the muscles contracts, it opens a protein channel which can trigger the muscles on the opposite side to contract. The fish is also equipped with a pacemaker to coordinate the

frequency and rhythm of the contractions. As a result, this closed-loop system recreates the muscle contractions of a pumping heart, highlighting the role of feedback mechanisms in the heart muscular pump. The good news was that the fish could swim around for more than 100 days, which hinted that the researchers could build a long-lasting muscular pump from human stem-cell derived cardiac muscle cells, which was part of their aim to replace a child's malformed heart. Noelle Lee

ECOLOGY

A new method to eradicate invasive species

Over the recent centuries, invasive species have posed a threat to fragile ecosystems all over the world and people have come up with all sorts of methods to rid that areas of them. However, recently chefs and conservationists alike have agreed on a method to eradicate invasive species: by eating them. This new food movement is called invasivorism in which invasive species are incorporated into everyday and gourmet dishes. This method has 9

already been adapted in many places around the world, for example in the Caribbean Sea where restaurants serve the invasive lionfish, or in the where UK restaurants serve grey squirrel. However, though at face value it sounds amazing, there’s one important thing that everyone should keep in mind: eating invasive species should be to reduce or eradicate the species and it is not intended to create a market for that creature. Ludmila Neil

MEDICINE

NUCLEAR PHYSICS

Third person is cured of H.I.V. using novel stem cell technology

Nuclear Fusion Breakthrough The UK-based Joint European Torus (JET) laboratory (nuclear fusion reactor) beat the record for the most amount of energy extracted from squeezing two atoms of hydrogen together at unprecedented temperatures and pressure. Nuclear fusion is a type of energy source that if created on Earth would essentially be a mini star contained within a nuclear reactor from which scientists could extract large quantities of energy mirroring the magnitude of the sun's processing power (known as fusion power). This experiment which lasted five seconds produced 59 megajoules of energy! That is enough energy to boil 60 kettles full of water at once, or 14kg of TNT going off!

Budding HIV virions

Using a stem cell transplant from an umbilical cord, a woman suffering from leukaemia and HIV (whose identity remains disclosed) has become the third person to be cured of HIV, a virus that targets the immune system, thus increasing susceptibility to cancers and infections. Two other men had been previously cured of HIV, but this case is substantially more ground-breaking: being a woman of mixed race is "really important scientifically" said Dr Steven Deeks, an AIDS expert at the University of California, San Francisco who was not involved in the work. HIV infection is thought to progress differently in women compared to men, but while women account for more than half of HIV cases in the world, they make up only 11 percent of participants in cure trials.

only

11% of participants in trialsare women

Previously, the two men cured received bone marrow transplants, which brought about adverse side effects. From the donor cells attacking the recipient's own body, to extreme hearing or weight loss, one patient almost died following his transplant. The woman, who received a slightly different treatment, did not experience such side effects. She received cord blood to treat her leukaemia from a partially matched donor (despite not being of a similar race), where the donor's cord blood cells contained a mutation that blocked HIV entry into cells. Due to an engraftment period of 6 weeks, she was given additional blood stem cells from a firstdegree relative to provide a temporary immune defence. After numerous blood tests 14 months later, the patient showed no signs of HIV in blood tests. Though reasons as to why umbilical cord stem cells are more effective than those taken from bone marrow are unclear, a possibility is that they are more capable of adapting to a new environment, said Dr Koen Van Besien, director of the transplant service at Weill Cornell. “These are newborns, they are more adaptable,”. Regardless, the successes of the cord transplant provides promise that umbilical stem cells could pave the way to Lily Pfaffenzeller further breakthroughs in the future.

JET interior with superimposed plasma (Image: UKAEA)

A new combination of materials and isotopes used resulted in the record-breaking plasma shots: instead of graphite, metals such as tungsten and beryllium were used in the walls of the JET to act as a sponge for the hydrogen isotopes used to create plasma. A mixture of hydrogen isotopes were used this time too in contrast to the typical choice of sole deuterium, as a combination of deuterium and tritium ensured fusion could occur at much lower temperatures. Unlike its cousin nuclear fission (in which hydrogen atoms are split, rather than fused), the ever-persistent issue of radioactive waste isn't produced through fusion, in addition to the low carbon supply the process advantageously demands. Though JET was only able to maintain the plasma for 5 seconds, this record solidifies the potential of better power that could be wielded from nuclear fusion, bringing us one step closer to reality. Ludmila Neil

CONSERVATION

Poland’s Steel Wall Border Threatens Species Poland is in the process of building a five metre tall steel wall along the Poland-Belarus border which spans 186 kilometres in an attempt to counter the entry of migrants from Belarus. The wall will demolish one of the largest wildlife corridors in the world. Currently there is a three-metre tall razor-wire fence which has already killed or entrapped many animals including bison and moose. As the steel wall begins to grow, more environmental effects will be observed, especially since the border will separate Ludmila Neil the oldest lowland forest in all of Europe into two. 10

SCIENCE NEWS IN BRIEF

March ENVIRONMENT

An end to plastic pollution?

Plastic Pollution in Kanapou Bay, Kaho‘olawe, Hawaii

It isn't news to us that the world has a problem with plastic. Each year eight million tonnes of plastic enter the world's oceans, destroying habitats, disrupting wildlife and contaminating the food chain, all on a global scale.

5 trillion

pieces of plastic are in the world's

pollution. Importantly, the treaty acknowledges lower-

Considering plastic takes hundreds of years to break down, its persistence as a problem will only worsen alongside its widespread use in society. Such implications were discussed during the United Nations Environment Assembly (UNEA) on the 2nd of March in Kenya. From production and use to their disposal, the full life cycle of plastics was placed at the forefront of the assembly,

income countries that suffer the most from plastic and pollution, calling for the need of an additional financing model to overcome plastic reliance. With the treaty comes substantial pressure, being described as one of the world's most ambitious since the 1989 Montreal protocol which phased out ozone-depleting substances. Environmental groups mirror such expectations, calling for clear global standards that incentivise nations to reinforce

shedding light on the impacts of the crisis: in addition to the negative impacts on marine life, there are fears it may affect our health too. Most plastic originates from lower and middle-income countries with less capacity to burn or recycle it, further perpetuating these adversities. "We need a global

new rules and regulations concerning plastic, while penalising harmful products and practices. Considering the unfathomable harm our use of plastic has inflicted on the environment in the space of a decade, it's about time we move towards putting things Lily Pfaffenzeller right again.

oceans

agreement to enable us to deal with the widespread challenges that plastic gives us as a society." advised Professor Steve Fletcher from the University of Portsmouth. Indeed, a global crisis calls for a global solution: as a result, 175 countries signed a legally binding treaty to end plastic

MATERIALS

New fabric can hear sounds

Researchers sewed in two panels of acoustic fabric in the back of a dress shirt. Courtesy of the Finke Lab

A new fabric created by Wei Yan and his colleagues as part of a collaboration between the Massachusetts Institute of Technology and Rhode Island School of Design unlocks another avenue in wearable technology. The new fabric converts sound vibrations into electrical signals, which can detect a wide range of noise

listening for heart murmurs analogous to the use of a stethoscope. The successful proof-of-concept could have exciting implications for nonintrusive monitoring and diagnostic tools - “this fabric can imperceptibly interface with the human skin, enabling wearers to monitor their heart and respiratory condition in a

levels like a microphone. These researchers modelled the fabric

comfortable, continuous, realtime, and long-term manner”,

after the human ear: sound travels in pressure waves causing the eardrum to vibrate, which the cochlea translates into electrical signals. Similarly, they created a fibre containing cotton fibres and Twaron (a stiff material) which convert sound into vibrations. They wove piezoelectric materials into the fibre as well, which are materials that generate a voltage when mechanical stress, in this case from the vibrations, is applied. To test the fibre, it was incorporated into a shirt. The researchers clapped at different angles from the garment, and the fibre accurately matched the distance and direction of the sound’s source. They further investigated the fibre’s ability to monitor the heart through this wearable technology,

says Yan.

The fabric was able to detect the angle of

sound

3 metres away to within 1 degree

Apart from that, the new fibre could be used in many ways. If embedded into buildings, it could be used to detect cracks. Its ability to distinguish the direction of sounds could be used to aid those with visual impairments. And, of course, there is the cool futuristic possibility of us being able to answer phone calls through our acoustic garments, a foolproof way to confuse other pedestrians. Vanessa Yip

Things to look out for… GEOLOGY

Are we in a new geological epoch?

Since the last major ice age, we have been living in the Holocene epoch, also known as the Anthropogene epoch which

represent a record of methane emissions, and so on. In the second half of this year, a group of 34 researchers in the

translates to “Age of Man''. For the past 11,650 years or so, the Holocene epoch has seen

Anthropocene Working Group (AWG) will agree on the primary marker most

everything from the evolution of civilisation and recorded

representative of human activity, considering both the

history, to the expansion of human knowledge and technology. This all comes at a price, however, and we are increasingly seeing the effects of human activity on the environment. This has singlehandedly led scientists to conjecture over the possibility

clarity of this marker and its impact worldwide. They will also choose a site that provides the clearest evidence of a significant change to the Earth’s biosphere requisite for a new epoch to exist, with 12 candidate sites currently in the running (Figure 1). This will act

of us having entered a new geological epoch: the

as the Global Boundary Stratotype Section and Point

Anthropocene era (“Anthropo” is Greek for “man” and “cene”

(GSSP), an official boundary that separates geological units

for “new”). Humanity’s impact has left many key markers in

of time. After voting for the site, this will go through further

our environment - nuclear weapons have created radionuclides, ice cores

voting to confirm the existence of the new epoch itself. While we wait for announcements

Human impact shown on a global scale, taken from NewScientist

that may come in 2024, there is increasing controversy surrounding both the year that marks the dawn of the Anthropocene epoch, and its existence itself. AWG proposes the epoch started in the 1950s with the Great Acceleration which saw environmental impacts from human activity surge dramatically, while some posit it started in the 1800s due to the Industrial Revolution. In the meantime, there is no doubt we can agree the current debate is more jarring evidence of our deleterious Vanessa Yip relationship with our planet.

GENETICS

The first full human genome has been sequenced

Human genetics has its own dark matter equivalent: 20 years ago, the first sequenced human genome left a mysterious 8% of the genome undeciphered. The quest to produce a complete genome from “telomere to telomere”, in the words of Adam Phillippy, bioinformatician at the National Human Genome Research Institute, persisted throughout the last few decades, leading to a recent breakthrough. Endowed by advancements in technology that notably include long-read sequencing technology, which allows long stretches of DNA to be read, scientists have filled in many gaps left in the human genome puzzle. They were able to sequence repetitive DNA segments, a major obstacle scientists encountered when the first draft of the human genome was published. This is because technology then meant these repetitive sequences could easily be skipped or read incorrectly. These newly-added DNA segments reside in the centre of chromosomes (centromeres) and at the ends (telomeres - think of them like the Vanessa Yip protective caps at the ends of your shoelaces).

PHYSICS

Will the Standard Model break? Physicists normally use 5 sigma as the level of significance to count something as a ‘discovery’, where sigma represents the divergence between the value you can and the mean, but the difference between the W boson mass measurement and that predicted by the standard model is even higher, at the significance level of 7 sigma. The mass of W boson is calculated by analysing the particles, electrons and neutrinos, that it decays into. If the discrepancy is not affected by systematic errors, the result will suggest the breakage of the Standard Model which hints at exciting new physics. The deviation may provide evidence for the physics not included in the Standard Model – the interaction between graviton with dark matter or the existence of a new type of neutrino. The disparity may also break the ‘Model Dream’ that exists in most of the physicists’ minds and reveal the real side of the Universe – chaos. Margaret Liu

SCIENCE NEWS SPOTLIGHT

The Russian invasion of Ukraine and challenges scientists face

7.1 million people in the Ukraine have been displaced, and a further 3 million have fled the country. These numbers are undeniably mammoth in magnitude, yet barely account for the additional people affected globally since the genesis of Russia’s unprovoked invasion of Ukraine. Science is no exception, with students and researchers alike feeling the reverberations across the globe. Scientists have come together on this front, expressing the urgency to unite, act and support afflicted scholars in their recent letter:

"We, scientists of Ukrainian, Russian and Belarusian descent, currently working in the US, UK and Canada, resolutely condemn aggression against Ukraine and call for the Russian government to stop the military operation in Ukraine. We call for far-reaching support to Ukrainian scientists who have been deprived of an opportunity to perform research at their home institutions and study at their home universities because of destruction and death brought by the war in Ukraine." An extract from the letter, originally published on the website of the Georgia Institute of Technology. But have these calls been heard and addressed? Indeed, if we are to restore what science once was for individuals and institutions, what exactly has and ought to be implemented moving forwards?

Concerning Russia From energy to Eurovision, the world has been quick to boycott Russia from various respects, including science. Organisations internationally have severed collaborations with Russian scientists alongside withdrawals of funding and resources. A rapid response from Germany's largest research funders demonstrated exactly this: “...it is recommended that academic cooperation with state institutions and business enterprises in Russia be frozen with immediate effect until further notice, that German research funds no longer benefit Russia, and that no joint events take place of an academic nature or those pertaining to research policy.” The statement released by the Alliance of Science Organisations in Germany

On the same day, the Massachusetts Institute of Technology (MIT) in Cambridge, United States issued a similar statement ending their relationship with the Skolkovo Foundation, a Moscow-based nonprofit organisation centred around innovation. UK science minister George Freeman followed suit on the 27th of February, declaring that he had launched a rapid review of research-innovation funding from the UK government to Russian beneficiaries on Twitter. Perhaps the most stinging of the condemnations came from the European Organisation for Nuclear Research, otherwise known as CERN. It was here, specifically at the Large Hadron Collider, where the Higgs Boson was discovered, a particle sought after for decades. The World Wide Web was also invented at CERN to enable physicists to easily share data. These successes reflect CERN’s founding ethos of "bringing people together for the peaceful pursuit of science" since its establishment following World War II. In going against exactly what CERN stands for, the lab declared that it would not engage in any new collaborations with the Russian Federation “until further notice” and suspended it from its observer status at the lab. 13

An observer status entitles delegates from a nation to observe the council meetings which govern the laboratory’s operations. Stripping Russia from this role elicited mixed feelings. Nobel Laureate Kip Thorne (who had working relationships with Russian astrophysicists since the 1960s) deemed CERN’s decision as necessary, while Lisa Randall, a theoretical physicist at Harvard, conversely stated: “Unless the scientists are responsible for the actions of their country, it is unfair and contrary to the international collaborative spirit of CERN to make this move.”

