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MONDAY JULY 13 - JULY 19 2015 16 PAGES Rs 5

POSTER : ARJUN KAPOOR

Dear TTIS Tigers and Readers, We have introduced a new TTIS monthly e-Newsletter, TigerPost . It will keep you informed about theupcoming cover stories and articles that you can contribute to

and notify the date of the next Tiger Meeting.The TigerPost has been e-mailed to the Tigers and Readersin our database. If you are new to TTIS and would like to receive the e-Newsletter and become a TTIS Tiger, send us a request at -edit.ttis@gmail.com.

Here’s a piece of Good News for You!Here’s a piece of Good News for You!See Pages 14-15

The Next TTIS Meeting is on26 JULY, 2015, Sunday

at 10.30 a.m. at The Frank Anthony Public School

BE THERE & ROAR!!!

CallingAll

Tigers!

In his article, Ex-Tiger reporter, Mansit Das, gives us a comprehensive idea about the various segments of Biomedical Science.

Tiger reporters, Dharitri Chaudhuri, XI,Garden High School & Mahashweta

Chakravarti, XII, Modern High School forGirls, explore the psychological

and physiological aspects of Dreams and Illusions.

Biomedical Science

Fighting Diseases with Technology

See Pages 12-13

Dreams &Illusions

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The Telegraph In Schools �� Monday July 13 - July 19 2015

Published from Calcutta

1414 COVER STORY

Healthcare is one of the mostcritical issues in the main-tenance of the well-beingof a community. It is a

composite network of medical profes-sionals, who complement each otherand function as an inter-disciplinaryteam. Our interaction is usually limitedto physicians, the primary element ofthis modular system. However, this sci-ence which is involved in the backyardof modern medicine is quite fascinating.Not only does it offer a rewarding aswell as challenging career, but alsooffers an opportunity to use scientificskills and expertise to save lives andmake a difference.The biomedical science is a dynamicand collaborative discipline where sci-entists and engineers use their knowl-edge of chemistry and biology to under-stand how the systems interact in ahuman body. It helps us to evaluate thecause of a disease and accordinglydesign a treatment. It also involves thedevelopment of laboratory methods topromptly diagnose a medical disorderby analysis of fluid and tissue samplesfrom patients.In this article, we will try to talk aboutthe major segments of biomedical sci-ence and how each of them impactshuman lives.

DRUG DESIGN ANDDEVELOPMENT

Whenever we suffer from a medical condi-tion, our doctor prescribes us a combination ofdrugs. These drugs are chemicals which whentaken into the body can affect the biologicalfunctions in a specific way and can cure usfrom diseases. However one needs to under-stand that each condition is unique and there isno single way of dealing with problems likeheart disease or pain. In clinical research, thebiological mechanism has to be identified forevery single medical disorder and compoundsare synthesised which can interact with thetarget system. Once a new drug is developed,years of clinical trial follows to accumulatedata about its safety and effectiveness; the side-effects are monitored and once it is establishedthat the benefits associated with the druggrossly outweigh the risk, the health authorityof the country gives approval and it can bemarketed. So, when we see the doctor prescrib-ing us a certain medication, we are only seeingthe tip of the medical science iceberg!

It is probably confusing that how a drug canaffect a complex biological system like ahuman body. On a molecular level, the bodilyfunctions are nothing but a highly orchestratedarray of chemical reactions. So, a drug admin-istered into our body is just a chemical driving

a chain of reactions towards adesired goal.

As you all might know, thestructural and functional unit of our

body is termed as cell. Each cell con-tains a boundary wall known as cell mem-

brane made of a group of chemicals calledphospholipids and proteins, which encapsu-lates the contents of the cell embedded in the

thick cellular fluid cytoplasm. Inside the cellwe have the nucleus - the ‘control unit’ whichcontains the DNA carrying the genetic code (aset of rules by which information is trans-ferred to proteins via the intermediate RNA).The code is the 'recipe' for designing all theenzymes the cells require. These enzymes actas a catalyst to guide sequences of complexreactions that are going on every moment inour body. The drugs act mainly on these molec-ular targets -the lipids, proteins and the nucle-ic acids (DNA & RNA). Since a detailed discus-sion of all kinds of drugmechanisms is beyondthe scope of this article, we would talk prima-rily about a major family of drugs which revo-lutionised medical science in the twentiethcentury- the antimicrobials.

