QUANTUM

ULTIMATUM THE ANNUAL MAGAZINE OF THE MONCRIEFF-JONES SOCIETY

MJ 2014 - 15 ISSUE

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FOREWORD - DR BRUCE GRIFFIN Last December, I was invited to Caterham School to deliver a lecture to members of the Moncrieff-Jones Society as well as parents and staff on “Obesity and Coronary heart disease”. On arrival I was encouraged to talk in as much detail as possible for as long as I wanted. I wholeheartedly took up this challenge and spoke for over an hour about the effects of diet on health. The questions from students after my presentation were pitched at an incredibly impressive level, rivalling some of those from my university students. There were so many questions that even after the talk had officially ended, there was a long queue of keen students waiting to ask me more questions in person. I’d like to also say thank you for presenting me with a Moncrieff emblazoned tie and notebook. Both are very smart and a brilliant keepsake of such an enjoyable evening. The articles in Quantum Ultimatum are captivating likewise. I have to offer my sincere congratulations to all the students brave enough to step up and take the challenge of undertaking such a talk. The Moncrieff-Jones society provides a great environment allowing both speakers and audience members to branch out in science topics outside the curriculum. Professor Griffin is a biomedical scientist with expertise in lipid metabolism, nutritional biochemistry and cardiovascular disease. After his BSc in medical laboratory science (1984), he gained his PhD on the effects of exercise & diet on human plasma lipoproteins at the University of Aberdeen (1988), and undertook post doctoral research in Pathological Biochemistry at Glasgow Royal Infirmary until 1994. Since then, he has held academic posts as a Lecturer, Senior lecturer, Reader and Professor of Nutritional Metabolism at the University of Surrey. His numerous publications are indicative of his interest in the effect of dietary fats on the body. Hence the topic of his talk at Caterham School: “Coronary heart disease and Obesity”

PR E SID E N T’S IN TR O DUCTI ON

MJ

Ladies and Gentlemen welcome to Quantum Ultimatum! Quantum Ultimatum is the annual publication of the Moncrieff-Jones science society. It contains articles from each of this year’s speakers summarising their talks as well as an insight into what goes on in the Caterham science department.

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The Moncrieff-Jones society is without a doubt the greatest asset of Caterham School (well in my opinion anyway). Every fortnight on a Tuesday afternoon, sixth form students and staff from all over the school, MJS notebook in hand, crowd into the Physics project lab (ironically one of the smallest classrooms) to experience the great Moncrieff-Jones talk! It isn’t just anybody who takes to the stage, to stand a chance in conquering the MJS presentation one must be prepared to talk for 30 minutes, assisted by a trusty Power Point, and have the courage to be cross-question by a harsh and knowledgeable audience for almost 40 minutes. The talks are massively rewarding for the student audience, who get to learn about fascinating topics that they wouldn’t otherwise study in class, as well as for the speakers who gain invaluable research and presentation skills. Science has changed our lives and will most certainly continue changing them way into the future. We live in a time when scientific research into areas such as the genetics of cancer, the evolution of super resistant bacteria or the nature of our universe could not be more important. The Moncrieff-Jones society is about getting people to ask questions, letting them discover their thirst for knowledge and allowing them to defeat their curiosities about how the world works. We inspire people to love science so that perhaps one day someone will be able to cure cancer, defeat the superbug or even understand the universe. I’d like to give a massive thanks to all the speakers this year for the enormous effort they put in to their talks. The reason this society has continually thrived is because of the quality and enthusiasm of the presentations, and this year was no exception! An enormous thanks must be given to Mr Quinton, not only for entrusting the success of such a prestigious society to a couple of sixth formers, but also for how much time and energy he has put into the society over the years. Without his passion and enthusiasm (as well as the tough questions he asks) the society would simply not be what it is today. Finally I’d like to extend my thanks Cesci Adams, the Vice President, for doing such a fantastic job in helping me run the show. Best of luck to Tom Land and Emily Yates who will be taking over the roles of President and Vice President. Over the past year Cesci and I have got so much out of leading the Moncrieff-Jones society and we hope that you do too! Enjoy the magazine! Yours Ollie Hull

Quantum Ultimatum is an exclusively student written magazine. No teacher input has gone into creating it. Edited by Ollie Hull and Cesci Adams, President and Vice-President of the Moncrieff-Jones society

CONTENTS

6 THIS YEAR AT MJS 8 MJS NOTEBOOKS 9 TALKS 10 RABIES Bethany Quinton 14 LAMB SHIFT Dan Pook 18 GM MOSQUITOES Dan Puntan 22 HIV Robbie Hill 26 TEACHERS’ EXPERIMENTS 28 THE ORIGIN OF LIFE Tom Land 32

SKIN GRAFTING

Emily Yates

36 AROMATIC CHEMISTRY Anthony Baston 40 WHAT HAPPENED TO BRUCE BANNER? Nikita Komorov 44 SNAKE VENOM Eva Wang 50 CLUBS 52

TRIPS

58 BREAKING BAD 60 Past MJS topics, past MJS presidents, vice presidents and endorsers 62 SOCIETY SUMMARY Dan Quinton

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THE YEAR AT MJS The 2014-2015 academic year has been a record breaking time for the society with the largest ever turnout to Bethany Quinton’s talk “Rabies; what are we doing wrong?” and on the same night we had our first ever question asked and answered in Spanish! On top of this we have had 8 other first class lectures as well as our Christmas event lead by the eminent guest speaker Bruce Griffin. Highlights have included Thomas Land’s immense

enthusiasm for his twist on the origins of life, the ever smiling Dan Puntan and his fascinating solution to malaria and Eva Wang reducing the audience to tears of laughter with her little comments and random giggles during her knowledge packed talk on the power of snake venom. It has been great to see so many new faces from the lower years and even from the language department frequenting the science corridors on a Tuesday evening. 7

THIS YEAR’S BIG NEW ADDITION As the new leaders of the society, Cesci and I wanted to add something that would not be forgotten. So many people leave the talks every fortnight with their heads full of fantastic scientific knowledge but within a few days it is all forgotten. What do we need? Our own Moncrieff-Jones embossed notebooks of course! We created the design seeking something that would represent the society – a striking but professional look. When the finished product arrived and the boxes were opened (it felt like Christmas all over again!) we gave one to every committed Moncrieff-Jones member and within a couple of months we had handed out almost 100 books. They are now used prolifically in every talk and have become a key feature of the society. I hope that the tradition is continued in future years. To give you a true sense of the amazing science that is scribbled down into these notebooks every fortnight we have filled the inside cover with a fantastic collage of notes.

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TALKS Getting a large audience to attend your

Moncrieff talk is a skill in itself, one that is

left completely up to the student doing the presentation. They do everything from covering the school in posters to making overenthusiastic announcements in school assemblies. This year’s bunch has done a

A Moncrieff-­‐Jones   Society  Talk    

fantastic job to increase the popularity of

Rabies

the society even further. Here are some of the posters from the past year.

Bethany Quinton  

th

This Tuesday  9  September  2014   4.15-­‐5.30  

Physics Project  lab  

Are Genetically  Modified  Mosquitoes   the  solution  to  malaria?  

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Moncreiff Jones  talk  on   Tuesday  the  7th  of  october   Dan  Puntan  

Skin Grafting:

The Future of Cosmetic Surgery

A MONCRIEFF  JONES  SOCIETY  TALK  

THE ORIGIN  OF  LIFE   Moncrieff Jones Talk by Emily Yates

BY THOMAS  LAND  

Physics Project Lab

Tuesday 27th January

TUESDAY 13TH  JANUARY  

4:15

WHAT HAPPENED TO BRUCE BANNER?

AR MATIC

A Moncrieff-Jones Society talk by Nikita Komarov

Chemistry

Tuesday, March 3rd, 2015 Physics Project Lab

ANTHONY BASTON   MONCRIEFF  JONES  SOCIETY   TUESDAY  10th  FEBRUARY   4:15  

Food and Drink provided

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RABIES 10

Hi, I’m BET HA N Y QU I N TON I’m in Upper Sixth and am studying Biology, Chemistry and Spanish, though I also studied maths last year. Having attended many Moncrieff-Jones talks over the years I was very excited to be able to present one of my own. I loved having a variety of age groups attend my talk, and the challenge of making my talk interesting for those studying science at 6th form level, but yet accessible for those preGCSE pupils. I hope you enjoy reading my article!

Rabies is a very curious disease indeed. I am sure that many people reading this magazine will have at least heard of it certainly a few times in their lives, but why is this? Many other less ‘famous’ diseases kill far more people each year, so why is it that we place rabies on a pedestal? I first decided to research rabies when I was reading a Biological Sciences Review magazine, which briefly outlined how rabies worked – that it not only is transmitted in the saliva, but that it also damages the host’s brain so that the animal is more likely to bite, thus more likely to pass on this virus to another organism. All I could think was what amazing biology that must be. And hence, this article – finding the truth behind the extraordinary ‘life’ of this virus, and if it really does deserve the fame it has.

The virus itself is classified as; Mononegrivales, Rhabodoviridae, Lyssavirus, Rabies – which means that it has non-segmented negative RNA, is bullet shaped, and causes encephalitis (swelling of the brain). The structure is simple – its outer-most ‘membrane’ is that of its original host. When budding, it cases itself with a bit of ‘stolen’

membrane from the host cell. Underneath this is the Matrix protein which retains the structure of the virus, is bound to the glycoproteins used for entry into foreign cells, and encases the ribonucleocapsid. (The matrix also has been proved by many studies to have an enormous impact into the quantity of budding rabies viruses – a 500,000 fold decrease in the number of budded viruses was shown when they had no matrix, opposed to only a 30 fold decrease when no glycoproteins were present). There is much speculation as to why there is even a nuclecocapsid (protein) at all, however there are two suggested theories; to keep the RNA molecule stable, so it doesn’t react or get broken down (mRNA lasts for 20 minutes in a normal cell), or to prevent the single strand of RNA from hydrogen bonding to itself. If this happened another enzyme would have to be used to break these bonds which could form in many different places and combinations, taking time and using energy. Finally, there are two further proteins (the rabies genome codes for 5 proteins in total), L and P. The L protein is the polymerase enzyme which binds each RNA nucleotide together and the P (phosophoprotein) appears to activate, or act as a coenzyme, to the L protein.

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R A B I E S

Rabies enters the body via one ‘route’ – by infected saliva entering broken skin or mucous membranes. Surprisingly in America, though dogs are stereotyped as the main vector of rabies, bats are responsible for over 95% of rabies cases. But how does the virus actually gain access to your cells? Surprisingly this virus never enters the blood stream, instead it enters the neurones near the site of broken skin via two main receptors; Nicotin Acetlycholine receptors (which are to do with the initiation of muscle contraction and relaxation) and Neural cell adhesion molecules (they help the cells to interact and stick together). The gylcoproteins on the surface of the rabies virus bind to the receptors on a neurone and move into the cell by endocytosis. Once inside the cell, RNA replication takes place and the envelope is removed. RNA nucleotides from the neurone itself are used for RNA synthesis (for ‘new viruses’ and mRNA synthesis for the translation of mRNA into polypeptides in the rough endoplasmic reticulum of the neurone). A surprising thing to note is the viral RNA does not interact with the host cells’ DNA which is atypical of most viruses. Another fascinating point is that the matrix protein inhibits the transcription of the viral RNA (5 separate strands of the genome) and stimulates the entire replication of the genome (to make the RNA which will be encased in the ‘new’ viruses). This makes sense, because if there is a high concentration of the matrix protein in the neurone, more RNA is needed rather than mRNA to make more matrix and other proteins. A further fascinating part of the biochemistry of rabies is the movement of it up cells with the use of cell-like ‘motorways’ – protein microtubules which are used as pathways by dyneins (a type of motorprotein). These structures ‘walk’ along the microtubules towards the negative end of the cell –towards the cell body. This would also suggest that the virus uses the motor neurones rather than sensory neurones to access the brain, as a sensory neurones’ cell body is at the centre of the axon rather than at one end – also the motor neurones would have the nicotin

