a36851 haberaske scope issuu 2010

The Haberdashers’ Aske’s Boys’ SchoolButterfly Lane, Elstree, Borehamwood, Hertfordshire WD6 3AF

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The Scientific Journal of the Haberdashers’ Aske’s Boys’ School

Scope 2009/10SCOPESCOPE

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Dear Reader,

Having been first published 20 years ago, this anniversary edition of Scope aims to contain articles aboutsubjects at the forefront of man’s scientific understanding. On the content front we have attempted to ad-dress the issue of a fair balance of articles to represent more adequately the full range of scientific interestsat Haberdashers’. On the literary front we have further pushed the boundaries with a new ‘Review’ Section.This new section provides an opportunity for discussion on the implications and nature of science, as wellas interviews with prominent scientists. I am grateful to the Science Society for working with us to providean unparalleled calibre of scientists to feature in Scope.

Indeed this new exploration of the very nature of science is of fundamental importance to those concernedwith it. To borrow a phrase from the evolutionary biologist Richard Dawkins, the power of science lies in itsability to relieve “the anaesthetic of familiarity”, its innate curiosity, its power to remind us to disengagewith existing in a sedative of dull ordinariness, and to gently poke us out of a slumber of ignorance. In un-derstanding science we might also wonder how far science has come throughout history. One of the bestanalogies to keep us in perspective of man’s endeavours is to imagine the history of life on our planet asrepresented by the span of one’s arms; from the origin of life to the present day. From one end to your op-posing shoulder, all that existed was bacteria. Invertebrates (which still constitute 95% of all life forms pres-ent today), eventually emerge at approximately your elbow furthest from the origin. Move along. Thefingernail of your middle finger represents roughly the proportion of time that Homo sapiens has inhabitedthe planet. And finally, what of recorded human history? Wiped off in a nail filing. I think that puts into per-spective the time frame and transcendental quality that science operates in. It is this very style and natureof debate and question I hope you will find herein.

I am indebted to my team who have provided outstanding literature for the magazine, as well as lively de-bate and strong opinions about the construction of the magazine. It is a testimony to them that we havemanaged to move into full colour print and perfect binding, giving full justification to the high quality of thearticles, without an increase in our budget. Lastly, I would like to thank Mr. Delpech, whose encyclopaedicknowledge, careful guidance and unfailing support have ensured the success of this magazine for manyyears.

Enjoy the magazine,

Casey SwernerChief Editor of Scope.

Scope 2009/10 Scope Team

The Scope 2009/10 Team

Casey Swerner - Chief Editor

Raj S Dattani - Senior Editor Neeloy Banerjee - Senior Editor Johan Bastianpillai - Senior Editor

Wajid Malik - Editor Wei-Ying Chen - EditorSahil Patel - Editor Karthigan Mayooranathan - Editor

Vishal Amin - EditorNicholas Parker - Editor Adrian Ko - Technical Advisor

Mr. Roger Delpech - Master i/c Scope

Ameya Tripathi - Editor

Bhavesh Gopal - Senior Editor

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CONTENTSPHYSICAL SCIENCES

The Riemann Hypothesis.....................55

The Role of Computational Automationin Science.............................................77

Visual Effects Engineering...................99

Superconductors: Supermaterial of theFuture?...............................................1111

Einstein’s Annus Mirabilis..................1122

Quantum Of Solace: Heisenburg’sUncertainty Principle................................................1144

Atmosphere: Earth’s Great Defence...1155

The Path Towards Finding a MagneticMonopole...........................................1177

Chemiluminescence...........................1188

REVIEW

The Rowboat’s Keeling......................2200

An Interview With Simon Baron-Cohen.................................................2233

An Interview with Michael Lexton.....2244

Entropy & The Theory Of Evolution....2266

An Interview With Aubrey de Grey......2288

BIOLOGICALSCIENCESAbiogenesis: The Origin Of Life..........3311

Evolution Of The Nervous System......3333

Alzheimer’s: Hope At Last?................3344

Cocaine Dependance: Implicications &Treatments.........................................3355

The Role of Pharmacogenetics InModern Medicine...............................3377

Cancer Therapy: Treatment & TreatmentRealities.............................................3399

The Application Of Nanotechnology InMedicine.............................................4411

Heart Transplants: End Of An Era?.....4422

Haemophilia A: How Successfull HasThe Genetic Engineering ofRecombinant Factor VII Been?...........4444

Swine Flu Epidemiology &Pathology............................................4466

Ozone Therapy In Dentistry................4488

Bibliography.......................................5500

A36851 HaberAske Scope TEXT AW:A31822 HaberAske Skylark 12/3/10 10:35

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The Riemann HypothesisAndrew Yiu

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In chemistry, we are taught that all matter ismade up of atoms. If you continuously cutsomething into smaller and smaller pieces, youwould eventually end up at the atomic level. Inthis context, prime numbers are the atoms ofmaths. In other words, all positive wholeintegers greater than 1 can be expressed as aproduct of prime numbers. Suppose this claimis false. In this case, there must be a smallestnumber that cannot be expressed as a productof primes. Let this number be N. Also, since Ncannot be a prime number (as it would just bea single product of that prime), it can beexpressed as a product of two non-primenumbers. Hence:

N=ab (where a and b are both non-primes)

N is the smallest number that cannot beexpressed as a product of primes, so a and bcan be written as a product of primes. Suppose

a has prime factors p1p2···pm, and b has

prime factors q1q2···qn, then N can be

expressed as the product p1p2···pm q1q2···qn,which is in fact a product of prime numbers.There is a contradiction and therefore the claimis true.

Not only this, but the Fundamental Theorem ofArithmetic also states that an integer greaterthan 1 can be written as a unique product ofprimes i.e. there can only be one set of primesthat multiply to make a certain number. So ifindividual prime numbers are like atoms,products of prime numbers are like strands ofDNA, with each number having a distinctstrand that makes it different from the rest.

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A very important use of prime numbers is inthe world of internet security. Public KeyCryptography is a popular method of shieldingcommunication from third-parties by the use ofan asymmetric key system.

The basic idea is that a user has a public keyand a private key. The public key is publishedin a directory of other network users and canbe accessed by anyone. The user keeps theprivate key secret. In order to send a messageto another network user safely, you would takehis/her public key and encrypt the message.When it is sent, it would be almost useless toany third-parties, as having the encryptingpublic key would be of no use. To read themessage, a decrypting key is necessary andthis is only in the hands of the receiver. To helpvisualize this, imagine two people called Aliceand Bob. Alice gives out open padlocks, forwhich only she has the key. Bob wants to senda confidential letter to Alice but knows that

anyone along the way can open it and lookinside. Therefore, he takes one of the openpadlocks and locks a box with the letter inside.Now no-one can open it until the package getsto Alice. Of course, the padlock could be pickedbut this is made very difficult to the extentwhere it is virtually impossible to do in a shortamount of time. This is where primes comeinto the story.

Firstly, to create the public key, two randomlarge primes, p and q (at least 100 digitseach), are multiplied together to create n. Thetotient of n (Written as φ(n))is a functiondefined as the number of positive integers lessthan or equal to n, which only share a commonfactor of 1 (also known as coprimes), e.g. Thetotient of 10 is 4 (1, 3, 7, 9). This is calculatedby the product of (p-1) and (q-1). Then e ischosen as an integer between 1 and φ(n)which is coprime with φ(n), eg. If n=10, e canbe 3, as 3 and 4 have 1 as their largestcommon divisor. Now n and e are published asthe public key.

The private key consists of n and d, the latterbeing the vital item for decryption. It mustsatisfy the relation:

de≡1 (mod φ(n))

Seemingly complicated but all it means is that(de – 1) divides into φ(n) without remainder,e.g. If n=10, φ(n)=4, e=3, then d can be 7, asde - 1= 20, which divides cleanly into 4.

So now that the public and private keys aremade, a message can be encrypted and sent.Say Bob wants to send message M to Alice. Heconverts it into an integer m and calculates thevalue of:

c= me (mod n)

Once Alice receives the message, she wouldcalculate:

cd = m (mod n)

As a result, she recovers the original messagefrom Bob.

As a working example, say p and q are 11 and13 respectively. The value of n would be 11 x13 = 143. The totient is (p-1)(q-1), so φ(n)=10 x 12 = 120. 7 does not share a commonfactor with 120 apart from 1 so the value of ecan be 7. The public key is 143, 7. A solutionfor d can be 103, as de –1 = 720, whichdivides into 120 without remainder. The privatekey is 143, 103.

Bob’s message is converted into the integer m,which equals 5. Following

c= me (mod n), c = 78125 and in mod 143(the remainder from dividing by 143), it is 47.For Alice to decrypt this, cd = m (mod n) isused. 47103 (mod 143) = 5, as 47103 has aremainder of 5 when divided by 143.. In the

end, Alice receives the original message mfrom Bob.

The picking of this lock is done by factorising ninto p and q, then proceeding to work out (p –1)(q – 1), which would allow the picker to workout d, enabling decryption of an encryptedmessage. The security therefore relies on theextremely long process of factoring largenumbers. This is not a question of patience,factoring a potential 200 digit number usingbrute force would take several times thecurrent age of the universe even if the attackeris in possession of a powerful computer whichcan compute millions of numbers per second.As there is currently no algorithm to solvethese large factorisations, this technique ofpublic key cryptography is thought of as beingvery safe. However, this cannot be proven as ofyet. In the words of Bill Gates;

"Because both the system's privacy and thesecurity of digital money depend on encryption,a breakthrough in mathematics or computerscience that defeats the cryptographic systemcould be a disaster. The obvious mathematicalbreakthrough would be the development of aneasy way to factor large prime numbers.”

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The first step in making the factoring processeasier is to discover patterns in the primes andhence, a way of predicting where they willcome. The problem is that the distribution ofprimes is seemingly random and they showlittle evidence that there is any kind of rule thatgoverns whenever they show up. However,some patterns do occur. For example, allprimes but one are odd, all primes but two arenext to a multiple of 6 and, though not proven,the frequency of primes appearing seems todiminish as the numbers get bigger.

The Prime Number Theorem can be written as:

� (n)~ n / ln(n)� (n) is the number of primes that are lessthan a certain real number n (e.g. � (15) = 6for (2, 3, 5, 7, 11, 13)). This number isapproximate to n divided by the naturallogarithm of n. Despite it providing a good ideaof � (n), the theorem is still just an estimatewith a margin of error, though the error getssmaller as n increases. Another approachcomes to mind.

The Riemann Zeta Function is defined as:

This function was initially discovered by the

Scope 2009/10 Physical Sciences


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Figure 1

Showing the general idea of the‘complex’ plane

Figure 2

Complex plane showing the critical line and strip for the Riemann Zeta Function.


great Swiss mathematician Leonard Euler, wholimited s to a real number value greater than 1,the reason being that the answer would be afinite one (eg. For s=2, the function wouldequal 1/12 + 1/22 + 1/32 + 1/42 ...whichconverges to a value of � 2 /6.) If s= 1, (1+1/2+1/3+1/4...) the value would diverge toinfinity, a sequence known also as theharmonic series.

So where is the connection with primes? Euleralso proved that:

The left side shows the zeta function, while theright side shows the infinite product for allprimes.

A huge step forward was taken by theinfluential German mathematician BernhardRiemann, after he redefined the function for allcomplex numbers s ≠ 1, which he then usedto investigate the pattern of primes. Hishypothesis remains to be arguably the greatestunsolved problem in mathematics.

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A complex number comes in the form a+bi,where a and b are real and i is imaginary. i isequal to the square root of –1, something thatcannot be defined as a real number. The valuesof real numbers can all be plotted along a one-dimensional line, which does not show muchabout the pattern of primes. On the other hand,when complex numbers come into thequestion, a separate line can be plotted,perpendicular to the real number line, andpatterns can now be seen in two dimensionswith two axes (Consequently, calculus can nowalso be used for analysis). This is called thecomplex plane. Points are plotted with the x-value for the real part and the y-value for theimaginary part.The real part of any non-trivialzero of the Riemann zeta function is ½.

The Riemann zeta function was alreadydescribed earlier and the real part refers to the

a in the complex number s in the function. Thetrivial zeros are the answers generated when sis a negative even number (ie. ζ(-2) = 0).However, the ones that interested Riemannwere the ones made using complex numbers.An infinite number of zeros lie between realparts 0 and 1, also known as the critical strip.Riemann went one step further andconjectured that ALL zeroes, which are notfrom negative even numbers, are located onthe line real part ½. This is shown in thediagram to the right. Therefore, where

ζ(s) = 0, s must be in the form s= ½ + biIf the hypothesis is true (and bear in mind thatthis is a very simplified approach), one of themost significant consequences would be aclosing in the gap of the Prime NumberTheorem. This could (although this is notcertain) result in a breakthrough in largenumber factoring, and as described before,may spell disaster for the Internet world. TheRiemann Hypothesis is such an importantquestion, that it is one of the seven ClayMathematics Institute’s Millennium PrizeProblems, with the institute awarding$1,000,000 to anyone who can solve it.


The Role Of ComputationalAutomation In ScienceMatthew EarnshawTTeecchhnnoollooggiieess tthhaatt eennhhaannccee oouurr ddaattaa ccoolllleeccttiioonnaanndd ssttoorraaggee ccaappaabbiilliittiieess ccoonnttiinnuuee ttoo cchhaannggee tthheeffaaccee ooff sscciieennccee.. Traditionally, scientists havecarefully hypothesized and collected data,spending many years of dedicated work tryingto determine its significance. This traditionalscientific model is set to change as wecontinue further into our digital age. The datastream from the detectors of the Large HadronCollider reaches up to 300GB/second . TheEuropean Space Agency's Gaia mission willgive us the electromagnetic spectra andastrometric positional data of approximatelyone billion stars. These projects have specialdedicated networks to collect and store thisvast amount of data. As our data collectionabilities continue to expand, we will be forcedto look to methods of computational analysis tohelp us effectively utilise the data and continueto make scientific discoveries. Soon thetraditional model of discovery will no longerremain a feasible option.

There is no doubt that computers are fasterthan humans. IBM’s Roadrunner, the fastestsupercomputer in the world, can sustain aperformance of over one quadrillion (1015)floating point operations, or calculations persecond, approximately 50000 times faster thanthe average modern PC. Computer technologyhas unequivocally revolutionised science andhas permitted its expansion far beyond whatanyone would have predicted a few decadesago. Scientists have widely harnessed thisastonishing calculatory power, withsupercomputers being heavily utilised indisciplines ranging from meteorology toastronomy. However, as we seek to explain newscientific phenomenon from today's expansivedata sets, we need artificially intelligentsystems that can distill the laws themselvesfrom the inputted data, in addition to thecomputers that merely calculate results basedon known, traditionally derived, laws andprinciples. In an age where data can beobtained and handled in such abundantquantities, it is surprising that automatedcomputational analysis of this data has notadvanced in step with our data handling andcollection abilities. Perhaps there is a certaindisconcerting feeling associated with roboticautomata replacing the human worker, andtherefore an underlying resistance to suchsystems. Nevertheless, there has at last beensome recent progress in this field.

In "Distilling Free-Form Natural Laws fromExperimental Data", Cornell University’s

computational biologist Michael Schmidt andcomputational researcher Hod Lipson describetheir algorithm, a set of computationalinstructions, which is able to automaticallyreverse engineer non-linear natural systems.Armed with only a few simple mathematicalbuilding blocks, groups of basic operators;addition, subtraction, division andmultiplication, the algorithm was able toautomatically identify specific fundamental lawsof nature without any prior knowledge aboutphysics, kinematics or geometry. Lipson said,“One of the biggest problems in science todayis moving forward and finding the underlyingprinciples in areas where there is lots and lotsof data, but there's a theoretical gap … I thinkthis is going to be an important tool.”

Schmidt and Lipson’s algorithm first takes thederivative of every pair of variables from a setof collected raw experimental data to see howthey vary with respect to one another. It thenrandomly assembles the simple mathematicaloperators to produce some random initialequations. Symbolic derivatives of each pair ofvariables for these initial candidate equationsare taken and then compared to the numericalderivatives taken from the raw experimentaldata. By finding the difference between thevalues, the system is able to evaluate therelative accuracy of the randomly generatedequations, most of which are initially trivialinvariants.

The genius of the algorithm is in its so called“genetic” design. The best equations areupheld and are continually modified and re-tested, while the trivial results are discarded.Over time the equations ‘evolve’, hence“genetic algorithm”, and after many iterationsthe computer converges ever more closelytowards producing equations that are able toreplicate the raw experimental data andaccurately project data for yet untested states.An algorithm that is able to find invariants andrelationships in data is one thing but Schmidtand Lipson’s program can also decide whatlevel of significance they have.

With the most basic of apparatus Schmidt andLipson’s algorithm was able to derive wellestablished natural laws from experimentaldata of simple physical systems such that youwould find in any school's Physics department,like an air track oscillator and a doublependulum. When they ran their algorithm onposition data obtained from motion tracking thependulum, the algorithm soon converged onthe equation of a circle, as the pendulum isconfined to a circular path. When they fed itwith position and velocity data over time for theair track and pendulum, the system eventually

converged on the Hamiltonian and Lagrangianequations, the respective energy laws of thesystems. Furthermore, when the computer wasgiven acceleration data, it produced equationsof motion corresponding to Newton's secondlaw. In the 1750s Joseph-Louis Lagrangespent 20 years researching and deriving hisequations and Isaac Newton worked with“obsessive devotion” in the 1670s to draft hislaws of motion. In 2009, Schmidt and Lipson'ssystem made the very same discoveries - in amatter of hours.

While the algorithm’s ability to derive theselaws without any prior knowledge of physics,kinematics or geometry is astonishing, this isan artificial environment because we do indeedhave prior knowledge of these things. Byseeding the algorithm with laws the systemhad already derived for the simple pendulum,Schmidt and Lipson reduced the computationtime to derive motion laws governing thedouble pendulum from forty hours to sevenhours.

In a stroke of scientific genius Schmidt andLipson decided to present their algorithm withrandomly generated data in an attempt to faulttheir own system. The algorithm successfullyfailed to distil any equations from the data. Thefundamental and generic nature of thealgorithm means that the algorithm can bepotentially applied to just about any dynamicalsystem from weather patterns to populationgenetics. There may even be cryptanalyticalapplications, finding predictabilities incryptographic systems and in evaluating theentropy of pseudo-random number generatoralgorithms. The laws of motion and energyfound by the algorithm likely pale incomparison to the complexities of lawsgoverning complex biological systems like thebrain. Although such systems are notoriouslycomplicated, thus making the discovery of thelaws that govern them a real challenge forscientists, the principles of Schmidt andLipson’s algorithm are theoretically scalable tothis level.

Now that such an algorithm has proven itsfunctionality, what’s next? What if the algorithmcould not only analyse experimental data butalso be able to independently obtain it in thefirst place? Scientists at Aberystwyth Universityare experimenting with a robotic ‘colleague’whom they have dubbed “Adam”. While robotshave long helped scientists in the lab withlaborious tasks like the sequencing of genomesor obtaining nuclear magnetic resonancespectrographs, Adam is the very first robot tohave made a scientific discovery on its ownwithout any additional human input. This is the

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first time a robot has been able to formulate ahypothesis, design and perform an experiment,and return meaningful results. Crucially, Adamis also able to form new hypotheses based onits own results, thus closing the feedback loop.Don’t worry though, despite the worryinglyanthropomorphic name, Adam comprises aroom full of interacting scientific instrumentssuch as centrifuges, incubators and computers,and bears no human resemblance.

Adam was given knowledge about yeastmetabolism and was also provided with adatabase of information about genes andproteins related to the metabolism of variousother organisms. Adam devised a hypothesisand designed experiments to test it. In order tofind out which genes coded for particularenzymes, Adam systematically grew yeastcultures with certain genes removed, and kepttrack of how well these new strains grew.Adam recorded the results and was able tolearn something basic about the genedepending on the growth of the cultures. Therobot is able to carry out over one thousandsuch trials each day. Over the course of severaldays Adam devised and performed experimentsfor twenty hypotheses and twelve of thesehypotheses were confirmed. For example,Adam hypothesised that three genes it hadidentified through previous trial and errorexperimentation coded for an enzymeresponsible for producing the amino acidlysine. This result was manually confirmed byAdam’s mortal human counterparts.WhileAdam's findings are relatively simple they arenonetheless useful and Adam was able tomake the discovery in a much shorter timethan his colleagues would have been able to."It's certainly a contribution to knowledge. Itwould be publishable”, said Ross King, acomputational biologist at Aberystwythuniversity leading Adam’s development.

Adam is rather specialised as his array ofinstruments are very biologically focussed,making the range of performable tasks limitedto highly repetitive brute force style

experiments where many hundreds of samplesmust be identically analysed. Adam’s algorithmis currently not quite as elegant as whatSchmidt and Lipson have devised being moreof a trial and error approach, rather than agenetic algorithm but the combination of thesetwo systems holds great promise. Whencoupled with an inherently more genericalgorithm that has potential to be able to distilmuch more complex results from data, whoknows what our artificially intelligent colleagueswill be able to achieve in the future.

Should scientists fear for their jobs over theseemerging technologies? No, at least not yet.The processes of initial creativity required forinput and the recognition of significant outputare still heavily reliant human judgement.Humans are indeed required to curate thesystem and explain the significance andimplications of its findings. Schmidt andLipson's algorithm produces a shortlist of theten most accurate equations it has found but ahuman researcher must hand pick the mostsignificant and interesting equations from thecomputer generated shortlist and balance theequation's ability to reproduce and extrapolatefrom the data set, and its parsimony, thenumber of terms it contains. Although it seemsas if Adam only needs non-intellectual humanintervention to remove waste and ensure it hassufficient supplies, the task of interpreting andusing the results effectively, such as creating anew drug, remains solely a human concern. Inany case, the robot’s range of tasks remainsvery limited. Quite the opposite of scientistslosing their jobs, the near future holdsincreasingly productive human-robot scientificpartnerships and an increase in the rate ofscientific discovery in this increasingly data richera.

While neither system is perfect yet, for the firstof their kind they are exceptionally impressive.The ability of these systems to derivefundamental physical laws in a day and makean independent new scientific discovery, givesgreat promise to the role of such systems in

the future. For the moment, the uniquerecognition and creativity of humans remains arequirement. As this field matures however, thequestion will be asked, For how long?.

Figure 1 (above)

Showing the derivation of the laws governing the motion of a double pendulum.(A) A computer observes the behavior and dynamics of a real system, (B) collects data using motion tracking cameras andsoftware. It then automatically searches for equations that describe a natural law relating these variables. (C) Without any priorknowledge about physics, kinematics, or geometry, this algorithm found conservation equations and invariant manifolds thatdescribe the physical laws these systems obey.



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Visual Effects EngineeringSahil PatelFFrroomm aaddvveerrttss iinn oouurr tteelleevviissiioonnss aatt hhoommee ttoocciinneemmaass,, nnoowwaaddaayyss wwee aarree ssuurrrroouunnddeedd bbyyssoommee ffoorrmm ooff vviissuuaall eeffffeeccttss wwhheerreevveerr wwee ttuurrnn..Visual effects have become a fundamentalelement in almost all of the films made butthere is a lack of understanding of how photorealistic images are made. Visual effects are abroad, open aspect of films and there areseveral definitions that have been adopted overthe years so the best definition thatencapsulates this topic is:“Practices, methods and technologies relatingto the creation and manipulation of elementswithin moving images that enable storytellersto guide an audience’s conception of time,space and/or reality, thereby eliciting a desiredemotional response and/or conveying criticalstory information.”

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Motion Capture (Mocap) involves translatingreal human movements onto a 3-D model thatmimics those actions and ultimately behaveslike a human does. The process is relativelysimple; an actor wears a suit dotted withmarkers and the actors’ performance iscaptures and stored as animation data. Whenthe data is seen on a computer, the dots thatrepresent the outline of the actor can bemapped onto a 3-D model. The model can bedesigned as required but still retains thehuman actions from the motion capturesession. One huge advantage is the freedom toplace and move the camera wherever desiredso the perspective of the shot is flexible at alltimes. However, the technique is limited in thesense that creating characters that do notfollow the laws of physics cannot be captured.

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There are several techniques which all classifyas animation so there is no single definition ofanimation. However, the three types inchronological order are traditional, stop-motionand computer animation. 90% of all animatedproductions are computer generated andtraditional has almost completely been phasedout of use since children’s cartoons can nowbe computer generated. CGI stands forComputer Generated Imagery and is a termused often and sometimes haphazardly.Computer animation is by definition, the sameas CGI but nowadays films like Wall-E arecategorized as animated films so CGI wouldtherefore generally refer to the creation of images intended to appear realistic and blendinto the live action of the frame. Most films areshot in a 2:35:1 aspect ratio at 24Hz (frames

per second). A single frame of a complexanimated film such as Wall-E would range from2-15 hours to render completely. Averagerendering times for one frame of CGI haveincreased in the last 10 years which doesn’tseem logical when GPU/CPU speeds andmemory space have been doubling every 18months. The reason for longer rendering times,even with faster computers, is that big-budgetfilms are demanding more complex andrealistic shots and with advances in renderingand ray tracing capacity, films can afford to bemore ambitious. The perfect and well-knownexample of intricate CGI is the Transformersfranchise where any frame which has 3 ormore transformers moving in it will typicallytake 38 hours to render.

The key to making an image realistic is raytracing (see definitions) which makes a CGImodel blend and react realistically to lightsources in the live-action part of the image.The realism of a visual effect is often judged byhow detailed or sharp it is, however, itsreaction to light and other objects surroundingit are the determining factors to impressiveCGI. So an image with a resolution of 4000pixels by 3000 pixels but rasterised will lookfar worse in terms of realism than the imageabove that has been ray traced at 1920x1080pixels. In conclusion, we come back to ourdefinition of visual effects to guide anaudience’s perception of reality by obtaining asrealistic an image as possible.

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I have explained (see definitions) rotoscopingas the way of creating composite images bypasting or drawing over filmed backgroundsuse of traditional rotoscoping was in theoriginal three Star Wars films, where it was used to createthe glowing light saber effect, by creating amatte based on sticks held by the actors. Toachieve this, editors traced a line over eachframe with the prop, then enlarged each lineand digitally added the glow. In the latter threeStar Wars films, green screen was used tocreate the light saber effect. The actors stilluse sticks which make it seem like oldfashioned rotoscoping is still being used butsticks are used to make saber sequenceseasier to film practically. The light saber isadded through CGI in post-production.Green screen is effectively the modernalternative to rotoscoping as it is the same ideaof modifying or adding a CGI element to afilmed scene. The process is simple; the greenscreen is green because it the shade which isfurthest away from skin colour so a goodseparation from the foreground (actor) to thebackground can be achieved. The desired background can be added in post-production

(keyed out). A blue screen serves the samepurpose as a green one but is less sensitive tocameras so more light is needed to filmagainst a blue screen. The reason for greenbeing more sensitive is that more pixels areallocated to the green part of the spectrumthan red or blue.

Definitions

TTrraaddiittiioonnaall aanniimmaattiioonn-- By usingdrawings for each frame (createdby an artist), the drawings arephotographed onto motion picturefilm. The final product will run atabout 8 frames (drawings) persecond to create a fluid animation.

RRoottoossccooppiinngg-- Invented by MaxFleischer, rotoscoping is a waytracing an object, a silhouette(called a matte) is created that canbe used to extract that object froma scene for use on a differentbackground.

SSttoopp--mmoottiioonn aanniimmaattiioonn-- Usingphysical objects and/or models andmanipulating them and capturingthe modified models onto film oneby one. The most famous modernexample of stop-motion animationis Wallace and Grommit: TheCurse of the Were-Rabbit whichused clay models to capture eachframe.

CCoommppuutteerr aanniimmaattiioonn-- This isessentially the successor to stop-motion animation in the sense thatthe computer creates each frame,but each new image is advanced inthe time frame. 3-D models can bebuilt using simple animationsoftware and by rigging the modelwith a virtual skeleton, facial detailcan be added before rendering thefinal frame.

BBaayyeerr FFiilltteerr-- filter pattern used forsensor chips in a digital stillcamera. More pixels are dedicatedto green than to red and blue,because the human eye is moresensitive to green, producing abetter colour image.



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Definitions

RRaayy TTrraacciinngg-- A process for rendering3-D models by tracing light rays asthey would bounce off the modelfrom a light source. This ensures themodel reacts to light realistically bytaking into account reflection,refraction, depth of field and highquality shadows. See MicroScopeRay Tracing article for more detail.