Antimicrobial Agents

The living world is dominated by thousandsof different species of organisms. One of themajor threats to these living organisms arepathogens which are infectious agents likevirus, bacterium, and protozoa. Thesepathogens can disrupt the normal physiologyof its host and can cause a disease or illness.Every year, millions of people die worldwide ofbacterial (Cholera, Tuberculosis, Typhoid,etc.), protozoal (Malaria being a major cause ofdeath in developing world) and viral (AIDS,Chicken Pox, Influenza, etc.) infections.Medical science has progressed a lot over thelast hundred years and we have been able tofight against a range of pathogens with ourarsenal of antibiotics. It has significantlyincreased our lifespan and cut down mortalityrates. However, we can't afford to relax as thesepathogenic strains have a monstrous ability of

gaining resistance against drug overuse, andthe search for new drugs is a never-ending.

Chemotherapy (use of chemicals againstinfection) dates back to the early twentieth cen-tury, pioneered by scientists like Paul Ehrlichwho won the Nobel Prize in 1904, for his contri-butions to immunology (study of the immunesystems). The early principle was quite simple-to search chemicals that could interfere with

the growth of micro-organ-isms at a concentrationbearable to host, in thiscase the human beings.However it was more of atrial and error method, asbatches of chemicals wereblindly tested againstmicrobes and then inpatients to evaluate theireffectiveness and toxicity. Itwas more of a drug discoverythan design.

Antibacterial Agents

One of the earliest drugs that tipped thewar against bacterial infections was the dis-covery of penicillin, a compound isolated frompenicillium fungi in 1928. The compound isnature's way of defending the fungi from bacte-ria and gives them a competitive edge in theirfight for nutrients. Penicillin was an impres-sive breakthrough and it was found effectiveagainst many bacterial infections though notall. Naturally, there was a need of more antibi-otics to fill in the gap.

After penicillin's success, a scientific goldrush followed as researchers all over the worldtried to isolate new antibiotics by methodicalsearch of soil organisms. Streptomycin wasdiscovered in 1944 and was the first effectivetreatment against tuberculosis. As the searchcontinued after World War II, many more drugswere discovered. However over continued use,the problem of drug resistance came intobeing. Most of these original "magic bullets"were found to be ineffective. So, development ofan understanding of the physiology of micro-

organisms, their interaction with human bodyand the working principle of these antibioticswas considered essential to identify new tar-gets and synthesise modified antibiotics. Thiswas when rational drug design started. For thefirst time, we were no longer shooting in thedark and started engaging our snipers to take afoccussed aim.

The animal cells and bacterial cells essen-tially differ in their structure and in theirbiosynthetic pathways - the way they producetheir cellular components. So, it is possible toblock the metabolic pathways, the chain ofreactions in the bacteria without affecting thehost human. All we have to do is to block a par-ticular enzyme responsible for the cellularmetabolism that is unique to the bacterial cells.Once the enzyme is inhibited, the reactionscannot progress or slows down and the cell can-not function properly.

As we have mentioned before, theseenzymes are biological catalysts that facilitatea reaction. The starting molecule which iscalled a substrate comes and sits on the enzymewhich converts it into a different moleculecalled product. Now imagine this enzyme as alock which can be opened by a key which is oursubstrate. Now, what happens if we use a dif-ferent key and try to open the lock? The lockwon't open and in the worst case, it will get

stuck and result in damage. This isexactly what happens with

many of our drugs. Weidentify a particular

biosynthetic pathwaywhich is associated

with our disease,and design a chem-ical which hasvery similarstructure to thesubstrate. Theenzyme can't dis-tinguish between

the substrate andthe drug and allows

it to anchor on itssurface. Once it binds

itself, the process isinhibited, temporarily or

permanently depending on theway the drug was designed. There

are however different biochemical mecha-nisms that are unique to the bacteria which aretargeted with different classes of antibioticshaving different chemical structures and thusdifferent modes of action.