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acetlychloine receptor as they’re responsible for stimulating a muscle contraction. Having travelled up from the wound site primarily along motor and relay neurones the virus reaches the brain, and what it does to its host here is just mind-blowing – it changes its personality. The virus, when budding and replicating, damages neurones and damage to certain areas of the brain can be associated with the symptoms rabies causes. For example, damage to the hippocampus (situated where the spinal cord ends in the brain) would explain the sudden moments of rage and then depression often seen with furious rabies, as this area of the brain is involved with the limbic system – emotions, (motivation, fear, anger) and also the reward pathway. Damage to the cerebellum (the base of the brain) causes Ataxia (the inability to co-ordinate multiple muscle contractions) causing the lack of the ability to balance, can also slow movements and cause tremors – these symptoms can be seen in the few patients ever to have survived a bout of rabies, following the Milwaukee Protocol. The infection of the brainstem is perhaps an important area to focus

on however, as it is key to the core functioning of the body. It maintains the rhythmic pulsing of the heart and also controls breathing and consciousness, therefore infection in this area would cause the symptoms seen in paralytic rabies, and the ultimate cause of death in all cases of rabies - respiratory paralysis. It should be noted that the rabies virus itself does not cause damage to neurones due to perforin proteins or apopdosis but rather encephalitis, which is the swelling of the brain. This swelling causes pressure to be exerted in certain areas of the skull – damaging cells. The use of receptors by the viruses or budding from cells can also alter the ability of the neurotransmitter to stimulate cells, causing further problems in the central nervous system. Before describing the most up-to-date techniques for the diagnosis and treatment of rabies, it is first of all important to briefly describe the symptoms seen. There are 3 main phases; the Prodromal phase, the Acute Neurological Period and Coma. The Prodromal phase can appear any time between 2 days and 6 years after the initial infection (dependant on number of viruses transmitted and the location of the bite) and lasts between 2 to 10 days after being bitten, but common complaints of patients are non-specific at this stage, for example: a slight temperature, chills, headache, nausea, sore throat, photophobia and musculoskeletal pain. There may be a tingling sensation felt around the area of the bite however the symptoms are very general and can be experienced with a number of different illnesses, therefore one would not assume that they had contracted rabies, nor would doctors. It should be noted that a diagnosis at this point is tricky as rabies would only be assumed if the patient had been bitten, and bat bites often go unnoticed. After the Prodromal phase comes the Acute Neurological or ‘Excitation’ phase, which can last between 2 to 7 days. The stereotypical symptoms of rabies begin, starting with nervousness, anxiety, agitation, restlessness, aggression, impulsive behaviour and phobias to bright light and loud noises. At this stage over twice the normal volume of saliva is produced per day (which would increase the chance of viral transmission to other organisms). The sudden change in behaviour indicates the entry and replication of the rabies virus in the brain. Eye conditions can also be seen, such as palsies (tremors) and the eyes dilating and constricting uncontrollably explaining the development of photophobia. Finally, lack of muscular coordination results in visible weakness of facial muscles and lack of urinary retention or extreme urinary retention can be seen. An interesting symptom seen in humans with paralytic rabies is hydrophobia, and is due to the paralysis of the larynx which causes pain

in the throat when the patient attempts to swallow. Seeing water encourages swallowing (the thought of drinking) therefore sufferers appear to be phobic of water, though they are not. A doctor can diagnose rabies from the Acute neurological phase, by that stage it is far too late to treat and the patient is made as comfortable as possible. Coma later ensues, followed by death, usually caused by respiratory paralysis. So how on earth do we go about treating or curing people of a disease which is seemingly impossible to diagnose? Advice for treating a bite wound suggests basic first aid, usually washing with antiseptic soap or alcohol,(that is, if you are aware you have been bitten), before going to hospital where, even in the UK which is ‘rabies free’, the patient will be treated with rabies immunoglobulin. These are monoclonal antibodies against rabies which are injected into the muscle surrounding the wound site, and in another muscle elsewhere. After this, a series of four doses of the rabies vaccine is given over a period of 1 month (called Post Exposure Prophylaxis). The vaccine itself is the same as the vaccine used to ‘immunise’ patients if they travel to countries where rabies is a risk those inoculated still need medical treatment if bitten by a rabid animal, however only 2 doses of the vaccine on day 0 and 3 are needed and no immunoglobulin is necessary. Though these preventative measures are perhaps reassuring, they won’t be much help if a patient is bitten and is not aware, and then proceeds to develop symptoms. All is not lost though as a new treatment called the Milwaukee Protocol is being trailed, which defies all belief that rabies is an incurable disease. Though it has saved only 3 of the 25 people tested, it shows hope to a future where rabies is not fatal, by putting the patient into a medically induced coma to reduce brain activity and therefore protect it from swelling and damage while the virus replicates in the brain. It is not fully known however how or why this treatment works. The first ever patient to have this treatment was in a coma for 6 days and hospitalised for a month but made a full recovery. The only lasting damage caused by the rabies virus is that she now lacks the ability to balance due to damage to the cerebellum, however her huge success in being cured of rabies for the first time provides hope for more successful treatments of this disease in the future. I hope that my brief delve into the world of rabies has shed some light into the intriguing biochemistry of this tiny virus. Perhaps its methods of accessing and hyjacking the body are no more amazing (and scary) than any other virus of its kind, however I do believe one thing, that as humans we are right to be terrified of its capabilities to infect and damage other organisms and indeed our own bodies, in such complex and indeed beautiful ways.

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HOW DID THE

LAMB SHIFT C H A N G E T H E WAY WE THINK ABOUT ELECTRODYNAMICS?

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Hi, I’m DA N P O O K . I have been intrigued with physics from a young age and this has led me to pursue the subject as a degree at university. I hope to go into research after I complete my degree to better my understanding of the complexities of the universe.

Electrodynamics refers to the interaction of electrical and magnetic phenomena over time. It is the branch of physics that examines the way that the electromagnetic force behaves and the interaction between moving electric charges, or electric currents, and magnetic fields. Classical electrodynamic theory explains many observations in the macroscopic world but the discovery of the Lamb Shift – an unexpected shift in the predicted energy levels of the hydrogen atom – fundamentally changed the way we think about electrodynamics. Lamb’s Shift could not be explained by classical theory and as a result new theories had to be developed in order to understand what was happening at an atomic level. In so doing we gained a much greater understanding of the quantum world and opened up a whole new field of study, often referred to as quantum electrodynamics.

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L A M B

S H I F T

DE VE LO PING MO DE RN Q UANT U M E LE CT RO DYNAMICS (Q E D)

T H E L A MB S H IF T In 1947 Willis Lamb and Robert Retherford carried out an experiment using microwave techniques to stimulate radiofrequency transitions between the energy levels in the hydrogen atom, specifically the 2S1/2 and the 2P1/2 levels. The microwaves allowed them to use lower frequencies than for optical transitions (stimulated using light) and so Doppler broadening could be ignored (Doppler broadening is proportional to frequency). In the experiment Lamb and Retherford observed an energy increase of about 1000MHz of the 2S1/2 level above the 2P1/2 level. This small energy difference became known as the Lamb shift. It describes a small difference in the energy of the 2S1/2 and 2P1/2 orbitals in the hydrogen atom, which were previously believed to be the same energy level as predicted by the Dirac equation and the Hydrogen Schrodinger equation. The Hydrogen Schrodinger equation stated that the energy levels of the hydrogen electron should only relate to the principle quantum number n. E X P L A I N I NG T H E L AMB S H I F T When Lamb discovered that the observed experimental values for the 2S1/2 and 2P1/2  orbitals did not match the predicted theoretical values a new way of looking at them was needed. In 1947 Hans Bethe was the first to explain the Lamb shift in the hydrogen spectrum and thus helped to lay the foundations for modern quantum electrodynamics. The breakthrough came at the Shelter Island Conference (New York) on the “Foundations of Quantum Mechanics” when leading physicists gathered to discuss the direction of post-war research. The Lamb shift was a major talking point with a number of explanations proposed. It was suggested by Oppenheimer and others that this was due to quantum fluctuations of the electromagnetic field, however pre-war quantum electrodynamics and the equations developed by Dirac gave absurd infinite values for this. The Lamb shift showed that the quantum interactions were both real and finite. “Renormalisation” was proposed as a solution but no-one could do the calculations. However, Hans Bethe managed to work it out on the train on the way home, arriving at a value of 1040MHz, very close to the experimental figure. The results of his work were published in the Physical Review in August 1947 in a paper that was only two pages long but which was extremely influential in shaping the future of quantum electrodynamics.

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Richard Feynman is probably the man most famously associated with the development of modern quantum electrodynamics (QED), receiving the Nobel Prize for his work in 1965. The Nobel citation specifically referred to the development of Feynman diagrams – graphical representations of the way in which subatomic particles behave. Feynman’s contribution provided an explanation in terms of the exchange forces between particles. The exchange forces are not only applied in quantum electrodynamics (the theory associated with the electromagnetic force at quantum levels) but also in understanding the nuclear weak force, the nuclear strong force and gravity at a quantum level. QED can be considered to be a subset of quantum mechanics which includes Einstein’s theory of special relativity. From this Richard Feynman built upon QED and in doing so created a way to visualise the interactions. There are two main pillars to Feynman’s work: his path integral formulation; and the Feynman diagrams. Both formulations consider every possible pathway from one state to the next and then add all the possibilities to give a sum of all possibilities. However, Feynman did not actually prove that the rules for his diagrams followed mathematically from the path integral formulation – this was done later by others. Similarly he could not formulate QED as a Feynman but his work did pave the way for others to do this using super-Feynman integrals. FE YNMAN DIAG RAMS

fig 1 The easiest way to represent QED is to visualise the interactions in the form of Feynman diagrams. These show how the virtual particles transmit energy and momentum between interacting particles. In a Feynman diagram time is on the Y axis and space on the X axis. One of the simplest of these diagrams is of two electrons scattering off each other. We can only measure the energy and momentum of

the electrons before and after the interaction because if we try to observe the actual reaction we would interfere with it and cause it to change. This is known as the bubble of ignorance. Hence the Feynman diagrams show all the possible reactions that theoretically can take place. In figure 1 a virtual photon is emitted from the electron on the right. This is then absorbed by the second electron causing a force as the electron has gained energy and momentum in line with that of the virtual photon. The electromagnetic force in figure 2 is due to a continuous exchange of virtual photons between the electrons:

fig 2

CO NCLU S IO N

The diagram on the right shows what can be observed and measured when examining the interaction between electrons (e-). The circle in the centre represents the bubble of ignorance however, the Feynman diagrams below allow us to explore what happens within the bubble of ignorance. The arrows that the interacting particles follow are not its trajectory but its progression through time (vertical axis) and space (horizontal axis). e

e

After

e

Before

e-

e

After

e

Before

? e

fig 3

? e

transferred. The virtual particle in this case is symbolised as a photon which is defined as an electromagnetic quantum of energy (i.e. a photon is not a particle but just energy hence it has no mass which allows it to travel at the speed of light). The photon is the virtual particle for the electromagnetic force, whereas the strong nuclear force and the weak nuclear force have different force carriers (virtual particles). Thanks to the work of Paul Dirac, Hans Bethe, Richard Feynman and many others, quantum electrodynamics analysis was finally able to explain the Lamb shift. In the hydrogen atom the electron was interacting with itself, causing an energy shift of about 0.1 Fermi. This interaction was caused by the proximity to the proton, effectively causing a smearing effect on the charge of the electron, hence its attraction to the proton is faintly weaker than it is normally. This explanation of the cause of the Lamb shift revolutionised particle physics and our understanding of the quantum world.

fig 4 There are several ways in which the particles can interact. figure 4 only shows two possibilities in order to illustrate the sort of interaction that could occur. In the diagrams the straight arrows represent the electron as it moves and the wavy line represents the energy and momentum passed between electrons (by virtual particles). The yellow balls show the point at which the energy and momentum is

In answer to the question of how the Lamb shift changed the way we think about electrodynamics, it quite simply revolutionised it. Physics moved from an understanding of classical electrodynamics based on the 18th and 19th Century work of Ampere, Coulomb, Maxwell, Lorentz and others, which was ultimately only able to provide an approximation of observations at the macroscopic level; to a much more fundamental understanding of electrodynamics rooted in quantum mechanics and the behaviour of subatomic particles and the associated virtual particles. The first half of the 20th Century saw the development of quantum theory but it was the observation of the Lamb shift in 1947 that demonstrated conclusively that the theoretical predictions made by Paul Dirac were real and finite. This completely changed our thinking, understanding and overall knowledge of the subject and thus has propelled us to even greater discoveries. The basic principles and concepts developed through the study of quantum electrodynamics was carried over into work on the nuclear strong force, the nuclear weak force and the gravitational force – in other words all four of the fundamental interactions observed in the world around us – as well as being a model for other quantum field theories. Feynman diagrams for example were subsequently used to advance knowledge of string theory and were extended topologically so that the lines become tubes to allow better modelling of complicated objects such as strings. Scientists like Richard Feynman also went on to speculate about the possible applications of this knowledge, proposing the future development of quantum computing and the manipulation of material properties at the nanoscale, or nanotechnology – concepts which have now become commonplace in the 21st Century and are starting to shape the technological advances we see around us. 17

Hi my name is DA N P U N TA N and I’m currently applying for medicine to study at university. Biology has always been one of my greatest interests and my love of the subject was what led me to want to become a doctor as it combined my favourite science and desire to want to work with people day to day. My Moncreiff Jones presentation was a thoroughly enjoyable and interesting project and really allowed me to look at a scientific challenge with greater depth than ever before!