RRaasstteerriissaattiioonn-- Rasterising an imageis when an image in vector format(polygons) is converted to rasterformat which is into pixels ready tobe displayed immediately on acomputer screen. Compared to raytracing, rasterisation is much fasterand more suited to video gameswhich run in real-time and need toreact instantly to user input. RayTracing is better for visual effects infilms where still frames can berendered ahead of time so the effectsare ready just before the film isreleased.

SSpprriittee VVooxxeellss-- A sprite is a term forany 2-D/3-D image that can beincorporated into a larger graphicanimation. Voxel stands for VOlumepiXEL which is a pixel spread over 3dimensions rather than 2 in astandard pixel. So using a spritevoxel means animating a piece of theframe elsewhere and thenincorporating it into a larger scene.Voxels are also used in Medicalimaging such as tomography.

HHaarrdd DDyynnaammiiccss-- This is the namefor a visual effects program to makepieces react according to Newton’slaws and equations that physicssoftware can apply to an interactiveenvironment so basic concepts suchas momentum, friction anddisplacement are applied to theframe.

So since blue screens are impractical, theyare used when the foreground has green in it.Therefore, the imperative rule to greenscreening is to keep whatever is in theforeground a different colour to the brightgreen backdrop so the camera distinguishesthe two planes of images. An example of howvital this rule is is the scene in Spider-Manwhere the both Spider-Man and Green Goblinare in the air, Spider-Man had to be shot infront of the green screen and the GreenGoblin had to be shot in front of a bluescreen, because Spider-Man wears acostume which is red and blue in color andthe goblin wears a costume which is entirelygreen in color. If both were shot in front of asame colour screen, one character wouldhave been partially erased from the shot.

110000%% CCGGII

So far I’ve only discussed animation andcomposite images which mostly involve greenscreening. Completely CGI images are moredifficult to make them look real as an entirelyvirtual environment has to be made. Figure 1is an example of an explosion of a renderedCGI model and some aspects of how an artistwould manipulate the model to reactrealistically (pyrotechnics).

TThhee ffuuttuurree ooff VVFFXX

With the emergence and success of newformats like Blu-ray, it is clear that thingsmust be changing in visual effects. The nexttwo examples are some of the upcomingtechnologies which could revolutionisecinema and the way we can create a “desiredemotional response”.

Real-time ray tracing: Earlier I stated theproblem that ray tracing ahead of time is theonly way to create realistic graphics like wesee in modern films. Videogames userasterisation to render images almostinstantly and produce underwhelming resultsevery time. A new graphics company calledCaustic Graphics believes it has uncoveredthe secret of real-time ray tracing with a chipthat enables your CPU/GPU to shade withrasterisation-like efficiency. The new chip off-loads ray tracing calculations and then sendsthe data to your GPU and CPU, enabling yourPC to shade a ray traced scene much faster.Whether Caustic's unique ray tracingextensions are good enough to match orsurpass film ray tracing remains a mysterybut real-time ray tracing is developing at arapid rate; on June 12 2008 Inteldemonstrated Enemy Territory: Quake Warsusing ray tracing for rendering, running in abasic high-definition resolution. The gameoperated at 14-29 frames per second. Thedemonstration ran on a 16-core Tigertonsystem running at 2.93 GHz.

Emotion capture: Motion capture is used oftento create surreal characters’ faces; however,audiences are always brought down to realitywhen they see subtle facial expressions andeye movement. The current technology isfocused on creating more and more detailedmodels and simply pasting the actors’performance into the model. This can result in

film like The Polar Express and Beowulf whichalthough won Oscars in technical categorieswere critisised for creating characters thatsuffer from problems like ‘dead eyes’ whichalmost wastes the performance of the actorduring motion capture as the actions are lostin rendering. Over the last few years, directorJames Cameron has created a motioncapture technique (unofficially called Emotioncapture) that transfers 99% of the actors’performance into the final image. The keyideas and techniques are promising and theirfirst use in a feature film has been in Avatar.We can expect top directors to start usingthese new technologies in the future.


Figure 1: Creating a CGI Image (above)

Top image: ‘hard dynamics’ along with multiple collision objects are used to creategeometric damage.

Second image: image sequences of explosions are fire were timed and coloured to be usedtogether to self-illuminate sprite voxels to create a fiery explosion

Third image: the geometric damage incorporated with timed explosions shows the image atabout 60% completion.

Bottom image: the final ray traced screenshot. The differences to above is the contact ofthe missile hit can be seen and the damage it causes on the other side of the ring.


11

Superconductors: Supermaterial Of TheFuture?

Neeloy BanerjeeOOnnllooookkeerrss wwiitthh ggllaazzeedd eeyyeess aanndd sslliigghhttllyybbeeffuuddddlleedd bbrraaiinnss aarree uussuuaallllyy ssoommeewwhhaattccoonnffuusseedd bbyy wwhhaatt tthhee pphhyyssiicciisstt mmaayy ttaallkkaabboouutt wwiitthh gglleeee aanndd aannttiicciippaattiioonn.. Physicistsare, however, on the verge of discoveringsomething with profound everydayapplications; a room temperaturesuperconductor.

Superconductors are materials that have zeroelectrical resistance below a specific criticaltemperature, and their applications aretremendous. The behaviour ofsuperconductors was not well understooduntil 1933, when Walter Meissner and RobertOchsenfeld stumbled upon a property ofsuperconductors- they repel magnetic fields.A magnet moving by a conductor inducescurrents in the conductor. This is the principleon which the electric generator operates. But,in a superconductor the induced currentsexactly mirror the field that would haveotherwise penetrated the superconductingmaterial - causing the magnet to be repulsed.This phenomenon is known as strongdiamagnetism and is today often referred toas the "Meissner effect”. The Meissner effectis so strong that a magnet can actually belevitated over a superconductive material. TheMeissner effect also helps explain how thesuperconductor can transmit current for aninfinitely long time. We already know thatsuperconductors oppose a magnetic field. Itdoes this by setting up electric currents nearits surface. It is the magnetic field of thesesurface currents that cancels out the appliedmagnetic field within the bulk of thesuperconductor. However, near the surface,within a distance called the ‘Londonpenetration depth’, the magnetic field is notcompletely cancelled; this region alsocontains the electric currents whose fieldcancels the applied magnetic field within thebulk. Each superconducting material has itsown characteristic penetration depth.Because the field expulsion, or cancellation,does not change with time, the currentsproducing this effect (called persistentcurrents) do not decay with time. Thereforethe conductivity can be thought of as infinite:a ‘superconductor’. In the following years, aplethora of superconductors were found,many of them alloys containing Niobium orSilicon. The critical temperature ofsuperconductivity of each of these alloys wasalways slightly higher than the last.

A shock to the scientific world occurred whenin 1986, researchers found a ceramicsuperconductor whose critical temperaturewas 30K (Kelvin - the SI unit of temperature),the highest recorded at that time. What’smore, ceramic materials are, at room

temperature, insulators. The material behavedin a way contrary to all contemporarypredictions and so began a flurry of activitywithin the scientific world to test copper-oxidesubstances (cuprates). As superconductorswere found that had temperatures higherthan that of liquid nitrogen (an easilyattainable coolant), the world looked on inbewilderment at the speed of the rise of thecritical temperature.

QQuuaannttuumm EExxppllaannaattiioonnss

The way to imagine what happens in asuperconductor is to visualise the electronspairing up with each other. Usually, due tothem having the same charge, electronswould repel, but at such low temperaturesand low energies they encounter an attractionwhich causes them to form Cooper Pairs.These pairs of electrons require only smallamounts of energy to be separated into theindividual electrons, explaining the lowtemperatures necessitated by thesuperconductors. Their pairing constitutesBosonic behaviour, as both electrons in thepair occupy the same energy level. Due to thecold temperatures the vibrations of the atomsin the material are diminished. Themathematical models of this refer to thevibrational energies of the molecules as“Quantum Harmonic Oscillators”. Since eachatom is bonded to other atoms, they do notall vibrate independently of each other, so thevibrations take place as collective modesthroughout the material. There are equationswhich define the energies of the vibrations,and they explain that the energy levels arequantised, meaning that the oscillators canonly accept or lose discrete amounts ofenergy and not a continuous spectrum of it.The Cooper Pairs of electrons do not have anenergy equal to the discrete level needed bythe atoms in the material, and as such passthrough them uninhibited. Resistance iscreated by electron collisions with vibratingatoms, and since those are avoided theresistance of the material drops to zero.

PPrraaccttiiccaall AApppplliiccaattiioonnss

Working on the assumption that materialswith critical temperatures >273K (zerocelsius) will soon exist, the applications ofthese conductors are wide and varied. One ofthe first things to be truly revolutionised bysuperconductors will be transport throughmagnetic-levitation. The strong, easilymaintainable magnetic field created by thesuperconductors would be able to fullysupport trains, effectively eliminating frictionbetween the rails and wheels. Furthermore,no electrical energy would be wasted as heat(since no energy is dissipated due to zeroresistance). Another useful application ofsuperconductors would be in electricitypylons. Currently, high voltages are used to

keep the current, and thus energy lost asheat, as low as possible. But if no energywere to be lost as heat again, the need forhigh voltages would be reduced and millionsof pounds would be saved in step-up andstep-down transformers. Room-temperaturesuperconductors would cheapen MagneticResonance Imaging, removing the need forcostly cooling systems and allowing morepeople to be scanned and at a lower price.However Korean Superconductivity Groupwithin KRISS has carried biomagnetictechnology a step further with thedevelopment of a double-relaxation oscillationSQUID (Superconducting QUantumInterference Device) for use inmagnetoencephalography. SQUID's arecapable of sensing a change in a magneticfield over a billion times weaker than theforce that moves the needle on a compass.With this technology, the body can bescanned to certain depths without the needfor the strong magnetic fields associated withMRIs.

Finally, the most famous use ofsuperconductors and an area where they canmake a real difference is in particleaccelerators. Originally the SuperconductingSuper-Collider in Texas required them, andmore recently the Large Hadron Collider (whatis a physics article without reference to theLHC?). Both of these particle accelerators aimto recreate the moments after the Big Bangand need strong magnetic fields to acceleratethe protons to high enough speeds in order tocollide them at sufficient energies. Themagnets they use have to be cooled to nearabsolute zero (0K) in order to besuperconducting and earlier this year amalfunction with the cooling system meantthat the magnets were raised above theircritical temperature, delaying the wholeoperation by five months while the magnetswere repaired. That catastrophe would nothave happened if room temperaturesuperconductors had been available.

IInn CCoonncclluussiioonn

To put everything into perspective, physiciststalk of the exponential advancement in allbranches of physics, from astronomy, throughparticle-physics to zeolite-materialsengineering. However, the rapid advancementin the theory and synthesis ofsuperconductors is something trulyremarkable and in the coming years may wellbe one of the most important areas ofresearch in physics.



Einstein’s Annus Mirabilis Casey Swerner

12

AAllbbeerrtt EEiinnsstteeiinn iiss oonnee ooff,, iiff nnoott tthhee mmoosstt,,rreennoowwnneedd sscciieennttiissttss oonn tthhiiss ppllaanneett.. In 1905,he revolutionized modern physics with histheory of special relativity and went on tobecome a twentieth-century icon- a manwhose name and face are synonymous with"genius."

1905 was a very good year for Albert Einsteinindeed. In a frenzy of work, Einstein produced4 papers which he himself called “veryrevolutionary’’. Before one goes into thedetail, we must explain why these paperswere so very important. They come at a timewhere many widely accepted that “There isnothing new to be discovered in physics’’ astold by the Lord Kelvin to the British Instituteof the Advancement of Science. Newtonianmechanics were widely accepted as theabsolute truth, and thus physics wasregarded as finished business. Yet, it wasAlbert Einstein, the patent officer who hadbeen unable to get a teaching post at anyuniversity in Europe, who had the imaginationto revolutionize our understanding of physics.

""OOnn aa HHeeuurriissttiicc VViieewwppooiinntt CCoonncceerrnniinngg tthheePPrroodduuccttiioonn aanndd TTrraannssffoorrmmaattiioonn ooff LLiigghhtt””

This is the paper that gave Einstein his onlyNobel Prize. The paper can be seen as one ofthe fundamental starting points for quantumtheory, one of the most important aspects oftheoretical physics to date.

Ironically, this quantum theory is one whichEinstein became eerily skeptical about in hislater years which he spent trying to disputeuntil his death.

Light and other electromagnetic radiations,such as radio waves, are obviously waves—or so everyone thought. Maxwell and Lorentzhad firmly established the wave nature ofelectromagnetic radiation. Numerousexperiments on the diffraction and scatteringof light had confirmed this. Imagine the shockwhen, in 1905, Einstein argued that undercertain circumstances, light behaves not ascontinuous waves, but as discontinuous,individual particles. Although Einstein was notthe first to break the energy of light intopackets, he was the first to take this seriouslyand to realize the full implications of doing so.(It is important to note here that Einstein’s“light quanta’’ and “photons’’ are the sameentity, and thus may be referred tointerchangeably.)

In essence, Einstein explained that light maybe seen as a wave and separate particles atthe same time, known today as the wave-particle duality.

HHooww??

When a metallic surface is exposed toelectromagnetic radiation above a certain

threshold frequency, the light is absorbed andelectrons are emitted.

In an experiment, carried outby Phillip Lenard,cathode rays (electrons) are emitted by singlecoloured light beams hitting a metal. When heattempted to increase the intensity(brightness) he observed that the emittedelectrons did not jump with increasedintensity. Rather, a greater number ofelectrons were freed at the same speed.Further experiments proved that thefrequency (i.e. infra-red, red, violet, ultra-violet) gave the effect of more energy to theelectrons.

This proved at odds with the wave theory oflight. If the light behaved as a continuouswave, then an increase in the intensity shouldgive an increase in the intensity of the waves,giving the particles extra speed.

Einstein took this data and hypothesized thatlight “consists of a finite number of quanta’’.Far from simply using theoretical knowledge,Einstein explored whether photons behavedmuch like a gas, which we know is composedof particles. He found using various statisticalformulas (e.g. Boltzmann entropy formulae)that photons behaved similarly to a gas.These findings agreed with Lenard’sexperiments and thus the idea of photonswas born.

It is important to note that he did not do awaywith wave theory; which he felt useful as itdescribed light as statistical averages ofcountless quanta particles. This duality is asimultaneous event, and not an ‘either/or’situation.

In conclusion, the photon, can be consideredas the energy released when an electron, thathas jumped from a low energy orbital to ahigh energy orbital, returns to its originalposition (thus the photon equals thedifference in energy of the electron), anddepending on its magnitude of the change,will be emitted as a wave form within theelectromagnetic spectrum.

““AA NNeeww MMeeaassuurreemmeenntt ooff MMoolleeccuullaarrDDiimmeennssiioonnss && OOnn tthhee MMoottiioonn ooff SSmmaallllPPaarrttiicclleess SSuussppeennddeedd iinn aa SSttaattiioonnaarryy LLiiqquuiidd’’’’

While this paper may seem, on the face of it,rather mundane, it is one which lays downthe principles of Brownian motion, and thusallowed other scientists to set about provingthe existence of the atom, which at the timehad not been proven conclusively.

By giving the subject of Brownian motion amore intense study than had ever beenundertaken, Einstein was able to calculate thenumber of water molecules per square inchas well as to provide statistical andmathematical formulas for the motion.

His theory was based on the assumptionsthat as small particles (such as pollen grains)move about in a liquid, which are beingpushed about by much, much smaller atomsin every direction. Normally, there are roughlythe same number of atoms on each side ofthe pollen grain, all pushing and bumpingagainst each other in random directions; sonaturally, such movement should tend tocancel each other out most of the time.Seeing as it truly is a random process,however, because of the tiny nature ofparticles overall it will be that the pollen grainis pushed a little bit more in one direction, soit moves that way, and then later is pushed ina different direction and moves another way.Here Einstein hypothesizes that it was notnecessary to measure the velocity of theparticle in question throughout its journey, butrather that, all that was needed was tomeasure the whole distance (and thusaverage velocity) the particle moved. Thisallowed other scientist to empirically proveatoms and Avogadro’s number.

““OOnn tthhee EElleeccttrrooddyynnaammiiccss ooff MMoovviinngg BBooddiieess""aanndd ““DDooeess tthhee IInneerrttiiaa ooff aa BBooddyy DDeeppeenndd uuppoonnIIttss EEnneerrggyy CCoonntteenntt??””

(Due to the exceedingly mathematical natureof the above papers, the article will continueby using analogies to explain the underlyingprinciples over the proofs themselves.)

SSppeecciiaall RReellaattiivviittyy

The theory of special relativity is concernedsolely with objects moving at a straight line ora constant speed. The first postulate statesthat the laws of physics are unchangedregardless of an object’s relative motion. Thesecond states the speed of light (c) does notchange regardless of the relative motion of anobject

.It should also be noted that the theory holdsthat motion is relative to another frame, andthat there is no absolute still reference frame.

Thus the time lapse between two events isnot invariant from one observer to another,but is dependent on the relative speeds of theobservers' reference frames; thus time canbe dilated and is not absolute.


Figure 1

Diagram of Lenard’s results, wherelight strikes the surface of a metalcausing electrons to be released.


Einstein’s Annus Mirabilis Casey Swerner

13

Therefore, we see that two events that occursimultaneously in different places in oneframe of reference may occur at differenttimes in another frame of reference. For example, if you were on a ship (atconstant velocity) and dropped a ball from themast, you would see it fall directlydownwards. However, a bystander from thebeach would see both the ball and the shipmove forward until the ball hits the deck.

Secondly, the theory shows that a bodycannot move from a state of motion less thanthe speed of light, to one above it. Althoughwith Newtonian mechanics an increase, orresultant speed, of an object can bedetermined by simple addition, this is not truein special relativity and thus acceleration doesnot break the first postulate. Also, fast movingobjects will begin to distort and appearshorter to an observer, due to Terrell Rotation.Therefore, if one was on a spaceshiptravelling very near the speed of light, from astationary bystanders point of view, thespaceship will become distorted in thedirection of the movement (i.e. its will squashhorizontally), however, to the pilot of the ship these apparent effects will not be noticeable,and he will see himself as normal sized,because he is moving at 0km/h relative tohimself. According to special relativity, both viewpoints are correct. Whilst there are manystrange effects one can see from relativitythere are some facts to bear in mind:

Time does not slow as speed increases. Itonly slows relative to another reference point.Objects do not shorten as speed increases,only relative to another reference point.Onlycrossing the speed of light barrier from eithera faster or a slower speed is disallowed, itmay still be possible to have greater speeds.

EE==mmcc22 ((TThhee mmaassss eenneerrggyy eeqquuiivvaalleennccee))

((EEnneerrggyy == mmaassss xx ssppeeeedd ooff lliigghhtt22))

This formula was derived from KE = ½mv2

(kinetic energy = 1/2 x mass x velocitysquared) and applied to the laws of specialrelativity. By creating a relative motion, andapplying the hypothesis that all mass can beconverted (theoretically to 100%) energy, onegets to Einstein’s most famous and elegantformulas.

This has a bearing on our knowledge of thespeed of light. This is because when oneapplies this formula it becomes apparent thatthe energy required to overcome resistiveforces begins to increase with an increasedvelocity. As an object accelerates close to thespeed of light, relativistic effects begin todominate. In particular, adding more energy toan object will not make it go faster as theresistive forces begin to increase until wereach an infinite energy stage. So the energyis added to the mass of the object, asobserved from the rest frame. Thus, we saythat the observed mass of the object goes upwith increased velocity. Mathematically, byextending from force = mass x accelerationone ends up with the following equation;

m0m = ----------------

√ (1-v2/c2)

By looking at this we see that when v=c(velocity=speed of light) the mass relative tothe rest frame (original mass = m0) must beinfinite, thus impossible.

The other big impact this equation has, is onnuclear physics. Einstein himself explains ‘Itfollowed that... mass and energy are both butdifferent manifestations of the same thing’.

Now, since E = mc2, the energy equivalent ofa very small mass can be very large indeed.Thus, in fission, when atoms are split,photons (in the form of gamma radiation) areemitted, in which a very small sample willgive off a huge amount of energy. So, as onecan see Einstein’s Annus Mirabilis papers canbe seen as ‘’revolutionary’’ because theypaved the way not only to a new perspectiveof physics, but created the conditions for awhole century’s worth of work anddiscoveries in the physical world, fromEinstein’s later general relativity to Quantummechanics.

Figure 2 (a)

Shows ball moving relative tocrewmembers reference frame.

Figure 2 (b)

Shows ball moving relative tobystanders reference frame.



14


Quantum Of Solace: Heisenburg’sUncertainty PrincipleNeeloy Banerjee““HHooww ccaann ssoommeetthhiinngg ccoommee ffrroomm nnootthhiinngg??””wwaass tthhee qquueessttiioonn ppoosseedd bbyy tthhee mmaatthheemmaattiicciiaannaanndd pphhiilloossoopphheerr RReennéé DDeessccaarrtteess wwhheennccoonntteemmppllaattiinngg tthhee oorriiggiinn ooff tthhee uunniivveerrssee..Indeed, it seems rationally illogical to assumethat from a vacuum, mass appeared and foryears philosophers of science wrestled withthis question, struggling to make headwaywith it.

PPllaanncckk’’ss CCoonnssttaanntt

Before we delve into the uncertain realms ofquantum physics, let us first ground ourselvesin the necessary physics ‘lingo’.Firstly, h, represents Planck’s Constant. Thisis roughly equal to 6.63 x 10^-34 Joule-seconds (Js). The history behind the discoveryof this number would equate to anotherarticle, but in short, whilst studying black-body radiation, Planck noticed discrete energylevels that corresponded to the formula E=hf,where E is the energy of the emission, f is thefrequency of light produced and h, this newconstant, linked the two. The units of h areJoule-seconds, Js, which makes for aninteresting digression. The Joule-second is anaction, which is a novel concept because itdoes not relate to anything physical (trythinking of something tangible that requiresyou to multiply energy and time). Instead itremains absolutely constant and has thesame size for all observers in space and time.According to Einstein’s Special Theory ofRelativity, any object in space – for example aline – will look different to observers thattravel at different speeds relative to it. Thisline can be thought of as existing in fourdimensions, and as it moves ‘through’ time ittraces out a four dimensional surface, ahyper-rectangle whose height is the length ofthe stick and whose breadth is the amount oftime that has passed. The area of therectangle (length x time) comes out to be thesame for all observers watching it, eventhough the lengths and times may differ. Inthe same way this metre-second is absolutein four dimensions, so too is the action.Diversions aside, the next thing the physicistrequires is the understanding of ħ. ħ = h/2�(which is roughly equal to 10^-34) and it isan important number because of itsapplication in the Uncertainty Principle.

HHeeiisseennbbeerrgg’’ss UUnncceerrttaaiinnttyy PPrriinncciippllee

This principle states that, if you measure twoproperties, p and q, of, say, an electron – takefor example momentum and position, thenthe uncertainty in each of thosemeasurements are Δp and Δq. Heisenberg

proved that Δp.Δq ≥ ħ . Now since ħ issuch a tiny number, for most experiments thisis of little consequence. But when performingquantum experiments, this inequality mattersa great deal.

Scientists were horrified at what they thoughtwas an accusation made by Heisenberg thattheir equipment and techniques were notgood enough for the experiments. Inresponse, Heisenberg proposed a thoughtexperiment.

HHeeiisseennbbeerrgg’’ss MMiiccrroossccooppee

In viewing any image of any object, we mustfire photons at the object. Photons have norest mass and only miniscule amounts ofenergy so when interacting with a largerobject they have little effect. But when lookingfor the precise position of an electron, as wecan see above, by firing the photon at theelectron, we distort the very position we weretrying to measure! Not to mention changingits momentum in the process.

IImmpplliiccaattiioonnss ooff tthhee UUnncceerrttaaiinnttyy PPrriinncciippllee

The implications of this principle aretremendous. Take any two properties of anelectron, that when multiplied, have units Js(Joule seconds) and you will know that youcannot measure them exactly. As mentionedabove, the momentum, position dilemmaarises. In measuring more and moreprecisely, say, the momentum, the lessprecisely you measure the position. Thisactually has profound implications in that noweven theoretically we cannot measure andtherefore know the position and momentumof all the particles in the universe. Since, inorder to predict movement, we need bothposition and momentum of things, this meansthat we cannot predict a particle’s exactfuture behaviour.

Another two properties that we can measurein experiments are that of energy (E) and time(t). Since they multiply to give the units ofaction (Js) they can be incorporated into theUncertainty Principle. ΔE.Δt ≥ ħ . Looking atthis more carefully can reveal a startlingpicture. We can look at this in two ways.Firstly, let us assume we are trying tomeasure the energy as precisely as possible.The more precise we become, the lessprecise we have to be with measuring time.The consequences of that are that we don’tknow whether, during our experiment, timehas travelled uniformly. A positron travellingforwards in time is equivalent to an electrontravelling backwards in time and this kind oftime flexibility could give rise to particlestravelling backwards in time during theexperiments and we would know nothing

about it. Secondly, this time we want tomeasure the time as precisely as possible.This time, ΔE is much larger. Thistheoretically means that the energy couldfluctuate in the time period specified. Andsince Einstein confirmed that energy isequivalent to mass, this means that therecould be a fluctuation of mass in the timeperiod. To further expound this point, take an‘empty’ space of a vacuum and measure atime period very precisely (say, where Δt ~10^-44, requiring ΔE to be ~ 10^10). In thistime period that means that potentially,energy, and thus mass has been created fromconditions without energy in the first place!“How can something come from nothing?”asked Descartes, many years ago. Well, usingHeisenburg’s work, scientists today haveproved that it can.


15

Atmosphere: Earth’s GreatDefence Manesh Mistry““CCaappttaaiinn JJoosseepphh WW.. KKiittttiinnggeerr,, JJrr.. ooff tthhee UUSSAAiirr FFoorrccee iiss tthhee mmaann wwhhoo ffeellll ttoo EEaarrtthh aannddlliivveedd.. Only twenty miles above our heads isan appalling hostile environment that wouldfreeze us, and burn us and boil us away. Andyet our enfolding layers of air protect us socompletely that we don't even realize thedangers. This is the message from Kittinger'sflight, and from every one of the pioneerswho have sought to understand ouratmosphere. We don't just live in the air. Welive because of it.”

So writes Gabrielle Walker in “An Ocean ofAir: A Natural History of the Atmosphere”.Engrossed by the prologue of this book whichtold the story of Kittinger’s fall from theheavens, I decided to read on. Kittinger'scalculated risk was only one of a series ofexperiments carried out over several centuriesas human beings attempted to understandthe ocean of air that surrounds us andsupports our existence.

EElleemmeennttss ooff tthhee AAiirr

Robert Boyle first carried out the famousexperiment to show that sound cannot travelthrough a vacuum by placing a watch in a jarand pumping the air out of the jar (the handskeep moving but the ticking sound disappearsas air molecules are forced out). Boyle alsoobserved that a flame needed air to burn andthat life could not survive without it. This laiddown the first tentative steps tounderstanding that there were constituentparts to our atmosphere, rather than a largeabyss.

Joseph Priestly is the man credited with firstdiscovering oxygen in 1744. Priestley used amagnifying glass to focus the sun's rays on asample of the compound mercury (II) oxide:

2HgO(s) 2Hg(l) + O2(g)

He discovered that heating this compoundproduced a gas in which a candle would burnmore brightly. This gas was oxygen. AlthoughPriestley could not accurately interpret theseresults using the scientific knowledge of thetime, his work was later used by AntoineLavoisier. Lavoisier showed that the massgained by lead when it forms its oxide isequal to the mass of the air lost. He showedthat the remainder of the air turned out to beincapable of supporting further burning;hence proving that part which had reactedwas different. Lavoisier had discovered thatcommon air was not a single, indivisibleelement.

Lavoisier also demonstrated the role ofoxygen in the rusting of metal, as well asoxygen's role in animal and plant respiration.Lavoisier conducted experiments that showedthat respiration was essentially a slowcombustion of organic material usingabsorbed oxygen.

Priestly and Lavoisier had also inadvertentlyisolated the major ingredient of ouratmosphere: nitrogen. Priestly correctly saidthat we would all be “living out too fast” ifonly oxygen was present in the air. Oxygenand nitrogen make up the vast majority of theair we breathe but there was another gas yetto be discovered which is responsible forevery scrap of food on Earth.