Russia's response Russian scientists also echo the cries of condemnation, with thousands deeming the actions of their government as reprehensible alongside the rest of the world. Researchers thus came together to organise a letter signed by more than 5000, around 85 of which are scientists who are members of the Russian Academy of Sciences, a government body that oversees the majority of the nation’s research. Contrastingly, others still vocalised the lack of condemnation from Russian academic institutions. Another open letter from the Academy of Sciences of the Higher School of Ukraine urged restrictions on Russian scientists to be all-encompassing: “We urge that researchers with an affiliation of such institutions not be admitted to international grant teams, not be invited to international conferences, and not be published in leading international scientific journals.”

A protest in Times Square following Russia's invasion on the Ukraine. Credit: Rhododendrites, Protest of the Russian invasion of Ukraine in Times Square (62491), CC BY-SA 4.0

#ScienceForUkraine Besides the backlash against Russia, action has also been taken to ameliorate the ramifications felt amongst the Ukrainian scientific community. Looking to help wherever they can, research groups around the world have now been compiled into a list, volunteering scholarships, accommodation and job offers, accessible online under #ScienceForUkraine. Initiated by Ilfa University of Latvia and supported by national organisations, this list has grown to include more than 600 universities and has been circulated to all universities in Ukraine. With some predictions warning of an emergence of 6300 academic refugees, of which one fifth will not choose to return to Ukraine, actions such as these are crucial.

6300 academic refugees Additionally, the list is a promising opportunity for female scientists too, given that Ukrainian men aged 18-60 are forbidden to leave in anticipation that they may be called to fight. Others have already witnessed the list come into play, with Michael Bojdys at King’s College London receiving an email from an analytical chemist at Kyiv University with her two children who was seeking work.

Further measures Alexander Kabanov, a Russian-US chemist at the University of North Carolina at Chapel Hill who co-organized a letter from the Russian researchers living overseas, believes further support should be implemented: “The Western academic community should develop programmes of support for Ukrainians who need education and scientific training. I believe the laboratories should be open for them.” Despite the thousands of Russian scientists who signed the open letter acknowledging that Russia had "doomed itself to international isolation" with its invasion of Ukraine, they are undoubtedly suffering too. With funding being frozen and widespread cuts in communication as aforementioned, it’s important that the impact remains directed at governmental power as much as possible, so as to reduce further disruption to Lily Pfaffenzeller individuals. It’s imperative that we continue to discuss the situation at hand and those impacted. If you want to join the effort in helping those affected, you can donate to The Disasters Emergencies Committee (DEC), which is the charity college has chosen to support. If you're on issuu, access DEC through this link: https://www.dec.org.uk/

ART PHOTOGRAPHY

Photography Staff and student submissions Australia

Praying Mantis, Queensland It has five eyes, can span up to six inches long and a head that revolves 180 degrees. Among all these idiosyncrasies, it is the four prominent legs that the Praying Mantis is named after, with the insect you see crouched in the photograph crouching in a prayerlike stance. Generally, you'll find they prefer warmer climates, particularly around tropical and subtropical latitudes. Though the majority are thus found in Asia, others are also dotted around the globe, with 20 species being native to the USA, or a much more substantial estimate of 160 species in Australia, such as this one found in Queensland. Though small, the Mantis is mighty: surviving off a carnivorous diet, you can often find one munching on a variety of insects, such as moths, crickets, flies or... other Praying Mantises? Yes, you read that right: adult females often chomp down on their mate just after—or even during—mating, though explanations as to why are hazy.

Lorikeets, Sydney Pictured below are Sparkles and Lollipop, two lorikeets in Sydney, Australia (we're not sure which one is which, though). A special thank you to Tony Dear, a friend of Miss Black's who took both photographs!

Miss Black, Drama-PGC | Tony Dear

Why you are lighter at the top of the London Eye? If you recall the force you felt in your ‘London Eye’ experience, you may remember that you felt heavier at the bottom but lighter on the top. This is because of the two dominating forces acting on the Eye - centripetal force and gravity. The centripetal force always points towards the centre of the Wheel and gravity always acts downwards. Therefore, the centripetal force you feel at the top, 'C1', is pointing downwards (negative) and it is positive at the bottom. Since

F = ma the centripetal force can be rewritten as mp, with p as the acceleration of the centripetal force. The reaction force, 'N1', you feel at the top follows the equation:

N1 - mg = mp and the reaction force you feel at the bottom follows:

N2 - mg = mp Put them together, you get:

N1 = m(g-p) N2 = m(g+p) Why buildings are so straight? Have you ever wondered why high buildings are either straight or get sharper and sharper towards the top? Gravity plays an essential role in the overall shape of buildings. A building will crash if its centre of mass is not directly over the perimeter of its base. Therefore, it’s better for buildings to have a symmetrical shape with a big base, so gravity will not drag the unsymmetrical part down to the ground. This property makes cylinders, cones and rectangles popular candidates. The sharp top of high buildings lowers their centre of mass in order to increase their stability. However, why are cylindrical and conical shaped buildings less common than rectangular buildings? The answer lies behind the cost, since it’s cheaper to purchase flat glass and rectangular rocks.

Therefore, you feel more force at the bottom. More interestingly, the force you experience during the whole cycle can be plotted as a cosine graph and the rate of change of force you feel can be plotted in a negative sine graph. This is how mathematics relates to physics and how physics relates to real life!

Margaret Liu, SFC1 16

ARTICLES GENETICS

Epigenetics

Louisa explores how your environment could change the genes you Willan, SFC1 inherit. Ever since DNA was first discovered in the 1860s, genes were always thought to be completely unalterable; your genotype was set in stone from the moment the egg and sperm fused. However, since the start of the 21st century, a new field of biology has been developed that contradicts this idea: epigenetics.

Of mice and STEM Epigenetics is the study of how environmental factors can change the expression of your genes. The excitement surrounding this idea started in 2003 at Duke University. At that time, a study was conducted on a group of fat, yellow mice; these 2 characteristics of the mice are caused by a gene called agouti. The scientists at Duke separated these mice into two groups: one was fed a normal diet, and the other was given vitamin supplements. The mothers in the first group unsurprisingly gave birth to fat, yellow babies whereas in the second group, the mothers gave birth to thin, brown mice – the long line of fat, yellow mice that came before suddenly ended. The discovery led to massive excitement in the genetic world and past ideas about heredity had to be scrapped. What had happened was that the agouti gene in the mothers who had been given supplements had been ‘switched off’ in the mouse embryos. The compounds in the vitamins included methyl donors, which are molecules that form methyl groups. Methyl groups bind to a gene and change the way they are expressed in a process called DNA methylation. This is what occurred with the agouti gene in these mice. As well as being brown and thin, the offspring in the second group also had lower rates of diabetes and cancer - diseases associated with the agouti gene. With this study, it was suddenly understood why good nutrition whilst pregnant is important for the health of your offspring.

Ill u s t r a ti o n b y C h a r m a i n e L a i

Another clear demonstration of methylation includes the vole, which is either born with a thick coat or a thin coat depending on the time of year when the mother gets pregnant. Higher levels of light sensed by the mother vole can cause methylation of the gene for a thick coat, causing it to not be expressed in the offspring’s phenotype. The gene is still there but not active. Another example is a specific species of lizard that also exhibits DNA methylation. These lizards can be born with either a long tail and big body or a short tail and small body, which is simply determined by whether the mother smelled a snake whilst pregnant.

Like grandmother, like daughter Interestingly, it is not only the behaviour of your parents that can affect the methylation of your genes; the behaviour of your grandmother when she was pregnant with your mother could also have affected you. This is because when a female foetus is born, she already has a full set of eggs in her ovaries. The epigenetic signals passed from your grandmother to your mother when she was pregnant were also passed to your mother’s eggs, and one of these eggs provided half of your genetic information. In LA, a group of researchers noticed that children whose grandmothers smoked whilst pregnant were more prone to getting asthma, even more so than those whose mothers smoked whilst pregnant. Since the first breakthrough in epigenetics in the 2000s, this connection is now better understood. However, the reason why the smoking habits of the grandmothers affected the foetuses’ eggs more than the foetus itself remains a mystery.

if one twin develops breast cancer, this does not necessarily mean that the other will too. This is due to different environmental factors such as diet, exposure to different chemical agents and smoke, which can contribute to the development of different methylation patterns. In cases where only one twin developed cancer, this would be because of varied methylation of oncogenes and tumour suppressors.

Oncological advances Evolution Revolution Discoveries in epigenetics have also sparked a controversial theory about evolution: epigenetic changes reflect evolution’s attempt to change an existing genome. This theory started when it became apparent that methyl markers can be inherited, or in other words, traits acquired by your grandparents or great grandparents can be passed on from generation to generation, leading to evolution at a much greater pace.

Effects from birth Although most DNA methylation occurs during embryonic development, it also occurs after birth. A study on rats carried out by Michael Meaney at McGill University in 2004 showed that rat pups who received a lot of attention from their mothers after birth grew up to have very different traits to those who were neglected. The different levels of attention provoked varying levels of methylation of certain genes. Genes involved in brain development showed to have decreased methylation in the pampered rats, causing them to become more confident and relaxed, whereas the neglected rats became nervous and more easily stressed. The inability to handle stressful situations in the neglected rats was due to the underdevelopment of the part of the brain that dampens the stress response.

The link between cancer and the methylation of specific genes is now strongly supported by a lot of different research. A German company called Epigenomics has investigated the connection between breast cancer recurrence and the amount of methylation on a gene called PITX2. They found that 90% of women with low methylation of the PITX2 gene did not have a recurrence for 10 years. In contrast, only 65% of women with high methylation of the PITX2 gene were cancer-free in the same timespan.

This information has helped doctors decide whether chemotherapy is necessary after tumour removal for women with low methylation of the PITX2 gene. This kind of research can allow cancer treatments to be more custom-tailored to the individual and enable doctors to opt for a less aggressive and more comfortable treatment for the patient. As well as aiding treatment choices, methylation can also be used as a warning sign for cancer. In India, the company Reliance Life Sciences has developed a test measuring the methylation of genes, which strongly increases the risk of oral cancer. Millions of people in India are addicted to betel nut chewing, a highly carcinogenic substance that can trigger hypermethylation of three cancer-fighting genes and greatly increases the risk of getting oral cancer. Since oral cancer has very few symptoms until it is in its late stages, it is often fatal at the point of diagnosis. 70% of people diagnosed with oral cancer in India eventually die of it. Being able to test how methylated the cancerfighting genes are in betel nut chewers allows doctors to see how far away patients are from contracting oral cancer and warn them before it's too late. This kind of technology would make early diagnosis and higher survival rates possible.

Nature and nurture?

The varied development of diseases in identical twins also proves that methylation can occur after birth. Despite having identical DNA, identical twins face different risks of certain diseases;

The initial idea that acquired characteristics could be inherited was first proposed by Jean-Baptiste Lamarck in the 18th century and was widely ridiculed and dismissed. Now, 300 years later, this concept doesn’t seem quite as inconceivable. There are still countless things we have yet to explore and discover. Questions such as "Can epigenetic variation result in evolution at a much faster rate than initially realised?", "Could a better knowledge of epigenetic markers during pregnancy vastly improve the health of the next generation?" and "Could drugs be developed to induce methylation of specific genes as a form of genetic modification?" are still in the progress of the investigation. 18

FEATURES BIOLOGY

The origins of life Vanessa explores the age-old question of where and how life came about. Tsui, SFC1 You go into the shower and this thought springs into your mind: "How did I come into existence?" At first the answer seems obvious to you: you were birthed from your mother. But what about before her? What starts the evolution of complex organisms, or even simple organic life itself? Scientists have been trying to answer this question for years. While not entirely dismissing the possibility of extra terrestrial origins, they might have come up with some theories in the past century.

In the beginning... In the 1920s, two scientists, J. B. S Haldane and Alexander Oparin theorised that life may come from a ‘prebiotic soup’ or a primordial soup; they imagined the early ocean was rich with complex molecules produced by natural chemical reactions. In this soup, further reactions can take place, eventually producing living cells. This speculation actually dates back to 1871 when Charles Darwin wondered if life could have formed from o ina L chemicals "in some warm little y Reg Ill u s t r a ti o n b pond". It is thought that about 4 billion years ago was the earliest possible time that the first life could emerge on Earth, a period called the habitability boundary. Fossil evidence shows that microbes existed about 3.7 billion years ago, known as the biosignature boundary. At some point between the habitability boundary and biosignature, non-life became life. This miraculous arising is what scientists call Abiogenesis. But what is life? At school, we learn MRS C GREN, the checklist for the characteristics of life of what we know today. The earliest life, however, is a lot simpler. The definition for life is so vague that many scientists refuse to bother with it. In 1944, however, Schrödinger defined life as ‘a struggle against entropy, the persistent resistance to decay, the preservation of disequilibrium’. That is to say, a thing is considered alive when it fights for survival, and it also means that life will constantly evolve to better adapt to survive.

‘A struggle against entropy, the persistent resistance to decay, the preservation of disequilibrium.’ 19

The soup of life Going back to the primordial soup, Darwin’s and Oparin’s ideas were only speculation and not legitimate hypotheses since no one could find a way to test or observe them back then. In 1953, two other scientists called Stanley Miller and Harold Urey tried to replicate the formation of life by simulating early Earth conditions in the lab and carefully watching what happened. They designed a water apparatus to model the ancient ocean and gently boiled to mimic evaporation. Along with water vapour, they chose methane, hydrogen and ammonia as the gases in the atmosphere. As a source of energy, they added electrical sparks using 2 metal electrodes to simulate lightning. Their goal was not to recreate life, but to test the first step of Oparin’s model - can simple chemistry naturally give rise to the complex molecules of life? After running the experiment for a week, their ocean became brownish-black. Careful analysis revealed that many complex molecules indeed formed, such as amino acids (the building blocks of life) which were previously thought to only be produced inside our bodies. However, scientists later criticised this model because they couldn’t know for sure if the gases used by Miller really were the most common gases of the ancient earth. Because of this, many other simulations have since been done to show that the molecules of life can form in a wide range of environments, including hypothermal vents or on the earth with the help from the sun’s radiation.

The experimental set up for the Miller-Urey experiment. Image credit: "Miller and Urey's experiment," by CK-12 Foundation, CC BY-NC 3.0.