Antiviral agents

Viruses are undoubtedly the 'super villains'of the pathogenic underworld. They spentmost of the time in the body of the host cellwhere it effectively masks itself from theimmune system and the circulating drugs. Forworse, they use the body's biochemical reac-tions to multiply and hence it is difficult toidentify targets that are unique to the virus.Talk about a terrorist cohort taking innocentcivilians hostage and using all their resourcesto sustain themselves. The cops can't touchthem as they run into the risk of harming thehost! Hence, viral infections are difficult totreat with drugs and there are very few antivi-ral drugs available.

Continued on Page 15

MANISIT DAS an ex-TTIS Tiger ......He graduated from Indian Institute of Technology (IIT), Kharagpur, in 2015 with an IntegratedMasters (B.Sc. + M.Sc.) in Chemistry. Manisit is actively interested in pursuing research in somefast developing areas of biomedical sciences like Nano medicine and Biosensor development.Motivated by his scientific aspirations, he is going to join as a Graduate Research Assistant inthe University of North Carolina at Chapel Hill, US, for undertaking a Ph.D. in Biological andBiomedical Sciences. He was associated with TTIS from 2005 to 2008 and looks back to thosedays with fond memories.

Cutting edge Solutions to our DiseasesBIOMEDICAL SCIENCES

Alexander Flemming

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1515COVER STORYFrom Page 14

Many of the viral diseases can be preventedwith vaccines. Most of you had been adminis-tered vaccines of smallpox, MMR (Mumps,Measles and Rubella) and Polio in your youngage. So what are these vaccines exactly?Usually, a dead or a weakened version of thevirus is introduced in your body which can'tlead to infection itself. The immune system ofour body scans the molecular fingerprint ofthe virus (antigens) and develops its owndefence mechanism (antibodies). When anactual viral infection takes place, these anti-bodies can protect the body against fatality.However, it is always not possible to develop avaccine because many of these viruses canconstantly change their composition by geneticmutation (changes in the geneticinformation leading to changes toprotein structures), thereby changingtheir molecular fingerprint and dis-guising themselves against theimmune system.

About 1.5 million people died ofhuman immuno-deficiency virus-HIV related illnesses in 2013. Thisparticular virus infects the T cellswhich are vital to our immuneresponse and therefore a direct threatto our immune system. With a weak-ened system, the patient is vulnerableto a range of secondary infectionsand hence the name 'AcquiredImmune Deficiency Syndrome'(AIDS). Till 1987, no anti- HIV drugswere available in the market due tolack of understanding regarding thelife cycle of the virus. Also, there wasthe problem of rapid genetic muta-tion. But with increase in under-standing of the physiology and devel-opment of drugs that can target mul-tiple enzymes, it has been possible todelay the progression of the diseaseand increasing the chance of sur-vival, but we are yet to achieve a com-plete cure. Before concluding this dis-cussion on antibiotics, let us try to getan idea about some anti-viral drugswhich works against HIV.

HIV is an RNA virus containing two identi-cal strands of Ribonucleic Acid (RNA), a typeof genetic material. When the virus approachthe host cell, its surface proteins anchor thevirus on the surface of the cells. They pull thevirus and the cell together allowing the mem-brane to fuse. Once the fusion is over, anenzyme called protease disrupts the proteinlayer and release the viral RNA and proteinsinto the cell cytoplasm. This RNA is not capa-ble of directly coding for the viral proteins. Itgets converted to DNA and incorporated intothe host's DNA which is then tricked to synthe-sise all the viral proteins. Now human cellsdon't convert RNA to DNA. Thus HIV carriesits own enzyme called reverse transcriptase todo this job. Since this enzyme is unique to thevirus, it is a potential target. The class of drugswhich work against the reverse transcriptaseare referred to as Nucleoside Reverse tran-scriptase inhibitors. Protease is also anothercommon target as inhibition of that enzymecan prevent viral components from beingreleased into the cell. At present a combinationtherapy is practiced where drugs which workagainst reverse transcriptase and protease arebeing used but finding drugs which can workagainst a third target is a necessity.