In the 1750s, Joseph Black stumbled acrossa gas he dubbed “fixed air”, which we knowas Carbon Dioxide. He found limestonereacted with acids to yield this gas which wasdenser than air. The gas did not support lifeor flames. He also demonstrated that the gaswas produced by animal respiration and whencharcoal was burned. Theses reactions areshown below:

2H+(aq) + CO32-(aq)

H20(l) + CO2(g)

C(s) + O2(g) CO2(g)

6O2(g) + C6H12O6(s)

6H20(l) + 6CO2(g)

Carbon Dioxide is both a crucial anddangerous element of the air. Along withoxygen and nitrogen, it helps transform thelump of rock which is our Earth, into a living,breathing world. We need it for food andwarmth but we abuse it only at our peril. Atno point in the last 400,000 years have CO2levels been anywhere near where they aretoday (Fig.1).

John Tyndall explained the heat in the Earth'satmosphere in terms of the capacities of thevarious gases in the air to absorb infraredradiation. Tyndall was first to prove that theEarth's atmosphere has a Greenhouse Effectand he showed how CO2 plays a big part inthis. The sun's energy arrives on the groundas visible light mostly, and returns back upfrom the ground as infrared energy mostly,and he showed that water vapour, CO2 andsome other gases substantially absorbinfrared energy, hindering it from radiatingback up to outer space. Temperature andCO2 levels are clearly linked as shown byfig.1:

BBrreeeezziinngg ppaasstt

There is the story of Christopher Columbus’voyage to the Americas and his equallysignificant (and inadvertent) discovery of theTrade Winds. These were only truly explainedsome 350 years later by William Ferrel. Hedemonstrated that it is the tendency of risingwarm air in the northern hemisphere, as itrotates due to the Coriolis Effect, to pull in airfrom more southerly, warmer regions andtransport it poleward. It is this rotation whichcreates the complex curvatures in the frontalsystems separating the cooler Arctic air to thenorth from the warmer continental tropical airto the south. Finally there is the story of thegreat aviator, Wiley Post, who discoveredwhat we now call jet streams which are fast-flowing rivers of air which circle the world inboth hemispheres. The global winds have greatsignificance as the redistributors of both heatand water which are both indispensible to life;without its effects we would not survive.

FFrraaggiillee CCrraaddllee

So far, we have seen how air has provided lifeon Earth and allowed it to flourish. However,our atmosphere also serves to protect usagainst the hazards of space.

Figure 1

CO2 levels (ppm) and temperature change in the last 400,000 years



16

Above the clouds, layer after layer of airprotects us from space. The very first of theseprotective layers was nearly destroyed beforewe discovered it.

OOzzoonnee

W.M. Hartley was curious about a recentlydiscovered gas, ozone (O3). A puzzling issueof the time was that ultraviolet (UV) rays withwavelength less than 293nm did not arrive atthe surface of the Earth while visible light andUV rays with wavelength between 400 and293nm did. Hartley noticed that ozone gashas a tendency to absorb low wavelength UVrays and showed that it was a layer of ozonewhich prevented these high energy (energy isproportional to frequency (E=hf); lowwavelength = high frequency for EM waves)UV rays reaching the ground. If these wavesreached the ground they would weaken thehuman immune system, cause skin cancerand eye cataracts and destroy algae whichour vital to food chains.

In 1930, General Motors charged ThomasMidgley with developing a non-toxic and saferefrigerant for household appliances. Hediscovered dichlorodifluoromethane, achlorinated fluorocarbon (CFC) which hedubbed Freon. CFCs replaced the varioustoxic or explosive substances previously usedas the working fluid in heat pumps andrefrigerators. CFCs were also used aspropellants in aerosol spray cans and asthmainhalers.

Until the 1970s, CFCs were seen to be apractical solution to the refrigeration puzzlebut this view was destroyed by the work ofseveral scientists who began to unravel whathappened to CFCs as they rose through ouratmosphere. The CFCs would rise safely untilthe altitude of ozone molecules until theybecame exposed to the high energy UV rayswhich ozone is trapping. A chlorine atomcauses devastation here when it is releasedby a UV ray. Chlorine radicals form whicheffectively deplete the ozone layer by thefollowing overall reaction:

2O3 (g) 3O2 (g)

According to complex calculations, onechlorine atom could destroy 100,000molecules of ozone. A worldwide ban of CFCswas demanded by the two scientists, Molinaand Rowland, who had made the shockingdiscovery that 30% of the ozone layer wouldbe depleted by 2050. However, the industrywas unlikely to fold so easily, and it needed ahole in the ozone layer the size of the USA togradually emerge over Antarctica to cause achange in the law. This was discovered over adecade after Molina and Rowland’s discoverywas made public and was the final nail in thecoffin for those backing CFCs. A worldwideban on CFCs wasn’t enforced until as late as1996.

UUpp,, uupp aanndd aawwaayy!!

Some 100km above the Earth’s surface, theair crackles with current in the ionosphere.

This high electrical layer soaks up rays fromspace so deadly that life could not exist belowwithout it. Without realising it, Marconi tookadvantage of this layer of air to transmit hisfirst messages across the Atlantic Ocean.Marconi’s waves allowed the world to knowthe fate of the Titanic and how everyone onboard would have died without them. Thewaves were explained by Heaviside whoapplied the fact that wireless waves would bereflected by something that conductselectricity. Although the air is very thin at theheight of ionosphere, a few molecules of gasdo exist which can be ionised by cosmic rays.This leaves a spray of positive and negativeshards which would allow the air to become“electrical”. This reflecting mirror in the sky isnow called the Heaviside layer in honour of itsdiscoverer but its secrets were unveiled byEdward Appleton.

Appleton had observed that the strength of aradio signal from a transmitter was constantduring the day but that it varied during thenight. This led him to believe that it waspossible that two radio signals were beingreceived. One was traveling along the groundand another was reflected by a layer in theupper atmosphere. The variation in strengthof the overall radio signal received resultedfrom the interference pattern of the twosignals. To prove his theory, Appleton usedthe BBC radio broadcast transmitter atBournemouth. This transmitted a signaltowards the upper reaches of theatmosphere. He received the radio signalsnear Cambridge, proving they were beingreflected. By making a periodic change to thefrequency of the broadcast radio signal hewas able to measure the time taken for thesignals to travel to the layers in the upperatmosphere and back. In this way he wasable to calculate that the height of thereflecting layer was 60 miles above theground.

The final protective layer of the atmosphere isdriven by both the electricity of theionosphere and the magnetism above it.Thousands of kilometres above the Earth’ssurface are sweeping lines of force from theplanet’s magnetic field which protect us fromradioactive space. This layer is alsoresponsible for the formation of the auroraborealis (Northern Lights) and ties into thecomplex physics behind van Allen belts whichultimately protect us against the dangerousradiation from space.

If you cannot believe that air, too thin for us tobreathe, is a strong enough to defend theplanet, then may we remind you of the eventsof October 2003. Don’t remember it? You’relucky you don’t. If you did remember it, itwouldn’t be for very long, as you and the restof organic life, would have been immediatelyconsumed by the output equivalent of 5,000suns’ worth of x-rays, without ouratmosphere’s blanket of protection.

“In October 2003, a series of explosionsrocked the outer surface of the sun. Amassive flash fried Earth with x-rays

equivalent to 5,000 suns. A slingshot ofplasma (ionised gas) barrelled towards us at2 million miles an hour. The most massiveflare since records began and one of thebiggest radioactive maelstroms in historytogether met a far more formidable foe. Theyeach arrived, and then, one by one, theysimply bounced off… thin air.”



The Path Towards Finding TheMagnetic MonopoleWajid Malik

17

MMaaggnneettiissmm iiss oonnee ooff tthhee mmoosstt ccoommmmoonnllyykknnoowwnn ffoorrcceess oonn tthhee ppllaanneett;; iittss ddiissccoovveerryyddaatteess bbaacckk mmaannyy tthhoouussaannddss ooff yyeeaarrss..Magnets are seen in a wide variety ofeveryday locations, from electric bells toparticle accelerators, but these magnets allexist as the classical idea of a magneticdipole. The concept of a magnetic monopoleis one that has been extensively theorised;however these rare particles have yet to bediscovered.

TThhee FFuunnddaammeennttaall FFoorrcceess

There are four fundamental interactions ofnature (ways in which particles interact witheach other): The strong interaction, the weakinteraction, gravitation and electromagnetism.Electromagnetism concerns theelectromagnetic field, in which relativelymoving electrical and magnetic fields induceeach other. From this it has been deducedthat electricity and magnetism are interlinked,which implies that properties exhibited by oneshould be apparent in the other. This causesa problem when it comes to the magneticmonopole; single electrical charges can easilybe isolated and are abundant in the worldaround us (take the proton or the electron, forexample) but magnetic poles are only foundin North and South pairs. This fuelled thesearch for the magnetic monopole; a free-moving magnetic ‘charge’ that does notcancel out with the opposite pole.

TThhee iimmppoorrttaannccee ooff tthheeiirr eexxiisstteennccee

One of the largest tasks in science isdescribing how the universe began. The BigBang is the generally accepted cosmologicalmodel but it needs to be developed and builton by other theories to fully explain how it allcame about. An area of theoretical physicsthat is currently being researched is that ofunified field theories. The idea of this hasbeen around for some time, but there is noaccepted theory to date. Magnetic monopolesbecome very important when it comes toGrand Unified Theories. These theories predictthat at very high energies (such as thosearound the time of the Big Bang), three of thefour aforementioned fundamental forces: theelectromagnetic force, the strong nuclearforce and the weak nuclear force arecombined into a single field. It is hypothesisedthat from there they splintered off into theseparate forces. However a necessary factorin making this work is the existence of themagnetic monopole; this type of monopole,known as the GUT monopole, is thought to bevery rare and massive, making both itsdiscovery and its creation (in a particleaccelerator) very unlikely. The existence ofmonopoles also has implications insuperstring theory and would help to developthis further.

OObbsseerrvvaattiioonn ooff tthhee mmoonnooppoollee

The numerous failed attempts to successfullydetect the magnetic monopole made itsdiscovery seem ever more improbable;however on the 3rd September 2009scientists from the Helmholtz Centre Berlinclaimed to have successfully observedmagnetic monopoles for the first time. Theirexperiment involved using the process ofneutron scattering to make the orientation ofthe Dirac Strings able to be determined.Neutron scattering is the process of usingneutron radiation (a stream of neutrons) tointeract with another substance, which in thiscase was a crystal of dysprosium titanate(Dy2Ti2O7). This is a material known as a“spin ice”, which essentially has the sameatomic arrangements as water ice, but in thiscase has certain magnetic properties.Thecrystal was cooled to temperatures between0.6 and 2 Kelvin and the neutron scatteringexperiment was begun. Since the neutronscarry a magnetic moment, they interactedwith the Dirac strings and scattered ina way that represented the arrangement of these strings inthe crystal. Using a strong magnetic field, the orientation of the string network could be manipulated to favour theobservation of a monopole, and eventually a

field like that of a monopole was observed atthe end of the strings.

The observations made during the neutronscattering experiment show propertiesresembling monopoles; however the actualmonopole particle has not been isolated inthe same way as, say, an electron can be.The results of this experiment do providesubstantial evidence that monopoles do exist;however one thing is for certain; the search isnot yet over.

Figure 1 (above)

Diagram showing the Electric (E) andmagnetic (B) field lines generated bymonopoles and by their motion withvelocity v. (a) Electric monopole withelectric charge e. (b) Magneticmonopole with magnetic charge g.


Figure 2 (below)

Schematic diagram of the neutronscattering experiment: Neutrons arefired towards the sample, and when amagnetic field is applied the Diracstrings align against the field withmagnetic monopoles at their ends. Theneutrons scatter from the stringsproviding data which show us the

strings properties.


18

ChemiluminescenceLLiikkee aannyytthhiinngg tthhaatt lliigghhttss uupp,, tthhee sscciieenncceebbeehhiinndd cchheemmiilluummiinneesscceennccee ccoommeess uunnddeerrtthhee nnaattuurraall pphheennoommeennaa ooff lluummiinneesscceennccee..In the simplest sense it is a transfer ofenergy, from chemical, thermal orelectrical into radiant energy, (a sourceof energy which causes the atoms of asubstance to vibrate). If enough energyis delivered, the electrons of the atomscan be excited to a higher energy state,and when it falls back down to theiroriginal state, energy is released as lightphotons with energy proportional totheir frequency. In some cases thisfrequency is within the range of visiblelight and we can see the substance glowa certain colour. In chemiluminescence,the atoms are excited when chemicalcompounds react exothermically,releasing a large amount of energy.

LLuummiinnooll RReeaaccttiioonn

The most basic reaction that exhibitschemiluminescence is that of luminoland hydrogen peroxide:

Luminol + H2O2 → 3-APA (3-aminophthalic acid) → 3-APA + light

Luminol is first activated in a solution ofhydrogen peroxide and a hydroxide saltin water. In the presence of a catalystsuch as an iron compound the hydrogenperoxide is decomposed:

2 H2O2 → O2 + 2 H2O

Dianion is formed when luminol reactswith the hydroxide, which then reactswith the oxygen produced from thehydrogen peroxide. The product is anorganic peroxide that is highly unstableand immediately decomposes to produce

3-APA in an excited state. When theelectrons then fall back to the groundstate, photons are emitted and thesolution appears to light up.This is the process that you often see onCSI when they find traces of blood.Investigators will spray a solution ofluminol with hydrogen peroxide onto thefloor, and the iron present in thehaemoglobin in blood is enough tocatalyse the reaction and cause theblood traces to light up.

Glow sticks use a similar principle to theluminol reaction, however the maindifference is that the decomposition ofthe chemical doesn't produce an excitedchemical, but instead gives out energyto excite a dye. This has manyadvantages, the main being that the dyecan be specifically chosen to emit aparticular colour. This reaction isactually the most efficientchemiluminescent reaction known, up to15% quantum efficiency. In theory, onephoton of light should be emitted foreach reaction. However in reality, non-enzymatic reactions seldom exceed 1%efficiency. Other factors such as pH andtemperature also affect the quality andintensity of the light produced, howeverthe reason why is too complicated to gointo.

UUsseess ooff cchheemmiilluummiinneesscceenntt cchheemmiiccaallss

Unfortunately we don’t know thecomplete reasons as to whychemiluminescence occurs. However,scientists have discovered a greenfluorescent protein (GFP) from jellyfish.The protein is able to attach to othermolecular structures, allowing us to seevarious functions of the cell and howproteins interact with each other. Inmore modern times, the need to

measure the precise concentrations ofsolutions is growing, therefore it is nosurprise that chemiluminescence isbeginning to play its part in the use ofmeasuring quantities. An immunoassayis a biochemical test that measures theconcentration of a substance in abiological liquid and with technicaldemands of these assay markets rising,the requirement for highly sensitivedetection technologies is vital.Chemiluminescent processes aresufficiently sensitive, not prone tointerference and easy to use thereforethey seem perfect for these applications.The measurement of light intensity isfairly simple and since there is barelyany background light produced from thesample, the ability to provide a largerange of measurements is possible, evenwith simple instrumentation. Howeverthere is often some difficulty in choosingthe correct detection reaction. Scientistsare currently using methods ofcovalently labelling one of thesubstances that are being analysed witha chemiluminescent chemical. Bytriggering the chemiluminescent label toundergo the light-emitting reaction, asignal will be produced for detecting thesubstance. There are not many suitablechemiluminescent compounds inexistence, which is why the researchinto these chemicals is a growing field,and at the moment, scientists are tryingto find reactions which demonstrate anadequate chemiluminescence quantumyield for good efficiency.


Wei-Ying Chen


19

RReevviieeww


20

The Rowboat’s KeelingAmeya TripathiOOnn aa ssuummmmeerryy lluunncchhttiimmee ttwwoo jjuullyyss aaggoo,, iinn aaddrroowwssyy ccllaassssrroooomm,, II aatttteennddeedd aa pprreesseennttaattiioonnooff tthhee nnaasscceenntt HHaabbeerrddaasshheerrss GGeeooggrraapphhiiccSSoocciieettyy. It was being addressed by aformidable speaker: Mark Maslin.

Like many of his colleagues, Professor MarkMaslin is possessed by global warming.Though he is an energetic and youthful man,his dark hair has become speckled withslivers of silver, the like of which can onlyhave been brought about after examiningportentous climate models. Nevertheless, hespeaks with a cadence and clarity that evincea sharp mind.

Maslin does far more than speak to students;as the director of the Environment Institute ofUniversity College London, he is one of theleading climatologists in the world. A prolificwriter in journals such as Science and Nature,Maslin has long been a passionate advocatefor changing our ways. In an effort to advancethe issue, he attends a massive annualconvention at that Mecca of conferencecentres, Las Vegas.

This is where a whole group of scientistsconverge and every year declare to the wholeworld - politicians, sceptical oil barons,grumbling developing countries and eagerecomentalists, roughly the same message:firstly, there is a consensus that globalwarming is caused by humans, and secondly,that we’re about to enter a geological phasecalled the ‘Anthropocene’ and everything isgoing to fall to pieces; hurricanes, flooding,droughts, heatwaves (not just the 29° onesyou scoff at) and the door to Bedlam shallgenerally be poked ajar, swung off its hinges,and burned as firewood, belching yet morenoxious vapours into the atmosphere.

The New Scientist featured a rather spookyand alarmist feature which furthers thismessage, entitled ‘Earth 2099: PopulationCrashes, Mass Migration, Vast New Deserts,Cities Abandoned’. Perhaps the mostforeboding part of the front cover of thatparticular issue is the next subtitle - ‘How tosurvive the century’. While somewhatfatalistic, it increasingly represents the view ofmany scientists, such as the fondlynicknamed ‘Grandfather’ of global warming,James Hansen, the head of the NASAGoddard Institute for Space Studies. Recently,he was profiled by eminent, authoritative andlucid writer Elizabeth Kolbert (who has writtenthe absolute must read: Field Notes From ACatastrophe) in an aptly titled piece, ‘TheCatastrophist’. She and Hansen form part of agrowing number of observers who believe thesituation to be close to irrevocable. She writesin Field Notes the following about our abilityto prevent warming:

“Perovich offered a comparison that he hadheard from a glaciologist friend. The friendlikened the climate system to a rowboat: “Youcan tip it and just go back. And then you tip itand you get to to the other stable state,which is upside down” .

Just in case you thought it was so close toirrevocable as makes no difference, there aresome scientists who are slightly less gloomy,perhaps because they’re not as battle-scarredand wisened about the ways of industry andpolitics, perhaps because they’re moreaudacious. One of those people wasProfessor Maslin, who seemed intent on nottoeing the ‘We’re all going to die’ line. Thereason these scientists are silent isn’tbecause they’re afraid, or apathetic; rather, itis because they’re all far too busy arguingamongst themselves. There is a great debateraging between and within the worlds ofscience and politics. What is beingdetermined is what type of mitigation theywish to pursue. They are debating overwhether geoengineering, or a type ofmitigation which I shall label anthropogenicengineering, is the best way forward, or acombination of the two, or an entirelydifferent concept, adaptation.

These are fairly exact concepts, so let usdefine them accurately.

Adaptation, in the lexicon of climatology, is allabout survival. Tsunami shelters, sunscreenthat can block ultraviolet rays, extraterrestrialcolonies, renovating the Thames Barrier,evacuations - all the sort of last resort stuffwhich we do when we realise we can’tactually stop it; the rowboat has capsized.

‘Anthropogenic engineering’ is aboutchanging human behaviour i.e. reducingreliance of fossil fuels, replanting therainforest, banning ozone eatingchloroflourocarbons, cycling to work like Mr.Boris Johnson, holding onto our polyethylenebags, buying a Prius, not indulging in airtravel to destinations we could amble to etc.,etc.

It’s the tough one which no one really likes,as it’s a fundamental, systemic change in theway we have functioned for centuries.Especially opposed to the proposition areChina, and India, and other developingcountries who hold the dubious honours ofbeing some of the biggest emitters in theworld (They do claim that if one were toexamine emissions on a per capita basis, theyare squeaky clean). This ‘anthropogenicengineering’, is firstly expensive - no onewants to buy photovoltaic cells and adorntheir roof tiles with them if they’ll only pay foritself long after the Earth is roasting in anoven of carbon dioxide and self-pity - andsecondly, seems to be geopolitics’ Gordianknot as demonstrated by the pitiful failure ofthe 1997 Kyoto Protocol.

The sexier option, the ‘have your cake andeat it too’ option, is a type of mitigation calledgeoengineering. Instead of changing humanbehaviour (or in conjunction with it), why notchange the behaviour of the Earth’s systems?Tinker with wind patterns, solar fluctuations,migrations, forestation? It seems like the roleof a Bond villain cast in an episode of TheSimpsons. The image that first came to mymind when someone told me this is ofsomeone putting a giant lampshade aroundthe sun. I found that image rather absurd(perhaps in part, because the sun waswearing sunglasses), yet one of the ideas atthe heart of geoengineering isn’t actually thatfar off.

It involves placing a massive, reflectivesunshade in orbit, using satellites and a moreadvanced version of tin foil, comprising 16trillion small reflective disks, at an altitude of1.5 million kilometers, with a diameter of1800km. All of this would result in adeflection of 2% of the sun’s long waveradiation, enough, scientists claim, to stopglobal warming. Whilst that might soundexpensive, this singular solution, costingsome tens of billions on dollars, is probably alot cheaper than changing our wholecomfortable lifestyle and culture of disposablefashions and general consumption. There is anuance to be considered; this obviously willhave a negative effect on say, photovoltaiccells - a good example of why combinationsof the two approaches tend to be tricky.Moreover, a recent article by the BritishAntarctic Survey noted that the reflectivesunshade would still climate change, due tothe different temporal and special forcing ofincreased CO2 compared to reduced CO2radiation. These include: significant cooling ofthe tropics, warming of high latitudes andrelated sea ice reduction, a reduction in theintensity of the hydrological cycle and anincrease in Atlantic overturning. In addition,the reflective sunshade fails to mitigatecertain causes such as ocean acidification.

The other oft-discussed geoengineeringmethod is founded on a principle called ThePinatubo Effect. In 1991, Mount Pinatubo, amassive active stratovolcano in thePhilippines erupted ultra-Plinian style (itejected a gaseous plume that was tall enoughto extend to the stratosphere, akin to theeruption of Mount Vesuvius, or Krakatoa).

The inhabitants had thankfully beenevacuated and the situation was safe. Not sothankfully, the volcano had ejectedapproximately 15 million tons of sulphurdioxide. The sulfur dioxide rose into thestratosphere, where it reacted with water andformed a hazy layer of aerosol particlescomprised largely of sulfuric acid droplets.Over the next two years, strong stratosphericwinds spread these particles around theglobe. Unlike the lower atmosphere (ortroposphere, which extends from the surface

Scope 2009/10 Review


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The Rowboat’s KeelingAmeya Tripathi

to approximately 10km), the stratospheredoesn’t have rain clouds as a mechanism toquickly wash out pollutants. As aconsequence, the heavy influx of aerosolpollutants from Pinatubo remained in thestratosphere for years until the processes ofchemical reactions and atmosphericcirculation filtered them out. The result was ameasurable cooling of the Earth’s surface foralmost two years. Why? Steven Platnick ofthe NASA Langely Research Center explains:

“Because they scatter and absorb incomingsunlight, aerosol particles exert a coolingeffect on the Earth's surface. The Pinatuboeruption increased aerosol optical depth inthe stratosphere by a factor of 10 to 100times normal levels measured prior to theeruption. Consequently, over the next 15months, scientists measured a drop in theaverage global temperature of about 1°F(0.60C)”.

What does this mean? Firstly, it caused asudden blip in a sequence of the hottestyears on record. Note the flattening of thecurve on the Mauna Loa graph above 1992.Secondly, it gave geoengineers an idea: to‘seed’ the atmosphere with sulfur dioxideaerosol particles. Rather confusingly, thesulfur dioxide also did tear open the ozonehole even further, but, they insisted, theaverage temperature did cool down for ashort period of time. So is it feasible? It hasbeen estimated that seeding the atmospherewith sulfur dioxide would cost $100 billion ,trump change compared to the recent $800billion economic recovery package in theUnited States.

Why not do it? I asked a similar question toProfessor Maslin, ‘Is geoengineering, such asplanting the atmosphere with sulfur dioxide,the stuff of Hollywood, or is it tangible?’. Atthe time I was left feeling a littleunderwhelmed. Here’s a paraphrasing of whathe said:

Well, while it is agreed that geoengineeringwould reduce global temperatures on a macrolevel, we’re not really aware of the microeffects: what would happen in each country,whether it would be politically just; whetherthere would be mass warming in one place tocompensate for mass cooling in the other.Averages are rather crude, really.

What he seemed to suggest was, ‘We’re notsure about this whole geoengineering thing,so let’s wash our clothes on 30° instead.’(This is a crude stereotype, but itdemonstrates the notion of geoengineeringtrumping anthropogenic - or ‘gesture’ -engineering).

What he was actually referring to were theseconcepts like sulfur dioxide causing ozonedepletion, ecological issues, etc. in addition tothe politics of it. He just didn’t have the timeto explain all of these shortcomings.

There are other methods for geoengineeringtoo. Perhaps two years away from productionare a series of carbon scrubbers, a type ofsynthetic tree designed to purify air, beingproduced at Columbia University. These couldtake one ton of CO2 out of the air per day.Smaller than a standard shipping container insize, and at about $200,000 in price, thesecarbon scrubbers trap CO2 entering them onan ion exchange resin. The CO2 then can beeither buried or used in other ways.

Another idea is to fertilize trees with nitrogen.The idea here is said easily enough: fertilizetrees with nitrogen to stimulate their ability toabsorb more carbon dioxide and, byincreasing their albedo, reflect more solarradiation back into space. Voila! You’ve beguncooling the planet. Not so fast says climateissues writer Jeremy Elton Jacquet ofTreehugger:

“Even if the nutrient does act as a switch thatchanges the leaves' structure to increasetheir albedo, only certain species would beable to take advantage of this property... if wewanted to apply this method on a sufficientlylarge scale to effect carbon emissions, wewould have to plant entire forests made justout of those few species... all theenvironmental downsides associated withhigh nitrogen concentrations: nitrous oxideemissions... groundwater contamination anddrying (trees that consume larger amounts ofnitrogen need more water), just to name afew.”

Aerial reforestation is another idea; puttingseeds in biodegradable shells and droppingthem out of a Cessna. This was tested on aDiscovery Channel documentary, ProjectEarth, but unfortunately, rates of successfulgermination were very low. It seems likegetting out a spade and planting trees is theanswer, but doing that in the depths of thesweltering Amazon rainforest may not bereasonably practicable.

These are just some of the big ideas beingfloated, but what is immediately apparent isthat geoengineering is still very much up inthe air and anthropogenic engineeringremains tricky and expensive (plus, you know,we don’t really care for it). It seems likehumanity is stuck between a rock and a hardplace, and the words of doomsayers such asHansen and, to a lesser extent, Kolbert, areworth heeding.

So I’ve just ruled out our ways out beatingglobal warming, and told you that we shouldlisten to the catastrophists and the questionfacing us is the one on the New Scientistcover, ‘How to survive the next century’ ratherthan the question that we want to beanswering - ‘How to stop global warming’. Aquestion of adaptation rather than mitigation.Sounds like a rather gloomy analysis.

There’s something missing, though. There is

one glimmer of hope. I looked at whygeoengineering isn’t there yet and so, inshort, it is currently a non-option. But thechanging of our behaviour, anthropogenicengineering, is.

Why? Well, geoengineering, that form ofBlofeldesque planet tinkering, has only beenaround for a few years. Anthropogenicengineering had been around for decadesand has had a proper chance to develop intoa fully fledged cooling behemoth. Somepeople call this ‘Gestureengineering’ becausethey think our behaviour doesn’t matter (inany case, the Chinese will be polluting tentimes of what I recycle anyway, right?). Butit’s not true. Guffawing about what willhappen to your solar powered car when itgoes into a tunnel is no longer a terminativerebuff - as shown by the phenomenal TeslaRoadster and the general improvement ofrenewable energy technology. Rapidly,renewables, recycling and all of the rest of itare dispelling long held stereotypes.

Photovoltaic cell efficiency, for example, hasrocketed from a record level of 17% in 1992to 42.8% today, which isn’t that far off thephotosynthetic capabilities of the leaves ofsome plants - this means they pay forthemselves faster, and are overall, cheaper.

Another fine example is that of CFCs. Thereduction of chloroflourocarbon andrefrigerant use yielded a 30% shrinkage ofthe ozone hole in area between 2006 and2007 - a tangible example of anthropogenicengineering actually working.