What comes next? Despite the possible limitations of the model, organic molecules needed to somehow give rise to cells for the first life to appear. In 1977, a piece of the puzzle was uncovered that involved rocks, in particular, minerals. It was found that the amino acids assemble on the clay surfaces to form small proteins once the water has evaporated. It turns out that clay minerals have the ability to take up organic molecules, protect them against the UV radiation in addition to concentrating and catalysing their polymerisation. And so, some minerals could support the synthesis of large protein chains, a first step to protein synthesis. One of the necessities of a cell is their cell membrane as they require something to compartmentalise inner contents, keeping it from escaping into the surrounding waters. The solution to this is a membrane with lipid molecules. Since lipids do not mix well with water, how can they possibly surround the aqueous cell? It was found that those from egg yolk mixed with water spontaneously give rise to tiny spherical vesicles with lipids surrounding them. The two layers of lipids cleverly arranged themselves in a way that their backs were away from the water and the part of the molecule that tolerated water was in contact with it.

An example of micelle formation in a PEGylated Liposome, which shares a structure similar to a cell membrane (Muralidharan, 2014).

Hence, a membrane-bound vesicle is formed when clays are present and encourages lipid molecules to form membranes. These vesicles undergo multiple cycles of growth and division. If a vesicle also contains some material such as nucleic acid, water would move in by osmosis and the vesicle would fuse with empty vesicles, increasing its surface area. This would then stimulate it to divide into smaller vesicles. Later, natural selection would choose the best vesicle to be the primitive cell.

All hail bacteria

If I were to ask you to describe our relationship as humans with bacteria, "partner in crime" would probably not be the first phrase to come to mind. Yet, bacteria are our ancestors. Without them, we could not have been the complex organisms we are, or have even come into existence. 3.5 billion years ago, the earth's atmosphere mainly consisted of nitrogen, carbon dioxide and methane, lacking the fundamental gas for us aerobics - oxygen. All oxygen is locked up in molecules such as water. Due to the absence of a protection ozone layer, the land was bathed in lethal levels of UV radiation so that the only shelter for life was underwater. The ocean was therefore populated with anaerobic microorganisms which did not require oxygen for growth, where they would have died or reacted negatively if exposed to large amounts. Until one day, somewhere around 2.5-3.5 billion years ago, a microbe evolved to photosynthesise. This very special microbe is the primitive cyanobacterium. This is the single cell organism that caused the first mass extinction on Earth and paved the way for complex life. The chlorophyll that evolved in their cells could harvest the energy from sunlight, turning carbon dioxide and water to oxygen and sugar which they used for energy. Photosynthesis gave these cyanobacteria a huge advantage over other species. They could now produce their own energy from an endless supply of raw ingredients. Their population skyrocketed, and they started polluting the atmosphere with a new waste product: oxygen. This was so toxic to the anaerobes that it caused an extinction of virtually all life on Earth, leading geologists to denote this as the Oxygen Catastrophe. Eventually, life adjusted as aerobic organisms evolved and increased, absorbing the excess oxygen until oxygen levels reached the 21% of air we know today. This event was so pivotal because it gave organisms the boost of energy they needed to diversify since aerobic respiration produced much more energy than anaerobic respiration. Cyanobacteria were swallowed by a larger microbe in the process of endosymbiosis, leading it to become a more complex organism with the combined abilities of both. It is thought that cyanobacteria are the ancestors of plant cells in this way. The endosymbiotic theory did not stop there… mitochondria originated as oxygen- breathing bacteria with their own DNA were somehow absorbed into an eukaryotic cell. Working together with their host cell and dividing inside them, this allow the evolution of a more complex organism providing them with the energy for growth and replication. And this is what makes life as we know today. 20

ARTICLES MATHEMATICS

Why is Euclid’s fifth postulate unproven and invalid? Chloe ditches the fifth postulate as she turns this fundamental mathematical rule we're all used to on its head. Ching, UC4 Maths has always been a part of our society. From Euclid to Pythagoras to Archimedes to Gauss, all these people have made significant discoveries in the field of mathematics to become the famous mathematicians we know today. One person that stands out to me is Euclid.

prepared to interpret them as we learn, in order to search for absolute perfection. One controversial topic discussed largely amongst mathematicians would be Euclid’s fifth postulate seen in Euclid’s Elements, book 1.

The fifth postulate

Who was Euclid?

The fifth postulate, also known as the parallel postulate, states that

“If a straight line falling on two straight lines makes the interior angles on the same side less than two right angles, the two straight lines, if produced indefinitely, meet on that side on which the angles are less than the two right angles.” In easier words, this postulate says that if angle alpha and angle beta shown in the figure below do not sum to 180 degrees, then there will be a point were line 1 and 2 will eventually intersect.

Euclid was most famous for his works in geometry, inventing many of the ways we conceive space, time, and shapes. He wrote one of the most famous books that is still used today to teach mathematics: "Elements", which was well received at the time and is praised today for its thought and understanding. In school, we often memorise theorems and proofs given to us by our maths teachers, but how many of us truly understand why the theorem exists, and how the proof came about, be it the area of shapes, circle theorems or The Poincare Conjecture? I’ve certainly never paid much attention to it. But more importantly than simply understanding it, we must keep an open mind to these mathematical formulas and be

c li d

The reason why some people think that the parallel postulate is wrong and thus invalid is because it cannot be drawn if you could draw and satisfy the first four postulates. However, the question is, even if it cannot be drawn, does that mean the geometry is wrong? Furthermore, if we hardly know anything about the universe, can we really understand if the parallel postulate is valid or not?

Different hypothetical forms of geometry, with non-Euclidean geometry being the hyperbolic and elliptical forms on the left and right respectively, either side of Euclidean geometry depicted in the centre.

For example, Einstein argued that the 5th postulate isn’t really true as the parallel lines that it talks about aren’t actually straight and are curved instead, causing the two parallel lines to intersect eventually, unlike what the 5th postulate states. But this is only true if we go with Einstein’s world of Non-Euclidean geometry. Even if it's wrong in our world of space-time, it doesn’t necessarily

Famously, Albert Einstein used non-Euclidean geometry as well to describe how space-time becomes warped in the presence of matter, as part of his general theory of relativity.

mean it’s wrong in other possibilities and universes as well. And that is something that we need to consider. Therefore, this is why the fifth postulate has confused mathematicians from Aristotle right up to Gauss and Einstein.

The shape of space So what if the parallel postulate was never true all along? If the parallel postulate was not true, this would give rise to entirely new and alternative geometries, which mathematicians call NonEuclidean geometries (see figure above). The main difference between these geometries and ‘normal’ geometry we study is that these two different geometries depend on a different curvature of the surface upon which the lines are constructed. It appears that Euclid only described one possible way to look at the universe when writing his fifth postulate. (Honestly, who can blame him? After all, people in his time still thought the Earth was flat!) So what are the different ways we could look at the universe and therefore look at his postulate? Well, flat surfaces behave one way, while positively and negatively-curved surfaces behave in a totally different way due to the different characteristics. At first these alternative geometries were found to be strange, but soon they were found to be equally adept at describing the world around us. For example, navigating our planet requires elliptical geometry while much of the art of M.C. Escher displays hyperbolic geometry.

The bending of space time exhibits non-Euclidean geometry. A massive object, such as the sun, causes a deformation of the spacetime grid, while another object such as a planet or a light beam follows the shortest path (a “geodesic”) on this grid. To an observer, this looks like a deflection of the trajectory caused by gravity, shown by the blue arrow.

Consequentially, a collapsing star can form a black hole so dense and massive that it creates a region of infinite curvature (a “singularity”) so that—inside the event horizon—light cannot escape. A wormhole is formed as space time is warped, which is also an example of a non-Euclidean geometric structure. Illustration: Carin Cain

To prove or not to prove... Due to our limited understanding on the matter of space-time as well as the different possibilities of geometry in the universe, it is safe to say that the fifth postulate is unprovable because infinite possibilities in the universe simply leads to infinite results and theorems. While the postulate may satisfy one geometry, it does not satisfy all geometries of all possibilities, with non- Euclidean geometry being an example. Therefore, Euclid’s fifth postulate is thus proven to be unprovable.

A split comparison of Escher's hyperbolic pattern Circle Limit IV, with the original on the left depicting angels (the light background) and devils (foreground) next to the analysed Circle Limit IV pattern on the right showing the underlying hyperbolic geometry.

ARTICLES ENGINEERING

An exeat week

Azra introduces us to supersonic flight, and the prospect of more efficient Bakrie, SFC1 international travel... is it time to get our passports ready?

It's a plane! An integral part of breaking the sound barrier is to have a streamlined plane. The plane must be streamlined enough to break the wall of air pressure ahead to exceed Mach 1. As a swimmer, streamlining is familiar territory which is incredibly advantageous to reduce milliseconds, or even seconds of your time. The Illust

What if I told you that you could go have an exeat, or even a day trip to Japan or New York? This actually has happened, as you may be aware, with Concorde, the supersonic flight that would only take 3.5 hours from Heathrow to JFK. However, due to economic and physical reasons, Concorde flights were terminated from 26 November 2006. Enter Boom Overture, an aircraft claiming to be the fastest and most sustainable supersonic airliner. Will the next generation of flights all be supersonic, gliding commercial planes further towards supersonic speeds?

ration

by N

oelle

Lee

fuselage must be needle-like to reduce the drag of air. Though this is very uneconomical as it reduces the maximum payload, there is no alternative as reducing drag and increasing fuel efficiency is the most essential part of a supersonic aeroplane.

Supersonic Fundamentals Concorde was not the first supersonic aircraft, but the first commercial one. Supersonic aircraft are widely used in the military, mainly for fighter jets. To classify as supersonic, the aircraft’s speed must exceed Mach 1 (around 1200km/h), which is the speed of sound. Many factors hinder most flights from becoming supersonic, mainly aerodynamics and friction, but cost-effectiveness stems from them as well. Aircraft must be designed to minimise air resistance to maximise its fuel consumption in order to surpass Mach 1.

It's a bird! Taking from the Concorde and future Overture, the plane has (ogival) delta wings, different to the swept-back wings you would see on an Airbus or Boeing. The delta wings are designed to fly at subsonic and supersonic speeds, unlike other wing types. The aspect ratio (wing length/wing width) for delta wings is below 3, which is considered a low aspect ratio. This helps provide manoeuvrability and a smaller bending moment for the aircraft, but it doesn’t help the endurance of drag of the aircraft. Together with delta’s low wing loading (body mass/ wing area), it helps generate lift for the plane. Additionally, the use of a delta wing means that the plane doesn’t need any horizontal tail stabilisers (Concorde) so it reduces the weight of the aircraft. Aircraft geometry showing a top, side and front view.

end to Japan Fuel Let's be material scientists for a little bit now. A lot of energy is needed to provide enough thrust for the plane's speed which means blazing heat is emitted from the engines. Not only that but the faster the speed of flight, the higher the effective ambient temperature which can cause planes to expand up to 30cm (Boom Overture). Materials must withstand the stress induced by heat. Concorde used aluminium but the new and improved Overture uses carbon-fibre composites, maintaining strength at elevated temperatures. The main reason for Concorde’s failure is due to financing. Fuel is one of the largest expenses of aviation companies as planes won’t fly without it. Concorde used four Snecma Olympus 593 (Rolls Royce) turbojet engines, and used afterburners during take off and to reach the supersonic speeds (once they are no longer over land, more about that later). Afterburners were not cost-effective at all, so "why use them?" you may ask. Back then, engines were not powerful enough to fly at supersonic speeds with the standard jet engines alone. Afterburners increased fuel consumption by 78% but only added to 17% of the thrust - sounds pretty useless, right? As technology has improved, Overture will use three turbofan engines. There are many advantages and benefits to using turbofan engines over turbojet engines, one of which being that they produce less noise pollution.

Doppler at large Imagine the doppler effect at a subsonic level. As the object producing sound is moving towards the observer, the observer will hear a higher pitch. As you know, this is because of the serried wavefronts. But now imagine the object is moving very fast, faster than the speed of sound. The wavefronts will be compressed together, and as they don’t have enough time to move away from each other, they interfere. As a result, the wave produces a conelike shape of a shock wave. The area of land in contact with the shock wave will experience a sonic boom, which seems to have come from behind to the pilot. This is a nuisance that many engineers and scientists are trying to reduce or even remove entirely. Removing the effects of the sonic boom will help commercialise supersonic flight enormously. The FAA will no longer ban overland supersonic flights since the ban reduces the market by 80%.

Disruption of air exhibiting the Doppler Effect at different extremities

Supersonic Cacophony Now that I’ve given you a quick whistle-stop tour on how to build a supersonic commercial airliner, why aren’t they everywhere? As already mentioned, they are not cost-effective. But, they are “technically” banned as well. The FAA (Federal Aviation Administration) banned supersonic flight over land. Operation Bongo II in 1963 proved to FAA that supersonic flight was not feasible without disrupting many people and animals. There were reports that chickens and other farm animals went crazy after the sonic boom. Supersonic aircrafts produce sonic booms (imagine thunder but much louder) when they break the sound barrier.

Future or fiction? A common phrase ‘time is money’ demonstrates the multitude of advantages of supersonic flight. Supersonic flight will help accelerate globalisation and the exchange of different ideas. People can take a day trip for their job and return home for dinner for their families. Picture an exeat weekend trip to Japan (disregarding the extortionate costs and whether FAA will allow intercontinental flights). Personally, supersonic flight is a concept I would need to get used to before boarding the Overture as I have a big phobia of flight! 24

ARTICLES MFL

The father of modern surgery

rg st

A biography in Spanish

ts is e n lc a s u Ab

Rosie nos enseña sobre los orígenes de la cirugía y el español, todo en un artículo, ¡qué ganga! Evans, (Rosie Evans teaches us about the origins of surgery and Spanish, all in one article SFC2 what a bargain!)

Abulc

Español

asis

English

¿Sabes que la cirugía moderna fue inventada en la España de la Edad Media? ¡Quién lo hubiera sabido! Abulcasis, mejor dicho, Abū ’l Qāsim Khalaf ibn ‘Abbās al-Zahrāwī, fue un médico y científico que nació en Córdoba entre 936-40. Vivió en AlÁndalus, o sea, la península ibérica bajo poder musulmán. Su libro más famoso se ha convertido en un libro clave para las próximas generaciones de médicos. Fue pionero en el uso de los fórceps y descubrí la causa principal de parálisis. También, inventó herramientas quirúrgicos para las operaciones de cesárea y cataratas. Se considera Abulcasis “el padre de la

Do you know that modern surgery was invented in Spain in the Middle Ages? Who would have known! Abulcasis, better known as, Abū 'l Qāsim Khalaf ibn 'Abbās al-Zahrāwī, was a physician and scientist who was born in Córdoba between 936-40 BC. He lived in Al-Andalus, that is, the Iberian Peninsula under Muslim power. His most famous book has become a key book for future generations of doctors. He pioneered the use of forceps and discovered the leading cause of paralysis. Also, he invented surgical tools for caesarean section and cataract operations. Abulcasis is considered "the father of modern surgery".

cirugía moderna”. Aunque muchas de sus ideas ahora no se usa, la cauterización todavía es ampliamente utilizada .