As you might know, antimicrobials is justan iota of the entire spectrum of medicinesavailable to us to treat different kind of disor-ders. We have specific drugs with specificmodes of action to treat a range of disorders;drugs which treat diseases of digestive sys-tems, heart problems, those which control ourblood pressure and sugar, medicines that act oncentral nervous system and stabilise our men-tal state to chemotherapeutic agents in ourfight against the 'emperor of all maladies' - can-cer!

Drug distribution and delivery

Unfortunately, identification of the mecha-

nism of a disease and designing a drug whichcan bind to the target is nowhere close to abreakthrough. The human body's defencemechanism is quite a cynic and it tries to elim-inate every possible intruder that tries to crossits path. So, we need to ensure that the drugremains stable enough to survive its gruellingjourney through the circulatory system of thebody. It needs to dodge all the barriers anddelivered specifically on the target, because themore it travels to other sites, the risk of side-effects spikes up. However, it is not as simple asit sounds.

When you are prescribed a drug, you gener-ally take it in the form of a capsule or a tablet.Although injections are another way of admin-istering a drug, but we'll skip that bit for the

moment. Now this pill needs to dissolve in anaqueous solution like water. It reaches thestomach where it has to survive the acid and beabsorbed into the bloodstream from digestivesystem by crossing the hurdles of cell mem-brane. It needs to prevent itself from gettingdestroyed by the liver and its enzymes and theenzymes present in blood. Depending on itschemical structure, whether it is lipophilic(fatty) or ionic (charged) it can be trapped bydifferent tissues, proteins and nucleic acids. Ithas to prevent itself from being excreted bykidneys or the bile duct. If it needs to reach thebrain, it has to pass through another 'tricky'membrane called the blood-brain barrier. Toreach its target enzyme, it needs to cross anoth-er cellular membrane before it finally reachesits desired receptor or enzyme after a danger-ous trip! Drug delivery is a very importantbranch of biomedical science and holds a keyto targeted therapies against many serious dis-eases, like cancer.

A major challenge in cancer chemotherapyis targeting drugs effectively against tumourcells than normal cells. Though there are morethan hundred different types of cancer, rough-ly each of them involves an unregulated cellgrowth regime which affects normal cell func-tioning and may ultimately cause death. Apartfrom use of surgery to remove tumours andradiation therapy to kill cancer cells,chemotherapy is used to specifically destroycancer cells by exploiting differences in molec-ular signatures between the two sets. Theactive drug is a cytotoxic agent (a chemicalwhich is toxic to a cell) often attached to otherchemical structures which can act as 'homingsignals' by recognising certain molecular fin-gerprints in cancer cells and thereby renderingminimal damage to normal cells. Although weare nowhere close to providing a permanentcure, thanks to the progress made in targeteddrug delivery the chances of survival of apatient is quite promising if the cancer isdetected in early stages of its proliferation.

DIAGNOSTICS

Pathology and ImagingGranting that we have spent a considerable

length talking about drugs- the first line oftherapy against diseases, we must not forgetthat a treatment can't be prescribed unless weare successful in making an accurate diagno-sis. Whenever you go to a physician, he/she byvirtue of his/her expertise makes a prelimi-nary diagnosis by checking your signs andsymptoms. But most of the time, they want fur-ther evidence to support their assumptions forwhich they refer to diagnostic tests. Now thereare primarily two broad classes of diagnostics,pathology and imaging. Pathology is the ana-

lytical study of body fluids,tissues and cell samples tocheck for abnormalities. Aswe have discussed before,different type of moleculesare circulating in our bodywhich have specific func-tions. Under normal condi-tions, the body maintainsthem at a specific concentra-tion. If the concentration tipsfrom its ideal level (either too littleor too less), it becomes a medical condi-tion. So, these abnormalities serve as molec-ular markers of diseases. A study of their lev-els often give us a conclusive idea of what'sgoing wrong with our system. Similarly wehave the discipline of histopathology where tis-sue sections are taken from a body, stained withdyes to give contrast to specific cell compo-nents and viewed under a microscope. A com-parison with the normal structure can tell a lotabout designing a treatment protocol.