The Honda FCX Clarity, a car powered entirelyby hydrogen, proves to be another example ofthe rapid advancement of energy production.The Clarity works in a very simple way. At theback of the car is a fuel tank, exactly whereyou expect it to be, but instead of it beingfilled with diesel or petrol, it is filled withcompressed hydrogen. This hydrogen iscombined with oxygen from the air in the fuelcell. In the fuel cell, an adapted form ofelectrolysis generates electricity: protons areconducted through a polymer electrolytemembrane, separating them from electronswhich follows an external circuit to acathodeThis electrolysis is used to drive theelectric motor, which is all controlled by anonboard computer.

When the Clarity runs out of juice, one justpulls into a hydrogen fuel station. This avoidsall of the plug socket gimmickry of previouselectrical cars. Admittedly, there are very fewhydrogen power stations, so in the meantime,Honda has built a Home Energy Station whichreforms natural gas (and electricity from yoursocket) to create hydrogen. Hydrogen costsroughly the same as petrol and yields you270 miles of driving for a 2 minute stop atthe pump, quite unlike the twelve hourcharging from a plug socket that the previousgeneration of green cars required.



22

The crucial factor is this: while not technically‘renewable’, hydrogen is the most abundantelement in the universe. Even better, the onlypollution comes in form of trickling waterdroplets out of the exhaust, from thecombination of hydrogen and oxygen.

Another exciting and improving area is windturbine technology. The trend of bigger rotorsis better persists, as the longer the blades,the larger the area ‘swept’ by the rotor andthe greater the energy output. In addition,there are many different turbine designs sothere is scope for yet more innovation andtechnological development.

For some people, it is not enough to see thatrenewable energy has tangible results. It hasto be profitable, too.

Jiang Lin, who heads up the China EnergyGroup at the Lawrence Berkeley NationalLaboratory, said that solar thermal is likely themost promising technology in the entirealternative-energy field.

When asked when solar thermal can hit paritywith fossil fuels, Lin responded ‘now’. Thesesolar thermal plants, at their maximum, haveyielded 354 megawatts of energy becausethey’re built over relatively small areas. If theygenerate more than 500 megawatts ofenergy, (by economies of scale) it will costless than 10 cents per kWh. This isconsidered to be the magic number, at whichall industries will switch to solar, rain or shine,as it compares at least equally, if notfavourably, with certain fossil fuel costs.

So changing our human behaviour is sort ofthere; it has shown tangible results, and it isalmost economically viable (at least, in thecase of photovoltaic and solar thermalenergy). Economic subsidisation from theAmerican Reinvestment and Recovery Plan,cap-and-trade schemes (successfully trialledin Denmark) and private funding as investorsseek to dominate a future market shouldmake the adaptation of human behavioureven more economically viable. As well asthat, the recent UN meeting and theCopenhagen summit of December indicate areal desire to make a difference; President HuJintao’s recent overtures could prove telling. Itseems like our own adaptation is a slightlyless heady dream than the untested schemesof geoengineering. That ‘Gestureengineering’tag can bugger off, then.

The crucial point is this: mitigation, in theform of modifying our own behaviour, asopposed to the behaviour of the planet’ssystems, is better established and improvingrapidly, and therefore the former has a biggerchance of succeeding than the latter.

So we’ve reviewed anthropogenic engineeringand geoengineering, and I’ve suggestedanthropogenic engineering looks the moreefficacious a solution. Whatever methodologyyou think works best, there is one crucial partof the global warming issue, to return to thevery beginning. Instead of talking about it,and writing and reading about it, or havingmeetings about it and coming out with thesame consensus, we ought to do something.

There is hope the world’s policy makers willbe proactive in Copenhagen, later this year,when they form a new climate treaty, if it isn’taggressively whittled down by opponents tothe point of being ineffective as seems to bethe case with the Waxman-Markey ClimateBill that narrowly passed in the U.S House ofRepresentatives.

Why should we do something? Why shouldwe care? It’s not happening, to me, right now,is it? It certainly doesn’t seem dangerous, andyou know, polar bears had it coming.

This is a tricky dilemna to resolve. At whatpoint have we superseded what climatologistscall DAI (Dangerous AtmosphericInterference)? As of March 2009, carbondioxide in the Earth’s atmosphere is at aconcentration of 387 ppm by volume . Whatconstitutes too much? Aren’t catastropheslike Katrina and flooding in Bangladeshevidence enough? Is it 350ppm, as Hansenclaims at his new campaign, 350.org? Is it500ppm, or 550ppm, as the Chinese mightlike to lead us to believe? On an apparentlyunrelated topic, the great Sir. DonaldBradman said this of chucking in cricket:

“It is the most complex problem I haveknown...because it is not a matter of fact butof opinion and interpretation. It is so involvedthat two men of equal sincerity and goodwillcould take opposite views.”

This ambiguity is part of what lies at the heartof the inertia. Maybe we won’t know when itis dangerous until it slaps us in the face - theslapping hand coming in the form of anapocalyptic wave of Arctic meltwater.

Wired News makes the point to ElizabethKolbert that things getting warmer soundsquite nice as a notion. 2-3° degrees warmingseems harmless, even pleasant - notdangerous! We’ll be able to grow vines forwine in here rather than buying the Frenchstuff, and, not have to trek to Ibiza to holiday.

WN: Isn't part of the problem that peopleassociate ‘warm’ with comfortable?

Kolbert: “People think, "I won't have to go toFlorida anymore. Florida will come to me."People should realize that warmth doesn'tmean Florida. It means New York isunderwater. It may be that certain places likeSiberia are more comfy, but it also meansthat they have no water. If people say, "Whyshould I be worried about global warming?" Ithink the answer is, Do you like to eat?"

I bet you do like to eat.



23

Scope: What do you recall aboutHaberdashers' from the days you were here?

SBC: Haberdashers clearly aimed atexcellence and encouraged independence ofthought. Sure it was traditional, but it alsoheld up on a pedestal those individuals whowere creative in any way. it offeredopportunities if students wanted to take them.I remember singing in the school choir, actingin school plays, contributing to the schoolmagazine, going to after-school clubs insculpture and carving in the art department,and heading down to Tykes Water during thelunch hour for lots of fun! i have remainedgood friends with a handful of people frommy year at school and we meet for regularreunions. i spent from 1967-77 inHaberdashers, during which there weresignificant changes in society, and the schoolhad to adapt to these social changes.

Scope: Can you explain your 'Theory ofMindblindness'?

SBC: Theory of mind is also called thecapacity for "mindreading" and"mindblindness" is the flip side of the coin. Itdescribes individuals who cannot mindreadothers, who have difficulties in using a theoryof mind. I argued back in 1985 that childrenwith autism suffer from degrees ofmindblindness, which may explain their socialand communication difficulties, and this hasbeen amply supported by experimentalevidence.

Scope: Your most recent work published inthe British Journal of Psychiatry examined theeffect of Foetal Testosterone on normalchildren. Given testing the supposed link,between FT and autism, touted by the media,would require large study samples (as autismoccurs in only 1 % of the population), arethere any other methods, apart from suchstudies which could substantiate the theory?

SBC: The best test of whether FT is elevatedin autism would come from a large sampleand fortunately we have access to such alarge sample, through the Danish Biobank,who hold 70,000 samples of amniotic fluid.From these it is possible to identify 400children who went on to develop autism, soby the end of 2009 we will have tested these400 samples of amniotic fluid (againstmatched controls) to test the FT theory.

Scope: Your views on prenatal testing forautism have been much publicised, have theychanged at all?

SBC: My views have been variouslymisreported! But in brief, I think prenatal

testing for autism raises the same ethicalissues as prenatal testing for any medicalcondition and we should recognize it couldlead to a form of eugenics, under a differentname. i think autism is a very wide spectrum,and whilst some individuals with autism havemany severe disabilities (including learningdifficulties and epilepsy), others have socialdifficulties alongside unusual strengths ortalents. i am pro-diversity and would like tosee a society in which children with autismreceive support with their social difficultiesbut where their talents can blossom.

Scope: Clearly people with mental illness cancontribute positively to society, for exampleDavid Horrobin claims that 'schizophreniashaped society'. Do you believe a change inpublic perception regarding mental illness isrequired?

SBC: I think we need to de-stigmatize mentalillness, but equally psychiatry is itself is still inits infancy.

Scope:You have written in the New Scientistabout misrepresentation of your views. Whatdo you make in general of the developingtrend of trying to increase publicunderstanding of science ?

SBC: I think it is still important for scientiststo communicate with the public, and my piecein the New Scientist was a message tojournalists who report science to look morecarefully at what they do.

Scope: Working in the field of cognitivescience, what is your view with regard to thedeveloping field of nootropia and cognitiveenhancement?

SBC: This field is not that new and of coursewe've all been drinking coffee for years atwork, to aid our concentration! the key pointwith any drug is what its unwanted sideeffects are.

Scope: You were the first to develop a test forsynaesthesia; you plan any further research inthis field? What could further researchexamine?

SBC: It is true that in 1987 I published thefirst test for synaesthesia, which opened thedoors to two decades of research into thecondition. I also published the first brainscanning studies of synaesthesia, one ofwhich was published in Nature Neurosciencein 2002. My most recent foray back into thefield was to publish the first genetic study ofsynaesthesia (in 2009).

Scope: Has there been any significant research to contradict the view that autism isjust one extreme form of the male brain?

SBC: Not yet, though the hypothesis remainsto be fully tested at the neural level.

Scope: You were involved in the McKinnoncase, why do you think law courts rejected hisappeal?

SBC: I suspect there is still little sympathy forthe predicaments that people with AspergerSyndrome end up in, and that the USA wouldnot want to send out a message that if youhack into the Pentagon from outside the USAand get caught, you can avoid extradition ifyou have mitigating circumstances.

Scope: How far can the ability to mindread(recognise emotions) be taught to childrenwith autism?

SBC: We don't know what the upper limits tosuch teaching could be, but at least we havedemonstrated that such teaching does makea difference.

Scope: You identified two regions in the brainrelated to autism, leading to the amygdalatheory of autism; is there any scope formedication utilizing neurotransmitters in theseregions or is autism more anatomicallybased?

SBC: Medication may one day be usefultherapeutically in autism, even if autism has aneuroanatomical basis.

Scope: To what extent is Psychology adiscipline in its own right? Unlike psychiatry itdoes not require a medical degree, would yousee it as separate from the field of medicalscience?

SBC: Psychology is today largely cognitiveneuroscience. Psychiatry is distinct from itbecause it is also a profession that can legallyprescribe medication for mental illness

Questions by Raj Dattani & Casey Swerner


An Interview WithSimon Baron-Cohen


24


Could you give us a brief outline of yourcareer?

I graduated from Swansea University in 1969,and then proceeded to do a PhD in the samedepartment on the topic of gas kinetics aswell as the reactions of hydrogen atoms onalkenes in flow discharge tubes. Essentially Ianalysed the products and tried to figure outthe rates of reactions in the processes. Idecided that I didn’t really find a career inresearch an attractive proposition, and, havingdone a little bit of teaching I went toCambridge to do a PGCE. Once I got into thepractice of teaching I was hooked.

So it was love at first try then?

Yes - once you start and you enjoy theclassroom and you (like I) enjoy the subjectyou find that teaching that subject issomething amazingly rewarding andpleasurable.

Where did you go on from Cambridge?

I started teaching at Trinity School in Croydon.In 1977 I applied for a job here (HABS) afterfour years at Trinity, the department (at HABS)was bigger and seemed to be more dynamic,and as you know I’ve been here ever since. Ibecame the Head of Department (Chemistry)in 1982 and then the Head of Faculty(Science) in 1990.

Did this progression in role make your jobmore enjoyable?

Well I’ve never lost the enjoyment of theclassroom and keeping up with my subject,but yes I do also enjoy the managerial side ofmy job. I find that there are interestingchallenges and that there have been changesin the way the subject is taught - constantchanges in fact. You have to keep up andthere are concerns (as you see often in themedia) about ‘dumbing down’ inexaminations. I don’t think they have beendumbed down but regardless of what onethinks on that topic it doesn’t mean you haveto dumb down the teaching!

Are pupils stretched enough?

Yes. You see if all you teach is for theexamination then that’s all you will get out ofit as a teacher. You can always try to pushthem a bit harder, set material which is a bitmore challenging. Mostly the boys like thisand really respond to the challenges. Indeedthe boys here are no less bright than theywere 30 years ago and no less ambitious.They are a bit politer I think, but that may just

be imagination! You have to challenge themotherwise our pupils would be bored!

What are your reflections on the move to theAske (the new science building)?

I am very pleased with the outcome, it’s aterrific building. It’s a pleasure to teach in thelabs. Teaching in the temporary building wassurprisingly straight forward – the roomswere bigger and better than the old building!However we did face challenges in thetemporary building. The difference could beseen in the transition to this new building – itwas easier; not only because we could leavea lot of old equipment behind us, but alsobecause we had learnt lessons during ourtime in the temporary building.

Is the new building value for money? It wasvery expensive!

It is a building with a design life of 80 years –compare that to the design life of the original1961 buildings of this school - only 25 years.You can take a design life and extend that bydouble or more sometimes. So you’re lookingat a building that will definitely be here in a100 years time. It was of course expensivebut you cannot plan for the future unless youare willing to invest for the future. It was awell planned move in terms of architecture,design and finance.

Onto the curriculum – What was thereasoning behind the move IGCSE for thesciences?

We had reached the stage five years ago withthe old GCSE syllabus where we felt they didn’toffer enough of a challenge, they didn’t preparefor A level, and to be polite we were concernedwith the validity of the coursework investigation.IGCSE seemed an obvious choice. The syllabusmaterial suits our boys, with hard scienceswhich challenges and prepares.

What do you think of the new Chemistry Alevel?

Without a doubt the 2009 paper was difficult,although generally boys will tell you that thepaper was harder than past papers. This yearI agree that paper was indeed a tough paper.I think with examinations you have too breakit up and look at it like this. There’s thesyllabus which informs the content, the pastpapers which inform the style and theteaching which doesn’t necessarily have tomarry those two exactly. You can teach it in away which is appropriate as I explainedearlier. The new specification is not very different and the new changes are sensible;

they’ve removed industrial chemistry – it is avery “GCSE” topic. They include new materialsuch as entropy and provide a new approach– governed by the “How Science Works”concept - a promising teaching tool that alsopromises harder applied material. Difficultdoesn’t equal bad!

What do you think about science outside ofthe curriculum at HABS?

There is a lot of beyond the curriculum;Science Society and Scope at the forefront.Scope is an absolutely outstanding sciencemagazine. I have seen a lot of school sciencemagazines and there is nothing ofcomparable quality. Mr Delpech has taken itonto a new level in terms of quality in bothproduction and content. What’s laid on by theScience Society is amazing – we have hadsome very high quality speakers who travellong distances to speak to us and recentlyturnout has been considerably higher. [ In2009/10 the Science Society presented TheLord Krebs, The Baroness O’Neill ofBengarve, Dr. Aubrey de Grey, Prof. SimonBaron-Cohen, David Bodanis and will behosting Prof. David Nutt amongst others inthe near future...]

Elsewhere the Engineering EducationScheme, Junior Science Club, and the JuniorScience Fair (which my successor as Head ofDepartment, Dr Pyburn, pioneered) have allbeen marked successes. Add in the ScienceOlympiad extension classes in GeneralStudies which offer an opportunity to goabove and beyond with committed students.Boys have had a great deal of success – wehave had students compete at internationallevel and many others also gain medalsnationally. I am really proud of the way theschool offers these opportunities to pupils.Yes you have some pupils who will do thework and go home at 16.00 – you alwayswill. But what’s special is that we also havesome really committed students who reallywant to learn.

What recommendations do you have forimproving Scope?

Taking off my Head of Faculty cap and puttingon my Head of Department cap I would saychemistry is under represented normally.People do not appreciate the role ofchemistry in advances in all areas of science– materials, plastics, and medicine are allheavily influenced – for example surgicaladvances have always followed from medical[chemical] advances. Scope has, in pastissues, focused down on the medical side. Iwould like to see more physics too – particle

An Interview With MichaelLexton


25


physics and astronomy for example.

Do you think Chemistry’s role is more thanjust a ‘facilitator’ for the more applied aspectsof the sciences, such as medicine?

Chemistry has a bad press! This is a hobbyhorse of mine! If you pick up a newspaperand read the science section – you mightread about physics –the LHC (which brokeapart after 5 minutes !) or how medics areabout to cure Cancer or Alzheimer’s –headlines we have been having for manyyears ! If you see chemistry however you’llonly read about things like toxic materialleaks and the like. A very negative imagereally. I think that’s a great shame – itdiscourages people from going into chemistry– bright scientists might not feel itssomething they want to be involved in. Ithinders the advances which will bring realprogress in all sciences.

How could chemistry get a better press?

Chemists are at the forefront of materialsscience and a lot of the analytical progressesthat have been made have been discoveredby chemists promise all kinds of uses.Pharmaceuticals, medicine and drug designhave all been transformed by progress in thechemical sciences.

What are the major barriers science still hasto conquer?

That’s more difficult than it sounds. I read anobituary of some distinguished scientist(whose name I have forgotten!) some years

ago, and it described how in the 1930’s hewas inspired to study physics at university.His teacher told him not to bother as therewere only a “few loose ends left to tie up andthat would be that [in physics]”. He was toldhe would be better off doing something else.Nothing can be further from the truth! Physicshas been saying the above periodically – atthe end of 19th century for example. Thencomes along Einstein!

Could HABS do better in preparing studentsfor science at university?

The best of our students are well prepared totake advantage of the academicopportunities, but there are temptations atuniversity! You find too many people who areonly interested in getting a fairly good degreeand getting a good job in the city and soaren’t interested in their academicspecialism. As such people don’t get as muchpleasure out of it as they should. Theseopportunities won’t ever come around again.People are too busy with the peripheral –clubs and societies. Yes one should do that byall means, and do go out and socialise –these are things you must and should do! Butdon’t loose sight of the academicopportunities to engage with some the bestminds at the finest universities. Your learningcapabilities are at their peak at university, andyou never get that time again. Beware! I am not so sure the average HABS boy is fullyaware of that.

A reference to the often quoted criticism ofthe HABS boy: highly confident and ableverbally?

I think that is overrated personally! I really do!Boys here are very self confident, articulateand that can sometimes be interpreted asarrogance. Its not particularly true of theHABS boy, it is an illusion just like the illusionthat some have that this is an exam factory;that we make boys cram. Yes there are highexpectations, but remember that there is anawful lot going on here which has nothing todo with exams.

What will you miss about HABS?

I’ve always enjoyed coaching rugby – it’s agreat way of getting out of the classroom,doing something that I love, a game I love. Ienjoy dealing with boys in a different context– more than just a teacher. I don’t think I planto miss my career - I’ve had a good career –36 years! I feel I am ready to go.

Do you have any immediate plans?

No big plans – travelling is on hold for themoment. I also play a lot of chess – I playless than I used to – if I play and study a bitmore I might improve! I have an awful lot ofreading and music to catch up on!

Is that a musical wild side?

No, mainly classical - unless I point back tothe Beatles perhaps and that era, I am afraidpopular music has left me out!

Questions by Raj Dattani

Dr M J Lexton

Michael Lexton joined theHaberdashers in 1977. Hewas born in Cardiff, SouthWales, and at age 11 he wentto St Illtyd’s College, Cardiffwhere he took O-levels andthen A-levels in Mathematics,Physics and Chemistry. In1966 he entered UniversityCollege Swansea readingChemistry, graduating in1969. He went on to take aPhD at the same institution,and then later a PGCE atCambridge. His thesis wasbased on “The Reactions ofHydrogen Atoms with SimpleAlkenes”, a subtle andcomplex aspect of gaskinetics and yet an area ofchemistry that has realcommercial value, as it is areaction which is at the heartof the process that turnsvegetable oil into margarine.


26


Entropy & The Theory Of EvolutionJohan BastianpillaiWWhhaatt aarree tthhee LLaawwss ooff TThheerrmmooddyynnaammiiccss??

The First Law of Thermodynamics states that“during any reaction the total energy in theuniverse remains constant.” The Second Lawof Thermodynamics states that “during anyreaction the total useful energy in theuniverse will decrease.”

Using an example to illustrate this, consider aball at the top of a hill. It has a ‘useful’potential energy. As it rolls down the hill, thispotential energy is being transferred intokinetic energy, so that at the bottom of the hillthere is no more ‘useful’ potential energy todo any more work, as described by thesecond law.

Innccrreeaassiinngg eennttrrooppyy

The entropy in an isolated system canincrease in two main ways, due to constraintchange or temperature change.

Entropy will increase if the amount of kineticenergy is constant, but energy is beingdistributed in more ways in the final state of asystem after the particles have changed dueto reaction (i.e. more higher number ofproducts than reactants). However, oneprinciple to note is that if constraint onparticles, causing less freedom of motion,increases, entropy decreases. For example, ifthe number of particles decreases, thenentropy would decrease as there would beless ways to distribute energy, or whenvolume decreases or even when particleschange into a more organised phase (i.e. gasto liquid).

However entropy will also increase if there ismore kinetic energy, which can be distributedin more ways, even if the particles don’tchange. Here, an increase in temperature(measure of average kinetic energy) wouldcause an increase in entropy.

If we think of a system’s total entropy as‘constraint-entropy’ + ‘temperature-entropy,’an entropy change can be due to eitherchanges or a mixture of both. Often, as wewill see later, they can be conflicting asconstraint may cause enthalpy to decrease,but temperature causing it to increase.Usually, the temperature-entropy is thedominating factor, so there is an increase inthe overall entropy in the universe eventhough ‘disorder’ seems to decrease, as wecan see below.

Here are five examples from astronomicalevolution of reactions that involved twoparticles (electron and proton) and threeforces (electrostatic, strong nuclear andgravitational):

AA.. An electron and proton are attracted due toelectrostatic force and eventually (700,000years after the Big Bang) the temperature

cools enough for them to remain together toform a Hydrogen atom.

BB.. In space, H2 molecules are pulled towardeach other by gravitational forces, so theygain kinetic energy as they gain speed andthus they increase in temperature. When thistemperature is high enough, H2 moleculesare separated into their constituent protonsand electrons, in a reversal of reaction A.

CC.. As gravity continues compression, thetemperature rises, eventually causing protonsto collide with such force that the strongnuclear force overcomes electrostaticrepulsion between protons and pulls themtogether. This starts a chain of powerfulnuclear reactions which convert four protonsinto a helium nucleus, creating a star.

DD.. Later in some stars lives, a series ofnuclear reactions create heavier elementssuch as lithium, carbon, nitrogen, oxygen andiron, which form plants and our bodies. Somestars become larger supernovas containingthese heavier atoms.

EE.. When a supernova explodes it releases‘heavy atoms’ into space where gravitationalforces condense the atoms to form planets inthe solar system.

WWhhaatt hhaappppeenneedd aanndd wwhhyy??

For the five reactions, let’s look at thechanges in entropy caused by changes intemperature and constraint:

Changes due to constraint – In A, the numberof particles decreases as four particlesbecomes two (2e- + 2p becomes 2H) andthen two becomes one (H + H becomes H2).Constraint increases and this causes adecrease in entropy. In B and E, gravitycauses constraints which again decreaseentropy. The same can be said for C and D as

the strong nuclear force converts many smallparticles into few large ones, decreasingentropy.

Changes due to temperature – Entropyincreases in each reaction as they are pulledtogether by a force, increasing their kineticenergy and temperature.

Change of universe-entropy: In each reaction,a small entropy decrease (constraint) isovercome by a large entropy increase(temperature) which causes an overallincrease of entropy in the universe, consistentwith the Second Law.

Change of system-entropy: In an opensystem, entropy could decrease as in termsof temperature change, heat energy is movingout of the system into the universe, causing adecrease in system-entropy. An increase inconstraint on the system would again mean adecrease, so there is an overall decrease insystem entropy, but importantly, there is stillan increase of entropy for the universesystem + surroundings), which is describedby the Second Law.

Change of apparent disorder: In eachreaction, particles become more constrainedand ordered from molecules into planets andsolar systems. This is a period ofastronomical evolution, showing a decrease in‘disorder’ due to simple attractive forces

There are two important kinds of intuitionhere. There is everyday intuition which isbased on the fact that entropy is disorder andwill reach the wrong conclusions because ineach reaction, the ‘disorder’ decreases, soentropy should by this reasoning, decrease,but we have seen that it increases. Incontrast, thermodynamic intuition (based on acorrect understanding of entropy, which younow have) leads to the correct answers andconcludes that entropy increases in eachreaction.

EEnnttrrooppyy aanndd EEvvoolluuttiioonn

Now that we’ve sorted out that mess, let’shave a look at why young-earth creationistsbecome so excited by thermodynamics. HenryMorris, a creationist, explains his greatdiscovery: “The most devastating andconclusive argument against evolution is theprinciple of entropy (the Second Law ofThermodynamics). This principle impliesthat...evolution in the vertical sense(becoming increasingly complex) iscompletely impossible. The evolutionarymodel requires some universal principlewhich increases order...however the onlynaturalistic scientific principle which is knownto effect real changes in order is the SecondLaw, which describes a situation of universallydeteriorating order. The law of entropy is auniversal law of decreasing complexity,whereas evolution is supposed to be auniversal law of increasing complexity.”

WWhhaatt iiss eennttrrooppyy??

On a microscopic level, entropy is a property that depends onthe number of ways that energy can be distributed among theparticles in a system. Really, it is a measure of probability andnot disorder (a common misconception), because if energy canbe distributed in more ways in a certain state, then that state ismore probable. For this reason, chemicals in a system tend tothe equilibrium state in which the greatest number of ways ofdistributing energy amongst the molecules can occur.

The Second Law is a description of probability, recognising thatin every naturally occurring reaction, whatever is most probableis most likely to happen (all things considered). As probability isrelated to entropy, to state the Second Law in a more preciseform: during any reaction, the entropy of the universe willincrease.


27

Entropy & The Theory Of EvolutionJohan Bastianpillai

reaction.

EEnnttrrooppyy aanndd EEvvoolluuttiioonn

Now that we’ve sorted out that mess, let’shave a look at why young-earth creationistsbecome so excited by thermodynamics. HenryMorris, a creationist, explains his greatdiscovery: “The most devastating andconclusive argument against evolution is theprinciple of entropy (the Second Law ofThermodynamics). This principle impliesthat...evolution in the vertical sense(becoming increasingly complex) iscompletely impossible. The evolutionarymodel requires some universal principlewhich increases order...however the onlynaturalistic scientific principle which is knownto effect real changes in order is the SecondLaw, which describes a situation of universallydeteriorating order. The law of entropy is auniversal law of decreasing complexity,whereas evolution is supposed to be auniversal law of increasing complexity.”In laterstatements, Henry Morris claims that ALLtypes of evolution are impossible, because“evolution requires some universal principlewhich increases order, causing randomparticles eventually to organise themselvesinto complex chemicals, non-living systems tobecome living cells (chemical evolution), andpopulations of worms to evolve into humansocieties (biological evolution). Whatinformation codes tell primeval randomparticles how to organise themselves intostars and planets? (astronomical evolution)”

Have creationists found a “devastating andconclusive argument against evolution”? Toanswer this, scientific details are essential, sowe have to briefly look at two of the threevery different types of evolution: astronomicaland biological to understand whether HenryMorris is indeed making a plausible claim.

AAssttrroonnoommiiccaall EEvvoolluuttiioonn

The reactions previously essentially isastronomical evolution, as the protons andelectrons developed and changed into morecomplex atoms, molecules, then stars andplanets and eventually solar systems. This‘evolution’ was brought about as the particlesdid what ‘came naturally to them’, which wasto feel an attractive force and act upon them. The ordered complexity which resulted doesnot violate any principles of thermodynamicsas, contrary to the claims of Morris, theSecond Law is not a “universal law ofdecreasing complexity”. None of thesereactions violates the Second Law, andneither does the overall process. On the smallscale, yes entropy decreases as particles arecompressed together, however in the bigger picture, the universe is expanding overall,decreasing constraints and increasingentropy. Movement of these particlesincreases entropy due to increases intemperature, so universe-entropy increases.

BBiioollooggiiccaall EEvvoolluuttiioonn

An evolution of increasing biologicalcomplexity can occur while total entropy ofthe universe increases. Is the Second Lawviolated by either mutation or naturalselection, which are the major actions in neo-Darwinian evolution? No. And if an overallprocess of evolution is split into many stepsinvolving mutation then natural selection,each step is permitted by the Second Lawand so is the overall process. Randommutations which are beneficial can lead tomore developed organisms, proving thatnatural evolution can produce increasinglycomplex organisms. Admittedly, we can askscientifically interesting questions aboutcomplexity – how much can be produced,how quickly, by what mechanisms – but howdoes the Second Law fit as justification forthe creationist argument? The truth: itdoesn’t.