ARE GENETICALLY MODIFIED MOSQUITOES THE FINAL SOLUTION TO MALARIA? The question I will be addressing in this Moncrieff Jones article is whether genetically modified mosquitoes are the final solution to malaria. Firstly I will give an overview of the disease and the problems it causes and then will move on to the multitude of different GM methods there are to try and combat malaria followed by the advantages of these methods and the problems that could arise.

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ARE GENETICALLY MODIFIED MOSQUITOES THE FINAL SOLUTION TO MALARIA?

Malaria is a disease caused by the parasitic unicellular microorganisms of Plasmodium and the vector responsible for passing it on is mosquitoes. When a female anopheles mosquito is laying eggs it requires extra protein which it acquires from sucking the blood of other animals, if the animal the mosquito feeds from is carrying a malaria parasite in its bloodstream then the mosquito will transfer the parasite to the blood stream of any other animal she feeds from thereby giving them malaria. This parasite then travels to the liver of the animal to mature eventually bursting out of the liver cells to enter red blood cells which it attacks and destroys leading to anaemia and oxygen deprivation of the vital organs like the brain and lungs. Damaged red blood cells also cause blockages in small blood vessels and if this happens in the brain, it results in a coma followed by death, which is a common mechanism for many malaria fatalities. Around 300 million people per year are infected with malaria, mostly in tropical areas with warm temperatures and stagnant water which are perfect conditions for mosquito larvae. Even today, a child dies in sub Saharan Africa from malaria every 30 seconds even though there is treatment available. According to the WHO, 627,000 people still die from the disease worldwide but some estimates say

as many as one million per year lose their lives to malaria, emphasising what a major problem this still is. One of the big issues is that there is still no practical or effective vaccine for malaria due to difficulties caused by the parasitic diversity and the fact that pre/post treatment is too expensive and not readily available for the majority of people who get the disease, resulting in huge numbers of deaths. On top of this the current prevention methods, like mosquitoes nets and draining swamps have helped to lower the levels of malaria cases but have not been able to provide the ultimate solution of a malaria free world. Furthermore, insecticides used to kill the mosquitoes like DDT have either had bad effects on the environment like bioaccumulation and killing of other animals or have become resisted by the mosquitoes over time. Even more worryingly, people have been found with plasmodium resistant to malaria drugs for example resistance to artemisinins, (the most important type of antimalarials) has been found in Thailand, Colombia, and Guinea making it once again a very hard disease to treat, this means a cheap, widespread 20

and viable solution like GM mosquitoes is desperately needed. The main aim of nearly all GM mosquito solutions is to target the female anopheles as they are the ones that act as a vector and without them not only would the population of mosquitoes drop massively but the disease transmission would be hugely reduced. However one of the main difficulties is ensuring the GM mosquitoes introduced not only deal with the issues of malaria but also are able to outcompete and drive the ‘wild’ mosquitoes to extinction otherwise the projects would be useless. One method being considered involves giving a gene to male mosquitoes so when they are released and mate with the wild females all the offspring produced would not survive to adulthood, preventing the next generation of mosquitoes and cutting down infection rates massively. By this could lead to the extinction of that type of mosquito and therefore have negative effects on the surrounding environment. Another effort is to create mosquitoes that are unable to carry the plasmodium parasite, again preventing the spread of malaria among humans. However by not completely wiping out the species it would reduce the effects on the surrounding ecosystem. One of the ways the scientists managed to achieve this was by creating GM mosquitoes that produced the SM1 peptide in the lumen of their gut where the parasite develops therefore preventing this development from occurring and in turn stopping the parasite migrating to the insect’s salivary gland meaning that plasmodium could no longer be passed between hosts. Johns Hopkins researchers experimented with mosquitoes genetically modified in this way and put them in a cage 50/50 with the wild type. Over time they observed the GM type taking over and wiping out the wild type since even though the genetic modification left them weaker than the wild type as the parasite couldn’t develop in their gut they were therefore able to out compete and dominate the cages. Researchers from Imperial College London have also come up with a promising option, not via reducing the population numbers but instead targeting the males of the population for modification. They used a homing endonuclease called I-PpoI which can cut DNA at specific sequences that are very rare in most genomes. The researchers found that by chance some essential genes on the X chromosome of Anopheles mosquito contained binding sites for I-PpoI meaning the endonuclease was able leave the X chromosomes non-functional. The expression of I-PpoI happens during the production of sperm and cuts up the X-chromosomes meaning only Y-chromosome carrying sperm are produced resulting in all the offspring being male since during fertilisation XY combination would be the only possibility. The researchers then had to overcome the problem that I-PpoI is a persistent protein that has a long half-life so

it proceeded after fertilisation to cut up the embryo’s X chromosome leading to a miscarriage of the offspring. They overcame this issue by decreasing the stability of the I-PpoI protein and its half-life so that it would still cut the X chromosome in sperm production but then not affect the X chromosomes in the embryos produced. In the Lab tests they then ran 95% of the offspring produced were male, massively skewing the male-female ratio and therefore reducing the number of vectors for malaria drastically. The researchers followed this strong result by putting these genetically modified male mosquitoes into 5 cages containing ‘wild’ populations and in 4 of the 5 cages the entire population was eliminated after six generations due to lack of females. This shows what a promising option this is as it is self-sustaining because the males were able to produce mostly male offspring which then went on like their fathers to produce mainly male offspring themselves meaning they only have to be introduced once which is essential if this is to ever work in a large scale project. However like the first option mentioned this will give rise to the drawbacks associated with wiping out the population for example the negative effect on the surrounding ecosystem as mosquitoes act as food sources, decomposers and even pollinators. There are a vast number of different routes genetic modification offers and many different parts of the DNA that can be changed and yet still solve the problems faced with dealing with malaria. This means that if one option fails there are many other alterations that can be made, therefore making GM mosquitoes a very flexible and practical option to take. There are many different options of the type of genetic modification that could be used and each has different methods in how to introduce the new DNA. The following is one common method that is used in options like making mosquitoes who’s offspring don’t survive to adulthood. It all starts with the mosquitoes tiny eggs of length 1mm where small amounts of DNA are injected into the end of the egg using a very fine needle under a very high powered microscope. The volume given is as little as ten thousand millionths of a litre per egg as this is all that is required to be taken up by the mosquito cells and incorporated in to its own genome to leave it

genetically modified. However this is only successful in a very few number of eggs leaving the majority of them dead In those that do survive the insertion of DNA an even smaller number have it occurring in their sperm or egg cells which is essential if the genetic modification is to take effect and be passed on to their offspring and provide a long term solution to malaria. The eggs that survive this then hatch and are reared to adulthood, before being bred and their offspring with the genetic modification are checked to see whether the sperm or the egg cells of the new generation were altered as

well. It can be quite hard to look for visible signs to see whether the mosquito has been altered so in many trials the insects are also injected with a florescent gene as well as the ‘anti-malaria’ one so that those where the genetic modification has been successful are easy to tell apart due to the fact they are glowing in the dark. Although the chances of getting a mosquito that has successfully accepted the new DNA and can produce offspring that have the same alteration is tiny and may take thousands of eggs and attempts, once one such insect is obtained, a whole new population can be created from it. With every project set out with the words ‘genetic modification’ there is always some resistance from the public due to the deep set fear some people have of this branch of science, that includes everything from arguing that God’s handiwork should not be altered to more scientific grounds that the long term effects of these changes are unknown and could come back years later to haunt us. For those worried about long term effects of GM introductions like this, there is no evidence at all that these mosquitoes will suddenly turn into mutant monsters. Although no one can be 100% sure what will happen 50 years from now I think the relatively small risk is outweighed by the millions of lives that will be saved if malaria is dealt with once and for all. On top of this before any of these mosquitoes would be released into the wild they would have to go through rigorous testing, including being released into a controlled environment to see what potential negative effects that may occur following their introduction so precautions can be taken to ensure the safety in the solution. Overall I believe that genetically modified mosquitoes are the most promising solution to dealing with malaria once and for all and to ultimately save millions of lives However the best routes are the ones that don’t wipe out the anopheles mosquito population to reduce the impact on the environment, yet still tackle the problem effectively. Therefore producing genetically modified mosquitoes that can no longer carry the plasmodium parasite presents itself to be the best method as it achieves all the aims and minimises the negative impacts. 21

HIV WHAT ARE WE DOING WRONG?

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Hi I’m R OBER T H I L L , I’ve been at Caterham since first form and I’ve always loved science. I decided to do a Moncrieff-Jones talk on HIV because I really wanted to not only try and find out why the disease is such a threat but also because I really wanted to look into the deep biochemistry of the disease. Next year I will be studying medicine at Exeter University.

HIV has been a well-known and constant threat to millions of lives ever since its discovery in the 1950s. The virus itself is thought to have come from a slightly different strand of virus found in chimpanzee called the simian immunodeficiency virus or SIV. This virus then found its way into the human blood stream, most probably via hunting, and managed to evolve inside the human blood into HIV in the late 1940s. We all know how much of a danger HIV holds, but why so? There are thousands of other viruses us humans have been easily able to maintain medically, yet HIV, eventually causing AIDS, manages to affect the lives of over 30million people every year, killing 1.7million. Is this virus unstoppable or are we doing something wrong?

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HIV: WHAT ARE WE DOING WRONG?

HOW DO E S H IV WO R K ? HIV will get into your bloodstream most often via intravenous drugs or sexual intercourse then it will attack your immune system, more specifically CD4 T cells. These cells are the only cells that HIV will attack as there is a specific glycoprotein on the surface of the T cell called CD4, this protein is the HIVs way into the cell. First off glycoprotein 120 on the HIV cell binds to the CD4 protein. This then allows glycoprotein 41 on the HIV cell to bind to CCR5 protein in the T cell membrane. The membranes can then fuse, releasing the nucleocapsid into the human cell.

For an HIV cell to be able to successfully reproduce it needs to make the host cell produce the HIV proteins, and for this to happen the virus needs a copy of DNA for the host cell to transcribe and translate into HIV proteins. However the HIV cell carries its nucleic acid in the form of ssRNA (Single stranded) and so needs to convert this into DNA, this process is called Reverse Transcription and it involves the enzyme reverse transcriptase. First of all a tRNA primer will bind to the primary binding site of the relatively short ssRNA. Then the RNA polymerase will join together DNA nucleotides, from the cytoplasm in the host cell, to the complimentary base pairs on the RNA to produce complimentary single stranded DNA (cssDNA). The RNA strand is then degraded by the RNAse enzyme allowing the second strand of DNA to bind to the first strand, with the help of the reverse transcriptase to produce double stranded DNA. This process is extremely inaccurate compared to most replications of nucleic acids; this means that rates of mutation are extremely high. Now the viral DNA must be inserted into to the human genome to be read. After reverse transcription occurs the DNA becomes the Pre-Integrating-Complex. This complex contains many proteins including capsids to protect the DNA. The DNA is cut at the 3’ ends, by the integrase enzyme, so that there are ‘flaps’ of three nucleotides at the 5’ ends of the DNA. The nucleocapsid containing the PIC degrades, allowing the PIC to move into the nucleus through nuclear pores. Once inside the nucleus the PIC binds 24

to the LEDGF/p75 protein which is bonded to DNA. From here integration can take place. The Integrase enzyme will then catalyse the attack of the 3’ end of the viral DNA to the 5’ end of the host DNA, forming a phosphodiester bond between them. Then the gaps must be repaired, this requires three enzymes, DNA polymerase, DNA ligase and nuclease. • DNA Polymerase: This fills in the gaps created by the flaps with DNA nucleotides • Nuclease: This removes the viral DNA flaps at the 5’ ends • DNA Ligase: This bonds together the 3’ host DNA and 5’ viral DNA with phosphodiester bonds.