Although many of his ideas are no longer used, cauterization is still widely used. Cauterization means the burning of skin to

Cauterización significa la quemadura de piel para extraer una parte indeseada. Hoy en día, se usa la electrocauterización

remove an unwanted part. Today, electrocautery is used during surgery to remove unwanted body tissue. It is hard to imagine a

durante la cirugía para remover tejido corporal . Es difícil imaginar un mundo sin estas invenciones. ¡Gracias Abulcasis!

world without these inventions. Thank you Abulcasis!

Abulcasis Surgical instruments

Key Vocabulary Cataratas Cesárea

Unwanted

Musulmán

Muslim

La Cirugía

CC BY 4.0

Caesarean section

Indeseado

La Cauterización

Wellcome Images, Cauterization of the thigh, 16th Century Wellcome L0006330,

Cataracts

La Edad Media

Cauterization Surgery The Middle Ages

ARTICLES ENVIRONMENTAL

For What it’s Worth The cost of technology

Mr Gill sheds light on the technology that surrounds us, focusing on the works of Dillon Marsh. All photographs discussed are taken by him, which you can find out more about on his website, http://dillonmarsh.com/

Look at your phone, if you’re reading this on a phone. Or your laptop. How much did it cost? £300, £400, £1000? But what if that cost isn’t the only one? Your phone contains a whole host of elements; silicon, aluminium and oxygen in the glass screen, magnesium alloys in metal casings, carbon and hydrogen in the polymers that make up the plastic seals and body. But there are also small amounts of many metals, some incredibly rare. Gold and copper in electrical components, lithium and cobalt in the battery and neodymium in the microphone and speakers. Many of these elements are mined in areas of the world in which environmental protections are limited and the drive to make profits comes at the expense of the landscape and ecosystems. In the worst cases, illegal mining practices release tonnes of toxic waste into local water sources and some rely upon the use of child labour. You may have heard of blood diamonds, but some of the key chemicals have been described as ‘conflict elements’ as they are sourced from areas in which wars are taking place. The money made from the sale of the essential

Platinum - 136 million troy ounces

minerals required for the extraction of metals can flow directly to the groups participating in conflict. It may seem that there’s nothing individuals can do about the issues above. However, many of the elements can be extracted from unused devices and effectively recycled. The same is true of the elements used in the batteries of EV cars. Research undertaken by The Royal Society of Chemistry suggests that 45% of people in the UK have at least 5 unused electronic devices in their homes. Incredibly, over 80% have no intention of recycling or selling these. Dillon Marsh is a South African artist, whose series ‘For What It’s Worth’ uses CGI alongside photographs of locations in S. Africa to highlight the enormous impact the extraction of relatively small amounts of rare or valuable elements can have on the environment. This is just a small selection of the images he has created.

Kimberley Mine - 14.5 million carats of diamonds. The background to this page is also an in-

Jubilee Mine - 6,500 tonnes of copper

Iridium - 4 million troy ounces

detail photograph taken from the Kimberley Mine.

INTERVIEW BIOCHEMISTRY

One faulty cell An interview with Dr Anscombe Research is undoubtedly one of the most arduous yet rewarding careers in science. From trials and errors to meticulously analysing your findings, science research has the potential to shape the future of the world. Vanessa Y, Lily and Emma Tse sat down with Dr Anscombe to discuss her journey through a career in cancer therapy research. We’d like to thank Dr Anscombe for providing such great insight into the world of biochemical research - we hope you enjoy learning about her experiences as much as we did!

Background knowledge The cell cycle is regulated by cyclin-dependent kinases (CDKs). Kinases are enzymes that add phosphate groups to other molecules, a process called phosphorylation. Throughout the cell cycle, proteins called cyclins bind to CDKs, which allows CDKs to phosphorylate proteins such as pRb. pRb, short for retinoblastoma protein, is a tumour suppressor protein, which means it acts to inhibit cell proliferation through slowing mitosis or inducing apoptosis. Once pRb is phosphorylated, the cell is given the green light to continue to the next phase of the cell cycle; if not, the cell cannot progress further. When it comes to proteins themselves, understanding their 3D structure is imperative, because structure equates to function. X-ray crystallography is a widespread technique that can be used to find a protein's structure, which involves bouncing Xrays off a protein crystal and measuring the diffraction angles (in simple terms). Once the X-ray crystallography data is obtained, it's processed through a computer programme that executes a Fourier Transform, which is an image-processing tool that breaks down an image into cycles more specifically, their sine and cosine components. A simple analogy is to think of being given a smoothie and finding its recipe!

Could you summarise the research that you did for your PhD? There are four phases in a normal cell cycle, G1, S, G2 and M (mitosis), and within M you’ve got subphases. The protein I looked at was CDK2 (cyclin-dependent kinase 2) and that regulates the transition between G1, where the cell is growing fairly normally, and S, where it starts to replicate its DNA. Between each stage of the cell cycle, there are checkpoints that check, for instance, that there’s no damage to the DNA before replication, whether you’ve got the right number of copies of chromosomes, or that the cell is generally ready to enter the next phase of the cell cycle. We were looking at one particular cell cycle transition and the kinase involved in regulating it. We were essentially trying to halt that process because in cancer cells, the processes at these checkpoints become disrupted, so cancer cells escape the normal checks and balances a cell goes through. These checks keep cells functioning properly, avoiding things like DNA damage by UV or reactive oxygen species being passed down to the next generation of cells. Cancer cells usually have mutations that allow them to escape this G1-S checkpoint, so they don’t respond to pRb, for instance. So you want to switch off the CDK2 and upregulate the pRb activity. The idea we were looking at was whether we could reactivate those checkpoints and therefore stop cancer cells from dividing further. If we could, that would imply it could be used as cancer therapy! Essentially, the CDK2 phosphorylates another protein, and in order to do that, it has to bind ATP (the energy currency of the cell). In the binding site where the ATP binds to the kinase, we looked at developing inhibitors that bound there to stop ATP from working, and therefore stop the kinase from working. My PhD involved my team and I getting sent molecules, which were the potential candidates we would test. I was based at Oxford, and a lab in Newcastle would send us possible drug molecules that might potentially bind to this protein. We would see if they did bind and 27

if we could determine the structure of the protein, in addition to looking at the structure with the drug molecule it bound to, how closely it bound and whether it was a stable interaction or not.

So you’re basically trying to inhibit the CDK2, which is involved in the G1-S checkpoint, in order to reactivate that checkpoint. How exactly does that work?

Here is a simplified diagram of the cell cycle. This protein, pRb, which stands for the retinoblastoma protein, is a tumour suppressor. The function of this tumour suppressor protein, which determines whether DNA synthesis can start, is determined by CDK2. There are lots of cyclins in the cell cycle - CDK2 phosphorylates cyclin E, ATP has to bind to CDK2 in order to phosphorylate the protein, and if we can stop the ATP from binding to the CDK2, phosphorylation can’t take place.

In the process of your research, what did you do? The day-to-day process was that we would get sent a new set of chemicals to test - they’ve done all the basic chemistry and replicated all these potential drug molecules. They would send us a big batch to test, and we firstly did various assays to see if they-

In the process of your research, what did you do? -would bind to the proteins. I used radioactive phosphorus to follow the process of phosphorylation. We put the radioactivity under the photographic film and it makes a dark spot on the film which can be used to see if the kinase is still working. If the kinase has not been working, this suggests that the drug molecule bound to it has had some effect because the kinase is not phosphorylating things anymore. So this was a functional test. If the drug molecule was working, we would look at a picture of what the protein looked like bound to the drug molecule by crystallising the CDK2 and conducting X-ray crystallography, which is a way of taking a photo of a protein. We use X-rays because proteins are way smaller than the wavelength of light so they are too small to take a light photo. Usually, proteins are too small to get a good picture even with electron microscopy. X-ray crystallography is quite a complicated process - you make a crystal so you have a regular arrangement of proteins which amplifies the signal. You then shine X-rays at it and look at the scattering pattern. If you use some complicated maths called the Fourier transform, you can work backwards to the original structure. Lots of computer programs were involved, and you need an X-ray source and to do lots of maths afterwards. We used to go to Diamond Light source, which was a big synchrotron. The first time I went there I was amazed - you feel like you’re in a Bond movie! Inside, there are lots of beam lines and there is a smaller ring in the middle. They basically send electrons really, really fast around this ring structure, and when you bend an electron round a corner, it releases certain types of radiation depending on how much it bends. So, if you control how fast an electron is going and how much you’re bending them, you can get different types of radiation. We used X-rays, and we used to take our crystals here and we would get a few hours here to irradiate them and get a pattern at the end.

X-ray diffraction pattern of crystallized 3Clpro, a SARS protease Jeff Dahl, X-ray diffraction pattern 3clpro, CC BY-SA 3.0

But proteins are more irregular, so you get something that looks more like this (see diagram below) - lots of dots. In a nutshell you feed this into a computer program which does a Fourier transform and you have to do some interpretation of that yourself, so it’s a mathematical procedure that turns it back into an electron density map. And then you have to interpret that and try to drop amino acids that make up the protein into the right places and understand the protein structure. Once I got that protein, I looked at whether the drug molecule was bound and where it was bound - if it was in the binding site where the ATP should be, was it fully occupying it? Which bits of the protein were in contact with it? So we did that technique crystallography - and we did NMR as well as mass spectrometry which enables you to find out the Mr (relative molecular mass) of the molecule to find out whether the drug molecule was bound.

So what did you find in your results?

So a famous X-ray diffraction pattern you might have seen is that of DNA, and that’s because DNA has a regular structure with a double helix so you get a cross shape.

CDK2 was one of the protein targets I had. The other target I looked at was p53, another tumour suppressor also known as the “master switch” of the cell involved in processes like apoptosis (programmed cell death). In that regard, I was looking at p53 binding to another protein called MDM2, and I was looking at trying to disrupt that interaction between the two because that turns the tumour suppressor back on. I was looking for a drug molecule that bound in the interface between the two molecules by “getting in the way”. We managed to find some good candidates and structures, some of which are currently going through clinical trials. We got some patents on the drug molecules that we tested and they are currently being tested to see if they can be used. There’s a long process in drug 28

INTERVIEW BIOCHEMISTRY

development after you’ve done the basic research in cells and

cure for cancer, but I wanted to help with the effort. But I think,

you’ve got to test it in organisms, animals and eventually humans, and most tend to fail in that stage due to safety or functional issues.

whatever your best intentions are, especially as an individual researcher like a PhD candidate, you can’t really change what’s being funded. You don’t really have much say over what projects you do, you just choose between projects that are being funded and go for it. If you stayed and worked in science you could have an impact on what kind of research is funded, but it’s difficult because deciding what gets funded is more of a political issue. There’s a body called the National Institute for Clinical

If drug development wasn’t so confidential and more open to researchers, would developments happen quicker? It’s a difficult one with things like patents because there’s this argument that drugs should be cheaper. You get generic drugs, which is where a drug has gone out of patent and another drug company makes something with exactly the same structure and marks it with a different name. There’s a limitation for how many years a drug stays in patent for, kind of like copyright. The reason why the patent is there is to protect the investment of the companies that are going to spend lots of money developing it. Obviously, you have to also try to get the prices to come down because it’s not fair if prices are very high - you want as many people as possible to benefit from it, so I think it is right for drugs to come out of patent so that others can produce it. Since they haven’t put in as much money into the research, they can produce the drugs more cheaply as they can essentially copy what the other drug companies have done.

Since we’ve opened the ethical can of worms now, do you think patenting drugs is ethical if research is primarily directed in a way for companies to make profits? This means a lot of people go into cancer research because it’s very well-funded, and other diseases like Alzheimer’s get less funding as a result. Do you think that’s ethical? With patents, for me, I think they’ve got the balance probably about right at the moment, in terms of protecting the companies enough that you’re still able to fund things. If you don’t incentivise new developments, people will stop doing that research and stick with drugs they have, and research will slow down and stop. For example, if you look at the COVID-19 vaccines, there’s enough incentive for drug companies to want to produce this to make money so that we get vaccines quickly. The main issue is that drug companies will fund what they know will make them money. So that’s why things like cancer get funded a lot more, and things like malaria and orphan diseases (rare diseases) tend to get little funding. And there are other things like Alzheimer’s, which is becoming so much more of a problem as the population ages, that are still massively underfunded compared to cancer in terms of research. Some of that is to do with what we value in countries that are wealthier. In Western countries, rates of cancer are much higher, and Western countries tend to do most of the funding, therefore cancer is funded more. But malaria is more prevalent in other countries, so some of that has to change in terms of research to strike a better balance.

I agree - I remember reading a statistic that Alzheimer’s affects even more people than cancer worldwide, but Alzheimer’s gets much less funding than cancer shockingly. Yeah, and I think cancer is such an emotive thing because most people know someone - a relative or a friend - that has experienced it. When I was growing up, the reason why I went into cancer research was because my granddad died of lung cancer when I was 14, I didn’t really understand the concept that there wasn’t a single 29

Excellence (NICE) and they make a lot of decisions about what gets funded - BBSRC (Biotechnology and Biological Sciences Research Council) decides a lot of the funding. But there are charities that fund things independently, so that’s how you change things being funded. But it definitely is a difficult one.

How did you find research in general? I read a very interesting Chemistry World article that said 2/3 of people in academia would consider leaving in the next 5 years or so? I left research - I did enjoy it, and I found a lot of things I did interesting. I loved going to Diamond Light Source and I did projects in different places around the world as well and they were really interesting! But the thing that I missed in doing research was I spent a lot of time doing crystallography...

By yourself? Well, with this big robot thing. Occasionally some people would come in to check their crystals, say “Hi” and go, and I’d be stuck in this basement for quite a long time. Or I’d be pipetting stuff for hours on end. It is interesting, but the day-to-day bit that I missed was the social aspect. I’ve always enjoyed science communication, and one of the things I considered going into at university was science communication and science writing, like you’re obviously interested in.

(Lily and Vanessa laugh) So I considered doing a Master’s in science writing! I really missed the human aspect while working in research, and the nice thing about working here is being able to work with talented colleagues and interested pupils, and obviously have an impact on what they go on to study and what they do with their futures. I feel like I enjoy that more, having an overview of science. When you work in science, it can get really specific when you focus on only one project which is really, really interesting, but quite narrow. On the other hand, when you’ve involved in things like science writing or teaching, you get a much broader overview of everything. But it is fascinating to be at the cutting-edge of science - I really enjoyed it. I also think another issue with losing people from science is that women tend to struggle to move up the academic pathway. The proportion of women decreases from undergraduate, to master’s and PhDs and postgraduate students and professors. I think that should be addressed as well - why is that? I think they should look into it! Where have all the women gone? I was really lucky - when I was an undergraduate, I had a really, really inspirational female professor, Elspeth Garman, who did X-ray crystallography and I did my undergraduate project with her. She inspired me to carry on with research!