DDooeess eennttrrooppyy uunnddeerrmmiinnee tthhee tthheeoorryy ooffeevvoolluuttiioonn??

If you’ve followed the argument and thepoints put across, you should by now see thatMorris’ claims aren’t really backed up withthe scientific evidence. His claims are sayingthat all types of evolution are impossible. Asexplained previously, these claims aregeneralised and rely on an everyday intuitionand not thermodynamic intuition. His, is amisunderstanding of the Second Law and soreally his argument was flawed from theoutset. Does entropy undermine the theory ofevolution? No. In short, we must take away a message fromthis. The conflict has been around for sometime and when it was, people took it fairlyseriously. In this case, a simplemisinterpretation had lead to, albeit feeble,attempts to undermine a theory which hasbeen the fundamental foundation of modernbiology



28


Scope: Could you please explain on yourtheory of "The seven types of aging"?

AdG: Well, first of all it's not exactly a theory.It's just a way of classifying the variousmolecular and cellular changes in the bodythat accumulate throughout life as side-effects of normal metabolism and eventuallycontribute to age-related ill-health. I supposeit can be called a theory in some ways - first,there are a few changes that accumulate butthat I claim do not contribute to age-relatedill-health, and second, part of my claim is thatthere are no accumulating changes that do socontribute but that we haven't yet discovered.But the "seven-point plan" itself is just aclassification. So: well, the categories are cellloss, cell accumulation through failure of celldeath, cell accumulation through excessivecell division, mitochondrial mutations,intracellular molecular garbage, extracellularmolecular garbage, and extracellular proteincross-linking

Scope: Mitochondrial Aging and CancerousMutations are listed as 2 of the 7 types ofaging...are these forms of aging simplyentrenched in our process of cellularreplication? If so would this not be simplyimpossible to avoid?

AdG: Oh, for sure these things are impossibleto stop from happening - and actually, all theother five are also impossible to stop fromhappening. But SENS is not a plan forstopping these things from happening; it's aplan for stopping them from mattering. Inmost cases this is by repairing them afterthey've happened; in the two cases youmention it's by preventing them from causingany impairment of metabolism.

Scope: Some of your research on immuneaging has focused on interleukin 7 (IL-7);what is IL-7? Do you accept reports that"interleukin 7 (IL-7) can improve protectiveimmunity have produced disappointing results so far." EMBO reports 6, 11, 1006-1008 (2005)?

AdG: Yes I do. There are various problemswith the techniques that have been tried sofar, including the half-life of the injected IL-7and its localisation to the thymus - but thoseproblems are being addressed by variousgroups in new methods being developedcurrently. Also, IL-7-independent ways toregrow the thymus are being explored,including in a study that SENS Foundation isfunding.

Scope: You have claimed that ''mitochondria

with reduced respiratory function, due to amutation affecting the respiratory chain,suffer less frequent lysosomal degradation'.Surely this poses a significant challenge; howwould it be overcome?

AdG: It's very hard! In fact, I have neitherheard about nor devised any way to do this.That's why I still favour the approach ofrestoring those mitochondria to normalrespiratory function by introducing suitablymodified mtDNA into the nucleus.

Scope: Caloric restriction has been proven toreliably extend lifespan in many differenttypes of animals, and most notably mice. Doyou believe this endeavor will have muchvalue in expanding human lifespan?

AdG:No. I believe it will have non-zero value,but far less than in shorter-lived species,because the selective pressure to respond tofamine by altering one's metabolic priorities ismuch less when the outcome is a 20-yeardelay of aging than when it is only a one-yeardelay.

Scope: In your opinion how would the conceptof ‘immortality’ change how societyfunctions? Would post-natal humandevelopmental periods and life stageschange? What about overpopulation?

AdG: I don't work on immortality. I work onstopping people from getting sicker as theyget older, and I think I know how to do that sowell that they will indeed live a lot longer -but that's a side-benefit, not the motivation.Development will not change at all, no. Otherlife stages will change only in the sense thatthere won't be a stage of decline.Overpopulation will be a threat, as it alreadyis today, and we will address it by matchingthe birth rate to the death rate in whateverways society may choose.

Scope: Assuming that the eradication of agingwas possible would you envisage a societalparadigm shift to this or would it be more ofan individual choice?

AdG: I'm not really sure what you mean by asocial paradigm shift. I do expect thateveryone will want these therapies - I don'ttend to meet people who want to get sick asthey get older.

Scope: What is the role of the SENSFoundation in terms of anti-aging research?Why not simply act through a University?

AdG: The value of having an independentfoundation is that we can coordinate and

prioritise what research is done using thefunds that donors provide. We do indeed fundresearch in universities, but not just oneuniversity. And we also fund research in-house at our own research centre.

Scope: Have any public medical institutesbacked the SENS project, or is it entirelyprivately funded? If so why or why not (havepublic medical institutes backed the SENSproject)?

AdG: SENS's work is entirely funded byphilanthropy so far, but our most promisingresearch projects are now far enough alongthat we're in the process of applying forpublic funding to take them forward. Also,some projects essential to SENS are beingabundantly funded independently of SENS.

Scope: Ray Kurzweil and Eliezer Yudkowskyare working on the notion of a 'singularity', anotion where a hybrid biologicalorganism/machine will ensure that humanimmortality. Do you think this will supersedethe work of SENS?

AdG: I don't know - and nor do they. That'swhy I strongly support their work and theysupport mine: we all feel that the best way tomaximise our chances is to pursue allpromising avenues as hard as possible, inparallel.

Scope: How far down the line is SENS interms of research for each of the seven typesof ageing?

AdG: Some strands are very far advanced -late-stage clinical trials. Those are the areasthat the SENS foundation doesn't fundbecause we don't need to. Others areprobably 6-8 years away from demonstrationof proof of concept in mice.

Scope: When will you expect, if research goesas planned the first big 'break-through' inyour research?

AdG: There are breakthroughs all the time,but the really decisive breakthrough will bewhen we implement all the SENS strands inthe same mice well enough to give a two-year (or so) postponement of aging to micethat are already in middle age when we startthe therapy. I think that's probably now lessthan 10 years away.

Scope: Do you expect the maximum age levelto plateau, or that rather, scientific discoverieswill ensure that it keeps ever increasing?How soon are we likely to see significantchanges to life expectancy?

An Interview With Aubrey de Grey


29

AdG: Ever increasing, for sure and certain.When we achieve a few decades ofpostponement, the rate at which we're furtherimproving the therapies will far outstrip therate at which new problems are arriving. Ithink we have a 50% chance of getting tothat cusp within 25 years.

Scope: Some people might argue that inmany cases rather than the inherent ageingof the human body being the overarchingreason for death, a specific acute clinicalcondition such as a heart attack can be saidto be the cause. How would you answerthis?� �

AdG: Acute conditions, and indeed chronicconditions that afflict the elderly, are merelyaspects of the later stages of aging. They areage-related for that reason: otherwise, they'daffect young people just as much as theelderly. Thus, SENS can be viewed aspreventative geriatrics.� �

Scope: Do you think that SENS' and your ownattempts and to bring anti-ageing to forefrontof the wider non-scientific community hasbrought even more criticism from those whodo not accept it?

AdG: Oh yes - but that's a good thing.Opposition is the last step before acceptance.The problem is when one's just being ignoredor ridiculed, and I'm largely past thatstage.

Scope: Could you please explain what youmean by your 'engineering' approach togerontology?

AdG: It's really simple: it just says two things.First, that preventative maintenance is easierthan curative maintenance, and second, thatfor a really complicated machine that wedon't understand very well (like the humanbody) it's also easier than redesigning themachine altogether so that it needs lessmaintenance in the first place.

Scope: Many people have criticised yourwork, what is your reaction?

AdG: Relief. If you do science and no one iscriticising you, you're almost certainly notmaking much of a difference.

Scope: Do you think the wider scientificcommunity has become more accepting ofyour approach since the publication of theEMBO Reports in November 2005 attackingyour work?

AdG: Without doubt. In fact, many of theauthors of that article have becomesupportive. To a large extent they werealready far less dismissive than the articleindicated: there was a lot of politicsinvolved.

Questions by Casey Swerner

DDrr.. AAuubbrreeyy ddee GGrreeyy

Dr. Aubrey de Grey is the Chief Science Officer of the SENS Foundation(Strategies for Engineered Negligible Senescence). His main researchinterest is in the elimination of the effects of cellular and moleculardamage in aging. He firmly believes that “there is no differnecebetween saving lives and extending lives, because in both cases we aregiving people the chance of more life” and also that the first person tolive to 1000 years “may already be born”. He visited the School’sScience Society in January 2010.



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BBiioollooggiiccaall SScciieenncceessA36851 HaberAske Scope TEXT AW:A31822 HaberAske Skylark 12/3/10 10:36

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Scope 2009/10 Biological Sciences

Biological Sciences Abiogenesis: The Origin Of LifeNicholas ParkerTThhrroouugghhoouutt hhuummaann hhiissttoorryy,, tthheerree hhaavvee bbeeeennmmaannyy ppeeooppllee wwhhoo hhaavvee ttrriieedd ttoo aannsswweerr tthheeffuunnddaammeennttaall qquueessttiioonn ooff hhooww lliiffee aarroossee..Abiogenesis is a scientific theory that explainsthe origin of life from inanimate matter. Atpresent, this theory concerns only life onEarth (as no life has yet been foundelsewhere in the Universe). It shouldn’t beconfused with evolution, which is the study ofhow groups of living things change over time.

OOrriiggiinnss ooff AAbbiiooggeenneessiiss

Some would argue that spontaneousgeneration was the first “theory” resemblingabiogenesis. However, as spontaneousgeneration wasn’t a scientific theory - andwas eventually disproven by Pasteur, in hisexperiments using broth - it is, in my opinion,too different to abiogenesis for it to be aprecursor of it.

The first hypothesis on the natural origin oflife comes from Charles Darwin in a letter toJoseph Dalton Hooker dated February 1,1871:

“It is often said that all the conditions for thefirst production of a living organism are nowpresent, which could ever have been present.But if (and oh! what a big if!) we couldconceive in some warm little pond, with allsorts of ammonia and phosphoric salts, light,heat, electricity are present, that a proteinecompound was chemically formed ready toundergo still more complex changes, at thepresent day such matter would be instantlydevoured or absorbed, which would not havebeen the case before living creatures wereformed.”

For the next 50 years, no notable research ortheory appeared. Then in 1924 AlexanderOparin, in his book “The Origin of Life”,

proposed that life had once arisenspontaneously, beginning with self replicatingmolecules that evolved into cellular life.Around the same time, J. B. S. Haldane putforward a similar theory, providing the basictheoretical framework for abiogenesis.

SSoo wwhhaatt eexxaaccttllyy iiss AAbbiiooggeenneessiiss??

The biologist John Desmond Bernal, buildingon Oparin’s and Haldane’s ideas, suggestedthat there were a number of clearly defined"stages" that could be recognised inexplaining the origin of life:

•• 11:: TThhee oorriiggiinn ooff bbiioollooggiiccaall mmoonnoommeerrss

•• 22:: TThhee oorriiggiinn ooff bbiioollooggiiccaall ppoollyymmeerrss •• 33:: TThhee eevvoolluuttiioonn ffrroomm mmoolleeccuulleess ttoo cceellll

These stages provide an excellent framework for explaining abiogenesis as they brakedown the large theory into smaller, moredigestible steps. I will outline the mostinteresting one (“Genes/RNA first” model).Other models can broadly be divided into twogroups: “Proteins first” and “Metabolism first”,though there are a few models whichstubbornly refuse to fit in either.

SSttaaggee 11:: TThhee oorriiggiinn ooff bbiioollooggiiccaall mmoonnoommeerrss

Evidence suggests that the atmosphere of theearly Earth was composed primarily ofmethane, ammonia, water, hydrogen sulfide,carbon dioxide or carbon monoxide, andphosphate, creating a reducing atmosphere.In 1924, Alexander Oparin and J. B. S.Haldane independently hypothesised theorigin of life from a “primordial soup” undersuch a reducing (oxygen-free) atmosphere.Experimental verification of their hypothesishad to wait until 1952 when Stanley Millerand Harold Urey at the University of Chicagocarried out the famous Miller-Ureyexperiment. The experiment used water,methane, ammonia, and hydrogen, whichwere sealed in a sterilized loop. After just one

week of continuous operation, organiccompounds made up between one sixth ofthe carbon within the system, with 2%forming amino acids. In 2008, a re-analysisof Miller's archived solutions from the originalexperiments showed 22 amino acids - ratherthan 5 - were actually created in one of theapparatus used. Sugars, lipids, and some ofthe building blocks for nucleic acids(nucleotides) were also formed in theexperiment.

Other experiments conducted in the secondhalf of the 20th Century also producedbiological monomers, notably the formation ofadenine from a solution of hydrogen cyanideand ammonia in water by Juan Oró in 1961. This was grounbreaking. It showed that in theright conditions, biological monomers canspontaneously arise from simple moleculespresent in the early Earth’s atmosphere,confirming the hypothesis of Haldane.

Organic molecules could also have comefrom meteor impacts, as they are found quiteoften asteroids. This alternate theoryregarding the origin of life is known asPanspermia, and asserts that life on Earthwas seeded from space. The theory was firstproposed by Benoît de Maillet in 1743.

Nucleotides (the building blocks of nucleicacids such as RNA and DNA) are formed ofan organic base, a pentose sugar and aphosphate group . Phosphates were presentin the early atmosphere, and we have alreadyseen that sugars and nucleotides canspontaneously form under the rightconditions. Though the precise mechanism ofnucleotide formation is at present unknown, itis likely to be similar to the method livingorganisms today use to manufacturenucleotides. Other, simpler nucleotides havebeen found to exist and could have formednucleic acids that were the precursor to RNAand DNA.

(article continues over ...)

Figure 1

Nucleotides (the building blocks of nucleic acids such as RNA and DNA) are formed of an organic base, a pentose sugar and a phosphategroup. Diagram shows the structure of 5 nucleotides, pentose sugar andphosphate groups.


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SSttaaggee 22:: TThhee oorriiggiinn ooff bbiioollooggiiccaall ppoollyymmeerrss

We now have our monomers necessary forbuilding polymers: amino acids andnucleotides. The next step is to explain howthese simple monomers polymerise into longpolymers such as Proteins, RNA and DNA.

Nucleotides first joined together to formshorter chains of polynucleotides. Then,polynucleotides joined together to form longernucleic acid chains. Researchers in the1980s found that a clay calledMontmorillonite, abundant on the early Earth’ssea floor, acted as a catalyst for the formationof polynucleotides and nucleic acid chainssuch as RNA. Some other nucleotides, suchas Phosphoramidate DNA are capable ofspontaneous polymerisation in solution,forming new Phosphoramidate DNA templatesand extending existing templates. Freenucleotides can then base pair with a singlestranded template and can self ligate. In otherwords, the sense strand causes the anti-sense strand to form spontaneously.

Montmorillonite, as well as being a goodcatalyst for the formation of amino acids fromsimpler molecules, is also a good catalyst inthe formation of polypeptides and longerprotein chains.

SSttaaggee 33:: TThhee eevvoolluuttiioonn ffrroomm mmoolleeccuulleess ttoo cceellllss

The transition from molecules to cells iswhere the theories tend to vary the most. Iwill discuss a variation of the “Genes/RNAfirst” model.

RNA molecules can self replicate; this hasbeen demonstrated under laboratoryconditions. However, this replication isimperfect as mutations can creep in duringreplication such deletion, which change theRNA molecule. This variation between themolecules mean some are better suited totheir environment than others, allowingnatural selection to take place and evolutionto occur.

Apart from the obvious example that somemolecules could replicate faster than othersdue to variation, another advantageousmutation would be the ability for RNAmolecules to attract lipid molecules. As wehave seen from the Miller-Urey experiment,lipids were formed spontaneously under pre-biotic conditions. Lipid molecules have both ahydrophilic (water attracting) and hydrophobic(water repelling) end. As the hydrophobicends are repelled by water, they clumptogether to form micelles, with the hydrophilicends pointing out towards the water.

An RNA molecule that attracts thehydrophobic ends of these lipids towardsitself would be better protected from physicaldamage by the external environment thanthose without, and so would have a betterchange of survival and replication. Thesemicelles with RNA inside could be termedprimitive cells (see footnote 2) as they have

genetic material which can replicate itself anda lipid membrane to separate the inside ofthe cell from the outside, two basicrequirements of any cell. A better cellmembrane would be a vesicle, where theinside and the outside of the cell contain anaqueous solution. In Montmorillonite clay, lipidvesicles have been found to spontaneouslyform.

These lipid vesicles made from simple fattyacids are permeable to small molecules (likenucleotides), so any RNA inside couldreplicate itself by incorporating nucleotidesthat diffuse into the cell. When a vesiclegrows, it adopts a tubular branched shape,which is easily divided by mechanical forces(e.g. rocks, currents, waves), and during celldivision, none of the contents are lost. Thecell grows by incorporating free lipidmolecules into the molecules; “eating” isdriven by thermodynamics. The cellreproduces by copying the RNA inside, andthen physical forces breaking the lipid vesicleinto separate vesicles, each with RNA inside.

So we now have our basic cell with a lipidmembrane and genetic information. However,any chemical reactions inside the cell will beslow as there are no catalysts inside. Or are there? RNA itself can not only storeinformation like DNA, but can also act asenzymes (called ribozymes). Any cell whichcontained ribozymes would have anadvantage over other cells and so would beselected for as the ribozymes could enhancereplication, synthesise lipids and keep themintegrated within the cell membrane; all ofwhich would provide an evolutionaryadvantage over other cells.

Ribozymes can also catalyse the formation ofpeptide bonds; the bonds that hold proteinstogether. This means that proteins could havebeen formed, which themselves could haveacted as catalysts for reactions. As proteinsare better more versatile and specific thanribozymes, they are better catalysts and anycell that could synthesise proteins would alsohave an evolutionary advantage. With proteinsformed and self-replicating RNA alreadypresent, a mutation could cause the RNA in acell to become dependant on proteins forreplication (as proteins would reproduce theRNA more accurately than if the RNA selfreplicated) but still give the cell anevolutionary advantage. Another mutationcould have caused the protein thatsynthesised the RNA base Uracil to synthesiseThymine instead (this is because the onlydifference between Uracil and Thymine is thatThymine has a methyl side group on one ofits rings instead of a hydrogen atom in Uracil,as shown in the nucleotide diagram above). Afinal mutation could cause the protein to bondthe two strands of RNA (old and new) to formDNA.

Any cell that could regulate its division wouldtherefore be selected for as it couldreproduce faster and more precisely.

Voila! We have a self-replicating cell with alipid cell membrane, proteins and DNA thatcan synthesise all its constituent parts fromsimpler molecules by the input of energy. The“Iron-Sulphur” world theory suggests thatearly life metabolized metal sulphides (suchas iron sulphide lipid) for energy, but anyreaction that produced energy which usedreadily available reactants could haveoccurred.

These cells, while much simpler than eventoday’s simplest living organism (excludingviruses, which are classically non-living), werethe beginning of the ancestral line which hasdiverged and evolved into every living thingwe see on Earth today including you.

Footnotes

1. This evolution follows thequasispecies model, which is adescription of the evolution of self-replicating entities (including virusesand molecules such as DNA and RNA)within the framework of physicalchemistry. The rate of mutationbetween generations is higher than inconventional species models ofevolution.

2. Primitive cells considered to be theprecursors to DNA-based prokaryoticlife are called “protobionts”


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Evolution Of The NervousSystemAadarsh Gautam

PPeerrhhaappss tthhee mmoosstt ppeerrttiinneenntt ppiieeccee ooffkknnoowwlleeddggee rreeqquuiirreedd ttoo aaccccuurraatteellyy ddeessccrriibbee tthheeiinnttrriiccaattee ccoonnssttrruuccttiioonn aanndd ddeevveellooppmmeenntt ooff tthheeHHoommoo ssaappiieennss iiss tthhee uunnddeerrssttaannddiinngg ooff tthheeeevvoolluuttiioonn ooff tthhee nneerrvvoouuss ssyysstteemm aannddssppeecciiffiiccaallllyy tthhee ssppiinnaall ccoorrdd,, aass wweellll aass tthheennoottoocchhoorrdd aanndd tthhee pprriimmiittiivvee aaxxiiaall sskkeelleettoonnaarroouunndd wwhhiicchh tthhee vveerrtteebbrraattee ddeevveellooppss.. Thesub-phylum ‘Vertebrata’ constitutes a mere5% of all animal species further indicatingthat vertebrates (hence Homo-sapiens) musttrace their routes from invertebrates. Theevolution of the vertebrate from theinvertebrate is a seemingly gargantuan leap.This evolution has been found to come fromthe neural crest.

It is important to explain now what the neuralcrest is. Despite the myriad of obstructions inattempting to define the neural crest it is,roughly speaking, a series of cell “clumps”¬¬along the margin of the forming spinal cordthat give rise to spinal ganglia and otherneural cells in the process of embryogenesis(the process by which an embryo is formedand develops) in vertebrates.

The induction of the neural crest begins withthe interaction between a layer of pluripotentstem cells (which go on to form thesensory/nervous system) and the neural plate(a thick, flat bundle of outer protective cells –the ectoderm). Subsequently, neural crestcells form within the border regions betweengerm cells and the neural plate, which rise asneural folds, converging to form the dorsalmidline of the neural tube, and it is from herethat the neural crest cells will emerge information to give rise to the eventual spinalcord. These cells migrate into the periphery.During and after this migration process, aseries of cell differentiations occur which formmany of the essential “building blocks” ofvertebrates for example bone and dentine.These derivatives illustrate clearly then theimportance of the neural crest, as it isresponsible for the development offundamental constituents of vertebratephysiology.

Having described the importance of the roleof the neural crest, the origins of this featuremust be explored by tracing back toinvertebrates. The inherent intricacy of theneural crest gives rise to a lack of conclusivedevelopment theories. A possible explanationto the rise of the neural crest is thatvertebrate neural crest evolved from primarysensory neurons in prior invertebrates. Thishypothesis was more fully developed in thetheory that neural crest evolved from Rohon-Beard cells, a class of primary sensory

neurons that occur in the spinal cord oflowerchordates. It was then suggested thatglia in the dorsal root ganglia present in thespinal cord also evolved from Rohon-Beardcells that had broken apart from spinal cordsensory neurons and subsequently migrated.Under this scenario, peripheral Rohon-Beardcells would divide to form the sensoryneurons and glia of the dorsal root ganglia.This seems to be a specious explanation asneurons of the central nervous system havenot been observed to ‘de-differentiate’ andre-differentiate as would be required in thismanner. Evidence is present support this ideaas in Zebrafish (Danio rerio) embryos, (inwhich both Rohon-Beard cells and neuralcrest cells are present) they appear to bepart of a group of types of cells whichoriginate from a common precursor.

Alternatively, the hypothesis could be affirmedby instead theorising that evolutionary originsof the neural crest and the sensory neuronsand glia of the dorsal root ganglia are to befound in the migration of mitotically activeRohon-Beard progenitor cells (which wouldthen be capable of differentiating into aspecific type of cell). The multitude of theoriesmakes it difficult to identify a single holisticexplanation of the origins of the neural crest.

Perhaps the greatest hindrance in attemptingto ascertain neural crest origin fromexperimental data is that it is almostimpossible to experiment upon! Instead neuralcrest genetic identifications on a molecularlevel serve as a way to recognise thecharacteristics of neural crest, enabling theexploration of its invertebrate origins. This isbeing done by firstly identifying key molecularfeatures necessary to produce the neuralcrest in pre-natal development. Two groups ofinvertebrate chordates, the tunicates and thecephalochordates were used to test this asthey, for many years now, have beenaccepted as the closest living invertebraterelatives of the vertebrates. In comparing thetwo data sets, “neural crest genes” are beinglooked for, i.e. genes underpinning neuralcrest induction, differentiation and migration,and, in doing so the genetic construct of theneural crest can be identified. Such findingsas to the construct of basic fundamentalcomponents of vertebrates are invaluable inbetter understanding the make-up of humanphysiology.

Once again however the complexity of thisinvestigation means there are, in reality, few,if any, definitive ‘neural crest genes’ that maybe used in isolation as molecular signaturesof the neural crest and so attempts to find agenetic origin of the neural crest amonginvertebrate chordates, characterised by theexpression of a 'neural crest gene' havebeen vague. The data gained did show,

however, the role of groups of genes in theorganisation of the spinal cord and the centralnervous system, (or rather, parts related tothe neural crest) that are general to Bilateriaas a whole, as opposed to vertebratespecific.While it appears that neural crestcells with the ability to generate neurons andeventually the parts of the central nervoussystem could have evolved prior to theemergence of the vertebrates (i.e. suchprocesses could occur in invertebrates), theproduction of such derivatives is a differentsolely vertebrate function. From here there isscope to identify the evolution of vertebratefunction from the neural crest. Once againhowever this science is frustrating, as itscomplexity and seemingly unverifiable nature,makes drawing conclusions extremelydifficult. However it has once been said that“the only thing interesting about vertebrates,is the neural crest.” Although perhaps anexaggeration the maxim highlights theimportance of the neural crest inunderstanding vertebrate roots in theirinvertebrate counterparts.

The neural crest’s evolution remains unclearand even its function is still being explored.The origin of neural crest is a key question,but the later evolution has received littlescientific focus and may provide a key insightinto what separates vertebrates andinvertebrates at the embryological stage.However despite this scientific fog, what isclear is that vertebrate evolution isinseparably linked with the neural crest and adoor to great discoveries in evolutionaryterms of the origin of Homo sapiens. Despitewhat our Latin name may suggest, in biologyat least, we are just begging to know howlittle we knowledge we may actually have.


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Alzheimer’s: Hope At Last?Raj DattaniAAllzzhheeiimmeerr’’ss ddiisseeaassee iiss oonnee ooff tthhee ffuurrtthheessttrreeaacchhiinngg aanndd mmoosstt hhiigghhllyy ddeebbiilliittaattiinngg ddiisseeaasseessooff tthhee 2211sstt cceennttuurryy.. It is estimated that thereare over 26 million sufferers world-wide,experts believe this number may increase asmuch as four-fold by the year 2050.Alzheimer’s is a degenerative and irreversiblebrain disease. It is most common in thoseaged 60 and above and causes dementia,which is defined by the Oxford MedicalDictionary as ‘a chronic or persistent disorderof behaviour and higher intellectual function’.Amyloid plaques, deposits of a sticky protein,amyloid beta peptide appear in specific brainregions along with neurofibrillary tangles,abnormally twisted forms of the protein tau.

BBiioollooggiiccaall PPrroocceesssseess

Currently the most widely used hypothesis isknown as the cholinergic hypothesis. Thistheory is based on the fact that in Alzheimer’ssufferers the synthesis of theneurotransmitter acetylcholine decreases.Acetylcholine plays a vital role in memoryrecall; this is due to its effects on synapticplasticity through increasing synapticpotential. Synaptic plasticity is the strength ofthe synapse, and its ability to change instrength. As a memory is formed (a processknown as long term potentiation), theelectrical potential, (i.e. synaptic potential, ofthe cell immediately across from thesynapse), affects synaptic plasticity. Thereforeif levels of acetylcholine are decreased, thensynaptic potential, and so synaptic plasticityare reduced. This reduction in the function ofthe synapse causes lessened memory recallin line with Hebbian theory. This theoryproposes that memory is represented in thebrain by various networks of interconnectedsynapses, and so if these are lessened infunction then memory recall is decreased.Scientists therefore believe that the cognitivedecrease in memory could be due to the factthat the synthesis of a crucialneurotransmitter in memory recall isdecreased.

The second neurobiological phenomenon thatis evident in those suffering Alzheimer’s isthat NMDA receptor, a receptor for theneurotransmitter glutamate, is overstimulated. This means that very high levelsof both NMDA and glutamate bind to thisreceptor. As a result high levels of calciumions enter the cell. This calcium influx intocells activates a number of enzymes,including phospholipases, endonucleases, andthe protease calpain. These enzymes thendamage cell structures such as thecytoskeleton, membrane, and DNA, leading toneurone death. This phenomenon is known asexcitotoxixity, and it leads to the shrinkage ofa sufferer’s brain. Scientists believe that thisneurone death contributes significantly to the

cognitive decline of Alzheimer’s patients, forthe NMDA receptor is located in a synapse.This is in line with Hebbian theory, if neuronesin the synapse die, as a result of NMDA overstimulation, then memory recall woulddecrease.