The viral DNA is now integrated into the host DNA and will be read by the host enzymes via transcription and translation so that protein synthesis of HIV proteins can occur. Once these proteins have been synthesised they collect on the surface of the cell. Then by a process similar to Exocytosis the viruses leave the cell to infect other surrounding cells (See picture above). In fact the immune response that the HIV cells stimulate (via the antigens on the surface of the CD4 cell) actually attracts more CD4 cells to the surrounding area. H OW DO E S T H E DIS E AS E CAU S E AIDS? Once the HIV cells have reproduced enough the host CD4 cell will die. After a while this will affect the immune system, in fact this itself is AIDS. Officially the Acquired-Immunodeficiency-Syndrome is when there are less than 200CD4 cells pre micro litre of blood or when less than 14% of white blood cells are CD4 cells.

W HAT A RE W E DO I NG W R O N G? Diagonosis Diagnosis is a key part of helping to keep any disease under control. Any large problems in the process could result in HIV not being detected early, leading to higher death rates. HIV testing is difficult as the antibodies found in the blood that signify the virus appear up to 6 months after infection. Also 25% of cases are unknown, this is mainly because of the large number of rural cases of the disease that make diagnosis difficult. There is a monoclonal antibody test in which specific antibodies are used to detect the antibodies found in the blood, produced by the immune system, that signify an HIV infection. This test is extremely accurate, to about 99.99%, and can be done in 20 minutes to test rural areas. After a positive result is found the Western Blot test is used. This test involves detecting proteins in the CD4 cells. The cells are first cut open, spilling out the contents, and then the proteins found in the cell are separated from the organelles via ultracentrifugation. These proteins are then placed on a Sodium dodecyl sulphate gel, then a current is run through this gel causing the proteins to spread out according to charge, size and polarity. The distance moved by the proteins is recorded and compared to the distance moved by HIV proteins, this will then show whether there are HIV proteins inside the human cell or not. Problems One of the main problems with testing for HIV is over testing of low risk groups; this can then lead to a high percentage of false positives. For example take a population of 10,000 young women (20-29) in a developed country, they are a low risk group as they all have protected sex and do not use intravenous drugs, meaning the prevalence of HIV in them is 0.001%. In many countries the government could ask for all these women to be tested. This can result in a problem, see below. This diagram shows how only half of the people who test positive actually have HIV; this can cause large levels of unnecessary stress for the patient. In fact in the 1980s in Canada it resulted in many suicides as the government forced a nationwide test even though the virus had only just reached the country. What’s worse is that still today 25% of doctors refuse the idea of false positives and so patients are informed false information. T R E AT ME N T Nucleoside-Reverse-Transcriptase-Inhibitors (NRTIs) These drugs inhibit Reverse transcriptase from working and so stop HIV from producing DNA. They do this using nucleosides, these are just like nucleotides except they have a different group attached instead of a phosphate group meaning the chain of nucleotides in DNA stops.

However due to the high rates of mutation in the process of RNA there are now high levels of resistance to these types of drugs (such as AZT). This is a huge problem and means that more drugs must be produced and distributed rapidly, before a resistant strain occurs. This problem has also occurred for other treatments such as non-nucleoside inhibitors and Integrase inhibitors (these inhibit integrase, the enzyme involved in inhibition). To actually find a cure for HIV is so difficult, the virus is extremely small and can remain dormant inside CD4 cells for years. Homeopathic remedies are also used by some to try and treat HIV. These remedies are the idea that diluted toxin that produces similar symptoms to the disease itself can help to cure the disease. They hold a very small amount of scientific backing but can be used to produce a placebo effect. The only way that these can produce a problem for patients is when the patient is miss-sold Homeopathy as a cure with scientific fact. In some cases in less regulated developing countries people are sold these drugs as alternatives to western medicine by fraud companies. This can seriously affect the chances of survival for a patient. Moreover in many cases people can only afford these remedies as treatment and so have no choice. PRE VE NT IO N Preventing HIV is actually fairly simple; its main mode of transmission is via unprotected sex and so simply the use of safe sex would dramatically help reduce the rates. However the practice of safe sex is very unfavourable in many countries, in Swaziland for example, where HIV is 25% prevalent, condoms are hardly ever used even though they are given out for free. Even more surprisingly 25% of gay or bisexual men in the USA do not use condoms, increasing the prevalence of HIV even in developed countries. CO NCLU S IO N In conclusion we have seen how HIV is a truly dangerous disease, its rates of mutation are specifically potent as they leave many drugs useless, and further the misleading sale of homeopathic remedies means some people have to replace their scientifically backed medicine for alternative choices. We also saw how over testing of low risk groups of HIV can lead to a wastage of time and money and unnecessary anxiety for some patients, perhaps more testing time should be focused on those groups most at risk. However the most simple and devastating problem made by us is the lack of safe sex in both developing and developed countries. It is such an easy switch for people to make and there needs to be a real push to convince people to use protection in sex more as it would drastically help to reduce spread of HIV infection. 25

SOME OF THE T E AC H E R S ’ FAVO U R I T E P R AC T I C A L S

M I SS FA R ME R : Cloud chamber capturing fundamental particles “It is my favourite experiment because we get to play with dry ice!!”

MR MANSELL: Jacob’s ladder “Jacob’s ladder is certainly the most dangerous and scary class practical I will ever do!”

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M R S S E A L : Muscle contraction experiment “It is simply amazing The muscle is there, on the table, contracting in front of your eyes!”

MR MA RLOW: Genetically modified bacteria

MI SS P I L K I N GTO N : Rainbow flame throwing

“Glowing E. coli… They’re just so cool!

“I am just obsessed with metals and pretty colors!”

MR Q UIN TON: Limpet investigation at 1 o’clock in the morning “It is simply incredible to observe such an interesting

MR H I C KS : Ruben’s tube standing wave flame experiment “It is just amazing to see all the students’ eyes widen!”

organism, perceived by many as simple and unexciting, behave in a way that is rarely seen.

The fact that every single limpet went back

to the same place it started in shows how complex this amazing animal really is”

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Hi, my name is TOM L A N D and this year I was honoured to give the first talk of the lower sixth on the Origin of Life, a truly inspirational subject. For my A-Levels I am studying geography, chemistry and the subject closest to my heart, biology. I can only look forward to the year as the Moncrieff society goes from strength to strength.

THE ORIGI

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N OF LIFE One hundred thousand years ago a handful of Homo sapiens inhabited our planet. Half a billion years ago, a small fish was our ancestor. But if we jump back even further into the younger years of planet Earth - two billion years ago - only microbes existed.

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T H E

A

O R I G I N

ll life that you see today is related to these small single celled organisms, from the tiniest sulphur digesting bacterium to the might of the blue whale, and of course, humans. In 1859 Charles Darwin came up with the view that everything alive on Earth today is related to each other to some extent. All life works along the same structure of metabolic pathways; how the cell grows, how its energy is stored and what proteins are made of and when. But the question that he wondered about most is where did that first cell come from, where did it live and how did it live? Before we examine each theory we must actually distinguish the difference between Life and Being Alive. Life is the ability that sets apart animals and plants from an inanimate object. Whilst Being Alive means that the organism is considered to have a purpose and it carries it out through the seven life processes (Movement, Respiration, Sensitivity, Growth, Reproduction, Excretion and Nutrition). Because of this a simple virus, like a T2 bacteriophage is considered to have Life but not be Alive. Currently there are two main theories on how the tiny unicellular organism came to be on planet Earth; Slime theory and Space theory. Slime theory is that life started on our planet and has always stayed here, created by chemical reactions in a primordial soup. Space theory on the other hand is the story of how terrestrial life could have perhaps originated from a distant planet much similar to our own.

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O F

S LIME T H E O RY In order to make a cell you need certain molecules and elements. A vital part of the cell is the phospholipid bilayer. This is a membrane made of a double layer of lipid molecules that forms a waterproof bag separating the internal environment of the cell from its habitat. But a bilayer alone does not make up a cell, there are also organelles. The origin of these is speculated to be remnants from invasive organisms (like the Mitochondria) now working in a symbiotic relationship with the cell. One of the ways we can work out how they could have formed is through TopDown investigation, reviewing our evidence and basing theories off that. The first piece of evidence is the Stromatolites of Western Australia. These shapes would have been created when cyanobacteria deposited waste minerals in layers. These are all but fossils now, but have been preserved for 3.5 billion years. Back when they were alive they would have lived in a hot sheltered lagoon, provided with the minerals needed for growth. However in Greenland fossil filament bacteria were found 3.85 billion years old, a whole three hundred million years before the Stromatolites of Australia were alive. If these are indeed as old as we believe them to be then the Earth has been inhabited for 85% of its 4.55 billion year history. If we now look from a Bottom-Up perspective, creating theory off ideas that can be hard to prove, it seems that spontaneous generation is a very popular idea, the idea that life formed itself. However the problem we

L I F E

now face is that if you leave a sterile place sterile, like a young planet, the most likely outcome is that it stays sterile. This was reinforced when in a paper in the late 19th century Lord Kelvin stated; “Dead matter cannot become alive matter�. But there is a good chance they were wrong. Darwin came up with the idea that life came about in a sheltered pond, but perhaps it was something much larger that was needed, a sea. In 1953 Harold Urey and Stanley Miller carried out an experiment attempting to recreate the beginning of life. They put gases into a closed system with water and passed a charge through it, replicating the early atmosphere and weather. When left for two weeks the water had a red colour, this was due to amino acids, the building blocks of protein. Had they created life? Amino acids are now quite easy to make and they do not mean life. The atmosphere they chose was also wrong, on early Earth the composition of the atmosphere changed relatively regularly. Perhaps though, people were making assumptions based on our own highly complex DNA, after all the first cell was a lipid around a protein, incredibly simple compared to today’s cells. It was this simple organism that managed to survive and produce life as we know today. It would have taken luck, power on a planetary scale and extraordinary amounts of time, but it got there eventually. Some people however believe that it would be almost impossible for life to have formed on Earth due to our temperamental atmosphere that changed every 30,000 years or the lack of a certain molecule. These people think that life came from beyond Earth.

F RO M SPAC E Another entirely different theory is based around the fact that life could have come from a long way across the galaxy, in the form of a bacterial spore, in a state of hibernation waiting for contact with water so it would be able to rejuvenate itself and begin reproducing again. This is but a theory, the question is, is such a journey possible? In 1977 the Viking lander touched down on Mars’ surface, one of the missions it was there to carry out was the testing of Mars for any signs of life. First NASA tested the soil for signs of water, however the red dust on Mars is so dry it makes the Saharan dunes look like a swamp. The atmosphere was also tested, but it was only equivalent to Earth’s at a height of 35km, what we would consider the very edge of space. The search was considered a failure, no life could live on Mars. However completely unexpectedly, tiny microorganisms from Earth that had been picked up during launch were surviving remarkably well for somewhere with nearly no atmosphere. On Earth, further tests were carried out to see how resilient these microorganisms actually were in space. Japan mimicked a 250 year space exposure on a variety of extremo-

philes (organisms that can withstand the extremities presented to it). The conditions were -196 degrees centigrade, nearly a full vacuum and incredible amount of radiation. Amazingly 85% of organisms survived. The British then carried out a more realistic experiment of the effects of exposure to 2500 years of starlight on an organism. 99.9% of the microorganisms did not survive the tests. The 0.1% that survived however would not die, the radiation was further increased and still the resilient little organisms would not die. They were un-killable. Perhaps these little microorganisms did not come from across the galaxy, maybe they came from a much nearer neighbour: Mars. However if you wanted a tiny microorganism to planet hop a significantly sized impact would be needed to throw enough debris and rock into the thin atmosphere. This would mean that 10,000 units of G-force and temperatures of several thousand degrees would have to be experienced. Then only 7.5% of the ejected rocks will reach Earth, a third of these will arrive within ten million years. Although the chance is small it is entirely possible. Ten million years is a long time, could a bacterial spore survive this long? Bacterial spores have been found on Earth in the permafrost that are 3 million

years old, as well as in a bee entombed in amber, 40 million years old. Most extraordinary however is that these spores in the bee have been bought back and are dividing in a lab. But why has Mars been chosen as such a likely source of terrestrial life? Rock samples suggest that Mars once had an atmosphere like Earth’s, the features of the Martian landscape almost exactly replicate the twisting motion of rivers and seas. Mars also had tectonics, the super volcano Olympus Mons is a good example of this. If a Martian microbe were to have landed on Earth it would have found it very habitable, with the hot pools and superheated vents in the seas. There are a number of other factors that single Mars out as well; it is smaller and would have posed less of a target to passing meteorites, it cooled 4.5 billion years faster than Earth and therefore formed its atmosphere in 10 million years rather than the 2 billion years of formation it took on Earth. So it is very possible that life did in fact thrive on Mars and in the last 4 billion years of Earths’ existence that life would have almost definitely arrived here. That means that you, and I and everything around us right now could have descended from Martians. 31

SKIN GRAFTING: GOING BEYOND THE COSMETICS OF SURGERY Human skin is a highly specialised organ. Its integrity is essential given its role as a protective barrier between our organs and the external environment. It must constantly adapt to fit our needs whether we are growing, repairing or changing our surroundings.