ARTICLES BIOCHEMISTRY

The Science

behind the Sunny D Scandal

Freya warns us of the effects of drinking too much Sunny Delight by delving into the biochemical Dixon, SFC1 specifics of Carotenemia.

The Rise Illustration by Karolina Sliz

After initial success across the pond, American-born orange juice drink Sunny Delight first hit the shelves of the UK in 1998 and in less than a year, was the 3rd most popular drink in the country. It was a marketing phenomenon, leaving its competitors scratching their heads at the newcomer taking supermarkets by storm. Sunny Delight’s success was so massive that in 2000, it was set to overtake longtime front runner Coca Cola. The campaign aimed at young families couldn’t have been more high flying ... until it all came crashing down.

The Fa ll The beginning of the end was 1999, a year after the UK launch. Sunny Delight’s unprecedented popularity sparked an investigation by The Food Commission (an independent British consumer organisation), revealing that the orange juice drink was only 5% fruit juice. The 95% other ‘stuff’ was water, high fructose corn syrup, vegetable oil and most significant of all: beta-Carotene. That December, the BBC reported a 4-year-old girl in Wales who (in true Roald Dahl fashion) had turned bright orange after consuming the beverage. This already brand-damaging incident was accompanied by a badly timed TV advertisement featuring orange snowmen, prompting parents to believe that the drink was turning children orange on purpose. By 2001, sales had halved, and after multiple failed attempts to relaunch, Proctor and Gamble eventually gave up on Sunny Delight and sold the brand.

The Culprit: Beta-carotene The product’s stark orange colour was provided for by the compound beta-carotene (molecular formula C40H56). Despite the painfully low fruit juice content of the drink itself, betacarotene is found in carrots (what a surprise!) as an orange pigment in the vacuole of the cells. Aside from being such an aptlynamed biological pigment, beta-carotene is one of the most

The skeletal structure of beta-carotene

common naturally occurring sources of vitamin A, a nutrient that will be familiar to GCSE biologists as essential for healthy eyesight. During digestion, the enzyme BCO1 (beta-carotene dioxygenase) breaks down beta-carotene and forms retinal (a form of vitamin A) in the small intestine. Evidently, the beta-carotene compound is nothing more than a plant-derived, naturally occurring source of vitamin A. So, the question remains: how could a humble plant pigment be the downfall of such a successful campaign? It turns out that in the case of Sunny Delight, it wasn’t so much what the victims were drinking, but how much. The drink was so popular amongst kids and believed to be healthy by parents, that the volumes of drink consumed were completely unregulated. So, what might happen if someone - say, a small child - were to ingest large amounts of beta-carotene? Of course, a fair amount of the compound would be converted by the BCO1 enzymes into the vitamin A that we need. However, after a certain threshold, there just aren’t enough enzymes in the small intestine to work on such an abnormally large number of beta-carotene molecules. It is at this point that an excess of beta-carotene builds up in the bloodstream and deposits in parts of the body with thicker skin like the palms, knees, and elbows. Thus, the child starts to exhibit a startling orange tinge, a condition called Carotenemia. The 1999 case was especially dramatic. The 4-year-old was reported to have been drinking Sunny Delight at an absurd rate of 1.5 litres a day, which combined with her small body and pale skin, made her skin discolouration particularly alarming.

Do it yourself The average reader of the Chelt Scientist would need to eat 10-15 carrots a day (depending on how pale or dark your skin is) for weeks in order to raise the level of beta-carotene in the blood enough to see skin discolouration. I should warn those particularly adventurous readers that although Carotenemia is technically harmless, the orange hue is reported to take months of eating a balanced diet to fade (orange also probably doesn’t follow CLC uniform guidelines!)

Although this article focuses on the science of the scandal, Sunny Delight is often studied for the company’s marketing tactics. So, if you’re also interested in the business aspect of this article, I really recommend searching up "Sunny Delight Business Nightmares" on YouTube; there are some old news reports and documentaries that discuss the promotional campaign’s successes (and failures). Sunny Delight lives on today under the new name Sunny D and is still sold in the UK in case you want to try it! 30

FEATURES BIOCHEMISTRY

What we don’t see in the

and

appealing colours Noelle breaks down the colours all around us, exposing the deadly toxicity lurking underneath the surface of some... Lee SFC1 Pigments have added so much colour to our lives, influenced by the consumerist society to manufacture thousands of artificial colours. Yet what if someone told you that these pigments could be a deadly weapon? From bright red to platinum white to extravagant green, these pigments are considered three of the most poisonous pigments in the history of mankind.

(and orange and yellow) Cadmium is the 48th element in the periodic table, a scarce transition metal discovered in the 19th century, and an important pigment to artists which could produce bright reds, oranges and yellows in miniscule amounts. Featured in world-renowned artworks such as "The Scream" by Edward Munch and "Sunflowers" by Vincent van Gogh, it angered artists when the ban of cadmium paint was proposed in 2015 by the European Chemical Agency (ECHA) after Swedish officials suggested that artists polluted the water supply during cadmium paint disposal. As you wonder why cadmium paint is still widely used at present, cadmium only poses a dangerous health risk once inhaled, which is why dissolved lowconcentration cadmium paint is not the - biggest threat. In fact, we should be more concerned about the paint manufacturers who produce the paint from dry cadmium powder, which is why they can only produce paint a few days per year due to the hazards associated with inhaling cadmium. Cadmium, when inhaled, could bring detrimental or fatal effects to the human body. After entering the bloodstream, cadmium is widely distributed in the body, and mostly accumulates in the liver and kidney. 31

Does the body ever contribute anything into combatting cadmium toxication? In fact, it does. Metallothionein (MT) is a small cysteine-rich protein that is especially abundant in the liver and kidney and plays important roles in protection against heavy metal toxicity, DNA damage and oxidative stress. Due to MT’s high affinity for heavy metals, cadmium binds easily to it to form inert CdMT complexes, which are degraded by lysosomes to be excreted through urination. However, at higher levels of cadmium (Cd), Cd ions exceed the buffering capacity of intracellular MTs so are unable to stop cadmium from roaming around the body and destroying cells. Although we cannot blame our body for not producing enough metallothionein, cadmium undoubtedly brings irreversible damage to almost every system in the human body. What makes this heavy metal a deadly "wild card"? Instead of targeting certain organs, cadmium attacks vital substances and cell components in the body, such as DNA repair proteins and the mitochondria. Cadmium inactivates DNA-repair proteins, and those with zinc-binding domains (ZBD) are especially sensitive targets. Cadmium ions (Cd2+) like to displace ions of similar charge, such as Zn2+ ions, and by doing so, they inhibit ATP synthase and helicase activities - these are enzymes crucial to respiration and DNA replication respectively.

Inactivation of Zinc Binding Domains or Zinc Fingers. Downloaded by Virginia Commonwealth University on 20/03/2017 23:32:15.

Possible outcomes are changes in chromosome structure or number (chromosomal aberrations) and breaking of DNA strands, hindering cell growth and causing apoptosis (cell death) or inactivating tumour suppressor genes. We all know what follows: cancer. Directly or indirectly, DNA-protein inhibition increases the cadmium carcinogenicity, inducing lung, prostate and renal cancer.

One painful bone disease to remember One famous disease brought by cadmium is the Itai-Itai disease caused by the mass cadmium poisoning of Toyama Prefecture, Japan in the early 20th century, due to pollution of a river by a zinc mine. It was one of the most severe incidences of chronic cadmium poisoning, in which locals felt severe pain in the spine and the joints. The main reason is that cadmium can mimic actions by calcium. By intervening with calcium receptors and ion channels on the cell surface, it lowers calcium intake to the body. The story doesn’t end here—as the blood calcium level decreases, the parathyroid hormone (PTH), which regulates calcium levels in the blood, is triggered to release calcium storage from the bones. Calcium is released into the serum, softening the bones in the body and causes osteoporosis and several bone diseases. In fact, the name Itai-Itai means painful ( ) in Japanese and refers to the painful screams of patients.

痛い

The process of bone softening and consequential diseases that arises from PTH release during Cadmium poisoning.

To visualise the suffering of the Japanese locals is definitely heartwrenching, and despite the fact that Itai-Itai disease is no longer a threat due to stricter monitoring of cadmium levels in mines and farms, many factory workers wielding cadmium or producing cadmium paint are still exposed to cadmium poisoning every year, risking their health and possibly lives in their jobs.

Lead white was an important pigment through history, found in paint on pottery, ships and paintings, and ceramics to whiten the skin. Fun fact, it was the only white used in European easel paintings until the 19th century when the poisonous lead was banned in manufacturers.

Lead as the lead Whenever the element lead is brought up, we know that the heavy metal can bring detrimental effects to the human body. Due to a 2+ charge on its ion, lead is also a calcium and zinc mimicker, replacing many of its functions in the body. Lead competes with calcium on the same transport protein (such as facilitated diffusion pathways, like the Ca2+ channel), it is able to enter the red blood cell and inevitably reach the enzymes within the cell. As non-competitive inhibitors, lead ions also denature several types of enzymes, and one of them is the 5-aminolevulinic acid dehydratase (ALAD), responsible for haemoglobin production. Normally, a zinc ion is used to help catalyse this enzyme reaction, but when lead ions are present, they displace The structure of an ALAD enzyme the zinc ions, denaturing the enzyme. As a result, the formation of haemoglobin groups is hindered, leading to anaemia. Anaemia is caused by a lack of enough healthy red blood cells to carry oxygen to your body tissues, making the patient weak and fatigued all the time. Other symptoms include an increase in blood pressure and blood disorders. However, lead poisoning happens in your body and stays in your body. If you think that the poisoning of haemoglobinproducing enzymes is bad enough, lead poisoning is able to build up in the body. When lead enters the red blood cells and is distributed throughout the soft tissues of the body, it eventually accumulates in the bone and lasts for decades locked up. The reason is that lead forms very stable complexes with phosphate which can displace calcium in the calcium-phosphate salt in bones. As a result, lead can safely deposit in the bone, and also causes remodelling and weakening of the bone. The nightmare arrives as the bones demineralise when we age, releasing the lead stored in the bone for decades, causing a further absorption of lead by body tissues. 32

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Lead on the throne One famous example of lead-induced death is Queen Elizabeth I, who had used massive amounts of Venetian ceruse throughout her lifetime. Venetian ceruse was a popular skin whitener in the 16th century, composed mainly of water, vinegar, and lead. The flawless, impeccable white skin was considered nobility and earthly possession which, as a result, had caused Queen Elizabeth I to maintain such a makeup look throughout her life. In addition, she only took off her makeup once a week, opening doors to long-term skin absorption of lead. As she started to suffer from skin deterioration, she applied thicker and thicker layers of lead on her skin, and towards the end of her life, it was believed that her makeup was one-inch thick. Imagine that amount of heavy metal sitting on your skin!

When Swedish chemist Carl Wilhelm Scheele discovered the appealing deep green pigment, Scheele’s green, in 1775, people were extremely excited and got all their wallpapers, gowns, hats and toys coloured in Scheele’s green. Sooner or later those people became very ill and had severe skin lesions, ending up dead, leaving their beautiful houses behind. In 1862, many children were killed in an east London home after tearing down the wallpaper and the children licked the green colour of the wallpaper. In 1879, a visiting dignitary got ill after visiting Buckingham Palace, causing Queen Victoria to rip down all her green wallpaper. Who was the culprit behind all of this? In fact, Scheele’s green is formed by copper

This phosphate mimicking ability works the same in our bones. By displacing calcium phosphates to form calcium arsenate, arsenic accumulates in the bone marrow. We now return to the concept of irregular PTH levels, where on this occasion, the PTH level is high due to lowered phosphate levels in body tissues. Yet it does not do any good to the bones when PTH levels are high– bone loss resulting in fractures and bone softening are the only inevitable outcomes, causing severe bone marrow damage.

Glimmering skin or ravishing walls? Despite all the similarities we have seen between different dysfunctionalities in the body caused by different heavy metals, arsenic does have its own unique and most deadly targets: the skin. The reason is that arsenic likes to attack keratin tissues, such as hair, nails and the skin. Although arsenic usually does not accumulate in the body and after absorption is excreted in urine, keratin tissues absorb arsenic in the non-vascular tissues. One of the most significant impacts to the skin is arsenic keratosis, a growth of keratin on the skin, resulting in excessive formation of scaly skin on the palms and soles, a severe form of skin lesions. In the nails, transverse white bands of arsenic deposits are formed across the bed of the fingernails, known as "Mee’s lines". Apart from keratin tissue growth in the skin, arsenic increases tyrosine phosphorylation through intensifying the oxidative stress. Tyrosine is responsible for creating melanin, therefore in high

arsenite, and we all know arsenic is another very dangerous heavy metal. The story begins when arsenic enters the body from both

levels the skin gets abnormal skin pigmentation (hyperpigmentation) even when not exposed to sunlight! Arsenic

inhalation and ingestion, where it is highly absorbed through the lungs and gastrointestinal tract and widely distributed by blood throughout the body.

truly is attentive to every detail; not only does the body get weakened, it also strives to bring depression over the skin and nails… not something you wish to be an enemy with.

Swapping lives with phosphate In addition to suppressing respiration and increasing oxidative stress, arsenic can also cause severe DNA and ATP damage in its own style. We all know that phosphates are important building blocks of DNA and ATP, and arsenic, unfortunately, is somehow one period below phosphorus on the periodic table. This means that arsenic has a similar electron configuration as phosphorus, so the oxide ions they form are structurally similar. That is where arsenate does its job: a phosphate mimicker, passing through phosphate carriers in cells and wreaking havoc on DNA and ATP formation and processing. In an investigation led by biologists Yu Xu, Buyong Ma and Ruth Nussinov, it was found that the hydrolysis of adenosine triarsenate provides 2-3 kcal/mol less energy than ATP hydrolysis. The interaction with proteins by arsenate DNA/RNA is also slightly weaker than phosphate DNA/RNA, which may hinder rRNA assembly into a functional ribosome. As a result, the efficiency of these essential molecules are reduced, causing high potential toxicity and cancer. 33

Undeniably, most chronic metal poisonings in history were the result of insufficient understanding of the chemical compositions of these magnificent colours. If someone desired to murder someone with heavy metals, the poor victim probably would be vomiting, suffering from abdominal pain and severe muscle cramps, ending with a dreadful death. No one wants to experience such agony, and there are still so many secrets behind the mechanisms of heavy metal poisoning in different systems and organs to be discovered. Fortunately, the discovery of ignorance and technological advancements have helped us avoid falling victim to the hands of heavy metals just for the sake of beauty and aesthetics. In factories, levels of heavy metal exposure are monitored strictly to safeguard the wellbeing of workers. It is reported that, in the US, lead exposure has still been one of the factors causing over 400,000 deaths every year, despite heavy metal poisoning being no longer less common. Let us hope that the death rates will continue to decrease in the future.