BBiioollooggiiccaall SSoolluuttiioonnss

The solution to the problem shown throughthe cholinergic hypothesis is very simple.Patients are given a drug known as acholinesterase inhibitor- cholinesterase isresponsible for the break down ofacetylcholine (ACh). If it is inhibited then theneurotransmitter remains intact meaning thatthe cholinergic system at the synapse worksmuch better. These inhibitors work by eitherbeing a competitive inhibitor or a non-competitive inhibitor. In the former theinhibitor binds to the same active site as thesubstrate (ACh), so that the ACh cannot bindwith the enzyme, and as a result ACh is notbroken down. In the latter the inhibitor bindsto a secondary site close to the active site.Whilst the substrate can still bind to theactive site the presence of an inhibitor causesa change in structure, meaning the enzymecannot bind fully to the substrate on theactive site and thus this slows the rate of thecatalysis by the enzyme, effectively inhibitingthe break down of the substrate,acetylcholine. Approved cholinesteraseinhibitors are donepezil rivastigmine, andgalantamine, a competitive inhibitor.

To combat the problem of excitotoxicity adrug known as a NMDA receptor antagonistis utilised. The only approved antagonist forAlzheimer’s is memantine. Memantine works

by a method known as uncompetitive channelblocking. For the receptor to work the ionicchannel must be open to allow calcium ionsto pass through. Memantine simply blocksthis channel by binding to sites within it, thismeans that Ca ions cannot cause

excitotoxicity, and so solves the problem.

AAtteerrnnaattiivvee SSoolluuttiioonnss

The tau hypothesis asserts that the formationof neurofibrillary tangles inside the nervecells, causing the neurone’s transport systemto disintegrate and eventually leading to celldeath, is the major factor. Otherwise,investigating neuroprotective measures couldyield a successful solution

The amyloid hypothesis proposes that thedeposits of amyloid protein are thefundamental cause of the disease and thattheir formation is linked to the APP gene onchromosome 21. However a trial vaccinationin humans, against this mutant gene, whilstclearing the amyloid plaques, did not showcognitive benefits . Recent research howeversuggests that ‘remodelling of crucialAlzheimer disease-related genes... couldprovide a new therapeutic strategy.’

In conclusion we can see that research intothis problem is ongoing, The different viewstaken here boil down to which data is givenhigher validity, and ultimately only furtherstudies will be able to differentiate betweenthese.

Figure 1

An overviewof the histology, structure and physiology of a synapse (generic).


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Cocaine Dependence:Implications And Treatments Ravi SanghaniCCoonnssuummppttiioonn ooff aallll ppssyycchhooaaccttiivvee ddrruuggssiinnvvoollvveess rriisskkss. It is in our general knowledgethat cocaine poses much higher risks thanprescription medicines and impacts society ina number of ways, justifying its illegalisation.Severe anxiety and depression manifest fromthe abuse of cocaine, jeopardising mentalhealth, plus usage being a risk factor forcardiovascular diseases. In the first 60minutes after cocaine use, ‘the risk ofmyocardial infarction onset was elevated 23.7times over baseline (95% CI 8.5 to 66.3)’.

It is clear that cocaine use producesphysiological changes within the user and is astrongly addictive stimulant. Addiction issynonymous with criminal behaviour to seekcocaine. Rather than analyze this aspect, Ifeel obliged to comment on the environmentaleffects of the cocaine trade. This stance isregularly overlooked in the media but anunderstanding of the environmental (as wellas social) effects of cocaine adds moreweight to the arguements to try andendeavour to eliminate cociane dependancy.

The chemicals used in the extraction of thecocaine alkaloid from the leaf are kerosene,sulphuric acid and ammonia which areimmediately released into the heart of therainforest. With no means of treating thesechemicals or a removal system, pollution isabundant. Furthermore, because extractionrequires a nearby water source aquaticwildlife is threatened. The effect is toxicityfrom nitrates and death for many creatures,plus jeopardising healthy offspring. At lowlevels (<0.1 mg/litre NH3) ammonia acts astrong irritant, especially to fish gills causinghyperplasia . This is when the lamellaeepithelium thickens, increasing the number ofcells in the gills. Consequently, water flow isrestricted allowing parasites to accumulate.

Continuous extraction requires higherammonia levels (>0.1 mg/litre NH3) whichexacerbates hyperplasia and causesirreversible organ damage. Liver necrosis orabnormal cell growth (tumour) are typical

reactions. This is a significant issue to localpopulations who fish in these waters and thisis only a small side of the vast damage tospecies richness.

RRiissiinngg CCooccaaiinnee UUssee

IIn Western countries, which primarily reportthe abuse of cocaine, issues are beingtreated on several fronts. Drugs educationprograms with particular reach toadolescents, international law and thealleviation of poverty are utilised as means ofreducing cocaine use. However, the realproblem is the lack of medical treatmentsavailable to treat those already dependant oncocaine. Presently, drugs such as beta-blockers and ACE inhibitors can help todecrease hypertension protecting the heart;“yet there remains a genuine lack ofpharmacological drug treatments available totreat cocaine abuse or prevent its relapses’’.

The problem of addiction stems fromneurochemical events in the brain. Whencocaine enters the brain it disrupts theprocess of neurotransmitter endocytosis, byforming a chemical complex with thedopamine transporter (DAT). The flood ofthese chemicals prolonged in the synapse,before metabolism, produces intenseeuphoria and can lead to addictive habits.Whilst short term use temporarily raisessynaptic DA levels, producing the ‘high’, DAreceptors are depleted (‘down-regulated’) bychronic use. Recent studies confirmneurobiological changes from prolongedcocaine exposure can have knock on effectson whole other brain systems . There is aneed for encompassing solutions to accountfor this and an ethical call for the provision ofas much professional help as possible.

MMeeddiiccaall ttrreeaattmmeennttss ??

One approach is through using a group ofmolecules collectively known as kappa (k)agonists. In the same way that DA hasspecialized dopamine receptors, the k opioidreceptor is involved in synaptic DA levels. Onetype of opioid receptor, known as the kappa(k) receptor has, in recent medical studies,

been shown to inhibit dopamine release frommesolimbic neurons and attenuate therewarding effects of cocaine. This is asignificant step to lessen cocaine cravingsand cut down on abuse. Studies with lab ratshas shown that k receptors are involved inthe antagonism of drug-seeking behaviour,with k agonists “altering levels of thedopamine transporter; decreased cocaine-induced dopamine levels and blockingcocaine-induced place preference”.Enrichment of the DA system is the majordirection towards controlling addiction andbuilding a situation to then eliminate relapse.K agonists lead to decreased self-administration of cocaine which provides alarge window of opportunity for the addict tosafely wean themselves off cocaine anddissociate from psychological cravings.Administration with rats of kappa-agonist U-69,593 (0.32 mg/kg, subcutaneous) for 5days decreased DAT and D2 receptordensities, which remained after the 3 dayperiod’ hence the decreased DA uptake .These findings tell us that when addicts

administer cocaine in short successiveintervals with daily U-69, 59s the effects arequickly attenuated, maintaining this blockagewithout damaging the DA system. Thissolution can overpower the most addictiveproperties of cocaine at the molecular level.

Brain scans of ‘addicted’ users have shownlowered levels of prolactin. This is a hormonesecreted by the pituitary gland that is involvedin learning and axon myelination. Activation ofK receptors triggers a release of prolactin,which may be beneficial to neuronal repairsince myelination is fundamental to proficientimpulse conduction.

Nalmefene displays a strong ability to releaseprolactin, visibly above placebo levelindicating effectiveness amongst a controlledgroup. This drug is already being investigatedfor alcohol dependence, “With a number ofadvantages…, including no dose-dependentassociation with toxic effects to the liver,greater oral bioavailability and morecompetitive binding with kappa opioid

(cont...)

receptors.” Doses of 20-25mg are bestsupported with little difference in prolactinrelease with an 80mg+ range, which is ofeconomic sense to manufactures.

Kappa agonists do not entail addictiveproperties making them safe to be taken overlong periods. Methadone for example oftenmerely substitutes for heroin addiction in aminority. Research must reveal whethertolerance to k agonists rapidly builds which

Table 1: Relevant neuro-chemicals involved in synaptic processes

NNaammee ooff NNeeuurroottrraannssmmiitttteerr AAbbbbrreevviiaattiioonn ooff nneeuurroottrraannssmmiitttteerr nnaammee RReessppeeccttiivvee TTrraannssppoorrtteerr PPrrootteeiinn AAbbbbrreevviiaattiioonn ooff ttrraannssppoorrtteerr

Dopamine DA Dopamine transporter DAT

Serotonin 5-HT Serotonin transporter SERT

Norepinephrine NE Norepinephrine transporter NET


36


receptors.” Doses of 20-25mg are bestsupported with little difference in prolactinrelease with an 80mg+ range, which is ofeconomic sense to manufactures.

Kappa agonists do not entail addictiveproperties making them safe to be taken overlong periods. Methadone for example oftenmerely substitutes for heroin addiction in aminority. Research must reveal whethertolerance to k agonists rapidly builds whichwould mean abandoning this treatment. Kagonists must be safe for treating pregnantaddicts and not cause birth defects nor mustthey be carcinogenic. In monkeys, k agonistshave also produced side effects such assedation and emesis. A mixture of k agonistsis speculated to lessen side effects thoughthis needs to be explored and cost-effectiveratios determined.

GGVVGG

Another medical solution is the anti-epilepticdrug, GVG. An inhibitory neurotransmittercalled GABA reduces the amount of DA in theforebrain which is heavily involved inaddiction. This bears similarity to k agonistsand is a direct interaction between reducingthe extreme releases of DA from cocaine andimproving the expression of non-drug takingbehaviour. The BNL research team found thatgamma vinyl-GABA (GVG) increases theamount of GABA available to inhibit dopamineand “enables better communication amongbrain cells”. Overall, a quicker return to highcognitive performance and memory could bederived from enhanced communication, whichis not unlike the benefits from increasedprolactin levels. It is unambiguous that GVGreduces cocaine’s release of DA by 300% /their dopamine levels increase to no morethan twice normal levels. The rewardresponse has been blocked and fails topleasure the addict.

EExxppeerriimmeennttaall EEvviiddeennccee??

In a double-blind, placebo-controlled study 20subjects who wished to break their addictionwere given GVG daily. Eight managed toreach 28 days of abstinence and 4 patientscontinued use; albeit in smaller amounts.Early reports discussed visual disturbances byGVG, though anecdotal evidence from thisstudy found no problems. Those 8 “showedprofound behavioural gains in self-esteem,family relationships, and work activities”,conveying psychological control overdependence. Studies conclude that GVG hasa very reliable safety profile, having been FDAapproved after 20 years of clinical trials withlab rats and humans. Like k agonists, GVGdisplays the ability rebalance dopamine levelsby ironing out surges and reduce “relapseresulting from addiction-induced cues”. Thisis an immense step to defeating theneurochemical basis of addiction plus enablesthe addict to live in familiar surroundings butnot fall into relapse because of externalsignals. General information suggests that theanti-addictive effects persist longer from lowdoses of 0-150 mg/kg per day rather than asingle large dose of 150-450 mg/kg GVG.

Both solutions, if approved, would bebreakthrough medical treatments to treatcocaine abuse and cut relapse radicallyimproving the life of addicts. Promisingresults from GVG trials indicate it maybecome a treatment for addiction to a rangeof other drugs like nicotine and amphetamine.As I have previously mentioned, I uphold theview that research institutions investigatingthese compounds must remain committed totheir cause to ensure that a helping hand canbe offered to addicts.


The Role Of PharmacogeneticsIn Modern MedicineCasey Swerner

37


IInnddiivviidduuaallss rreessppoonndd ddiiffffeerreennttllyy ttoo ddrruuggss aannddssoommeettiimmeess tthhee eeffffeeccttss aarree uunnpprreeddiiccttaabbllee aattbbeesstt,, lliiffee tthhrreeaatteenniinngg aatt wwoorrsstt. Differences inDNA that alter the expression of proteins thatare targeted by drugs can contributesignificantly to an individual’s drug response.One of the most thoroughly investigatedstories is that of Mercaptopurine, used as achemotherapeutic drug for leukaemia.

Acute Lymphoblastic Leukaemia (ALL) is amalignant disorder in which blast cellsconstitute >20% of bone marrow cells. AcuteLymphoblastic Leukaemia is a cancer;whereby white lymphocyte cells rapidly dividewithout maturing which leaves people open toinfection. Furthermore, the cancer canbecome metastatic, causing the spread ofcancer to other parts of the body. Whilst only700 people are diagnosed each year in theUK, it is the most common form of leukaemiain children. Mercaptopurine (6-MP) works bycompeting with the purine base guanine forthe enzyme HGPRTase, inhibiting thesynthesis of purines (2 of the 4 base pairs inDNA) and therefore metabolising into DNA.This makes new DNA ineffective and leads tocell death. It is not known exactly how 6-MPcauses cell death, but its cytotoxic propertiesare very important.

11 sstteepp ffoorrwwaarrdd,, 22 sstteeppss bbaacckk??

Any potential medicine must be tested verythoroughly as it may be very successful atcombating a disease, but may be so toxic thatmore damage is done than good.Pharmacologists look at this issue by aimingto determine the efficacy of a drug relative toits toxicity (how much damage it can cause toa patient). This is important forchemotherapeutic drugs, because for themost part, they aim to destroy cells, and thusif not targeting solely cancer cells, seriousadverse drug reactions (ADRs) can occur. Insome patients the side effects may not beserious, but in others, side effects such asmyleosuppression may occur, (reducing bonemarrow activity) making patients’susceptibility to death from infection ormetastatic cancer even greater; defeating thepoint of treatment in the first place. Rates of acomplete cure for 80% in children and 40%in adults highlight the efficacy of 6-MP;however there are multiple ADRs which are aserious concern.

GGeenneettiiccss hhoollddss tthhee kkeeyy??

One way in which doctors are beginning totest patients who receive 6-MP is bycomparing the genetic makeup of those whohave adverse reactions and those who do not.This study of investigating the efficacy of

drugs and genetic variation is known aspharmacogenetics. To do this first of all onehas to consider how 6-MP works. As a pro-drug, it undergoes reactions in the bodybefore carrying out its function. In the bodyan enzyme TPMT (thiopurine S-methyltransferase) causes the breakdown ofthiopurines (of which 6-MP is one) intosubstances that are not cytotoxic.

Enzymes are coded for by DNA, and thus onehas to consider whether variations on theDNA sequence of the TPMT gene onchromosome 6 affect TPMT output. Mutationscan be tested for by a method known asHigh-Resolution-Melting analysis (HRM). Mostcommonly a single variation, called a SingleNucleotide Polymorphism (SNP) is tested for.A DNA sample is amplified by PolymeraseChain Reaction which replicates the area ofDNA required. Then during HRM the areatested, is heated from 50C to 95C at whichpoint the two DNA strands split. A fluorescentdye, which fluoresces brightly only whenattached to the double helix, is attached andthe fluorescence is measured as it reducesdue to DNA break up. If the tested DNA has aSNP then the fluorescence/temperature curveis different, caused by the different basespresent. The success of the method isdependent on having records of a non-mutated DNA strand, and highly sensitiverecording probes to determine the level offluorescence as temperature increases.

To ensure that TPMT levels have a strong tolink adverse reactions, numerous studieshave occurred examining the levels of TPMTand patient reaction to 6-MP. For example thestudy by Reiling et al shows that thefrequency of incidents of ADRs in patientswith leukaemia being treated with 6-MP were100% for deficient TPMT patients and only7.8% for patients who have fully functioningTPMT alleles.

Although this study contained 180 patients,and lasted a 2.5 year period, the fact that

only 2 TPMT deficient patients were testeddoes not show wholly valid results as to thelink between genetics and ADRs, with such asmall sample size. This criticism has beencited by Van Aken et al who state‘‘pharmacogenetic testing can help inavoiding some, but by far not all adverseeffects of drug therapy’’.

However, a study by Jones et al showed thatTPMT variants cause different levels ofmetabolites (active part of 6-MP), meaningthat mutant allele patients had a 6x higherconcentration of the active drug present,potentially causing fatal side affects.Furthermore, a study published in the Journalof Clinical Oncology corroborated the fact thattolerable dosage for any TPMT deficientpatient was required to be much lower toavoid toxicity. It’s finding that ‘‘the majority ofthese (TPMT deficient) patients (21 of 23,91.3%) presented with hematopoietictoxicity’’ also adds weight to the notion thatgenetic factors cause a predisposition tosevere ADRs.

In a test of ALL patients it was found that‘‘therapy with 6% dosageyielded...concentrations (6-MP) notassociated with prohibitively toxic effects’’and that when '‘dosage was adjusted, thesepatients were generally able to tolerate fulldoses of their other chemotherapy.’’It alsoimportant to note that this study found thatthere was ‘‘100% concordance between

TPMT genotype and phenotype in the TPMT-deficient patients’’.

GGeennoommee bbaasseedd tteessttiinngg

While pharmacogenetic genetic testing mayseem like a perfect solution to reducingadverse reactions, there are alternative viewson the issue. Some feel that ‘‘the science hasnot advanced much beyond a fishingexpedition...to identify important combinationsof genetic determinants of drug response’andthere is a feeling that one gene one drug is

Figure 1

The image shows the graphs for generic curves of polymorphism(s) and wild type allele,allowing scientists to observe if a mutation is present (by comparing to known wild typecurves).


38


not relevant for the majority of therapies.

The term 'pharmacogenomics', whichdescribes a polygenic or genome-wideapproach to identifying genetic determinantsof drug response, is being cited as the nextstep for genetic drug response testing. Oncea gene is linked to a drug response, large-scale epidemiological studies and animalmodels of the candidate gene polymorphismscan be used to further establish geneticvariability as a factor on drug response.

Ultimately this could potentially fuel thepharmaceutical industry to specialize ingenome based medicines, allowing for agreater diversity of drugs. This is shown in thecase of HER2+ breast cancer where lookingat the genetics of the cancerous tissueenabled a new drug, Herceptin, to be createdwhich was previously rejected and todaytreats 7% of all breast cancers. The productsof over expressed genes in cancer cellsrepresent plausible targets for inhibitors thatcould also reverse a drug-resistancephenotype.

WWhhyy iiss pphhaarrmmaaccooggeennoommiiccss ssoo rraarreellyy uusseedd iinncclliinniiccaall pprraaccttiiccee??

The range of mechanisms that account forgenetic polymorphisms (SNPs,insertions/deletions, splice variants) meansthat results for even a single gene are verydifficult to obtain. Ultimately, testing forpharmacogenetic polymorphisms mustovercome major hurdle of cataloguing gene-drug relationships.

One approach is to obtain genomic DNA frompatients entered on Phase III clinical trials,and then to determine genetic polymorphismsthat may dispose a small subset to severetoxicities. These trials should incorporaterigorous pharmacogenomic studies, coupledwith retrospective animal models thatreinforce genotype-phenotype clinicalrelationships. The idea is that those whopresent with severe toxicity could be identifiedbased on genotype. This would build up adatabank of drug-gene relationships andpotentially also save an efficacious drug thatwould have previously been rejected due toadverse reactions.

The main risk of pharmacogenetic testing isnot the testing itself, but the results of gene-profiling populations. The pharmaceuticalindustry may become heavily driven towardsproviding drugs to those that satisfy themajority of patients, leaving those who wouldhave an adverse reaction to conventionalmedicine either alienated, or having to paypremium prices for drugs which are not aslucrative for drug companies to produce.Pharmacogenetic testing may reducepharmaceutical costs from ‘‘$500 million to$200 million’’ but as the report from theNuffield Bio-ethics council states ‘‘developersof new medicines might seek instead tomaximize the number of patients who wouldbenefit from a medicine by usingpharmacogenetic information to identifymedicines most suited to large groups ofpatients’’. Pharmacogenomics has the

potential to translate some of the derivableknowledge of the human genome variabilityinto better therapy. Whether this is a realisticoutcome of the near future remains to bedetermined.

Figure 2

The graph shows the required dosage reduction of 6-MP for non-toxic results, for wild type (control), heterozygous mutant, andhomozygous mutant.

Definitions

WWiilldd TTyyppee –– The mostcommonly occurring allele pair(non-mutant).

HHeetteerroozzyyggoouuss –– Person has 1mutant allele and one (non-mutant) wild-type allele.

HHoommoozzyyggoouuss MMuuttaanntt –– Personhas 2 copies of the mutantallele.

PPhhaarrmmaaccooggeenneettiiccss -- the study orclinical testing of geneticvariation that gives rise todiffering responses to drugs inpatients.

AAddvveerrssee DDrruugg RReeaaccttiioonn ((AADDRR)) --anunexpected or dangerousreaction to a drug The study ofan unwanted effect caused bythe administration of a drug iscalled Pharmacovigilance.


39


Cancer Therapy: Treatment AndTreatment RealitiesBhavesh Gopal11 iinn 99 wwoommeenn ddeevveelloopp bbrreeaasstt ccaanncceerr dduurriinnggtthheeiirr lliiffeettiimmee aanndd aammoonngg tthheessee wwoommeenn,, jjuussttffeewweerr tthhaann ttwweellvvee tthhoouussaanndd ddiiee eevveerryy yyeeaarr..The NHS accounts for this low mortality rateon innovative new treatments and their breastscreening programme costing over seventymillion pounds annually. Breast screening isa method of detecting breast cancer at anearly stage. The first stage involves an x-rayof each breast (mammogram) which candetect small changes in breast tissue whichcould otherwise not be detected by touch.Women may be undergoing gruelling cancertreatment needlessly because as many asone in three cases of breast cancer detectedby screening prove harmless. The BritishMedical Journal claims that twenty three ofthe leading health specialists criticised theGovernment’s “unethical” failure to providewomen with full facts about the NHSscreening programme. They said that manywomen have breast cancer diagnosed even ifthey have benign tumours and may undergounnecessary surgery, radiotherapy orchemotherapy as a result. “As it is notpossible to distinguish between lethal andharmless cancers, all detected cancers aretreated. Over-diagnosis and over-treatmentare therefore inevitable.”

The stage of breast cancer is can bedetermined by the TNM system:

− TT describes the size of the tumour

− NN describes whether the cancer has spreadto the lymph nodes

−MM describes whether the cancer has spreadto another part of the body, such as the bone,liver or the lungs – this is called metastatic.

The problem with breast cancer is its abilityto carry out metastasis (spread to other partsof the body) which has made it difficult totreat ergo many women have died frombreast cancer. To begin the process ofmetastasis, a malignant cell must first breakaway from the cancerous tumour. In normaltissue, cells adhere both to one another andto a mesh of protein (extra-cellular matrix)filling the space between them. For amalignant cell to separate, it must breakaway from the extra-cellular matrix and thecells around it. Cells are held together withcell-to-cell adhesion molecules and thisadhesion also allows interactions betweennumerous proteins on the cell surface. Incancer cells, the adhesion molecules seem tobe missing. Cadherins, a family of intercellularadhesion protein molecules, play a big part inkeeping cells together. One subtype in thisfamily, E-cadherin, is the adhesion moleculefound in all cells. This molecule seems to be

the important factor in cell-cell adhesion. Incancer cells, E-cadherin is missing, allowingcancer cells to detach from each other. Onestudy has shown that blocking E-cadherin incancer cells turns them from non-invasive toinvasive. This work established theimportance of cell adhesion. These studiesrevealed cell adhesion's ability to inhibit acancer cell's capacity to invade, by keeping itbound to other cells. Tumours are capable ofcreating new blood vessels (angiogenesis)because of their need for nutrition, and thisgives cancer cells ample opportunity fortransport. Entry to the blood vessel requirespenetration of the basement membrane (thinlayer of specialized extra-cellular matrix). Anew location has been found where thecancer cells can grow.

TThhee tthheerrmmooddyynnaammiicc mmooddeell ooff cceellll iinntteerraaccttiioonnss

Malcolm Steinberg proposed the differentialadhesion hypothesis, which is a model thatexplains patterns of cell sorting based onthermodynamic principles. Steinbergproposed that cells interact so as to form anaggregate with the smallest interracial freeenergy; cells rearrange themselves into themost thermodynamically stable pattern. If celltypes A and B have different strengths ofadhesion, and if the strength of A-Aconnections is greater than the strength of A-B or B-B connections, sorting will occur, withthe A cells becoming central. After amutation has occurred in the nucleus, onecan propose that the cell adhesions becomeweak ergo they can break away andmetastasise.

CChheemmootthheerraappyy

Cancer treatments haven’t yet pervaded theUK in the NHS. Chemotherapy is the mostrelevant cancer treatment if cancer cells havemetastasized. Cytotoxic drugs are given topatients via the bloodstream as cancer cellsmay have carried out metastasis; it istherefore administered via an intravenousdrip. One chemotherapy drug used fortesticular cancer treatment is cisplatin (aplatinum compound). Patients receivecisplatin via a saline solution so it can enterthe bloodstream ergo cells can take it upactively or by simple diffusion. Hydrolysisenables cisplatin to replace a chlorinemolecule with a water molecule making itpositively charged. Cisplatin attaches to theseventh nitrogen atoms of the adenine andguanine bases which causes the formation ofcisplatin-DNA adducts (when two moleculesreact by addition forming two chemicalbonds). 1, 2-intrastrand adducts form whenthe seventh nitrogen atoms (N7) on adenineand guanine are replaced by ‘two chlorineatoms of cisplatin’ (below). These adductscause the bases to become de-stacked andthe DNA helix to become kinked.

The 1,2-intrastrand adducts affect replicationand transcription of DNA, and the ability torepair leading to an abnormality in the doublehelix. This is detected and triggers apoptosis(programmed cell death) in cancerous cells,halting metastasis. Chemotherapy is onlyeffective if the cancer-to-normal cell deathratio is high. If the decline of normal cells isgreater than expected, chemotherapy isdamaging more normal cells than expected;consequently more side effects will occur. If atumour has been removed by surgery,chemotherapy can decrease the risk of breastcancer returning again; this is known asadjuvant chemotherapy. Neo-adjuvanttherapy is effective in shrinking down a largetumour so it can be removed easily duringsurgery – the use of chemotherapy in theseways has made it easier to treat breastcancer.

HHeerrcceeppttiinn aanndd 2211sstt CCeennttuurryy TThheerraappyy

The HER receptors are proteins that areembedded in the cell membrane andcommunicate molecular signals from outsidethe cell to the inside of the cell.

The HER proteins regulate cell growth,survival, adhesion, migration, anddifferentiation—functions that are usuallyamplified in cancer cells. The HER2 receptoris defective and is continually ‘on’ ergo itcauses breast cells to reproduceuncontrollably enabling metastasis.Antibodies are molecules from the immunesystem that bind selectively to differentproteins. Herceptin is an antibody that bindsselectively to the HER2 protein. When it bindsto defective HER2 proteins, the HER2 proteinno longer causes cells in the breast toreproduce uncontrollably.

HER2 passes through the cell membrane, andsends signals from outside the cell to theinside. Signaling compounds called mitogensarrive at the cell membrane, and bind to theoutside part of HER2. HER2 is activated, andsends a signal to the inside of the cell. Thesignal passes through different biochemicalpathways. In breast cancer, HER2 sendssignals without being stimulated by mitogensfirst which promote invasion, survival and

Figure 1

TThhee cchheemmiiccaall ssttrruuccttuurree ooffcciissppllaattiinn..


40


growth of blood vessels of cells. When cellsdivide normally, they go through a mitosiscycle, with checkpoint proteins that keep celldivision under control. In breast cancer, theproteins (CDKs) that control this cycle areinhibited by other proteins. One protein is theinhibitor p27Kip1 which moves to the nucleusto keep the cycle under control. In cells withdefective HER2, p27Kip1 doesn't move to thenucleus, but accumulates in the cytoplasminstead – this is caused by phosphorylationby Akt (proteins that play a role in cellsignaling). Cells treated with Herceptinundergo arrest during the G1 phase of thecell cycle so there is a reduction inproliferation. P27Kip1 is then notphosphorylated and is able to enter thenucleus and inhibit cdk2 activity, causing cellcycle arrest. Also, Herceptin suppressesangiogenesis by induction of antiangiogenicfactors.

TTaarrggeettiinngg CCaanncceerr-- FFuuttuurree TThheerraappiieess??