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Hi, I’m EM I LY YAT ES and I am hoping to study Medicine at Oxford. This year I am aiming to do well in my AS level examinations in Biology, Chemistry, Physics and A level Maths. I chose to research skin grafting as it has helped many people overcome injuries that they would otherwise have died from whilst also being an extremely interesting and useful treatment for the future.

The dermis is the next layer down and contains collagen and elastin fibres which give your skin its flexibility and strength. It also houses all the accessory organs of the skin; sweat glands for temperature regulation and sebaceous glands which produce sebum, an oil that keeps the skin soft and supports the waterproofing of the skin surface. There are also hair follicles which affect our appearance and blood vessels which provide the skin with nutrients and have the ability to dilate or constrict aiding the body’s temperature control. Lastly, nerves are present providing sensation of pain, touch, pressure and temperature.

The anatomy of the skin is important to understanding wound healing and grafting.There are 3 main layers to the skin; the relatively thin, tough outer layer called the epidermis, the thicker middle layer, called the dermis and the deepest layer, the hypodermis.

The epidermis is a dynamic structure made up of different layers of cells which become increasingly flattened and full of keratin as they move towards the skin surface. The keratin produced in epidermal cells is an important material to the function of the skin as it is a water insoluble fibrous protein. It therefore provides a relatively waterproof layer and protects against mechanical injury, chemical hazards and bacterial invasion. The lowest layer of the epidermis is the stratum basale and we call the outer layers the apical layers. The basale layer arranges itself into folds called rete pegs. These extend into the dermis and provide an anchor for the epidermis to hold on to. When people lack these rete pegs it can cause a skin condition where the epidermis no longer remains attached to the dermis, called epidermolysis bullosa.

The hypodermis is the deeper layer and this houses fat which helps insulate the body, serves as energy source and cushions against trauma. The process by which the skin renews itself is called Epidermal Regeneration. In this process, the stratum basale cells divide by mitosis. As new cells in this layer form, they are unable to all squeeze into the basale layer. Therefore, one of the daughter cells produced is forced into the layers above while the other remains in the basale layer. As the cells migrate upwards, their shape flattens and they become increasingly keratinised and in this process replace the dead skin cells lost at the surface through washing and other daily activities. Eventually a collection of cells flake off and are lost to the skin surface. This whole process take 4 to 6 weeks. 33

SKIN GRAFTING: GOING BEYOND THE COSMETICS OF SURGERY

Partial thickness burns extend into the dermis; however the accessory organs remain. These organs are surrounded by dermal cells which divide and eventually, if the burn is simple enough, will fill the wound. These can also be very painful if the nerve receptors are still intact. Full thickness burns extend through the entire dermis, all the way to hypodermis. Because the burn extends through the whole of the dermis, all of the nerves are destroyed or damaged and, despite the severity of the burn, the patient may not feel pain. A skin graft is usually essential and can sometimes almost fully heal the burn, but if the burn is widespread, it can be fatal. There are different ways in which we naturally heal from wounds such as cuts and burns.

In superficial injuries where only the epidermal layer is damaged but the stratum basale layer is intact, there is no bleeding and repair starts in the stratum basale layer. These cells divide and as they proliferate, they migrate upward to fill the gap above. When an injury extends into the dermis, through the epidermis, bleeding occurs and an inflammatory response begins. Clotting begins and a scab forms temporally restoring the integrity of the epidermis. Cells of the stratum basale divide by mitosis and migrate to the edges of the scab. At the same time, the dermis is repaired by activity of the stem cells on the outer regions of the wound. These cells produce collagenous fibres and ground substance, holding the skin cells together. Then blood vessels grow in, restoring circulation. Damaged sweat and sebaceous glands, hair follicles, muscle cells and nerves are seldom repaired but are usually replaced by fibrous tissue. In the end, this process produces an inflexible, fibrous scar. If the dermis is severely damaged, it will not repair. Burns are injuries to the skin from heat, electricity, chemicals, friction or radiation. At temperatures greater than 44°C, proteins begin to lose their 3 D shape (their tertiary structure) and denature resulting in cell damage and death. These can be classified and treated in accordance with their depth. Superficial burns affect only the epidermal layer and are red without blisters. They usually heal well, with no scarring, but are very painful. 34

The ladder here shows methods of repairing wounds depending on the severity of the injury. Secondary intention is where the wound heals naturally without medical attention. Primary closure is used when the wound edges can be sutured without undue tension. Skin grafting is used when the wound is too large to suture and a piece of skin must be taken from elsewhere. Flaps are used for larger wounds where healthy skin is moved from nearby into the wound site. And finally, tissue transfers are used when the wound extends further than the hypodermis as their blood supply is incorporated during surgery. We can classify skin grafts in two main ways; the type of donor and the thickness of graft. First is by the type of donor. An autograft is the most common form of skin grafting. A section of healthy skin is taken from the patient’s own body and therefore it has absolutely no risk of rejection. This makes up 90% of all skin grafts used today. An allograft is when the donor skin is taken from a different human being and a xenograft is when the donor skin is of a different species.

Allografts and xenografts are not widely used unless there is no other option as there is a high risk of rejection. Rejection of a graft can be especially serious. Not only can it cause a degradation of the donor skin, but it can also cause a worsening of the original wound. Skin substitutes are a more modern option being researched at present to heal skin wounds For example, cultured skin cells. This involves taking a biopsy of the patient’s skin cells, then growing them in a medium of hormones and other chemicals to produce a larger area of skin. Very fragile sheets of skin are produced which unfortunately are prone to infection and the whole process takes weeks (too long to prevent the scarring of the patient). Alternatives such as stem cell therapy are being developed where stem cell DNA is manipulated to stimulate the cells to differentiate into new skin cells in a lab and then are transplanted onto the patient. This has great potential, but further advancements are required for use as a viable alternative to current practices. Another way that we can classify skin grafts is by their thickness. Partial thickness grafts include all the epidermis but only part of the dermis. These are taken from the donor site using a dermatome to gain correct thickness of skin. If a large amount of skin is required the skin can then be passed through a meshing machine, which punches tiny holes into it. This allows the grafts to be stretched over a larger area whilst also allowing blood to permeate through the skin, speeding up the healing period. The main advantages of split thickness grafts is that they have little restriction on the area they can cover and that when taken, the donor site heals fairly quickly with minimal scarring. On the other hand, split thickness grafts will contract as they are incorporated into

the wound and will not grow as the patient grows. They may also have a shiny appearance that might make it seem unnatural. Full thickness grafts are taken using a scalpel and are made up of the skin down to the hypodermis. They retain their preoperative colour, texture and thickness, experience little contraction and grow with the patient. However, they are restricted to small, well vascularised wounds and they cannot be taken without scarring the donor site. These advantages and disadvantages are how doctors decide which thickness of graft to take. After the surgery for a full thickness skin graft, the patients must stay in the hospital for monitoring while the graft is incorporated into the wound site. Once the graft is placed on the wound, it gains nutrition by absorbing blood plasma which is secreted into the graft from the wound bed. After a couple of days the wound bed tissue produces vascular buds and blood vessels begin to grow into the graft. The vascular buds join with the pre-existing blood vessels already inside the graft and this revascularisation process takes around 7 days. A dressing is placed over the graft during this period in order to prevent it from moving and a blood clot forming underneath. The dressing is also soaked in antiseptic to reduce the risk of infection. Research is currently being carried out into molecular biology, wound healing and immunology to improve the skin substitutes on offer. An interesting area of this research is synthetic skin, making a membrane that functions as a complex skin structure. I believe that we will be using this synthetic skin not only to replace the skin of severely injured patients but also to dress and treat normal, everyday wounds. Hopefully, within the next few years, skin grafting will be a much more common and regular part of daily life. 35

BENZ ENE

CARBON

HYDROGEN

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Hi, my name is A N T HON Y BASTON, I am in Lower Sixth and I have been at Caterham for my entire life. I have always known that I wanted to do something scientific with my life as opposed to writing poetry all day. Moncrieff Jones is one of the ways I challenge myself, stretching my abilities beyond the syllabus and spending hours over mind bending concepts, and scouring the internet to its deepest depths for the right pictures.

A R O M AT I C CHEMISTRY What does it mean? Well in 1855 a man by the name of August Wilhelm Hofmann coined the term “aromatic” as he was studying a species of chemical very similar to benzene, the molecule which is going to be the ornament on the mantelpiece of this article. Benzene contains six carbon atoms and six hydrogen atoms. Now try picturing what shape this molecule might take, are you there yet? Well if you thought of anything vaguely circle-like as opposed to straight lined, you are doing very well. The question of benzene’s shape vexed even the most advanced scientists of the day. See they were used to the fact that carbon forms four bonds and so they couldn’t quite figure out what it looked like.

The Kekule formula, the one on the far right, was not entirely accurate as it suggests that there are three double bonds (133 picometres long) and three single bonds (154 pm long), which is not actually the case. We now know that benzene consists of a sigma bonded framework, a bunch of electron clouds called sigma orbitals that overlap with the two other orbitals either side, and more importantly, a pi system.

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A R O M A T I C

Pi systems are where pi orbitals (another type of electron cloud that surrounds an atom) are filled with one electron (a pi orbital can hold up to two) and the other pi orbitals next to them are also filled with one electron and are equally spaced. So with benzene we get a completely regular hexagon in which the bond angles are all 120 degrees and the distance between the nuclei of each atom is constant (140 pm to be exact!). For those intrigued, the carbon atoms are sigma-pi2 (sp two not sp squared) hybridized which is a nice simple way of describing where we can expect to find the electrons when carbon is bonded in certain ways.

C H E M I S T R Y

Cyclo-octa-tetra-ene

So now we might come to the conclusion that we could shove an extra carbon or two, along with a couple of hydrogens, into the ring and this pi system might still be intact. Ah, this is where it gets awkward. See a dude named Erich Huckle, German I think, came up with this rule that says whether or not molecules can have a pi system and therefore become aromatic. By the way I ought to quickly define what it means for a molecule to be aromatic. An aromatic molecule must be: a) regular, so in other words a symmetrical polygon, b) cyclical and, given that it is regular, it needs therefore to be planar. Finally, c) every atom in this ring needs to be able to contribute something, such as a lone pair of electrons or in benzene’s case, an unpaired electron in a pi orbital. So now back to Huckel’ rule. Huckel proved, via quantum mechanical calculations that I dare not delve into, that the number of electrons that could get involved in a pi system follows 4n+2 where n is a whole number. We can now look at a molecule like cyclo-octa-tetra-ene (circle-eight carbons-four-double bonds) and say “aha!” since it has eight pi electrons (it has eight carbon atoms remember, so one electron from each) it cannot be aromatic as it will not follow Huckel’s rule. Try it: 4n+2 = 8, so 4n = 6, so n = 6/4, n = 1.5, which is not a whole number, so it won’t work.

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There is another uncanny thing about these pi systems. Using average bond enthalpies, i.e. the energy required to break bonds forcing the electrons back to where they came from, we find that benzene’s pi system actually requires more energy than we expect to break apart. This difference is called resonance energy. So, how does it work? Well if we examine cyclohexatriene (a molecule that doesn’t exist by the way, it is what Kekule thought benzene would be, in other words six carbons joined cyclically by alternating double and single bonds, and of course six hydrogens) then the heat energy given off when this theoretical molecule is hydrogenated is 360 kJ mol1. But breaking the “double bonds” in benzene and adding hydrogen only gives off 210 kJ mol-1. So an extra 150 kJ mol-1 has been used to break the pi system! This illustrates the stabilizing effect it has on the molecule.

fig 1 Now what are the common reactions of benzene? Well using some simple physics, like repels like, we can figure out that benzene reacts with mostly positive molecules. This is because the first thing any substance will come into contact with is the big negative pi system.