ARTICLES PSYCHOLOGY

The Monkeysphere How the size of your brain is affecting your relationships Maia explores the relationship between your brain, your environment and your social circles. Kantaria, SFC1 I want you to imagine one of your closest friends, an extended family member, your favourite teacher, someone you always smile at in the corridor, and someone you see but have never interacted with. Now picture this: your friend or family member miraculously meets The Queen and receives an invite for afternoon tea at Buckingham Palace. Upon hearing this news, you may be amazed, enthralled – and maybe even a little bit jealous! But what if this same experience happened to that acquaintance, who you don’t really know? Chances are you would not feel the same level of interest that you did when it was someone closer to you. This is because these people exist outside of your Monkeysphere.

Dunbar's Number The Monkeysphere, more academically known as Dunbar’s number, refers to the number of stable, social relationships a person can maintain at any one time, which is said to be 150. The people whom you see in your day-to-day life but never talk to exist outside of your Monkeysphere. In the 1990s, Robin Dunbar investigated the relationship between the size of the brain (relative to the size of the mammal) and the primate’s social behaviour. He found that the larger the neocortex, the greater the cognitive ability to form and manage relationships with others. The neocortex is a part of the brain located inside the cerebrum that is associated with higher neural functions, such as spatial reasoning, language acquisition, communication and processing sensory information. A higher level of cognitive information puts a strain on the neocortex, and for the brain to be able to remember, process and react to this sufficiently, it must have an increased volume.

allowing you to react to stimuli faster and have a higher cognitive awareness; linking to the idea of being able to form and keep track of your 150 relationships. Adding onto this, cerebral atrophy is a condition in which brain tissue is lost (and therefore cells and neurones too), physically causing the brain to decrease in volume. We can infer that a smaller brain results in a smaller neocortex hence less productive relationship building, as per Dunbar’s research. All of us experience cerebral atrophy, however: it is natural. Unfortunately, several external factors can accelerate the speed at which brain tissue is broken down, making the defect crucial. This includes injuries like motor vehicle accidents, falls or extreme force to the head. Someone suffering from cerebral atrophy may lose control of speech, spatial awareness and muscle movements.

Spheres within sphere The core of Dunbar’s work says that on average every person can maintain 150 social relations, but to expand on this, his theory goes on to state that the tightest inner circle contains five people, followed by a layer of 15 friends, 150 contacts or peers, 500 people you know of, and finally 1500 people you could recognize in a crowd. This makes his rules a lot more flexible and applicable to real life, where platforms such as social media exist, and it is easier for us to expand our social circles. So next time you forget someone’s name, do not blame yourself: they just exist outside your Monkeysphere!

A hard and fast rule? But surely you cannot generalise something so subjective and insist that every human being has the same number of relationships they can make and maintain efficiently? Not exactly, there are external factors that affect your Monkeysphere, however Dunbar achieved his results through many tests and found the average number of relationships one person could maintain at one time was 150. Of course, this may vary slightly from person to person, and there are many influences on your brain's size and functioning such as diet and injury. A diet consisting of foods such as fruits, vegetables, nuts, and fish is not only linked to a larger brain volume but also increases the presence of myelinated nerve fibres in the neocortex. These fibres promote the speed at which your neurones can send information around different areas in the central nervous system,

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FEATURES PHYSICS

references explained Whenever it comes to teaching the Doppler effect, physics teachers love whipping out that one scene from the Big Bang Theory. It’s Halloween and everyone is dressed as some DC or Marvel superhero, but not Sheldon. He shows up in an ambiguous suit of blackand-white stripes that resemble not those of a zebra, but wavefronts. He is the Doppler Effect. You really wouldn’t

Vanessa offers explanations to the jokes and Yip SFC1 references of everyone's favourite sitcom. Ill u

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expect anything less from him. This is just one of the many physics references scattered across the show, and when I was thinking of a topic to write about, I couldn’t resist the idea of explaining a few of these references. There were many I could choose from: in one classic episode, Sheldon hysterically dives around a ball pit and models particles with peas on his plate to come to a (very loud and public) revelation about why electrons behave as if they were massless when travelling through graphene. In another episode, upon encountering an indecisive Penny, Sheldon responds with an elusive reference to Schrödinger’s cat (you won’t know if the cat is dead or alive until you open the box i.e. give it a try because you never know!) Needless to say, Sheldon is my favourite character from the show and is involved in two other references I have chosen to explore in this article: supersymmetry and topological insulators. (I have to admit, I don’t think I’ve ever enjoyed doing research as much as I did for this article as it obviously entailed rewatching episodes from the show and getting a little sidetracked…)

Meet Supersymmetry, the new DC superhero The last episode of Season 11 (spoiler alert - skip ahead if you don’t want me to spoil the show for you), “The Bow Tie Asymmetry”, is probably my favourite episode of all time. Throughout the episode, Sheldon repeatedly notices the fact that his bow tie is askew. Minutes before their wedding (which, by the way, Mark Hamill 35

officiates), his lopsided bow tie leads Amy and Sheldon to a pivotal revelation about the work they’ve been doing on supersymmetry. The asymmetry of his bow tie serves as their eureka moment, inspiring them to invent the principle of “superasymmetry”. Unfortunately, while “superasymmetry” is not an actual theory, supersymmetry is a fascinating principle that holds massive potential in explaining three mysteries in physics. To understand supersymmetry, we must first have a grasp of the Standard Model. Much like the physics equivalent of a Periodic Table, the Standard Model outlines the fundamental particles and forces that make up our universe. The fundamental particles include quarks (different combinations of quarks make protons and neutrons) and leptons (electrons, for example). The four fundamental forces include strong, weak, electromagnetic and gravitational, but only the first three are included in the Standard Model. These forces are a product of exchanging force-carrier particles, and the forcecarrying boson for gravity has yet to be discovered. While this model has been successful in explaining a wide range of experimental results and predicting a plethora of others, there are still gaps left by it that fail to encapsulate all phenomena in physics.

Supersymmetry is a hotly contested extension of the Standard Model that potentially fills in these gaps. It is a theoretical principle

and detectable. They termed this elusive matter “dark matter”, whose existence keeps clusters of galaxies together. Among other

which many theories fall under, all of them sharing the common feature of equating force with matter. In other words, under this conjecture, matter and force are treated identically. All fundamental particles in our universe can be categorised as fermions or bosons, based on a property they have called spin (a particle’s intrinsic angular momentum). Fermions have half-integer spin and include electrons, quarks, neutrinos, and any particle

popular dark matter candidates (including sterile neutrinos, axions, WIMPs and more), supersymmetry posits another fitting dark matter candidate: the LSP (lightest supersymmetric particle).

composed of an odd number of fermions (e.g., protons and neutrons). In contrast, bosons have integer spin and include the force-carrying particles (e.g., photons and gluons), and any particle

high energies, a solution that demonstrates how these three forces are mere aspects of a single force which was unified in the early universe.

with an even number of fermions. According to the Pauli Exclusion Principle, no two fermions can exist in the same state, whereas the same constraint does not apply to bosons. This is where it gets interesting - these two seemingly disparate families of particles can potentially be linked together under the principle of supersymmetry. Symmetry exists everywhere in our world, especially in physics. It is relied on in the conservation of energy and momentum, in Einstein’s relativity and more. In the 1970s, string theorists looked at symmetry on a much smaller scale, spin, giving rise to supersymmetry. For every fermion in the Standard Model, they predicted a superpartner, a boson that shares its identical interactions, has an identical mass but a different spin, and vice versa. No conclusive evidence of the existence of these superpartner particles, or “sparticles'', has been seen. However, disproving supersymmetric theories does not necessarily mean the principle of supersymmetry is inherently wrong. Some physicists are still in favour of it because it could give an elegant solution to these three problems: the Higgs boson’s mass, dark matter and the unification of forces. The Higgs boson, whose confirmed existence won François Englert and Peter Higgs the Nobel Prize in Physics in 2013, is a detectable particle caused by an excitation of the Higgs field, which is an energy field that gives particles mass. The fact that the Higgs boson is light has perplexed many, since its interactions with particles described in the Standard Model suggest it would be heavy. Here, supersymmetry offers an explanation. With all the new “sparticles” predicted, they offset these interactions, yielding a light Higgs boson. Over 80% of matter in the universe is enigmatically known as “dark matter”, matter that cannot be detected by conventional means. Their presence was hypothesised from observations made of spiral galaxies. Expecting the outer edges of galaxies to move at a slower velocity than their centres, astronomers were puzzled by their observations: both moved at the same velocity. From this, they inferred that galaxies contained more mass than what was visible

Lastly, if correct, supersymmetry would demonstrate the unification of the strong, weak and electromagnetic forces. Under this principle, the strengths of these forces would be equal at very

As exciting as supersymmetry sounds, there could be lots of explanations as to why we haven’t found a “sneutrino” or a “selectron” yet. It could be that superpartners predicted are too heavy to be produced with current accelerators, or that these mysterious particles surreptitiously evade detection. Interestingly, a very recent new measurement of the mass of the W boson, a particle that carries the weak force, turned out to be significantly larger than its theoretical prediction (see "Will the Standard Model break?" on p12)! While some are sceptical of the methodology, results and potential implications, others have begun to theorise the explanation behind this. It has been proposed that the existence of “sparticles” contributed to the W boson being heavier - but, before you get too excited, this is just one of the many possible explanations, and physicists have warned against quickly interpreting this “as a sign of new physics”.

An insulator-conductor-all-inone The episode “The Thespian Catalyst '' in season 4 opens with Sheldon delivering a condescending lecture on topological insulators. When asked if they were familiar with topological insulators, most of the doctoral candidates in the room raised their hands, only to be met by a “Don’t kid yourselves.” What he thought was a “triumphant” lecture turned out to be badly received, which couldn't be more clearly demonstrated by “the entire lecture hall flipping him off” at the same time! Not only is this scene truly reflective of Sheldon’s character, it also perfectly illustrates how notoriously difficult it is to understand topological insulators. The discovery of topological insulators was groundbreaking in condensed matter physics, the field that studies the physical properties of solids and liquids. While you have the standard conductors and insulators, topological insulators are naturally occurring materials that have both properties. Interestingly, the bulk of these materials are insulating, while the edges of these 2D materials or the surfaces of 3D materials are conducting. For (relative) simplicity’s sake, this article will focus on 2D topological insulators. “Pure mathematics and physics are becoming ever more closely connected”, said Paul Dirac at a lecture in 1939, and topological insulators are an excellent example of the amalgamation between the two subjects.

FEATURES PHYSICS

Topology is a branch of mathematics that studies properties of space preserved through continuous deformations which include twisting, stretching but not tearing. For example, you can stretch a circle into an ellipse, so these two shapes are said to be topologically equivalent. If we think in 3D, a famous example showing topological equivalence is that of a doughnut and a coffee mug. Both objects have one hole, the topological property that is preserved when a doughnut is theoretically deformed into a coffee mug. However, converting a sphere into a doughnut would require tearing a hole through it, so these two objects are not topologically equivalent. Applying topology proved useful in understanding the quantum Hall effect, which fundamentally underlies how topological insulators work. Imagine you have a 2D film of electrons with a large magnetic field pointing upwards.

The edge states now propagate in opposite directions, and this is what physicists observed in 2D topological insulators. There is an even more complex reason for topological protection that arises in topological insulators: the opposite propagations at edge states are related by time-reversal symmetry. Time-reversal symmetry dictates that a system behaves the same whether time moves forwards or backwards, and it essentially yields a time-reversed partner, resulting in the counter-propagating edge states seen in topological insulators.

The magnetic field causes electrons to experience a perpendicular Lorentz force, which is the force exerted on a charged particle due to electric and magnetic fields. This causes electrons to travel in curved paths which quantum mechanics replaces with orbitals of quantised energies, leading to the creation of an energy gap that yields the insulating characteristic we are familiar with in the bulk of the material. However, electrons at the edges produce “skipping orbits” that propagate in one direction and are not quantised. The lack of an energy gap therefore gives the edge states conductivity which is “topologically protected”. This property endows the edge

Scientists are excited by the multitude of potential applications endowed by topological insulators, ranging from spintronics and quantum computation to cancer diagnosis and therapy. For example, current silicon transistors in computers generate heat when turning current on and off. Replacing these with spintronics, which control whether an electron’s spin is “up” or “down”, analogous to an “on” or “off” current, could theoretically yield ultralow-energy transistors. “For condensed matter physicists, this is like the Big Bang”, says physicist Yong Chen at Purdue University in West Lafayette, Indiana. You can guess why I chose this

band gap valence band Insulators

conduction band band gap valence band

Semiconductors

In topological insulators, the quantum Hall effect is invoked in a slightly different way which does not require extremely low temperatures and an external magnetic field. Instead, topological insulators rely on the quantum spin Hall effect, where the magnetic field is replaced by the interaction of an electron’s spin with its orbital motion, also known as spin-orbit coupling. Instead of one 2D film of electrons, imagine you have two that have opposite spin, and both are in quantum Hall states. 37

quotation!

energy

conduction band

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states with perfect conduction - imperfections at the edges will not disrupt or affect the current, similar to how no matter how you deform a doughnut, its hole is retained.

conduction band

valence band

Conductors

“For condensed matter physicists, this is like the Big Bang”

COVER STORY FEATURE

A deep dive into

DeepMind

Lily Pfaffenzeller delves into the development of DeepMind, the company that seems to be solving everything using artificial intelligence.

Who is the most intelligent person you know? A classmate? Curie? Einstein? Whoever you thought of, could there be someone even more intelligent? Someone so smart that they could take the problems plaguing humanity for millennia, and solve them in mere seconds? Someone so genius, that they could face the most complex enigmas of science and technology, regardless of a complete lack of training or knowledge? At first glance, this is a seemingly impossible concept: to concentrate this level of intelligence into a single locale, we would have to replicate and perfect the human mind. And yet in 2010, the company DeepMind succeeded. Well, almost. Although DeepMind’s AI systems are not 100% perfect (for now), the intelligence they have built is already redefining the world as we know it. From defeating chess grandmasters to unravelling the intricacies of protein folding, this is only the beginning of what DeepMind has to offer. Let’s dive a bit deeper into DeepMind’s past, present and future, uncovering the potential of their artificial intelligence.