Non-competitive inhibition is a type of enzymeinhibition that reduces the maximum rate of achemical reaction without changing theapparent binding affinity of the catalyst for thesubstrate. An inhibitor always binds to theenzyme at a site other than the enzyme'sactive site. This affects the rate of thereaction catalyzed by the enzyme because thepresence of the inhibitor causes a change inthe structure and shape of the enzyme whichultimately means the enzymes is no longerable to bind with a substrate correctly.

Normal cells typically show low levels of folatereceptors and cancer cells have evolved amechanism to capture folate more effectively.One idea has been based on using aminoacid oxidases & proteases which are used fordigestion in snake venom. ATPases couldalso be used which are used for breakingdown ATP to disrupt energy fuel use. A folatemolecule could be used as an inhibitor to anyone of these proteins. Now that the functionof these proteins has been inhibited, they can

be injected in the blood stream where theyare taken up by cancer cells. When the folatemolecule binds to the folate receptor thebonds between the folate molecule and thereceptor are stronger than that between thefolate molecule and its protein ergo the folatemolecule will be released from the protein.This allows the protein to affect the cellmembrane and thus the micro fibrils neededin the cell cycle will be released preventinggrowth. However, this is a heuristic view ofpotential treatments, and much furtherinvestigation is needed.

NNHHSS RReeaalliittyy:: TThhee ccoosstt ooff LLiivviinngg

Health economists from the University ofSheffield say Herceptin costs about £20,000per woman for a year's treatment at thestandard dose. Findings published in TheLancet show that Herceptin improves survivalafter three years by 2.7 per cent - describedas an "extremely uncommon" result aftersuch a short time by Professor Ian Smith. TheSheffield University team who advised NICEon its original decision to approve Herceptinsays they are now having second thoughts.Writing in The Lancet, a study in Finland hasshown that giving a fifth of the standardHerceptin dose, over a shorter time (nineweeks in this case) has equally good resultsin reducing the recurrence of cancer anddeaths in the treated women. If confirmedthe finding suggests women could be treatedwith Herceptin at a cost of two thousandpounds instead of twenty thousand pounds,reducing pressure on NHS budgets andallowing more women to be treated.

The Norfolk and Norwich Hospital have foundthat the cost of Herceptin every year would be1.9 million pounds for seventy-five patients.This eventually becomes 2.3 million poundswith pathology testing, cardiac monitoring,pharmacy preparation, and drugadministration costs.

As NICE guidance over drugs provides no

extra funding or suggestions of whichservices to cut, medical professionalsultimately have to make difficult decisions.Herceptin as an adjuvant therapy costs fourtimes as much as other adjuvant therapiesergo some patients are given a greaterpriority than others. The NHS has used the‘postcode lottery’ and some areas will nothave availability to the certain drugs. TheNational Institute for Health and ClinicalExcellence only issues “guidance” to the 152PCTs in England and Wales. Therefore if onelived in Birmingham, the vast array ofcytotoxic cocktails would be availablehowever if one lived in Oxfordshire, thischoice would be limited. Primary care trustsare responsible for spending more than 80%of the total NHS budget. It is possible, butdifficult, to challenge a PCT decision on drugfunding — the patient has to demonstratethat he or she is an “exceptional case”, butthe criteria for “exceptionality” varies fromPCT to PCT.

Some distress has been suffered by criticallyill patients who have had their NHS fundingwithdrawn because they chose to supplementtheir treatment by paying for “top-up” drugsnot available on the NHS. Ultimately, it isthese economic realities which often have thefinal say despite major therapeuticimprovements.

Figure 2

Herceptin’s main mechanism of action on cancerous cells.


41


The Application OfNanotechnology In MedicineKarthigan Mayooranathan

NNaannootteecchhnnoollooggyy iiss tteecchhnnoollooggyy tthhaatt iinnvvoollvveesstthhee mmaanniippuullaattiioonn ooff mmaatttteerr oonn aann aattoommiicc ssccaalleeaanndd iittss mmaatteerriiaallss aarree mmeeaassuurreedd iinn

nnaannoommeetteerrss.. Nanometers, 10-9m, are sosmall (the width of a human hair is around100,000 nanometers) that not even electronmicroscopes enable them to be seen –instead it relies on powerful atomic forcemicroscopes. The advancement ofnanotechnology has led to the formation ofthe sub speciality called Nanomedicine.

Although nanomedicine may appear as if it isstill on the drawing board, products havebeen made but they need to jump theessential hurdles of clinical trials. But howcan nanomedicine contribute to and improvethe medical field?

Most drugs prescribed to a patient will haveto be ingested orally; so this means that thedrug will reach the target cells/tissues but asa consequence will have to travel around thewhole body, via the systemic circulation(thereby giving the drug a lowerbioavailability). Nanomedicine can increasethe bioavailability of the drug which meansthat administered doses, and hence sideaffects, will be lower – thereby improvingtreatment of medical conditions.

One way of delivering drugs involves usingcarbon nanotubes. A team of UK researchersnot only found that the cell membrane couldbe penetrated by the nanotubes, but it couldpenetrate the membrane and enter thecytoplasm; without causing damage or deathto the cell.

Other methods of drug delivery do not deliverthe drug into the cell; for example, liposomescarry the drug to the cell but do not enter thecytoplasm of the cell. Thereby the drug stillhas hurdles that it needs to overcome inorder to enter the cell.

Properties of nanomaterials enable it to beused as a much more effective way oftreating cancer. Carbon nanotubules can beplaced into the cancerous cells and this cancause the destruction of these cells whenthese cells are exposed to infrared light.Infrared light usually passes through the bodyharmlessly but when carbon nanotubules, insolution, are exposed to an infrared emittinglaser the tubules in solution heat up to around70 0C in two minutes.

Therefore if thousands of these nanotubulesenter into cancerous cells then the cancercells will be incinerated -thereby destroyingthe cancer cells. To ensure that that thenanotubules only enter the cancerous cells,

they must be covered in folate molecules asthe surface of cancer cells has a very highnumber of receptors for folate moleculeswhereas healthy normal cells due not containas much of these receptors comparatively.This therefore ensures that the nanotubulesare much less likely to attach healthy cells, asthey are more likely to enter the cancerouscells.

Folic acid is needed by all cells butparticularly in high quantities for cancer cells,as they are essential to cells that rapidlydivide and multiply . This process efficientlydestroys cancer cells while minimisingsignificantly the destruction to normal cellsand tissues surrounding the site of a tumour.The method of using nanotubules andinfrared light could also solve the problem ofdestroying cancers that are resistant tochemotherapy. However further tests andresearch needs to be done before thismethod can be implemented.

Another potential way of treating cancer, bytaking advantage of the unusually highnumber of folate receptors, is by usingdendrimers. Dendrimers are man mademolecules that have a diameter of 5nanometers. Folic acid can be attached tohooks on dendrimers to carry anti-cancerdrugs like methotrexate. This “Trojan horse”method allows chemotherapeutic drugs to besmuggled into the cancerous cells. Folic acidis essential in DNA replication as they areused in the synthesis of DNA bases –therefore cancer cells have a very highnumber of receptors.The folic acid attaches tocancer cells as opposed to rapidly dividingnormal cells as cancer cells have evolved amechanism to acquire folate more effectively.When the folic acid attaches to the receptors(pictured right), the cancerous cellsinternalises the dendrimer – unknowinglytaking in the anti-cancer drugs. This thereforeallows the cancerous cells to be destroyedeffectively by the drug, as the drug crossesthe cancer cells membranes with ease.

This method of using dendrimers reduces thedose needed for cancer drugs. The lowerdoses prescribed means that less damage isdown to the surrounding normal cells andtissues – thereby reducing the side effectsthat could be caused by a drug. Dendrimersare also advantageous, as they do not triggera response from the immune system, as theyare so small. Dendrimers also provide asolution to the resistance of cancer cells todrugs used in chemotherapy as the drugs donot need to diffuse across the cellmembranes but instead are internalised bythe cancer calls due to the folic acid thedendrimers carry.

Nanotechnology can also be used in the earlydiagnosis of certain diseases. For example,

nanocantilevers can be created specifically tobind to molecules that are associated withcancer and cancerous cells, like altered DNAsequences or certain proteins associated witha particular type of cancer. If the cantileversuccessfully binds with molecules that arespecific to certain types of cancer then thesurface tension of the cantilever changescausing the cantilever to bend. This thereforeallows for cancer to be successfullydiagnosed at a much earlier stage, whichmeans that diseases are more likely to bedetected at much less advanced stage.

Finally, nanoparticles can also aid in themedical imaging of diseases. Quantum dotsof cadmium selenide (or other semi-conductor compounds) are crystals thatfluoresce in many different colours whenexposed to ultraviolet light. The variouscolours that they fluoresce depend on the sizeof the crystal. These quantum dots can thenbe engineered to bind with DNA or moleculesthat are unique to particular diseases. Whenthe crystals fluoresce under ultraviolet light,the DNA sequence will be made visible andthe diseased cells will become detected andits location known. Cadmium Selenidequantum dots can also be useful in surgicalprocedures; when exposed to ultraviolet lightthey will fluoresce and will therefore enablesurgeons to use crystals created to bid totumour cells enabling them to moreaccurately locate and hence remove thetumour.

Gold nanoshells can be engineered to bindwith the receptors on certain types of cells.This means that the nanoshells can be usedas effective biomarkers, as gold is veryunreactive, and therefore will not causedisturbances to biological reactions in thehuman body.

Similar to quantum dots, gold particlesfluoresce when exposed to ultraviolet lightand changing the thickness of the gold shellcan change the colour emitted. Both thesemethods of using quantum shells andnanoshells and provide a much better qualityof in vivo imaging and hence preventing theneed for a biopsy. Gold nanoshells can alsobe used to destroy tumours in a similar waythat carbon nanotubes do. Once largenumbers of gold nanoshells accumulate atthe site of the tumour and heat is applied –then the heat is absorbed by the spherescausing the death to the surrounding tissue .

Overall, nanomedicine is a prosperingresearch field that has made many medicalbreakthroughs. The advantages and benefitsof nanomedicine strongly outweigh the pitfallsbut until a better idea of whether this type oftechnology will be compatible in the humanbody needs more research and clinical trials.


42


Heart Transplantations: End of an Era?Brett BernsteinFFrroomm tthhee ffiirrsstt eevveerr ttrraannssppllaanntt iinn 11990055 ((aattrraannssppllaanntt ooff tthhee ccoorrnneeaa,, ppeerrffoorrmmeedd bbyyEEddwwaarrdd ZZiirrmm)),, ttoo tthhee ffiirrsstt hheeaarrtt ttrraannssppllaanntt,,oovveerrsseeeenn bbyy CChhrriissttiiaaaann BBaarrnnaarrdd iinn 11996677,, ttootthhee ffiirrsstt ttrraannssppllaannttaattiioonn ooff aa wwiinnddppiippeepprroodduucceedd ffrroomm tthhee ppaattiieenntt’’ss oowwnn sstteemm cceellllss iinn22000088,, tthhee pprroommiinneennccee ooff oorrggaannttrraannssppllaannttaattiioonn hhaass mmoosstt ddeeffiinniitteellyy ggrroowwnnddrraammaattiiccaallllyy oovveerr tthhee ppaasstt cceennttuurryy.. However,what this article will seek to find out iswhether heart transplantation specifically hasreached its peak, and is to start, or, indeed,continue waning in its usage and popularity.

Heart transplantation in this article will referto “heart allografts,” defined as the transfer ofa heart to a patient from a “genetically non-identical member of the same species”.

RReejjeeccttiioonn

The largest problem associated with allograftsis rejection, defined as “an attempt by theimmune system to reject or destroy what itrecognizes to be a "foreign" presence ”.Recipients and donors are matched based ontheir blood type, and the similarity of theirHuman Leukocyte Antigen system (HLA). Thisrefers to many antigens on the surface ofcells, as well as other proteins involved inimmunity, and is coded for by a “superlocus”(long length of DNA) on human chromosome6. Although, there is great diversity in HLA, itmust be matched as closely as possible,because “any cell displaying some other HLAtype is "non-self" and is an invader, resultingin the rejection of the tissue bearing thosecells”.

Often, B-cell antibodies begin to attack theorgan only minutes after transplantation, “andthe new organ may turn black and blotchyeven before surgeons have sewn up thewound” Although patients are normallyallowed to leave hospital after one week, atroughly this time, when T-cells (a type oflymphocyte) use their receptor to bind to aforeign Major Histocompatibility Complex(coded for by the HLA complex), most of thembecome cytotoxic, and attack the cells of thetransplanted heart, causing them to lyse(burst) and undergo necrosis (unplanned celldeath). This is known as acute rejection.

Necrosis is particularly harmful because, inthe process of cell death, damage to thelysosomes can cause digestive enzymes to bereleased, which digest surrounding cells,causing more necrosis, resulting in a chainreaction. “If a sufficient amount of [touching]tissue necrotises, it is termed gangrene”. Inaddition, other T-cells produce cytokines,such as interferon gamma, which attractmacrophages and neutrophils to thetransplanted tissue by way of chemotaxis(following a chemical gradient). Once there,these phagocytes begin the process of

phagocytosis (engulfing foreign / infectedcells) on the transplanted cells, causing evenmore cell death. In the myogenic tissue of theheart, this is particularly serious, becauseblood pressure and heart rate can quicklydrop due to the lack of myogenic tissue ableto depolarise and contract, and a myocardialinfarction may result.

The problem of the immune response isnormally solved by the usage ofimmunosuppressive drugs. These includecorticosteroids such as hydrocortisone, whichweaken the immune response, andcalcineurin inhibitors, such as cyclosporin,which inhibit the action of killer T-cells, bothresulting in reduced damage to thetransplanted tissue. As such, the benefits ofsuch immunosuppressants are manifest: thatthe transplanted tissue is not rejected by thebody.

However, there are also risks involved in theprescription of these immunosuppressants.For example, the weakening of the immuneresponse, caused by corticosteroids,consequentially causes the weakening of anybeneficiary immune responses, such asfighting other infections. Moreover,cyclosporin is chemotherapeutic andnephrotoxic (poisonous to the kidney), andhas been known to have very serious side-effects. Other side effects include gumsgrowing over the teeth, and growth of hair allover the body.

Ethically, a doctor must evaluate the potentialefficacy of a drug against its possible toxicitybefore its prescription, and must also reviewwhether the chance of contracting a moreserious disease from the post-operativetreatment outweighs the negative effectscaused by the patient’s current condition.Moreover, the cost of anti-rejection treatmentis roughly £10,000 per annum, and so,economically, it must also be assessed as towhether it would be more economical toinvest a greater amount of money in theprevention of the causes of heart transplants,than pay for post-operative treatment.

Alternatively, a recent discovery of a proteininvolved in heart transplant rejection by ateam from the University of California mayalso provide the basis for less toxic anti-rejection treatment . Researchers have provenon mice that the use of an antibody whichblocks the NK2GD protein on the surface ofkiller T-cells lessens the immune response,and makes the animals more receptive to atransplanted heart. Although early in itsdevelopment, such a discovery could greatlybenefit humans in the years to come.

IInntteerrvveennttiioonnaall CCaarrddiioollooggyy

The main cause for heart transplantation issevere heart failure One of the main causesof heart failure is coronary heart disease, anarrowing of the coronary arteries caused byatheroscelerotic build-up. Since 1977, when

the first pecutaneous transluminal coronaryangioplasty (PTCA) was performed by AndreasGruentzig, the procedure has given hope tothose with coronary heart disease, preventingmany potential heart attacks, and the needfor transplantation.

The procedure begins with the administeringof a local anaesthetic to an area of the skineither in the groin or arm. Subsequently, “acatheter (a fine, flexible hollow tube) with asmall inflatable balloon at its tip ” is insertedthrough either the femoral or radial artery asappropriate, and is guided towards thenarrowed coronary artery with the aid of acoronary angiogram. The balloon issurrounded with a stainless steel mesh calleda stent, and, when inflated with a pressure75-500 times normal blood pressure , thestent expands and squashes theatherosclerotic plaque, widening the lumen ofthe blood vessel. When the balloon is deflatedand withdrawn, the stent maintains its shape.

Originally, all stents were “bare metal”, thatis, uncoated stainless steel. However, aclinical trial in 2002 showed that a drug-eluting stent (in this case, sirolimus), resultedin lower rates of major adverse cardiac events(MACE). Two different types of drug-elutingstent are available in the United Kingdom,those coated with sirolimus and those coatedwith paclitaxel. Sirolimus is animmunosuppressant, and, as such, blocks theactivation of T and B cells, so the lumen ofthe coronary artery remains clear, with nobuild-up of unwanted lymphocytes. Paclitaxelworks as a mitotic inhibitor, breaking downthe microtubules used in cell division, and isused as an anti-proliferative agent, to limit thegrowth of neointima (scar tissue) around thestent.

SSoocciioo--EEccoonnoommiicc CCoonnsseeqquueenncceess

Presently, it is evaluated on a patient-by-patient basis as to whether it is economicallyand ethically better to use a drug-elutingstent, which costs more, or a bare-metal one,which needs a longer drug treatmentafterwards. Ethically, since drug-eluting stentsare more likely to decrease the probability ofrestenosis, ideally, they should always beused in preference to those consisting of baremetal. However, “the Cypher drug-elutingstent is being marketed in the UK at a priceabout fivefold that of a bare stent”, and soeconomically, the benefit of the reduction inrisk of restenosis must be compared to theincrease in immediate cost, and in addition,compared to the cost of after-care resultingfrom the usage of a bare-metal stent.Guidelines issued by the National Institute forClinical Excellence (NICE) say that drug-eluting stents should be used in particularlynarrow coronary arteries, as these are theones most susceptible to restenosis. Anti-platelet drugs such as aspirin or clopidogrel,and anti-coagulants such as heparin, will alsobe prescribed for up to six months for drug-


43


Figure 1

Graph showing number of heart transplants and incidence oftransplants per million population, 1997–2006

Heart Transplantations: End of an Era?Brett Bernstein

eluting stents, and longer for bare-metalones, to prevent clotting of blood around thestent.

Statistics show that angioplasty has a slightlybetter one-year survival rate thantransplantation: in the year 2006, there were2,192 heart transplants performed in theUSA. 74% of these procedures wereperformed on men, for whom the one-yearsurvival rate was 87%. In the year 2005,there were 1,271,000 coronary angioplastiesin the USA, with a one year survival rate of83-95%, depending on age.

From 1997 – 2006, in general, the number ofheart transplants in the United States hasdecreased. This indicates that preventative oralternative measures to transplantation haveincreased in use and / or efficiency over thistimespan. Socially, these measures benefitboth the patient, in view of the fact that theyundergoe a lower risk, less invasiveprocedure, and the hospital, as, economically,the cost of a PTCA and aftercare is less thanthat for a transplantation. With respect to theabove statistics, although it would beunrealistic to suggest that all those whounderwent angioplasties would haveotherwise eventually had to undergo atransplant, it is likely that the use of PTCA toprevent any irreparable damage to coronaryarteries has reduced the number of hearttransplants required over the past thirty years.

Moreover, as discussed, with the increasedefficiency of anti-rejection treatment and thepotential use of antibodies based on therecent discovery in California, transplantationis still a viable option for those whosecondition has deteriorated to a level wheretransplantation is clinically necessary.

Of course, beyond the scope of this article,

potential advances such as wide-spreadavailability of fully functioning artificial heart-pumps, increased stem-cell research, and,the commonly used coronary bypass, allindicate that the heart transplant is likely todecrease in usage over the next decade. Aseven more angioplasties are performed in thecoming years, in combination with the otheralternative treatments discussed, hearttransplants should decline in use, allowingmoney allocated for post-operative treatmentto be used for research, benefitting themajority of the population in the long-term.


44


Haemophilia A: How successful hasthe genetic engineering ofrecombinant Factor VIII been?Ronel Talker

HHaaeemmoopphhiilliiaa,, iiss aa hheerreeddiittaarryy bblloooodd ccoonnddiittiioonn,,wwhheerreebbyy,, aa vviittaall cclloottttiinngg aaggeenntt iiss ddeeffiicciieennttccaauussiinngg bblloooodd cclloottss ttoo ddeevveelloopp ffaarr sslloowweerr aannddtthhee hheeaalliinngg ooff wwoouunnddss iiss mmuucchh ddeellaayyeedd..

TThhee PPrroobblleemm

Although haemophilia A has a very goodprognosis and is quite rare (1 in 10,000births and 1 in 5,001 male births being thatof a haemophiliac), about 16,200 people inUSA suffer from Type A and 1,681 patientsdied in USA from haemophilia in 1999.Therefore, it is vital that a suitable treatmentiis found in order to enable these sufferers tollead as normal a lifestyle as possible.However, in the past, the use of blood-extracted Factor VIII has resulted in other life-threatening conditions arising. In essence,factor VIII levels in the bloodstream must beraised safely, in order to enhance clotting. Todo this, scientists are researching differentways in which genetically engineered factorVIII can be used.

TThhee RRoollee ooff FFaaccttoorr VVIIIIII

Factor VIII , otherwise known as anti-haemophilic globulin, is a glycoprotein that ispredominantly manufactured in the liver andafter synthesis, is transferred to the lumen ofthe endoplasmic reticulum. The Golgiapparatus then influences its compatibilitywith von Willebrand factor (vWBF), which isFactor VIII’s cofactor. Their association givesFactor VIII stability and protection againstdegradation as it circulates in the bloodplasma.

IIn the body there are 13 different clotting

factors, which all have slightly different

functions. As soon as there is a disturbanceiin the blood vessel wall, a complexcoagulation cascade takes place involvingalmost all 13 factors.

There are,two paths on which clotting takeplace. The extrinsic pathway begins in thebroken tissue outside the blood vessels withFIII (tissue extract) activating the release ofFVII in the bloodstream.

The intrinsic pathway is more complicatedand begins when FXII (Hageman factor) fromthe blood comes into contact with thecollagen in the damaged vessel wall. A chainof activations involving FXI, FIX and FVIII thenfollow, culminating in the meeting of theintrinsic and extrinsic pathways. Together,these activate FX, which catalyses theconversion of FII (prothrombin) to thrombin.This also acts like a catalyst in converting FI(fibrinogen) to fibrin. Finally, with the additionof Factor XIII, this forms a blood clot. In theseprocesses, each factor can be seen as adomino. Without one domino in the chain, theentire pattern falters. Similarly, without FactorVIII, a Type A haemophiliac’s blood cannot clotat all.

AA PPoossssiibbllee SSoolluuttiioonn –– GGeenneettiicc EEnnggiinneeeerreeddFFaaccttoorr VVIIIIII

In the 1970s, haemophiliacs were treatedusing Factor VIII derived straight from donatedblood. This blood was not tested or screenedbefore transfusion leading to an HIV/AIDS andHepatitis C epidemic amongst patients beingtreated in this way. As a result, about 60% ofhaemophiliacs contracted HIV (although mostdid not have AIDS) and subsequently, half thepopulation of haemophiliacs died. Since 1983and 1991, people infected with HIV andHepatitis C, respectively, have been excluded

from the donor list.

However, in 1993, scientists found a way ofgenetically engineering human Factor VIIIusing Escherichia coli bacteria and thereforeavoid many complications of blood-bornediseases. This process took advantage of therings of DNA called plasmids found outsidethe nucleus in bacteria and how they can betransferred from one bacterium to another.

Unfortunately, haematologists found aproblem occurring with the first generation ofrecombinant Factor VIII. The original purposeof this solution was to prevent the risk of aspread of the Hepatitis C and HumanImmunodeficiency Virus (HIV). The firstgenetically engineered samples of Factor VIII,manufactured in 1992 were very fragile andso the human protein albumin was used as astabiliser. However, it was discovered thatcontaminated human albumin caused thepatient to be infected with the transfusion-transmitted virus (TTV). So the next step inhaemophilia research was to find a stabiliserthat used less blood-based additives.

In June 2003, further advances were madeand it was found that the use of the sugartrehalose would result in no blood-basedadditives being used in the treatment ofhaemophilia A. Such a breakthrough meantthat there was no risk of being infected by thecontaminated blood products of the donor.EEccoonnoommiicc iimmpplliiccaattiioonnss

The first genetically engineered Factor VIIIconcentrates were available from 1993 andas this was a major step in safe and effectivetherapy for Haemophilia A, the drug was veryexpensive at the time. The primary reason forthis expense, according to Dr. Mary Mathias,a haemophilia consultant at Great Ormond

Varieties of Haemophillia

HHaaeemmoopphhiilliiaa AA - The most common type of haemophilia, presenting itself in 90% ofhaemophiliacs. A defective X-chromosome causes coagulation Factor VIII (F8) deficiency

HHaaeemmoopphhiilliiaa BB – Another X-linked genetic disorder, which involves the lack of Factor IX.This is rarer but not as severe as Type A

HHaaeemmoopphhiilliiaa CC – An autosomal recessive disease, which causes the blood to be deficientin Factor XI


45


Haemophilia A: How successful hasthe genetic engineering ofrecombinant Factor VIII been?Ronel Talker

Street Hospital Haemophilia Centre, is due tothe processes involved in the isolation ofplasmids and their insertion into thehamster’s ovary cell. However, as a patientbeing treated with the most recent versions ofrecombinant Factor VIII can achieve an almostnormal life expectancy, doctors such as Dr.Mathias believe that the treatment is worththe expense.

The overall cost of recombinant Factor VIIIconcentrates decreased considerably ascheaper techniques are being used to makethese products. However, plasma-derivedFactor VIII clotting agent, an alternativetreatment to the genetically engineeredcoagulation protein, has increased in cost. Infact, it started much cheaper thanrecombinant Factor VIII but is now almost asexpensive. Dr. Mathias concluded, “The mainreasons behind the rise in plasma-derived

Factor VIII prices are partly due to thedecrease in blood donors but mainly becauseof the extensive processes carried out toensure that the products are virally clean,especially necessary after the HIV andHepatitis C outbreaks.” Plasma-derived FactorVIII is described in more detail later on as analternative method of treatment.

RRiisskkss ooff GGeenneettiiccaallllyy EEnnggiinneeeerreedd FFaaccttoorr VVIIIIII

The only risk to patients is that of developingFactor VIII inhibitors. These are antibodiesproduced by the body’s immune system,which almost entirely degrade the activity ofthe infused coagulation factor. There is a riskof developing inhibitors whilst receiving anyform of haemophilia treatment because anyforeign body inserted into a human runs arisk of being rejected and not beingrecognised. Nevertheless, recent research hassuggested that the risk of gaining inhibitorsmay be slightly higher using geneticallyengineered Factor VIII rather than usingplasma-derived clotting factor.

AAlltteerrnnaattiivvee SSoolluuttiioonnss

Desmopressin (deamino-D-argininevasopressin)

This drug is a synthetic derivative ofvasopressin, a hormone produced by thepituitary gland in order to help retain water inthe body by varying the permeability of thecollecting duct in the nephrons of the kidney.Vasopressin is also called anti-diuretichormone (ADH). Desmopressin also happensto raise the levels of Factor VIII in thebloodstream but requires the patient toalready be producing some Factor VIII.Therefore this alternative can only be usedwith mild haemophiliacs and in some vonWillebrand sufferers (although it can have anadverse effect on the platelets in others).Theonly major side effect of this drug is waterretention and so patients’ fluid intake must berestricted. It can be given by an intravenousor subcutaneous (under the skin) injection oralso by intranasal administration.

Plasma-derived Factor VIII:

These Factor VIII concentrates are producedby fractionation of pooled human plasma andthen are subject to many methods of viralinactivation such as heating, pasteurisation,solvent/detergent treatment and monoclonalantibody purification. These steps of ultrafiltration are vital to avoid a repeat of theHIV/Hepatitis C epidemic. The end product isthen freeze-dried (lyophilised) so that thepowder form is stable and thereforerefrigeration isn’t necessary. Before injection,the powder is simply mixed with sterile waterand therefore makes home treatment easy.

This method is advantageous as it involves ahigh concentration of Factor VIII in a smallspace but suffers due to the necessity formany donors in order to compensate for theloss in activity of the clotting agent during theprocess. However, it is still important to keepplasma-products, even though recombinantFactor VIII can now be made to be safer and

very effective. This is because there are someclotting diseases such as Von Willebranddisease where there is no recombinantcoagulation agent as yet.