Benzene therefore reacts with electrophiles, electron pair acceptors. One typical reaction is sulfonation because sulfuric acid can (in a way) decompose yielding sulfur trioxide. Now although the molecule is neutral, the electron withdrawing effect of the oxygens yields a slight positive charge at the sulfur, enough to make it an electrophile and so react with benzene, pushing off hydrogen (see fig 1). Moreover this pushing off of the hydrogen is actually quite cool. We get what is known in the business as a sigma complex. An electron is quite literally plucked out of the pi system and the carbon that has snatched this electron is now sp3 hybridized, taking a typical tetrahedral shape. So a bond is formed between the electrophile that is reacting and the carbon is still bonded to a hydrogen. But the electrophile was positively charge right? So where has that positive charge gone? Well the pi system delocalizes it; take a look at the diagram below to see how (curly arrows indicate the movement of a pair of electrons). The positive charge is at the adjacent carbon where the electron was plucked out initially and then it moves around as it attracts electrons to it.

Now if we already have an extra group on benzene then we can get different products. As you can see with fig 2 there are three principle places for the electrophile to latch onto, ortho (carbons 2 and 6), meta (carbons 3 and 5) and para (carbon 4). Now given that there are 2 lots of ortho and meta and one lot of para the product ratio should be 2:2:1 (o:m:p) right? Wrong! The type of group plays a huge, gigantic, enormous, stupendous role in determining where the electrophile goes. If there is a slight negative charge next to the ring then it can get involved with the delocalisation of the positive charge when the sigma complex is generated. So with methylbenzene, by looking at We fig 3 we can see that the ortho and para complexes are the predominant products. Note there is less of para because: a) there is only one para position vs two ortho positions and b) because of steric effects (which is why the percentage of para is not exactly half the percentage of ortho).

Eventually the hydrogen ion will be plucked off the ring by the HSO4 anion made earlier and the electron will return to the ring.

fig 3

fig 2

This differing product composition happens because with the ortho and para complexes the positive charge lands on the carbon of the methyl group, which has a slight negative charge, so the methyl group can get involved in the delocalisation of the positive charge and hence the complex forms faster. Overall aromatic chemistry is a pretty cool topic. We have barely scratched the surface but already we have discovered that we can get different bonding places on benzene and also come across sigma complexes. Looking back it seems that Kekule almost got benzene right and hats off to him for doing so, but now it is time to go and make more discoveries. For example what happens when there are two pi systems joined together? Or maybe we should give our brains a rest for the time being‌

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My name is N I K I TA KO MA R OV and I am a Russian student here at Caterham School. I have been boarding since as long as I remember, and I have been sincerely in love with science long before that. I am very interested in the quirkiest depths of Biochemistry, Genetics and Medicine. I am, myself, an aspiring medic and I hope, someday, to leave a positive mark on our world.

WHAT HAPPENED TO BRUCE BANNER? From the 1884 story: “The Artificial Man. A Semi-Scientific Story” by Don Quichotte to the Teenage Mutant Ninja Turtles, people of all levels of intelligence have been fascinated by the idea of mutants and their superhuman powers. Bruce Banner, a fictional physicist studying Gamma radiation was exposed to enough radiation to be considered an “unhealthy dose”, which led to changes in his body, resulting in him becoming none other than ‘The Hulk’ (although, mostly when he is angry). But we all know that this is only fiction and can never happen in real life, right?

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W H AT H A P P E N E D T O B R U C E B A N N E R ?

Firstly, let’s discuss the concept of radiation. Radiation, by definition, is simply the propagation of waves and subatomic particles through space. However, we are here to talk about the fun kind of radiation. The type of radiation that is most commonly thought of in this sense is known as Ionising Radiation, and it consists of a subset of the Electromagnetic waves (Ultraviolet, X-ray and Gamma Ray radiation), as well as particle radiation - alpha, beta and Neutron. Ultraviolet radiation cannot ionise (affect the valence electrons resulting in the formation of an ion) all elements, as it has relatively low energy, unlike X and Gamma rays, which have the power to ionise any known element as well as the power to generally make you have a bad day. Alpha radiation is a particle consisting of two neutrons and two protons, which is highly reactive and does not travel very far at all through any medium, quickly pulling two electrons to form a helium atom and positive ions. Beta radiation is an energised electron, which can travel further than alpha particles, but quickly wants to be paired, creating a negative ion. Neutron radiation is not directly ionising, as it is simply a free neutron, but collides with nuclei of molecules, giving them energy which is released as Gamma radiation, or sticks to a nucleus to form an isotope, which is usually unstable, such as Carbon-13. So now that we are experts in radiation, we can discuss the effects of radiation on our bodies and, most importantly - DNA. Some think that life is simply DNA creating a host casing in order to recreate itself, but I’m a tiny bit less cynical than that. All we know is that DNA is the molecule of life, consisting of 4 bases: Adenine, Guanine, Cytosine and Thymine (fig. 1,2), which are in a sequence that codes for the creation of amino acids, polypeptide chains and eventually proteins. Each individual has his, or her, own genetic code (unless they are an identical twin). Any change to the genetic code is called a mutation. Mutations can occur for a plethora of reasons, from lifestyle, such as smoking; background radiation, errors during replication or, most commonly, the sun. One of the ways in which the sun emits energy is in the form of ultraviolet radiation (UV), a form of ionising radiation as discussed earlier. UV and other ionising radiation affect DNA in two ways: direct and indirect damage.

fig.2

Direct damage is the effect on DNA directly, i.e. affecting either the sugar backbone or the nucleic bases directly, either way changing the shape and function of the genetic material. Ionising radiation can break the phosphodiester bond which joins nucleotides, thus rupturing the DNA chain, however, the most common occurrence in the realm of direct DNA damage is formation of cyclobutane pyrimidine dimers, such as thymine dimers or cytosine-thymine dimers. This happens due to the breaking of the pi-bond between carbons in positions 5-6, making them reactive and leading to joining of two adjacent bases. This can be imagined with the following image:



fig.1 42

As is evident, the formation of pyrimidine dimers disrupts the shape of DNA and prevents complementary base pairing. This can have a variety of effects, and if this happens many times in a single cell, it can lead to errors during replication and transcription, leading to disrupted function or death of the cell.

Indirect DNA damage is a lot more common, simply due to the abundance of water surrounding DNA and nuclei. Indirect DNA damage by ionising radiation is pretty much what it says on the tin - damage to DNA caused by ionising radiation but does not involve a direct interaction between DNA and ionising photons. Instead, radiation affects water molecules as shown in the following mechanism:

fig.3 The formation of H+ ions, as well as hydroxyl radicals, can cause many a problem in the body. One of the ways in which this happens is through deamination of cytosine. Deamination of cytosine forms Uracil, which is structurally very similar to thymine, except for a methyl group on the carbon in the 5th position (see fig.1). Due to the structural similarity to Thymine, Uracil binds with Adenine in RNA, unlike Cytosine which binds with Guanine. Thus, an affected strand with a Uracil base will replicate to form a new, mutated, strand, as shown in fig.4:

fig.4 The new strand has a different base sequence and thus it will code for a different chain of amino acids, which will lead to the production of different proteins. Considering that this is only one, albeit the most common, way that DNA can be damaged, we can clearly deduce that these mutations can happen all the time within our cells. But does a single mutation mean that you are either a superhero, mutant or a cancer patient? Of course not (most of the time). Firstly, only around 1.5% of DNA codes for protein making, and over 50% of the DNA is non-coding, repetitive sequences. Additionally, it can take hundreds

of simultaneous mutations to cause cancer. For example, Colon cancer requires over 1,300 gene mutations to occur. These factors combined make the chance of cancer occurring less than 1 in 100 trillion. This means that it does still happen, and it is likely that one of your cells is currently cancerous; however the body is very effective at identifying and destroying mutated cells, but that’s a topic for another day. So let’s bring this all back to the original topic. Let us assume that Dr Bruce Banner, the Hulk by any other name, is on our Earth, right now. What is the idea behind that? Can a human transfer into a huge, green monster, really be real? Some scientific evidence seems to point that way. Let us look at some hypothetical scenarios. These are a chain of events that would have to happen in order for us to see a Hulk with our own eyes. Each link must exist in order for the final picture to come to reality.  LINK 1 Gamma radiation affects each cell in exactly the same way. The radiation that Dr Banner was exposed to must have had the same effect on each cell in his body. LINK 2 A new gene must be created. The radiation must have caused each of his cells to develop a gene for hypertrophy of cells like observed in some extremophiles such as the tardigrade. This is physical growth of the cell instead of replication; can happen more quickly and efficiently than mitosis. Hypertrophy induces growth of cells instead of their replication; thus reducing the amount of energy required for growth of the body. LINK 3 A hormone-induced activation and deactivation of the gene for hypertrophy. We know that Bruce Banner becomes the Hulk when he is angry or frightened, thus a release of a hormone such as adrenaline must induce the change. The mutations must be such that Adrenaline causes the activation of the gene for hypertrophy. This must also be a continuous process; i.e that while adrenaline is present in the blood, the gene is activated; and as soon as it stops being produced, the gene is deactivated, and cells shrink back to their normal size. You might think, “but this will make him increase in size when he is angry; but it doesn’t make him green”. You are almost correct. What would make the hulk green? Exactly the same thing that makes bruises a green-yellow tint - a molecule called Biliverdin. Biliverdin is a metabolite of Haemoglobin, produced when red blood cells are metabolised into by-products within bruises, and is a green colour. This would happen in The Hulk due to the stress that the skin cells would be put under when the transformation happens. The surface cells would bruise and it so happens that red blood cells are metabolised quickly in order for biliverdin to be formed. And there we have it, our transforming, massive, green being that transforms when he is angry or scared. Seems quite simple, doesn’t it?

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Hi! I am EVA WA N G and am currently in the Lower Sixth. There are two things that really fascinate me in my life – Baking and Science! I am especially interested in cell biology and neuroscience, and I am planning to do Biomedical Science at university. I really enjoyed my Moncrieff-Jones talk because of the interesting questions and all the positive feedback I had from my audience. It was great fun!

THE POWER OF SNAKE

VENOM As predators, snakes are missing a few key attributes. They have no legs to chase down their prey, no paws to knock down quarry, and no claws to hold their victims. But none of these deficiencies matter much, because evolution has handed snakes the ultimate weapon: venom.

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THE POWER OF SNAKE VENOM Snake venom is highly modified saliva containing a complex mixture of enzymes, peptides and proteins of low molecular weight. It mainly facilitates prey capture and defence and there are 4 types of venoms: neurotoxins, cardiotoxins, cytotoxins and hemotoxins.

Neurotoxic venom targets the victim's nervous system and works by affecting its activities, especiallyin the absence of neurotoxins, those at the synapse, leading to either paralysis or muscle spasm. When an action potential reaches the end of the axon, the membrane of the synaptic knob becomes depolarised. This causes the voltage-gated calcium ion channels to open, causing Ca2+ ions to diffuse into the cell down their concentration gradient. These Ca2+ ions bind to sensor proteins (synaptotagmin) on synaptic vesicles, triggering vesicle fusion with the plasma membrane and subsequent neurotransmitter release from the presynaptic neurone into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and bind to the receptors in the post-synaptic membrane, causing chemical-gated ion channels to open. The flow of ions into the post-synaptic neurone causes depolarisation and if the threshold level is reached an action potential is triggered in the post-synaptic neurone. Neurotoxins can impair neuronal transmission at any point, either presynaptic or post-synaptic. The neuromuscular junction connects the nervous system to the muscular system via synapses between nerve fibres and muscle fibres. β-neurotoxins affect the Axon terminal