In the beginning... Around 14 years ago, an idea drifted into the mind of Demis Hassabis. It's worth noting that his mind had already borne several successes: the former child chess prodigy completed his A levels two years early, and received a Double First from Cambridge University in Computer Science. On top of that, his PhD from UCL was followed by two postdocs from Harvard and MIT (you know, the usual). Amid his education, Hassabis had also become a videogame designer, with his first simulation game “Theme Park” that he had coded at 17 becoming a multi-million sensation. But this idea would be his greatest yet: “What if you could solve intelligence, and use that to solve everything else?” he wondered. Two years later, Hassabis embarked on a mission to do exactly that. Together with fellow researcher Shane Legg and childhood friend Mustafa Sullyman, the trio began building an army of scientists, researchers and ethicists, all working with Artificial Intelligence. Thus, the company DeepMind was born.

2010

2014

DeepMind is cofounded by Demis Hassabis, Shane Legg and Mustafa Suleyman

Google buys DeepMind for around $500 million

2013

Artificial Intelligence (AI) refers to intelligence shown by machines which can be utilised, manipulated and developed to automate intellectual tasks usually performed by humans.

An illustration of Demis Hassabis by the artist Lauren Crow

DeepMind publishes research on their AI systems that can beat Atari games 38

COVER STORY FEATURE

Me, myself and AGI If you go onto DeepMind’s website today, it won’t take you long to encounter three letters: AGI, otherwise known as Artificial General Intelligence. DeepMind has directed its aim of solving intelligence towards creating an AGI - a risky move, considering its controversial past. For one, muttering “AGI” two decades ago would most likely evoke an eye roll, and even today you may simply garner a dismissive response. Julian Togelius, an AI researcher at New York University for one, likened a belief in AGI to “a belief in magic”, though this statement seems to be ageing as well as J.K

While neurones pass these signals on as electrical impulses, these units would pass the inputs on as simple calculations within hidden layers. Finally, answers would be recorded via designated output units. When many different inputs result in the same output, pathways strengthen, and the computer model “learns”.

Rowling’s Twitter reputation.

“Belief in AGI is like belief in magic." As it has gathered wider acceptance, AGI has come to signify a type of Artificial Intelligence (AI) with an intelligence similar to that of a human. But if we want this system to take humanity’s enigmas and solve them, surely the AI’s intelligence should exceed that of a human’s? To aim for such an AI could be detrimental, however, as this similarity to human cognition is crucial in allowing humans to be able to interact with it. By developing artificial intelligence that understands the world the same way we do, DeepMind ensures that we can trust the explanations that an AI may offer us. This doesn’t exactly mean that it has to “think” precisely like a human either, since there are drawbacks in attempting to exactly replicate human or animal brains. Instead, the best components are considered and given to a system. In other words, the human mind is simply an inspiration, not a replica, for the AI has to take things further in its own way. This concept first emerged in the 1950s, where scientists programmed a first generation computer to learn with the human brain as a template. Similar to the brain's neurones forming a complex network, the programme also consisted of many basic units that received inputs from connected units - just like neurones receive signals from other neurones.

A neural network diagram, with the left most dark blue units representing the input layer, the middle three columns representing the hidden layers, and the light blue units on the right being the output layer.

DeepMind’s director of Neuroscience research Matt Botvinick was at the forefront of utilising and enhancing these neural networks, where he aimed to identify the aspects of our own intelligence that we could use for inspiration in building AI. It seemed that memory was a good place to start…

Memory Botvinick was particularly drawn to an aspect of memory known as replay. Replay is a phenomenon that was discovered in the medial temporal lobe within the hippocampus, where a specific pattern of neural activity suggests that past experiences are being replayed. In the Nobel winning prize work of John O’Keefe and others, it was discovered that as a rat scampered down a track, a particular pattern of neural activity would arise as it returned to travel down the same route. You can verify this by sticking some electrodes in an unfortunate rat’s hippocampus to conjure these same connections, showing a memory is being replayed.

2015 AlphaGo beats European champion Fan Hui

2020 AlphaFold's predictions achieve an accuracy score comparable to lab techniques

2019

2021

AlphaFold “solves” protein folding

DeepMind open sources the code for AlphaFold

Afterwards, during a period of rest (such as sleep), electrical impulses are spontaneously and rapidly refired down the same neural pathway, known as a replay sequence. Scientists found that by disrupting the sequences, they’d significantly impaired the rodent’s ability to perform a new task. Hence, O'Keefe and his team had not only realised replay's cruciality to memory, but more importantly its fundamental role in learning.

Awake

Footage taken from a video screen recording of DQN playing breakthrough. Credit: WIRED UK on youtube

Replay wasn’t only the force at work here, however. Deep reinforcement learning was also pivotal in shaping DQN. Replay Buffer

Neural Network

Asleep

Artificial neural networks collect experience by interacting with the environment, save that experience to a replay buffer, and later play it back to continue learning from it.

This factor wriggled its way into DeepMind’s development of AI when replay was put to the test in 2015. An Artificial Intelligence system termed “DQN” (deep Q-network) was thrown into a series of arcade games. By replaying memories of past moves, the AI could learn from its experiences and work out what sequences of moves worked well, which ones were mistakes, and find strategies that otherwise wouldn’t have been obvious. Such was the case when DQN was confronted with the game Breakout. You've probably played it before, but if it doesn't ring a bell, here's what the game entails: just break through a wall by controlling a bat to hit and direct a ball. But there was a catch: unlike the average human player, the AI had no clue what the objective was or what it was controlling. All DQN had to work with was the raw, rainbow coloured pixels of the game interface. And so, the agent began learning the game entirely by itself. When you watch the first 100 games, it's pretty obvious DQN is a rookie player: you can see from the left-hand image that the agent is pretty appalling, having missed the ball most of the time. After 300 games, DQN reaches human capabilities, grasping the bat-to-ball concept as it no longer misses the ball. 500 games later, the agent had identified an optimal strategy and began playing at the superhuman level shown on the right. The contrast between before and after couldn’t be starker. By replaying memories of past moves, the AI could learn from its experiences and deduce what sequences of moves worked well, which ones were mistakes and find strategies that otherwise wouldn’t have been obvious.

Deep Reinforcement Learning If you couldn’t get enough of Vanessa’s article on the Big Bang theory, then you’ll like this next bit. Season 3, Episode 3 “The Gothowitz Deviation” sees Sheldon trying to surreptitiously alter the habits of his roommate Leonard's irritating girlfriend, Penny. After dinner, she offers to take Sheldon’s plate to the kitchen. “How thoughtful!” Sheldon exclaims. “Would you like a chocolate?” he offers. Moments later, Penny apologises for talking too loudly, proceeding to shut up; Sheldon offers her chocolate. When taking a phone call from a friend she decides to leave the room for once; Sheldon offers her chocolate. Penny agrees when Sheldon asks her and Leonard to “keep the decibel level to a minimum” at night when - well, you get the point. Leonard picks up on this too, outrageously accusing Sheldon of “using chocolates on my girlfriend as positive reinforcement for what you consider correct behaviour!”. Indeed, this is exactly what Sheldon is doing: following each behaviour favourable to him with a reward makes it more likely that the behaviour will reoccur in the future. Similarly, DeepMind uses a method called Deep Reinforcement Learning to train its AI systems. Instead of being told directly what to do, an AI system, or agent, must find it out for itself by trial and error, just like DQN in hundreds of games of Breakout. Unlike Penny though, machines tend to lack interest in chocolate, so their reward takes the form of 1s or 0s. Thus, every time DQN hit the ball (the favourable action), it was rewarded with a signal of +1. And so, if a programme as small as DQN could learn through such methods, what was stopping DeepMind from thinking broader and bigger?

COVER STORY FEATURE

Ready, set… In the beginning, DeepMind began training AI with the simple Atari arcade games. Within one year they jumped to training AI with the hardest: Go. Go, or Weiqi, sounds rather similar to Chess at first, but in reality is much more complex. Two players compete on a board: one takes black, the other white. Each piece is a counter, which they alternate in placing on the board. The aim? To surround the largest total area on the board by capturing their opponent’s stones.

Black's move to "a" captures the surrounded five white stones

“Dear Mr Fan,... as the strongest Go player in Europe, we [DeepMind] would like to invite you to our offices in London… to share with you an exciting Go project that we are working on” In the next step of the project, Hassabis addressed the above email to professional Go player and 2013-2015 European Champion, Fan Hui. Hassabis wanted AlphaGo to play against Hui in a game of 5 rounds. “It’s just a programme,” Hui dismissively stated when confronted with the concept. He soon realised that this was perhaps more than a mere programme when he lost the first round. In the second game, despite a valiant effort to alter his style, Hui still lost. AlphaGo triumphed once again in the third, with such consistency being maintained throughout the fourth and fifth. In its first ever game of go against a renowned champion, AlphaGo won 5-0. Hui left London that day defeated, but AlphaGo wasn’t finished just yet.

Although these rules are massively simplified, the game is relatively easy to pick up regardless. Don’t let this deceive you, though: behind the invitingly easy façade lies a profoundly complex network of strategy, tactic and possibilities. In fact, there are more than 10170 possible board configurations - that exceeds the number of atoms in the known universe. This complexity is what cements Go’s title as the most challenging game for AI. Experts were convinced that an artificial victor of Go was yet to stroll onto the scene for another decade, if ever. All one had to do was take one look at the facts, which didn’t point towards a bright future: winning this board game required multiple layers of strategic thinking, a factor standard AI in the past fell short of. Standard AI systems, which test all possible moves and positions using a search tree, would collapse under the sheer number of possible moves while evaluating the strength of each possible board position. Knowing this, DeepMind attacked the dilemma from a new perspective. Drawing from deep reinforcement methods, a computer programme was thrown into countless games of Go. The AI that would soon become known far and wide as AlphaGo started small by playing games at an amateur level. Once it had gained a reasonable understanding of human play, AlphaGo went a bit Dr Jekyll and Mr Hyde, playing against different A professional game of Go in progress

versions of itself thousands of times. As time went on, Deep reinforcement learning methods began to take hold: as AlphaGo learned from its mistakes, the agent became increasingly stronger in both learning and decision-making. And so, AlphaGo was finally ready… 41

…go! 200 million people worldwide watched in anticipation as AlphaGo and legendary Go player Mr Lee Sedol came face to face in March 2016 in Seoul, South Korea. Sedol, who held the titles of 18 world championships, seemed just as unphased as the pre-game Hui in his preceding interview to the game:

“I don’t think it will be a close match. The level of the player that AlphaGo went against in October is not the same level as me, so given that a couple of months have only passed, I don’t think that it is enough for it to be able to catch up with me.” Logically speaking, Sedol wasn’t thinking erroneously: he held a 9p ranking (the highest possible) in the Go professional ranking system, which massively outweighed Fan Hui’s meagre 2p. Lee Sedol even predicted a score of 5-0 or 4-1. With the whole world watching, Sedol turned out to be correct, though perhaps not in the way many predicted: the ultimate score totalled 4-1, to AlphaGo. During the games, AlphaGo played several inventive winning moves, many of which - including move 37 in game two - were so surprising that they upended hundreds of years of wisdom. As a result, AlphaGo became the first ever machine to earn a professional ranking at the 9p level. More than this though, AlphaGo’s victory demonstrates that the capacity of AI and deep

Lee Sedol (W) vs AlphaGo (B) in game 2: black wins by resignation. Wesalius, Lee Sedol (W) vs AlphaGo (B) Game 2- BW, CC BY-SA 4.0

learning doesn’t just reach into the realms of games, but has implications for wider society too…

Crash course: proteins If a "universally most important molecule" competition existed, there’s no doubt that proteins would emerge victorious. Many of the world’s greatest challenges boil down to proteins and their roles, from developing treatments for diseases to finding enzymes that break down industrial waste. The field of biochemistry is dedicated to scrutinising the vast world of protein structure, and genetics similarly centres around the proteins that may arise from a genetic sequence, such as my personal favourite, ‘AAAAAAAAAAAAAAAAAAAAAAAAAA…’ - a bunch of Adenine bases, translating into the amino acid Phenylalanine. Amino acids are the fundamental building blocks of all proteins, linked together in a linear chain known as the primary structure. Teachers love using the analogy of a necklace: if you take a string of beads, a different shape would represent a different amino acid, with the string equating to the peptide bonds holding the beads together.

This necklace then coils and ravels up in a process known as protein folding: maybe some beads are magnetic and attract or repel each other, perhaps others are sticky - either way, these beads, or amino acids, interact very specifically with each other to give rise to a very specific shape. Even a change of one amino acid can produce an entirely different protein. Christian Anfisen, the 1972 Nobel Laureate in Chemistry, postulated this in stating that a protein's amino acid sequence should fully determine its structure. If you have the amino acid’s primary structure, then you can figure out its 3D shape, right? If only nature was so simple. It would take longer than the age of the known universe to enumerate all possible configurations of a typical protein by brute force calculation, with a chap called Cyrus Levinthal estimating 10 to the 300 possible conformations a typical protein could fold into. Out of the 200 million proteins we know of (and counting), only a small fraction of the shapes have been deciphered. If one were to embark on discovering a protein’s structure, much more painstaking and expensive methods - such as X-ray crystallography - would have to be called into play. An alternative possibility of determining a protein’s larger 3D shape from just its primary structure could revolutionise structural biology. But as Levinthal pointed out, this is not so simple. Thus, the 50-year-old protein folding problem was born.

A solution unfolds Enter DeepMind. Unsurprisingly, the company was drawn to the biological enigma because of a game called "Foldit". The aim is in the name: gamers would fold proteins the best they could, competing against other players in an attempt to score the highest. Although players typically weren’t biochemists, some were able to find breakthrough protein structures that would go on to be published in Nature.