PPoossssiibbllee ffuuttuurree iissssuueess aanndd ssoolluuttiioonnss

There are worries that haemophilia treatmentin the future may become extremelyexpensive because currently, medicine hasenabled haemophiliacs to lead an almostnormal lifestyle and therefore have children.As more haemophiliacs are able to produceoffspring, more genes coding for Factor VIIIdeficiency will be spread down generationsand so more people will end up being eithercarriers or sufferers of haemophila A. Atpresent, there is pre-conception counsellingand prenatal testing of the foetus’ blood

Stem cell scientists, such as Dr. DouglasMelton and Shinya Yamanaka of Harvard andKyoto University respectively, are makingdiscoveries that may soon see InducedPluripotent stems cells (iPS cells) with thegenes causing the disease to be replacedwith chemicals. These iPS-generated cellscould then be transplanted into people andperhaps reprogramming may also bepossible.. Unlike a stem cell that erases amature cell’s entire genetic memory, Dr.Melton’s method takes a mature cell backonly part of the way and simply gives it anextreme therapeutic change.

Research still continues into this method buthaving considered the benefits and risks,genetically engineered Factor VIII remains thesafest and most efficient method of treatmentaround.

Manufacturing recombinant Factor VIII

1. A DNA strand containing instructions for producing Factor VIII is cut from human DNA usingrestriction endonucleases

2. A plasmid from a bacterium is isolated and the same enzyme is used to cut the ring open

3. The DNA containing the new instructions are now spliced into the plasmid and DNA ligase usedto join the ends, leaving a recombinant plasmid that can code for Factor VIII

4. This plasmid is now kept in an environment filled with cells taken from either an ovary or akidney of a Chinese hamster until one of these cells ‘accepts’ the plasmid

5. The cell now reproduces several times until there are hundreds of these cells containing therecombinant plasmids, each of which produce Factor VIII along with their other products in a vat

6. The bi-products are all removed during heating and filtration. Antibodies can also be used tobind exclusively to the Factor VIII

7. The Factor VIII is now filtered once more to remove any remaining impurities before beingstabilized with human albumin, bottled, freeze-dried and labelled


46


Swine Flu Epidemiology & PathologyVishal AminEEaarrlliieerr tthhiiss yyeeaarr,, aa nneeww ssttrraaiinn ooff aann iinnfflluueennzzaavviirruuss eemmeerrggeedd iinn ppaarrttss ooff MMeexxiiccoo,, kknnoowwnn aasssswwiinnee fflluu.. The strain of the swine influenza Avirus (SIV) is known as H1N1 and it was soondeclared pandemic status. So what has led tothis state of panic, with a virus that hassimilar symptoms to that of seasonal flu?

HHaaeemmaagggglluuttiinniinn aanndd NNeeuurraammiinniiddaassee

The reason for their being so many differenttypes of influenza virus is down to the abovetwo proteins. In our bodies, haemagglutinin isresponsible for the clumping of red bloodcells which is released by antibodies. On theinfluenza virus, haemagglutinin allows thevirus to bind with the cell that it is going toinfect. Currently, there are 16 known forms ofinfluenza haemagglutinin and areappropriately named H1, H2 etc. The formswhich allow influenza to infect humans areH1, H2 and H3 although in some otherinstances, like H5N1 bird flu, H5 cansometimes infect our bodies.

Neuraminidase is another viral protein whichallows the virus to exit the cell once the cellhas been infected. There are 9 known formsof this protein and can sometimes combinewith haemagglutinin to form a single proteincomplex. This means that various strains offlu can arise through different proteins beingpresent on the virus. All of various forms ofthe two proteins have been found present inavian influenza A and it is thought the originfor all cases of influenza A in other animalsare down to avian flu.

AAnnttiiggeenniicc SShhiifftt

Antigenic Shift is where two differentsubtypes of the same virus, for exampleH2N2 and H3N2, combine together to form anew virus with the antigens of both previoussubtypes, therefore possibly creating a morelethal virus, with the capabilities of both itspredecessors. This can happen through anumber of ways, either two different fluviruses, such as bird flu and human flu, infectthe same cell, therefore transferring genes ofdifferent influenza strains to each other or adirect transfer of the virus, such as birds tohumans without the genetic makeup of the flubeing compromised. In this case, if the virusis not modified further, the virus would not beable to spread to another human and thisform of infection is rare.

The problem with swine flu is that theseanimals are susceptible to human, bird andswine flu viruses. This means that it is easyfor a two variations of influenza to infect thesame cell in a pig, causing new influenzaviruses with different genotypes from theirparents. The main problem concerningourselves today with the current swine flupandemic is that this virus is able to transferfrom human-to- human, being a member of

the H1 subtype, as well as havingcharacteristics and genes of swine flu,meaning we have little or no immunity to it.

TThhee OOrriiggiinnss ooff tthhee CCuurrrreenntt FFlluu

As it is widely regarded, the current strain offlu originated from Mexico. Extensive testshave been taken on the virus to determine itsorigin and how it has managed to spread soeasily. Through the analysis of the virus, it isbelieved that the virus was indeed derivedthrough the combination of several virusesthat we circulating in swine. Since 2007,there have been cases of H1N1 swineinfluenza in humans, due to a large amount ofvarying swine influenza viruses being presentin the USA. It is currently believed thatthrough antigenic shift, the current swine fluvirus is thought to be a combination of twoswine strains, one avian strain and onehuman strain of influenza viruses. This isfound out using genetic analyses, which try tomap the evolutionary path of an organism.

HHooww ddoo vviirruusseess aattttaacckk cceellllss??

As mentioned before, only H1, H2 and H3virus infect the cells in the human body. Buthow do viruses like H1N1 infect and destroycells in our body? On the influenza virus, thehaemagglutinin allows the virus to bind to themembrane of a particular cell, as it is able toattach the virus to particular cell receptors onthe cell surface membrane. In this instancethe haemagglutinin binds to sialic acidreceptors on the cell membrane. After thevirus has bound to the cell, it is moved intothe cell via a process called endocytosis,where a small vacuole is created around thevirus so that it is able to enter the cell. Onceinside the cell, the viruses protein coat allowsseveral proteins to escape, most importantly,enzymes and vRNA (viral RNA), and movetowards the nucleus. Once inside the nucleus,the viral enzyme polymerase copies thevirus’s genetic material and forces the hostcell to use energy and amino acids toproduce viral proteins. The process iscompleted by taking a small group ofmolecules from the host cell’s RNA andadding it to the viral RNA. In effect, the cellnow recognises the viral RNA as human RNAand creates multiple copies of it as well asother viral proteins. This process is completedby polymerase but the exact mechanism forthis process is still unknown. The viral RNA isthen released by the nucleus and movestowards the cell membrane and ‘wrap’themselves within a part of the cellmembrane to create a new protein coat. Butby creating a coat from the cellularmembrane of the host cell the virus ispreventing its own escape, as the cellmembrane contains sialic acid receptorswhich haemagglutinin binds to, so the virus isbound to the cell membrane. Theneuraminidase therefore breaks down thesereceptors allowing the cell to escape from thecell. The cell would die either from being

exhausted as it can no longer perform its ownfunctions, or the virus would trigger a ‘suicideswitch.’ One cell is able to produce millions ofinfluenza viruses which can then go on toinfect millions of other cells unless stoppedby our immune system.

MMeetthhoodd ooff IInnffeeccttiioonn && SSyymmppttoommss

As with all types of influenza it is passed onfrom one organism to another very easily,simply by breathing the same air as someonewho has been infected. The virus wouldusually be present in our respiratory tract andis expelled from our lungs through coughingand sneezing. The virus remains in the air, ina suspension of salvia, to be inhaled byanother organism, and if this organism is thesame species, this will cause potentialinfection, as the virus can then infect cells inthe respiratory tract, causing typical flusymptoms. This is the only way to catch theflu, and cannot be caught by eating pork. Thesymptoms for swine flu are the same asseasonal flu and currently seem to be nomore threatening. They include: high fever(over 38°c), coughing, tiredness, chills,aching joints and/or muscles, sore throat,sneezing, headache, diarrhoea and stomachupset.

As can be seen, these symptoms are not life-threatening, and swine flu has only causedserious problems in people with otherunderlying health conditions. Swine flu mainlyattaches itself to receptors in the nose ormouth and therefore does not cause a majorhealth concern such as leukaemia orpregnancy. On the other hand, if it were tomutate to a virus similar to the structure ofthe H5N1 bird flu virus, which attaches itselfto our lungs causing more serious conditionslike pneumonia. But scientists still claim thatthis is unlikely, as H5N1 has been around formore than a decade and not combined withseasonal influenza.

TTrreeaattmmeenntt aanndd PPrreevveennttiioonn

Currently the best way to treat swine flu issimple bed rest, like that of seasonal flu aswell as taking regular dosages of Tamiflu. TheDepartment of Health recommended to allthose with the symptoms of swine flu to stayin their homes for 5-7 days to prevent thespread of the virus. Tamiflu is an antiviraldrug that it able to slow down or stop theinfection of influenza in the body. Its chemicalname is Oseltamivir and it is known asneuraminidase inhibitor. It stops the activity ofneuraminidase, therefore does not allowviruses to leave the cell as they bound to thesialic acid receptors. It does this by providinga competitive inhibitor to sialic acid thereforeallowing neuraminidase to work on the drugrather than let the virus escape the host cell.


47


Swine Flu Epidemiology & PathologyVishal Amin

Ozone Therapy in DentistrySahil PatelOOzzoonnee iiss aann aalllloottrrooppiicc ffoorrmm ooff ooxxyyggeennccoommppoosseedd ooff 33 ooxxyyggeenn aattoommss.. Compared tothe more abundant diatomic oxygen (O2),ozone is far more reactive as its structure isvery unstable: The three atoms form a v-shape (similar to water) and the central atomforms an sp² hybridysation with one lone pair.This condition is usually short-lived before themolecule breaks up and forms diatomicoxygen and an oxygen atom.

Ozone is most famously known for the everdepleting ozone layer which is where highconcentrations of ozone filter out waves witha shorter wavelength than 320nm from sunrays. This includes ultraviolet light whichwould be much more harmful to humanswithout a protective ozone layer. On the otherhand, ground level ozone released from carexhausts and industrial processes can causerespiratory problems for humans and canaffect agricultural production. Although ozoneis hazardous when not in the ozone layer, thereason why it is beginning to be used in ahandful of private dental practices is itsproperty of being perhaps the most powerfuloxidant and antimicrobial agent. This is truewhether it is used by itself as a gas or addedunder pressure in water. In fact, it reportedlyhas a higher disinfection capabilitiescompared to chlorine and doesn’t produceharmful decomposition products. This is whyozonators, for example, are being used toreduce the amount of chlorine in swimmingpools and spas. It is also being used by thebottled water industry to disinfect waterbefore we drink it and has now beenapproved by the FDA (US Food and DrugAdministration) to treat food.

BBaacckk ttoo ddeennttiissttrryy

Ozone as a gas is toxic so the translation ofozone into a product that can be used safelyby dentists is important. Currently there arethree forms of ozone that are already in use:

1.Ozone gas application involves sealing theaffected area with a PVC or silicone cap andapplying ozone gas for one to two minutes.The disposable silicone caps fit onto the handpiece and after achieving a vacuum over thetooth, ozone can flow over the site. If the seal

is ever lost, ozone application automaticallystops. After the ozone gas is applied to thetooth through the suction-cap apparatus, it isthen sucked out of the cap and channeledthrough an ozone neutralizing filter thatconverts the ozone back into oxygenmolecules. A liquid pH balancer is theapplied. The pH balancer fluid neutralizes theresidual bacterial acid by applying xylitol andfluoride in high concentrations. Ozone gasunits made for dentists are typically priced atabout £12,000.

2. Ozonated water application has beenproposed as a cavity disinfectant and as ahard surface disinfectant and to soakinstruments prior to autoclaving. Autoclavingis the common technique used by mostdental practices to sterilise their equipmentby high pressure steam. The effectiveness itsuses are unproven and ozonated water unitscost about £4,500.

3. Ozonated Olive Oil application has beenintroduced for soft tissue lesions. These oilsare advertised to have a greater advantageover commonly used antiseptics andointments due to their wide range of activitiesduring all phases of the healing process.Patients are supplied with enough ozonatedoil in a disposable syringe for home use.

The sustainability in ozone is unclear andcontroversial as the only people supporting itare private practices and ozone therapy is yetto be approved by the British DentalAssociation or the NHS for medicalapplications. A spokesperson for James HullAssociates (a large chain of dental practicesoffering ozone therapy) claimed that ozonegas application works perfectly 90% of thetime against tooth decay. Compared to thetraditional technique of injections, drilling andfilling, ozone gas treatment takes 40 seconds.

The most prolific researcher in this field is Dr.Edward Lynch in Belfast, Northern Ireland. Dr.Lynch has been investigating how best to useozone in dentistry for over 10 years and hashelped bring the first commercially viableozone device on the market in most areas of

the world, except notably the U.S., where itstill awaits approval by the FDA. An advertfrom HealOzone presents new ways of rootcanal treatments using a needle to ozonatethe infected nerve. This treatment can becompleted in one session as opposed toseveral sessions for a normal root canaltreatment.

However, most organisations are notconvinced by ozone such as the FDA in theU.S. where it argues that ozone can only beeffective as a germicide when applied inconcentrations higher than that humans cantolerate. So ozone is nothing more than atoxic gas. The British Dental Association alsodoubts ozone therapy will prove to be usefulenough to use worldwide as most dental workis now preventative and cosmetic. Researchis still being carried out to ensure that ozonedoes not cause any adverse effects in themouth.

OOppeerraattiivvee ddeennttiissttrryy

There are many dental procedures whereozone has been used. During root canaltherapy where the nerve tissue of a tooth hasdied or is infected, ozone oils can be used tosterilise the root canal systems and to clearthe canals of necrotic debris. Ozone oils areozonated sunflower oil or olive oil orgroundnut oil. This ozone oil irrigation isbelieved by some to be faster and moreefficient in canal sterilisation thanconventional irrigation by the sodiumhypochlorite and sodium peroxidecombination.

Ozone can be applied to carious lesions,safely killing bacteria that have caused caries,thus making the treatment minimally invasiveto the patient and just a few seconds long. Incases of incipient caries, ozone can killbacteria in the demineralised part and thisdemineralised enamel then, can beremineralised using a special remineralisationkit, containing Calcium, Fluorine, Phosphorusand Sodium, all in their ionic forms.

Periodontal (gum) diseases represent a major

Figure 1

TThhee cchheemmiiccaall ssttrruuccttuurree ooff oozzoonnee

Figure 2

Diagram showing the generic stages of a root canal treatment.


48


concern both in dentistry and medicine. Themajority of the contributing factors andcauses of these diseases are reduced ortreated with ozone in all its application forms(gas, water, oil). The beneficial biologicaleffects of ozone, its anti-microbial activity,implicated in periodontal diseases and itshealing and tissue regeneration properties,make the use of ozone well indicated inperiodontal diseases.

Ozonated oil can be used in conjunction witha metal gauze to compress tissue after anextraction. Although the difference betweenthe two treatments on the healing of the softtissue is not obvious to non-dentists,ozonated oil has proved to help tissueregeneration compared to traditionalantiseptics.

Finally, ozone can be used to help in theintermediate stages of dental bridges andcrowns. A dental bridge is illustrated on theright and before seating in the permanentrestoration, temporary crowns are placed onthe two neighboring teeth. A commonoccurrence during this temporization phase incrowns procedures is hypersensitivity. Manyfactors might contribute in this symptom, oneof which is the presence of bacteria left insidethe gap between the tooth and the crown.Ozone gas applied before the temporarycrowns and permanent bridge perfectlydisinfect the area of bacteria and do notaffect the adhesive bonding of the ceramiccrown to the tooth.

PPhhyyssiioollooggyy

Although, it is claimed that if ozone therapy isused properly, it is well-tolerated by patientsthere are still side affects post-treatment. Inthe short-term patients can feel weakness ordizziness but the reason for extraordinaryreactions to ozone therapy is considered animbalance between the intensity of theformation of active oxygen and the activity ofpatients antioxidant defense system. Thetherapeutic doses of medical ozone act like"stress-stimulators" on the defense systemenzymes.

Earlier I mentioned that ozone gas is toxic tohumans as it affects our breathing systems.Ozone molecules will always tend to breakdown into diatomic oxygen producing a freeradical according to the equation:

O3 → O2 + O●

Free radicals are species that have freeunpaired electrons which makes them highlyreactive. When ozone is inhaled ozone breaksdown into oxygen free radicals which reactwith the organic lining in alveoli andsubsequently react with epithelial cells,immune cells, and with nerve receptors in theairway wall. This causes asthma-likesymptoms such as breathlessness andinflammation of airways. After dissolving inthe lining of the alveoli, ozone is harmful inthe bloodstream as it causes cholesterol toundergo ozonolysis where the double bond incholesterol is broken and replaced with anoxygen double bond forming 5, 6-secosterolwhich is involved in the build-up of plaques.

Plaques can cause atherosclerosis by stickingto the walls of the arteries and causing themto lose elasticity over time. The lack ofelasticity can result in inflammation which ismore likely in the presence of ozone as it is apowerful oxidising agent.

OOzzoonnee pprroodduuccttiioonn

Since UV rays from the sun sustain the ozonelayer, the most obvious place to begincreating man-made ozone is UV light. UVozone generators use a light source thatgenerates a beam of UV light to treat air orwater is swimming pools. The cold plasmamethod involves exposing oxygen to anelectrical discharge from two electrodes. Thediatomic oxygen splits into single atoms andthen recombines as triatomic oxygen (ozone).The concentration of ozone is typically 5%,which seems low but compared to using UVrays it has a much higher yield.

Ozone may be formed from O2 by electricaldischarges and by action of high-energyelectromagnetic radiation. Certain electricalequipment generate significant levels ofozone. This is true of devices using highvoltages, such as laser printers and arcwelders. Electric motors using brushes cangenerate ozone from repeated sparking insidethe unit. Large motors that use brushes, suchas those used by elevators or hydraulicpumps, will generate more ozone thansmaller motors. Ozone is similarly formed inthe Catatumbo lightning storms phenomenonon the Catatumbo River in Venezuela, whichhelps to replenish ozone in the uppertroposphere. It is the world's largest singlenatural generator of ozone.

TTeeeetthh WWhhiitteenniinngg aanndd bblleeaacchhiinngg

Due to the strong oxidation power of ozone,researchers have started looking at the abilityof ozone to whiten teeth. Ongoing in-vitroworks are studying the effects of long timeexposure of ozone on the dental hard tissuesand the pulp, as well as the application formsof ozone (gas - ozonated water). The resultsso far are publicised to be promising.

In root canal treated teeth, crowndiscolouration is a major aesthetic problem,especially in anterior teeth. Conventionalwalking bleaching (by placing a bleachingagent inside the root canal to lighten thetooth) requires much more time and resultsare not usually satisfactory. After removingthe root canal filler material from the pulpchamber, the canal is sealed tight at the levelof cemento-enamel junction (the line on thesurface of a tooth where the enamel on thecrown meets the cementum on the root).Then, the chamber is cleansed with sodiumperoxide solution to remove any debris,cement particles. Now, a bleaching paste ispacked in the chamber and the opening issealed with the Glass-inomer cement. Afterplacing the bleaching agent in to the inner ofthe tooth, the crown is irradiated with ozone.This ozone treatment bleaches the toothwithin minutes and gives the patient ahealthier-looking smile.

In conclusion, the consensus about ozone is

ambivalent as it can cause serious healthproblems with prolonged exposure butresearchers are determined to have itimplemented into mainstream dentistry. I feelthat there is too much optimism when itcomes to limitations of ozone therapy.Everyone can see that ozone is very oxidisingwhich would give it use as a germicide butwhether it harms the mouth is still uncertainwhich why most dental practices and the NHSrefrain from investing in an ozone therapy.Some private practices champion the use ofozone for all procedures as if it is vital inorder to give a successful treatment but it isall still under research. However, researchcould prove us wrong and show that ozonecan be used as effectively as promotersclaim.

The Haberdashers’ Aske’s Boys’ SchoolNurturing Excellence

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49

The Haberdashers’ Aske’s Boys’ SchoolNurturing Excellence

Stay with the team!

Please make sure we have your contact details whenever you move (yourpostal address, email, telephone and mobile).

• Call us on 020 8266 1820

• Register with Habsonline (top right menu bar) at www.habsboys.org.uk

• Post a letter to: Alumni Office, External Relations, Haberdashers' Aske's Boys' School,Butterfly Lane, Elstree, Herts, WD6 3AF


50

PPHHYYSSIICCAALL SSCCIIEENNCCEESS

TThhee RRiieemmaannnn HHyyppootthheessiiss

The Millennium Problems (2002) -Keith Devlin

Prime Obsession: Bernhard Riemann

The Greatest Unsolved Problem inMathematics (2003) - JohnDerbyshire

TThhee RRoollee ooff CCoommppuuttaattiioonnaallAAttoommaattiioonn iinn SScciieennccee

http://ccsl.mae.cornell.edu/

The Automation of Science - Science324 (5923)

Distilling Free-Form Natural Lawsfrom Experimental Data - Science324 (5923)

EEiinnsstteeiinn’’ss AAnnnnuuss MMiirraabbiilliiss

Einstein: His Life & Universe (2008) -Walter Isaacson

AAttmmoosspphheerree:: EEaarrtthh’’ss GGrreeaatt DDeeffeennce

An Ocean of Air: A Natural History ofthe Atmosphere (2007) - GabrielleWalker

TThhee PPaatthh TToowwaarrddss FFiinnddiinngg TThheeMMaaggnneettiicc MMoonnooppoollee

The New Quantum Universe (2003) -Tony Hey & Patrick Walters

CChheemmiilluummiinneesscceennccee

Chemiluminescence from luminolsolution after illumination of a 355nm pulse laser (1126) - Journal ofBioluminescence &Chemiluminescence

http://www.isbc.unibo.it/

RREEVVIIEEWW

TThhee RRoowwbbooaatt’’ss KKeeeelliinngg

U.S Department of Commerce -National Oceanic and Atmospheric

Administration - Earth SystemResearch Laboratory - GlobalMonitoring Division

Geoengineering vs.Gestureengineering, Wired Science -(24 July 2008)

Visible Earth: Global Effects ofMount Pinatubo - NASA LangelyResearch Center - Aerosol ResearchBranch

Issue No.2705 NewScientist - 23April 2009

The Catastrophist - The New YorkerJune 2009 (p.39) - Elizabeth Kolbert

EEnnttrrooppyy && TThhee TThheeoorryy ooff EEvvoolluuttiioonn

The Blind Watchmaker - RichardDawkins

Entropy, Information, and Evolution:New Perspective on Physical andBiological Evolution - James Smith,David Depew & Bruce Weber - 1988

BBIIOOLLOOGGIICCAALL SSCCIIEENNCCEESS

AAbbiiooggeenneessiiss

Synthesizing life - Nature 409 (2001)- Szostak et al

EEvvoolluuttiioonn ooff tthhee NNeerrvvoouuss SSyysstteemm

The origin and evolution of theneural crest - Philip C. J. Donoghue,Anthony Graham, & Robert N. Kelsh -Bioessays (30/6) - 2008

AAllzzhheeiimmeerr’’ss:: HHooppee AAtt LLaasstt??

The cholinergic hypothesis ofAlzheimer’s disease: a review ofprogress - Francis et al - Journal ofNeurology, Neurosurgery, &Psychiatry - 66 - (1999)

TThhee IImmpplliiccaattiioonnss ooff CCooccaaiinneeDDeeppeennddaannccee

Drug Dependence, a Chronic MedicalIllness - McLellan et al - JAMA284/13 - (2000)

TThhee RRoollee ooff PPhhaarrmmaaccooggeenneettiiccss iinnMMooddeerrnn MMeeddiicciinnee

Genetic variation in response to 6-mercaptopurine for childhood acutelymphoblastic leukaemia -Weinshilboum et al - The Lancet 336- July 1990

Nuffield Council on Bioethics -Pharmacogenetics: Ethical Issues(2003)

CCaanncceerr TThheerraappyy:: TTrreeaattmmeenntt &&TTrreeaattmmeenntt RReeaalliittiieess

www.nhs.uk/conditions/Herceptin

The Independant -Dosage loopholerestricts Herceptin for NHS patient -Jeremy Laurance (2007)

HHeeaarrtt TTrraannssppllaannttaattiioonnss:: EEnndd ooff aannEErraa??

Once again on CardiacTransplantation: Flaws In The LogicOf The Proponents – Dr. YoshioWatanabe - JPN Heart Journal(1997)

Why heart pumps could kill off thetransplant - Sunday TimesMagazine, (November 2nd 2008)

Mortality Statistics on BypassSurgery and Angioplasty -www.heartprotect.com/mortality-stats.shtml (January 2009)

HHaaeemmoopphhiilliiaa AA:: HHooww ssuucccceessssffuullhhaasstthhee ggeenneettiicc eennggiinneeeerriinngg ooff FFaaccttoorrVVIIIIII bbeeeenn??

Genetic Engineering of Factor VIII -Nature 342

SSwwiinnee FFlluu EEppiiddeemmiioollooggyy && PPaatthhoollooggyy

www.direct.gov.uk/en/Swineflu/DG_177831

Virolution - Frank Ryan (2009)

OOzzoonnee TThheerraappyy iinn DDeennttiissttrryy

The Use of Ozone in Medicine &Dentistry - Baysan et al - PrimaryDental Care (12/2) - (2005)

Scope 2009/10 BBiibblliiooggrraapphhyy

Bibliography


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Dear Reader,

Having been first published 20 years ago, this anniversary edition of Scope aims to contain articles aboutsubjects at the forefront of man’s scientific understanding. On the content front we have attempted to ad-dress the issue of a fair balance of articles to represent more adequately the full range of scientific interestsat Haberdashers’. On the literary front we have further pushed the boundaries with a new ‘Review’ Section.This new section provides an opportunity for discussion on the implications and nature of science, as wellas interviews with prominent scientists. I am grateful to the Science Society for working with us to providean unparalleled calibre of scientists to feature in Scope.

Indeed this new exploration of the very nature of science is of fundamental importance to those concernedwith it. To borrow a phrase from the evolutionary biologist Richard Dawkins, the power of science lies in itsability to relieve “the anaesthetic of familiarity”, its innate curiosity, its power to remind us to disengagewith existing in a sedative of dull ordinariness, and to gently poke us out of a slumber of ignorance. In un-derstanding science we might also wonder how far science has come throughout history. One of the bestanalogies to keep us in perspective of man’s endeavours is to imagine the history of life on our planet asrepresented by the span of one’s arms; from the origin of life to the present day. From one end to your op-posing shoulder, all that existed was bacteria. Invertebrates (which still constitute 95% of all life forms pres-ent today), eventually emerge at approximately your elbow furthest from the origin. Move along. Thefingernail of your middle finger represents roughly the proportion of time that Homo sapiens has inhabitedthe planet. And finally, what of recorded human history? Wiped off in a nail filing. I think that puts into per-spective the time frame and transcendental quality that science operates in. It is this very style and natureof debate and question I hope you will find herein.

I am indebted to my team who have provided outstanding literature for the magazine, as well as lively de-bate and strong opinions about the construction of the magazine. It is a testimony to them that we havemanaged to move into full colour print and perfect binding, giving full justification to the high quality of thearticles, without an increase in our budget. Lastly, I would like to thank Mr. Delpech, whose encyclopaedicknowledge, careful guidance and unfailing support have ensured the success of this magazine for manyyears.

Enjoy the magazine,

Casey SwernerChief Editor of Scope.

Scope 2009/10 Scope Team

The Scope 2009/10 Team

Casey Swerner - Chief Editor

Raj S Dattani - Senior Editor Neeloy Banerjee - Senior Editor Johan Bastianpillai - Senior Editor

Wajid Malik - Editor Wei-Ying Chen - EditorSahil Patel - Editor Karthigan Mayooranathan - Editor

Vishal Amin - EditorNicholas Parker - Editor Adrian Ko - Technical Advisor

Mr. Roger Delpech - Master i/c Scope

Ameya Tripathi - Editor

Bhavesh Gopal - Senior Editor

2

The Haberdashers’ Aske’s Boys’ SchoolButterfly Lane, Elstree, Borehamwood, Hertfordshire WD6 3AF

Tel: 020 8266 1700 Fax: 020 8266 1800e-mail: [email protected] website: www.habsboys.org.uk

The Scientific Journal of the Haberdashers’ Aske’s Boys’ School

Scope 2009/10SCOPESCOPE

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Documents

nature of science

power of science

scope teamthe scope

science society

understanding science

history of life

anniversary edition

new section