Muscle fibre

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presynaptic regions of the neuromuscular junction, and mainly act by inhibiting the release of neurotransmitters, such as acetylcholine, into the synaptic cleft. This creates a neuromuscular blockade which prevents signalling molecules from reaching their postsynaptic target receptors. In doing so, chemical-gated ion channels on the sarcolemma will not open and so there will not be a depolarisation of the muscle fibre. Muscle contraction will not occur and hence the victim of these snakebite suffer from muscle paralysis as well as profound weakness. Îą-neurotoxins act by binding to the postsynaptic acetylcholine receptors as competitive antagonists. This prevents interaction between the acetylcholine released by the presynaptic terminal and the receptors on the postsynaptic cell. In effect, the opening of sodium channels associated with these acetylcholine receptors is prohibited, again resulting in a neuromuscular blockade, causing paralysis and numbness in the muscles involved in the affected junctions. One symptom of a venomous snake bite is breathing difficulty, which is caused by the paralysis of the respiratory muscles. This can eventually lead to loss of breath and therefore death. Acetylcholinesterase, AChE, is located on the post-synaptic membrane, and terminates the signal transmission by hydrolysing ACh into acetic acid and choline. Fasciculins attack cholinergic neurones by destroying acetylcholinesterase (AChE). ACh therefore cannot be broken down and stays in the receptor. This causes tetany (involuntary muscle contraction), which can lead to death. Dendrotoxins work by blocking voltage-gated potassium (K+) channels in the axon membrane. The K+ channels control the excitability of nerves and muscles by controlling the resting membrane potential and by re-polarising the membrane during action potentials. By blocking them, dendrotoxins prolong the duration of action potentials and increase acetylcholine release at the neuromuscular junction, which may result in muscle hyper-excitability and convulsive symptoms. Cardiotoxins actually function in a similar way as neurotoxins - the difference is that they are specifically toxic to the heart. Various cardiotoxins are able to 1) block voltage-gated potassium (K+) channels, resulting in prolonged action potential, or 2) inhibit the calciuminduced calcium release from the sarcoplasmic reticulum and 3) increase the threshold level, making a stimulation above this value more difficult and hence depolarisation more difficult. This prevents heart muscle contraction. In effect, these toxins may either cause the heart to beat irregularly or to stop beating, causing death. Cytotoxins cause effects that are mainly localised around the site of envenomation and they are specifically toxic to cells. Snake venoms are rich sources of phospholipase A2(PLA2), which are enzymes that release fatty acids from the second carbon group of glycerol. It hydrolyses the bond releasing arachidonic acid and lysophospholipids. Due to the increased presence and activity of PLA2 resulting from a snake bite, arachidonic acid is released from the phospholipid membrane disproportionately. Under modification by enzymes such as cyclooxygenase and lipooxygenase, arachidonic acid is converted into active compounds called eicosanoids, which include various inflammatory mediators. For instance, prostaglandins and thromboxane. Many Spitting Cobras and members of the Adder Family contain cytotoxic venoms. Obvious signs of inflammation - pain and

swelling - occur almost immediately after the bite from a cytotoxic snake and gradually become worse in the next few hours. The exact signs of inflammation have been known as: calor (warmth), dolor (pain), tumor (swelling) and rubor (redness), and the eicosanoids are involved with each of these signs. However, arachidonic acid is not solely responsible for the damage caused. On the introduction of the snake venom, lysophospholipids are also produced as a product of the reaction of phospholipase A2. They are powerful surfactants capable of disrupting the distinct interface between hydrophobic and hydrophobic systems that is to say the plasma membrane in the human body. Like all typical detergents, lysophospholipids have a water soluble hydrophilic head and an oil soluble hydrophobic tail. These properties allow detergents to insert into and then dispense membrane - the membrane is solubilised and becomes more fluid and permeable. Finally, hemotoxic snake venom is responsible for disrupting the circulatory system, causing potentially severe damage to internal organs and other body tissue. This is extremely painful and can also eventually lead to necrosis. Hemolysis is the rupturing of erythrocytes (red blood cells) and the release of their contents into the blood plasma. This process is very similar to the one we have seen with cytotoxins, apart from the specificity to the red blood cells. In addition to the direct lytic action of phospholipase A2, there is also indirect lytic action of venoms as a two-step process: hydrolysis of exogenous lecithin to lysolecithin (lysophosphatidylcholines) and fatty acids, followed by lysis of the erythrocytes by these lecithin split products. The lytic effect of lysolecithin is thought to be exerted through the membrane cholesterol, either by the formation of a cholesterol-lysolecithin complex, or by displacement of cholesterol from the membrane. Cholesterol is an essential component in the plasma membrane, which regulates the integrity of the cell membrane. Internal bleeding is a loss of blood that occurs from the vascular system into a body cavity or space, and is often caused by hemorrhagic snake venom metalloproteinase. This induces internal haemorrhage by directly affecting mostly capillaries and small blood vessels. Although the exact mechanism is not known, it is suggested that hemorrhagic enzymes cleave key peptide bonds of basement membrane components and cause its proteolytic destruction, thereby affecting the interaction between basement membrane and endothelial cells. Capillary walls are weakened and gaps are formed in endothelial cells through which extravasation occurs.

Finally, various components of the snake venom disrupt blood coagulation, which is again very lethal. Snake venoms contain proteins which either have anti-coagulating or procoagulating properties, with them all affecting the level of clotting factors in the blood, especially prothrombin. The previous one aids the effect of haemorrhaging, preventing the formation of blood clot and thus repair of the ruptured blood vessels. The latter encourages blood coagulation and is capable of rapidly turning flowing blood into masses of blood clots throughout the body, thus cutting off blood circulation. It is hard to imagine, that such lethal and deadly snake venom, designed for killing lives, can actually be exploited and used to save many more thousands of lives. Indeed, whole venom exerts a devastating effect on the snake's victims, but each extracted individual protein unit of the venom can actually turn out to be very medically valuable. For instance, medicines derived from hemotoxins are used to treat heart attacks and blood disorders. ACE inhibitor was the very first drug derived from snake venom toxin, isolated from a Brazilian pit viper, used to treat high blood pressure. Others include eptifibatide and tirofiban, both of which are used as treatments for minor heart attacks or severe chest pain (angina). These medicines work by helping to prevent the formation of blood clots. Some haemotoxins are also used in medical diagnosis. The Textarin–Ecarin clotting test uses snake venom to determine the presence of anticoagulants in the blood that are produced by auto-immune diseases, such as lupus. Neurotoxic snake venoms are also potentially very good pain relievers. Known for its notorious effect on the blockade of neuronal signals, mambalgin-1 and -2 isolated from the venom of the black mamba's, are found to eliminate pain with as much potency as morphine. Finally, research has shown that snake venoms might even become the future cure of cancer. As mentioned before, specific compounds in snake venom can disrupt endothelial cells, which line the inner surface of blood vessels. Rupturing of these blood vessels will prevent or at least interfere with blood flow to the tumour, effectively leading to a deprivation of nutrients, starving the tumour cells to death. The advantage of these venom derived toxins is that they seem to act only on specific types of cells. Chemotherapy and many other drug treatments do not distinguish between tumour cells and other healthy cells, causing debilitating side effects. 47

GUEST SPEAKER BRUCE GRIFFIN GIVES US A FANTASTIC CHRISTMAS LECTURE ON OBESITY AND HEART DISEASE Hot on the heals of Moncrieff-Jones’ last guest speaker Alexis Bailey, December 2014 saw Professor Bruce Griffin give the annual Christmas Moncrieff-Jones lecture on the science behind obesity and heart disease. His remarkably in-depth approach would not have looked out of place in any university lecture. A testament to the society’s commitment to science was the great turnout, which packed out the Wilberforce Hall for this prestigious event. His captivating lecture was well received by an audience of varying scientific interest, yet was not only understood by all, but thoroughly enjoyed, as shown by the high standard of questions which followed the presentation.

This year the society was also lucky enough to be visited by MichaelBonsall, Professor of mathematical biology at St Peter’s college Oxford. His presentation to the upper sixth students on the use of maths to model the spread of diseases such as Ebola was not only incredibly relevant but also a fascinating topic.

BRITISH BIOLOGY OLYMPIAD This year 20 keen Upper sixth biologists volunteered to take part in the British Biology Olympiad, which involved 2 hours of extreme bio multiple choice questions from all areas of the subject. The Caterham students performed very well with 4 bronzes, 4 silver and 4 gold awards including Robbie Hill and Ollie Hull scoring in the top 2% of the country. This high score means that they qualify for the next round and get the opportunity to compete for a position in the UK Biology team. Congratulations to all participants and good luck to the lower sixth for next year. 48

MORE SCIENCE AT CATERHAM‌ As well as the Moncrieff-Jones Society, the Science Department is always buzzing with activity! From pigs’ brain dissections to observing limpets at two in the morning on a beach in Wales, there is so much cool science organised by staff and students alike. Here is a selection of articles written by the students themselves about the multitude of exciting clubs and trips that they have been involved with over the past year. We hope it will give you an insight into the wonderful world that is the Caterham Science Department.

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C L U B S

ANATOMY CLUB One of the newest additions to the science department is the redevelopment of an old club. In 2014 a society was introduced that let students of all ages learn about a certain species and then allowed them to dissect that organism. This year it was brought back by two lower sixth students (Thomas Land and Emily Yates) with new ideas for new dissections. The first organism to be explored was the Dogfish, a relative of the shark with a fascinating cartilage skeleton. It was unlike any other dissection the students had done and went down extremely well. Tom and Emily have a lot more new and exciting ideas that they are eager to bring to the club.

PROBLEM SOLVING It may seem odd however I like to think that you can only get a true sense of what goes on in the science department at lunch if you have a look in the classroom recycling bins. This cannot be truer than after a thrilling Monday lunch of problem solving in the physics lab. You will find catapults made from rubber bands and coffee stirrers, towers and bridges made of paper and even electrical circuits created using only aluminium foil and sellotape. At 1:00 the teams are set a challenge; “create something that will launch a tea bag as far as possible down the physics corridor” “Build the highest tower made only from straws and paper” and at 1:30 the designs are tested and the winning team is chosen.This year the top problem solvers in each age category competed for the school in SATRO’s annual competition held at St Bedes school in Redhill. The 6th form team managed a strong third place whilst the 4th year team destroyed the opposition coming first and qualifying for the finals.

CHEMISTRY EXTENSION CLUB This year saw the start of a new chemistry club for A level chemists. Every Tuesday lunchtime, a group of enthusiastic U6th chemists met to discuss some challenging Chemistry Olympiad questions. The topics covered ranged from chirality to tricky mole calculations to deducing organic mechanisms. Although the questions were tough, they were related to A level

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topics. Therefore, we all enjoyed putting our knowledge to the test and trying to stretch it that bit further. Hopefully this will have been good practice for the real Olympiad this Spring in which we are hoping for some excellent results like last year. A big thank you must go to Mrs Howgego and Mr Keyworth for giving up their lunchtimes to help to run the sessions.

ASTRONOMY CLUB

ROBOTICS CLUB Using a credit card-sized Raspberry Pi microcomputer, students in the Caterham Robotics Club worked in small groups to create a motor robot. Assembling the robot proved to be a challenge due to the care and precision needed in using a hot soldering iron to carefully attach wires connected to a pair of motor wheels onto the corresponding input/output pins on the Pi. Using the programming language Python, the teams successfully completed a fully-functioning robot capable of movement using wireless keyboard control. Some managed to take a step further by installing an ultrasonic sensor, enabling the robot to turn when an incoming obstacle was detected.

I do astronomy GCSE and I think I was right to choose it because the course is really fun! The theoretical work is difficult, but very interesting, and the coursework is very engaging because we get to use professional equipment, like telescopes. One of my favourite aspects of the course is that we get access to a robotic telescope, so we can order images of different objects in space and they can be taken especially for us. Astronomy is quite a big commitment, the sessions happen once a week and we have to give up extra time for homework and coursework. However, I still think it is worth it because space is awesome

ROCKETRY CLUB The Caterham Rocketry club has proven to be a great success and a fine addition to the physics department’s emporium of available clubs. This year saw the launch of a variety of rockets; from high velocity light rockets, to high-powered multistage behemoths, all constructed feverishly by students of a large range of ages across the school. These launches taught us about a lot of different areas within physics from drag that acts across rigid bodies and how this changes as velocity increases to the mechanics of a rocket engine. I look forward to another year of rocketry society in which I am sure the rockets built will be bigger and go higher than ever before! 51

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SUMMER SCIENCE EXHIBITION 2014 ROYAL SOCIETY

ST PETER’S COLLEGE, OXFORD TRIP On Wednesday 2 July, five Lower Sixth science students set off on a train to the University of Oxford ... at 6.24am! Tired but excited about the day ahead, we arrived at Oxford and separated to go to our relevant subject specific talks with the admissions tutors. These included a “mock interview” with a current student that was particularly useful as we were able to experience what the dreaded interviews might really be like and what sort of questions they are likely to ask. After having a couple of hours to look around some Colleges of our choice in the afternoon, we regrouped at St Peter’s College with Mr Quinton and Mr Keyworth. We then met with an admissions tutor at the College who was able to resolve some of our unanswered questions from the day. After a quick dinner, we performed our pre-prepared talks to the teachers, our peers, as well as Glen Gowers and Ross Hendron (Old Caterhamians who are currently studying Biochemistry and Biology at Oxford respectively). Each of us received a grilling from the panel and had the opportunity to ask each other some challenging questions. We stayed overnight at the College and ate a delicious breakfast in the College hall on Thursday morning. After this, we had a fascinating talk about the human brain from Professor Jan Schnupp, a professor in Neuroscience and a tutor for medicine at St Peter’s. Throughout the rest of the morning we did a few more activities to get us thinking about the Oxbridge process a bit more before heading off again in the afternoon for a final look around the city including a visit to Blackwell’s bookshop. It was both a thoroughly enjoyable and useful trip and on behalf of all of us that went, I would like to say a massive thank you to Mr Quinton and Mr Keyworth for organising it.