An example of a Foldit puzzle that a human can see the obvious answer to - fix the sheet that is sticking out! Credi: Foldit website

In mimicking a human Go player to create the successful AlphaGo, could DeepMind develop a similar AI to mimic human Foldit players that were folding proteins? Riding the high of AlphaGo’s successes, Demis proposed this idea to his team before they had even gotten off the flight returning from AlphaGo’s match in 2016. It wasn’t a bad idea - the protein folding problem already had ideal foundations laid out for DeepMind to begin working from: previous decades of work by experimental biologists had already determined some structures, and the CASP competition offered the perfect opportunity to put an AI to the test. The Critical Assessment Protein Structure Prediction, or CASP, is a regular global competition amongst biologists who use computers to fold proteins. One is challenged with a set of 100 protein sequences and asked to produce the 3D structure where results are compared afterwards. The accuracy of a CASP protein prediction is measured using the Global Distance Test (GDT): a visual sketch of the true folded protein is taken and the calculated competition entries are superimposed on top of it. The more amino acids that are in the correct position, the higher the score along the scale of 0-100, with 100 being an exact agreement with the experimental structure. If DeepMind could develop an AI that excelled in CASP, then they could ultimately verify that their system held the key to protein folding. And so, AlphaFold began its development. Their initial AlphaFold model involved repurposing an AI technique typically used in image analysis where the AI would work out which amino acids should be positioned close together in the final protein. As AlphaFold crunched through the different structures that could fit in a slow and highly computationally-power intensive process, it seemed to work. Thus in 2018, AlphaFold saw itself enter the CASP competition for the first time, coming out on top. However, its average GDT score of 58.9 was nowhere near close to the target of 90, which was the benchmark score that would officially deem a folded structure true. On this basis, DeepMind decided to redouble its efforts: AlphaFold2 saw the repurposed image recognition system eradicated, replaced by an AI that had been redesigned from the ground up solely to understand protein folding. The AI tool had been trained on thousands of previously solved protein structures to recognise patterns in the 3D structure based on its primary sequence. Once given a sequence, AlphaFold2 proposed a possible structure in a matter of seconds. That year in 2020, AlphaFold2 would follow in the footsteps of its older counterpart in the CASP competition. Up against 100 other groups, AlphaFold2 began folding its way through the 90 challenge sequences. A month

COVER STORY FEATURE

The ethical elephant in the room

had passed by the time results chimed in: AlphaGo2 scored an average of 92.4, across all targets.

AlphaFold2 scored an average of 92.4 out of 100 in the 2020 CASP competition In fact, it was so precise that structures contained atomic details, achieving a level so exact that it enabled results to be used for drug design.

Unlike this article, which has conveniently left the rather messy topic of ethics until the last minute, ethical concerns punctuate each of DeepMind’s milestones.

“We want AI to benefit the world, so we must be thoughtful about how it’s built and used.'' This is scrawled across their website section dedicated solely to ethics. Indeed, with great power comes great responsibility (to quote Spiderman): this new and novel era of Artificial Intelligence is unfolding rapidly, stirring up unease amongst the excitement. Beyond the confines of the DeepMind headquarters, how might AI be implemented, used and abused in society? Technology at heart is relatively neutral: a machine itself can’t be bad or good - it falls upon how others use it. Consider the GPS, for example. It was invented to launch nuclear missiles in the past, but you’ll now find them being used by Uber drivers. In a similar way, could DeepMind’s systems also have a hidden dark side?

Two examples of protein targets in the free modelling category. AlphaFold predicts highly accurate structures measured against experimental result.

It didn’t take long for the news about AlphaFold’s success to reach the labs of biologists. A collaboration with another research group saw several predictions of the SARS-CoV2 virus, with two of the structures, ORF3a and ORF8 later being confirmed. A follow-up announcement in July 2021 released the source code for the tool, alongside a publicly accessible database containing predicted structures of the human proteome (our entire set of proteins). However, AlphaFold has only made a sizable dent in the world of structural biology. The protein folding problem has yet to be officially solved, with DeepMind’s AI still falling short in several significant areas: predictions falter in accuracy when it comes to intrinsically disordered regions in proteins (areas that lack a defined structure due to their flexibility). AlphaFold also has yet to explore dimeric proteins, which are a type of protein whose structures change depending on their interactions with other proteins and molecules. Who knows… perhaps in a few years a new and improved AlphaFold3 may enter the protein folding scene.

"I think artificial intelligence is like any powerful new technology...it has to be used responsibly. If it's used irresponsibly it could do harm."

Demis Hassabis

Having already anticipated a handful of risks, the company signed public pledges against them, such as the use of lethal autonomous weapons. Additionally, DeepMind’s designated team of ethicists and policy researchers have become intrinsic to the AI research team, keeping a close eye on how technological advances may impact society, identifying and further reducing risk. With their ethics team on board, hopefully it’ll be some time before we’re launched into an AI-dominated dystopia, if ever.

Back to the surface

Improvements in the median accuracy of predictions made by AlphaFold2 compared to AlphaFold and previous winning scores of the CASP competition. DeepMind<https://assets-global.websitefiles.com/621e749a546b7592125f38ed/62277c4c42bcdc0bcf269b11_Fig%201.jpg>.

Credit:

DeepMind is a world of its own. Honestly speaking, this was barely a “deep dive” into DeepMind, but rather a casual paddle in this vast sea of innovation. I highly recommend exploring their website, or their Spotify podcast (presented by Hannah Fry) to learn about these discussed concepts in more depth. From the potential to combat climate change to cancer, keep a close eye on DeepMind for now: who knows what technologies will emerge from their labs, or when. But when it does, you won’t want to miss it.

Q&A We asked CLC to send science-related questions and we chose a few to answer...

Curiosity killed Schrödinger's cat... or did it?

Lily Christopherson asked...

Why does the Earth orbit the sun rather than being pulled into it? We know that the sun exerts a huge gravitational force on the Earth because of its immense mass, and the Earth is consequently being pulled towards the sun. But the reason why the Earth does not simply collide with the sun is that there is another force counteracting the gravity of the sun. The Earth in fact has a velocity in the direction perpendicular to the force of the sun’s pull. In other words, without the sun, the Earth would simply travel in a straight line. The outcome of this velocity balancing out with the gravitational force is the stable orbit of the Earth around the sun.

Pull of gravity

Sideways Motion

Giselle Chan asked...

Are we alone in the universe? Earth is the only known planet to maintain life. It includes living things, planets, stars, galaxies, dust clouds, light, and even time. There are many possibilities of other life in this universe, we just don’t have the resources to find out. There could be life but we can’t get a reliable source to prove that. “Alone“ is a world whose meaning can be easily stretched to fit different perspectives. In my opinion, no-one will ever be truly alone. You're all fitted with imagination and there’s always other things that are alive. So in conclusion no, we could never be alone, our own imagination stops that from ever happening.

Newton explained the nature of gravitational orbit in the solar system by using the analogy of a cannonball, also known as Newton’s cannon. He imagined an enormous cannonball fired on the Earth. Before it travels far off it simply hits the ground due to gravity. But if it is fired with a stronger force resulting in a greater initial velocity, it travels a bit further before falling onto the ground. If the force becomes extremely large resulting in a much greater velocity, the cannonball will travel far enough that when it falls due to gravity, it will miss the ground because of the Earth’s curvature. Eventually, when this force is big enough, the cannonball will end up constantly falling but never reaching the Earth, or simply, orbiting around the Earth. As there are no external forces that change the velocity of the Earth once it’s "fired", this is essentially how the Earth orbits around the sun without being pulled into it. Joanna Guan

Valerie Ostapchenko 44

Q&A

Nell Darby asked...

Why do we remember some dreams vividly and forget others? Sleep is a fascinating and seemingly straightforward concept that scientists are still trying to understand. It is known that we cycle through 4 stages of sleep every night, each lasting 90 minutes on average. One of these stages is REM (rapid eye movement) sleep,

thinking and introspective people are more prone to this ability. Dream recall may also be influenced by emotional impact, which is perhaps the most obvious answer. Vivid dreams, especially those associated with intense, negative emotions, such as those

which makes up about 25% of the night. Dreams occur all throughout the sleep stages, but REM sleep is where the most plotbased, narrative dreams occur, which help foster problem-solving abilities, memory consolidation and emotional regulation.

experienced in nightmares caused by stress or trauma, are recalled more easily. It is interesting to note that this form of memory bias can directly be seen in our waking memories as well! So whether you believe dreams are a window to the subconscious, or you just want some bizarre dreams to share over breakfast, tips to increase

There are a number of factors that may influence how well you recall your dream. First is the stage of sleep from which you wake we have a high chance of encoding dreams we’ve just had into longterm memory before waking. The process of turning dreams from short to long-term memory can be linked to the temporoparietal junction, a region in our brains that can process information and emotions. Studies have found that people who report a high dream recall showed increased activity in their temporoparietal junctions. In light sleepers particularly, a difference in electrical activity in the

dream recall include the basics: get adequate sleep and keep a notebook by your bed to record your dreams in the morning before Vanessa Yip touching your electronics.

temporoparietal junction can mean they are more responsive towards external stimuli during sleep, increasing their tendency of waking. High dream recall amongst light sleepers is therefore frequent as more of their dreams are encoded into long-term memory. Another factor is sleep quantity. Consistent insufficient sleep may sacrifice the quantity of REM sleep, diminishing your ability to recall dreams. Personality traits have also been posited to influence one’s ability to recall their dreams - specifically, creativeLudmila Neil asked...

Air is made of 21% Oxygen. Would life function more efficiently if it was 100% Oxygen? First of all, no. Especially not for humans. Breathing in 100% pure oxygen at normal pressure can cause oxygen poisoning, which could be fatal. When you take in oxygen from the lungs, the oxygen will diffuse across to a transport molecule in the blood called

haemoglobin. However, if you breathe air with a much higher than normal oxygen concentration, the oxygen in the lungs becomes too much for the blood to carry away. Instead, the excess free oxygen in the body will react with surrounding tissues, damaging the proteins, fats and nucleic acids in them. This in turn will cause major organs to become dysfunctional, such as your central nervous system and your heart. Broadly speaking, life would also definitely not function if the air was 100% oxygen. This is because, nitrogen, which makes up 78% of the air, has an important role for life function as well. It is especially essential for many microorganisms and plants to live. Some bacteria can fix the nitrogen in the air into nitrates, a mineral that plants can absorb, which in turn allows them to produce the proteins that our human bodies cannot make. Unlike oxygen, nitrogen is an unreactive gas, so it provides the atmosphere with a nice and stable environment. Even with more than 30% of oxygen in the air, many substances would spontaneously burst into flames meaning that life could not exist at all. Nitrogen "diluted" the oxygen to a concentration where it is perfect for life to develop on Earth. Vanessa Tsui

Lily Christopherson also asked…

What makes your hair straight or curly? If you look at other members of the Ape family, no other species have curly hair, so why did humans develop them and what exactly

To illustrate this point, when hair is straightened, heat overcomes the hydrogen bonds between the keratin proteins. When the hair

causes hair to be curly? All over your skin, there are deep pits known as follicles from which hair grows. Some theories suggest it is the shape of the hair follicle which determines your hair’s tendency to curly or straight. A study in New Zealand (unsurprisingly) looked at the hair follicles of sheep to see how they contributed to hair type. They predicted that the curly hair follicle would have more hair producing cells on one side of the follicle than the other, as this would make the hair grow asymmetrically (in other words, it would be longer on one side

cools, the proteins reset into a new layout and new hydrogen bonds re-form once again. Over time, the effect of the straightening wears off as the protein molecules move back into previous configurations. Equally, getting a perm involves breaking much stronger bonds called disulphide bridges using chemicals and heat and reforming them to form curly hair. Despite this being a sensible theory, hair is still a complex structure, and its properties are determined by a wide range of genes. A study collected genetic data on 6,000 people in order to find associations between genes

which would cause it to bend in one direction). However, they found no evidence that the shape or distribution of hair-producing

and their hair types. They discovered two genes, one which results in a structural hair protein called Trichohyalin (TCHH) and another

cells in the follicle had any effect on hair type. So, perhaps looking more closely at the structure of hair will help answer our question.

called EDAR (responsible for sending messages in the cells). TCHH plays a role in the way keratins interact with each other and EDAR

You may have seen microscope images of hair with an outer layer

promotes symmetrical hair growth. Interestingly, TCHH was found to have evolved in Europeans independently of EDAR, which

of dead cells which have a scaly appearance. Underneath this layer is a matrix made mostly from keratin proteins. Keratin is the same substance that forms a rhinoceros's horn, a horse's hooves and a sardine’s scales. Being a protein, keratin is formed from long chains of amino acids. Imagine a protein as a daisy chain, and if you had many varieties of daisy in a garden, you could make chains with many different colour variations. Similarly, proteins with different properties are produced when twenty types of amino acids are put in different combinations. These keratin proteins can form bonds between each other, known as hydrogen bonds, creating strands of protein called fibrils. This is similar to how a rope is formed from

evolved in East Asians, suggesting there is more than one way to get straight hair. Looking at other global populations may provide deeper insight into why hair is different. Whilst there is a plethora of stunningly creative African hairstyles - the predominantly coiled feature of hair of people of sub-Saharan descent is believed to protect from intense UV radiation whilst keeping the head cool. This may have evolved when early humans ventured from forested habitats into open savannah millions of years ago. At this time, humans also lost much of their body hair as we became more proficient at sweating - an adaptation which made us incredibly good at chasing animals for food. As humans migrated out of Africa

many small fibres. The subtle variations in amino acids of keratin proteins determine how they interact with each other. The uneven way they are laid out in the hair matrix will influence a hair's strength and, perhaps, determine its tendency to curl.

to higher, cooler and less sunny latitudes, coiled hair may not have been so beneficial. It was then that the TCHH and EDAR genes arose in European and Asian populations. So, why did these migrants lose their curls? A warm dense layer on the head, ears and neck would have helped keep humans warm during the colder winters. Others argue that our hair played a limited role in heat regulation, that perhaps it had a more important role in signalling social or reproductive status, or that it arose due to sexual selection pressures in those populations. From my research, it is a much more complex question than I first thought. Keratin protein interactions, mutations in genes and evolutionary selection pressures all combine to form a surprisingly fascinating puzzle. This perhaps might not be the definitive answer you were after, but uncertainty is the true nature of science. Mr Mallin asked one of his LC1s (Sophia Edwards) to draw an ancient mammal with the question “Why did they evolve hair?” and she came up with this - An Emo Therapsid. (Lily and Vanessa love it.

Comparison between the atomic scale and sub-nanoscale of α- and β-keratin from ScienceDirect

It’s genius).

Mr Mallin 46

The Chelt Scientist ISSUE 2

Articles inside

Q&A: your questions, answered

Feature: A deep dive into deep mindLily Pfaffenzeller

Feature: The Chemistry of colours

The science behind the Sunny D

Interview: A conversation on cancer research with Dr Anscombe

The father of modern surgery: a biography in SpanishRosie Evans

For what it's worthMr Gill

Feature: The Big Bang Theory references, explained

The MonkeysphereMaia Kantaria

Why is Euclid’s fifth postulate unproven and invalid?

The Russian invasion of Ukraine

The Tongan volcano eruption

The first pig heart transplant

March News in brief

February News in brief

Art: Staff and student photography

Feature: The origins of lifeVanessa Tsui

The James Webb Telescope