Last but not the least, we have the imagingand recording methods which helps us toreveal information about internal structuresconcealed by skins and bones. Among the mostcommonly used techniques we have X-rayimaging, Magnetic resonance imaging (MRI),electrocardiography (ECG), ultrasonogra-phyand computed tomography (CT). All thesetechniques have different modes of action butthe basic principle remains the same. Mostly, itinvolves application of some kind of radiation(waves with specific frequencies) to the humanbody. As they hit our body, the internal struc-tures interact with the radiation and respondin a specific fashion. This changes the charac-ter of the applied radiation and a detectorrecords this response from different directionsor over a period of time. The collected data isnow fed back to a computer which process itand generate a digital image following a set ofpredefined rules. Imaging techniques are fre-quently used in oncology (study of cancer),

neuroscience, cardiology (heart and blood ves-sels) and orthopaedics (study of muscles andskeletal system).

Biomedical Devices

The biomedical devices refer to a broadspectrum of instruments, apparatus,machines, implants and components which areused daily in the diagnosis, prevention or treat-ment of a disease. However, it must be notedthat devices which are used for medical treat-ments are not drugs. They are implanted withthe intention of affecting an internal structureof the body when the concerned structure isunable to achieve its primary purpose. Forinstance, pacemaker is a small device when

placed in chest sends electrical pulsesto the heart that forces it to beat in anormal rhythm. It helps in the treat-ment of arrhythmia (a disease ofirregular heartbeats which if sus-tained for long time can cause furthermedical complications).

Biomedical device engineering isa sophisticated technology as itinvolves a careful consideration ofthe possible ways in which the devicecan interact with the body. Forinstance, nowadays we commonly usea titanium alloy plate for internal fix-ation of a broken bone. But whileengineering a design we have tocheck whether it can address certainissues. Does the material get firmlyintegrated with the normal bones andtissues? Is the material compatiblewith rest of the body such that ourimmune system doesn't reject it?Does it interfere with any componentof the body apart from its site ofaction? Is it sufficiently stable and

doesn't release toxic productsinto the body? Thus, a good

biomedical device engi-neer not only needs

an excellent com-mand over funda-

mentals of engi-neering but ani n - d e p t hknowledge ofhuman anato-my and physi-ology as well!

M o d e r nmedical science

is the fruit of thelabour of genera-

tions of researchers,spanning a period of

more than a hundredyears. It is almost a pointless

exercise to present the scope of this huge col-laborative effort in a single article. Humanbody is the most complicated machine we haveever witnessed. Though we have made a signif-icant progress, we are yet to reach a completeunderstanding of it. With our weaponry ofantibiotics, we have succeeded in putting acheck to many infectious diseases and increas-ing our lifespan. But with longevity comes thediseases of lifestyle - cardiovascular diseases,diabetes and cancer. The pathogenic world isnot lagging behind. With the 'superbugs' grow-ing increasingly resistant against multipleantibiotics, we are at a significant risk of run-ning into a pandemic in near future.

You probably find your Biology textbookboring, but once you are a little more exposedto the biological world you are bound to find itcaptivating. Moreover, one doesn't necessarilyneed a degree in biology to be a part of thismission. Biomedical sciences require the skillsof a computer scientist, mechanical engineer,electronics and electrical engineer and a physi-cist as much as it involves chemists and biolo-gists.

If you want to indulge yourself in a quest oflife-long learning and challenges, this is some-thing you can look forward to. Come, plungeinto the battlefield. The war is on.

Manisit Das

The Telegraph In Schools �� Monday July 13 - July 19 2015

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