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In the final week of term before the summer holidays forty Lower Sixth scientists made their way up to London to visit the prestigious Summer Science Exhibition organised by the Royal Society. The event is an annual display of the most exciting cutting-edge science and technology in the UK. “It was incredible to be surrounded by so many world experts and what’s more they all were interested in chatting with you!” The highlights included learning about leaf cutter ants and how their symbiotic relationship with bacteria might save us from the resistant superbug crisis, understanding how they found the Higgs Boson and getting to grips with the science behind growing a tooth replacement from human stem cells. The trip was a fantastic opportunity to get an idea about how the science that we learn in class is being used to make important discoveries about our world.

UPPER SIXTH STUDENTS HEAR PROFESSOR PETER HIGGS TALK AT THE SCIENCE MUSEUM On the 12 November Upper Sixth Physics students visited the Science Museum to attend the opening of the exhibition ‘Collider’, which provides an insight into the workings of the world’s largest experiment, the Large Hadron Collider. The students were thrilled that the event was attended by the Nobel Prize winning

physicist Professor Peter Higgs who took a question and answer session. Topics ranged from his introduction to science to the process of predicting the existence of the elusive Higgs Boson. It was a very informative day, and a fantastic opportunity to hear from one of the scientific greats of the 20th century.

CAMBER SANDS At the end of the summer term, all the Lower Sixth biologists descended upon the sunny beach at Camber Sands with quadrats and tape measures in hand. Having quickly purchased some necessary refreshments (cheesy chips!) we headed out into the sand dunes to start learning about succession. We started off by lying down on the dunes to experience the harsh conditions pioneer organisms have to face. As we moved further and further back from the sea, crawling through the dense sea buckthorn, the conditions became a lot less harsh and we began to see greater diversity in the species of plants and animals present. Having quickly eaten lunch, we started the main event of the day - a 200m long belt transect from the start of the dune, right back to the road, collecting data about the species present at regular intervals, which we would later plot on a kite diagram at school. After a day of hard core Biology, the braver amongst us went for a swim in the sea before returning to school. We’d like to say a huge thank you to all the teachers for organising such a great day. 53

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VISIT TO THE ROYAL COLLEGE OF ANAESTHETISTS In March a group of potential medical students were given the opportunity to attend the Sixth Form Open Day at the Royal College of Anaesthetists in London. The day began with an interesting talk about the history of anaesthetics, from merely a drop of wine through to ether and on to anaesthetics as we know them today. We then rotated around stations including information about careers in the military, airway management, intensive care (complete with simulator) and resuscitation. We were lucky enough to attend a workshop which gave us a real hands on experience of the work of a doctor and even got to see some of the equipment used by anaesthetists. A talk by two medical students also gave us tips for the application process to medical school. The day gave us all a better understanding of what a career in medicine entails and how varied it can be. We would like to thank Mrs Seal for arranging the trip for us and for all the support she has given us in our medical school applications.

BRAIN SYMPOSIUM Last Spring, a squad of keen L6th Biologists attended a Brain symposium at Sutton High school. There were 3 main sections to the day: An Introduction to the brain, The process of sight and Abnormalities, and all the talks were delivered by top professors. After each talk, we broke off into small discussion groups to debate the content of the talk and come up with any questions we wanted to ask. On returning to the hall, a spokesperson from each group went to the front to ask the speaker the questions over the microphone. It was a thoroughly informative day, greatly enjoyed by all who attended.

PHYSICS IN ACTION On 5 December just shy of 60 Lower Sixth students had the opportunity to hear fantastic talks about Physics in Action in cutting edge developments from superconductivity research to LCD displays. Simon Singh was a highlight with the scope of his Big Bang presentation, as was Martin Archer, with his impressive fusion of his backgrounds as both a radio DJ on Kiss FM and as a space plasma physicist. His introduction of concepts from dark flow to electron wave functions through DJ techniques was striking, but perhaps did not have quite the wow factor of Andrew Steele’s tabletop Mag- Lev train, or Ben Hanson’s automated heartbeat. A memorable day out – I am sure many of the Lower Sixth will be seeing Physics all around them through the Christmas holiday. 54

UPPER SIXTH BIOLOGY TRIP TO DOWN HOUSE Charles Robert Darwin is an inspiration! He laid the foundations for the theory of evolution and transformed the way we think about the natural world. Seeing the house that he lived in for 40 years and wondering around his stunning gardens was an amazing experience that truly brought the many textbook descriptions of him to life. It was at the beginning of September that we piled into a bus and travelled the relatively short 10-mile journey to the famous house in rural Kent. The fantastic tour included Darwin’s old study filled with ancient bones, fossils and books, the wellknown Sand walk that he strolled along every day and of course the café. It definitely wasn’t there in the 1950s but did make a delicious carrot cake! All in all it was a fascinating excursion. 55

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DALE FORT

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2014 In the final week of our summer holidays, on Tuesday 26th August, 54 students along with 2 teachers embarked on the 5-day long learning extravaganza that is the Dale Fort Biology Field Trip. After the long journey to Pembrokeshire, Wales, we immediately met our tutors, Steve and Kim, and got stuck in with some Ecology, looking at rough periwinkles on two different shores. The following days were spent doing a belt transect up Jetty Beach and studying succession at the Salt Marsh. The Salt Marsh has a so-called “pit of ultimate despondency” where two students got very stuck! These evenings were spent learning the A level statistical tests until 10pm.

The next morning began with the 5km Great

Salt Marsh Run ending in a steep uphill climb back to the Centre, with Ross Powell, Louise Gardner and Cesci Adams joint winning amongst the boys and girls respectively. During the day, we studied the population of sandhoppers and diversity in both rock pools and an irrigation pond, but the real excitement came that night; having marked limpets in the evening, at 1:30am “The Limpet Gang” set out to investigate the animal’s nighttime behavior. These creatures, which we assumed were stationary, had in fact moved vast distances and we even observed one cross a large gap between two rocks!

The week had all been in preparation for the

Saturday, when we did independent group projects. These projects ranged from studies of crabs to waterboatmen and involved various techniques, including whisking to create water movement. On the final morning, we rode on the rib to collect plankton samples. We were then able to see some of the incredible zooplankton and phytoplankton under the microscope before making the journey home. Overall, it was a thoroughly enjoyable week and we all learnt a great deal. As Mr. Quinton put it, “Now that’s rock and roll!”

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Parents come back to school for a Breaking Bad themed science evening On Friday 13th March, the science department opened up to parents for a one night extravaganza of lessons so they could experience what we do every day. The main format of the evening was 3 lessons in Biology, Chemistry and Physics delivered by the respective heads of department followed by a short test to see how much they had learnt and a finale chemistry show. However, the night had a slight twist as it was “Breaking Bad� themed. The parents entered to the theme tune with Heisenberg himself greeting them at the door and were presented with a meth lab made by 8 of the U6th scientists, fully equipped with crystal (sugar) meth and scientists dressed in yellow hazard suits with gas masks and goggles. Having split the parents into 3 groups, they were given a whistle stop tour of the eye, flame tests and quantum physics before being wowed by Mr Hawkridge and Miss Pilkington as they performed an exhilarating Chemistry show. Many thanks must go to all those involved in organising what was a truly fantastic evening.

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PAST MONCREI FF TOPI CS

GENE REGULATION APOPTOSIS THE UNCERTAINTY PRINCIPLE

CARBON CAPTURE AND STORAGE COLLAGEN

SAVANT SYNDROME

KETOSIS TOPSPIN: AERODYNAMICS FROM LUPIS TO FAMILIARIS HOW WE MAKE SENSE OF SOUND

TIME DILATION

NEUROSCIENCE

THE HUMAN PAPILLOMAVIRUS DARK ENERGY ENZYME INHIBITION PLANT REPRODUCTION IS THE WAR ON CANCER UNWINNABLE? DEFENCE AGAINST DISEASE IN PLANTS

HOW ON EARTH DO YOU GET TO THE MOON? THE BIOCHEMISTRY OF TASTE

CROHN’S DISEASE

REGENERATION

HYPOTHYROIDISM AND HYPERTHYROIDISM

DEALING WITH DISEASE DISPERSION THE FOUR FUNDAMENTAL FORCES GM CROPS THE CHEMICAL CLOCK OPTICAL ISOMERISM

THE MITOCHONDRIAL GENOME

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ORIGIN OF THE HEARTBEAT

GIRLS KNOW BESTEVOLUTION BY SEXUAL SELECTION

STEM CELLS

ANGELMAN SYNDROME

TYPE 1 DIABETES

BUILDING BLOCKS: THE AMIDE GROUP

PAST MONCRIEFF PRESIDENTS, VICE-PRESIDENTS AND ENDORSERS

2007-2008 President Luke Bashford (University College London) Vice-President Edd Simpson (University of Leeds) 2008-2009 President Tonya Semyachkova (Balliol College, Oxford) Vice-President Raphael Zimmermann (University East Anglia) 2009-2010 President Alex Hinkson (St Catherine’s College, Oxford) Vice-President Alexander Clark (Robinson College, Cambridge) 2010-2011 President Oliver Claydon (Gonville and Caius College, Cambridge) Vice-President Sally Ko (Imperial College London) 2011-2012 President Glen-Oliver Gowers (University College, Oxford) Vice-President Ross-William Hendron (St Peter’s College, Oxford) 2012-2013 President Rachel Wright (St Peter’s College, Oxford) Vice-President David Gardner (University of Nottingham) 2013-2014 President Holly Hendron (St Peter’s College, Oxford) Vice-President Anne-Marie Baston (Magdalen College, Oxford) PAST AND PRESENT MONCREIFF-JONES SOCIETY ENDORSERS Dr Jan Schnupp, Lecturer in Department of Physiology, Anatomy and Genetics at University of Oxford Dr Bruce Griffin, professor at Surrey University, specialising in lipid metabolism, nutritional biochemistry and cardiovascular disease Dr Simon Singh, popular author and science writer, including the book “Trick or Treatment?” Dr Mark Wormald, Tutor of Biochemistry at Oxford University

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SOCIETY SUMMARY BY DAN QUINTON The Moncrieff-Jones Society is a very special group and is very dear to my heart. We live in an extraordinary technological age, brought about by Scientists. A world of Twitter and s ound bites. A world where ill-informed people will give their opinion without really understanding the facts. Science often requires a knowledge of a vast array of facts before you can begin to understand and certainly before you can give a worthwhile opinion. It requires incredible discipline yet is also, at the cutting edge, incredibly creative. The brave students giving lectures at the Society’s fortnightly meetings receive no help from staff, and are cross questioned by the audience for around 40 minutes – they must teach themselves a vast array of facts and then understand them if they are to survive a Moncrieff-Jones Lecture! MJS must be the ultimate in terms of independent learning – a skill the top universities are looking for in their undergraduates. The MJS talks have reached an extraordinarily high standard and there are always more students wanting to do MJS talks than there are weeks available in the term. I cannot thank Ollie and Cesci enough for all they have done this year. They have worked tirelessly to organise and promote the society and to maintain its position as the most popular and prestigious society in the school.

John Jones founded the Moncrieff Society in 1967, as a ‘liberal science society’ – its mission to address a gap in the range of 6th form societies. Sir Alan Moncrieff was an eminent Old Caterhamian in the medical field and John Jones was a Head of Chemistry at Caterham School for many years. When I took over the Society I decided it should be renamed the Moncrieff-Jones Society in the year that John Jones retired, as a way of recognising the massive contribution John made to Science at Caterham School. True to the liberal spirit in which MJS was formed, meetings over the years have included the reading of scenes from Brecht’s ‘Life of Galileo’, pictures depicting the beginning of life at hydrothermal vents, and even an entertainment based on scientific themes. Individuals have spoken on interests as diverse as cell biology and thermodynamics, and intellectual tours de force have ranged from the quantum world of the very small to the vast sphere of astrophysics. We live in an age of science. There has never been a greater time to study science. With the massive problems the world faces, it is through science that we look for solutions. It is a testimony to the input of so many generations of Caterhamians that the society survives and thrives some 45 years on. Dan Quinton is Head of Science at Caterham school

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Caterham School, Harestone Valley Road, Caterham Surrey CR3 6YA Telephone: 01883 343028 Email: enquiries@caterhamschool.co.uk Web: www.caterhamschool.co.uk