everyman’s science vol. xli no. 1, april ’06 — may ’06

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Everyman’s Science VOL. XLI NO. 1, April ’06 — May ’06��

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Vol. XLI No. 1 (April ’06 – May ’06)

EDITORIAL ADVISORY BOARD

Dr. S. P. Mehrotra (Pune)

Dr. D. Balasubramanian (Hyderabad)

Mr. Biman Basu (New Delhi)

Dr. Amit Ray (New Delhi)

Prof. D. Mukherjee (Kolkata)

Prof. Dipankar Gupta (New Delhi)

Prof. Andrei Beteille (New Delhi)

Prof. P. Balaram (Bangalore)

Dr. Amit Ghosh (Chandigarh)

Dr. V. Arunachalam (Chennai)

Prof. C. Subramanyam (Hyderabad)

Prof. Nirupama Agarwal (Lucknow)

Prof. C. M. Govil (Meerut)

Prof. K. R. Samaddar (Kalyani)

COVER PHOTOGRAPHS

Past General Presidents of ISCA1. Sir U. N. Brahmachari (1936)

2. R.B.T.S. Venkatraman (1937)3. Prof. Rt. Hon. Lord Rutherford of Nelson *(1938)4. Sir James H. Jeans (1938)5. Prof. J. C. Ghosh (1939)6. Prof. B. Sahani (1940)7. Sir Ardeshir Dalal (1941)

* Lord Rutherford unfortunately passedaway before the Science Congress andSir James H. Jeans presided over theCongress in his place.

For permission to reprint orreproduce any portion of thejournal, please write to theEditor-in-Chief.

EDITORIAL BOARD

Editor-in-Chief

Prof. S. P. Mukherjee

Area Editors

Prof. P. N. Ghosh(Physical & Earth Sciences)

Prof. S. P. Banerji

(Biological Sciences)

Prof. H. S. Ray

(Engineering & Material Sciences)

Dr. Suraj Bandyopadhyay(Social Sciences)

Convener

Prof. Avijit Banerji

General Secretary (HQ)

Editorial Secretary

Dr. Amit Krishna De

Printed and published by Prof. S. P. Mukherjeeon behalf of Indian Science Congress Associationand printed at Seva Mudran, 43, Kailash BoseStreet, Kolkata-700 006 and published at IndianScience Congress Association, 14, Dr. Biresh GuhaStreet, Kolkata-700 017, with Prof. S. P. Mukherjeeas Editor.

Annual Subscription : (6 issues)

Institutional Rs. 200/- ; Individual Rs. 50/-

Price : Rs. 10/- per issue

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Everyman’s Science VOL. XLI NO. 1, April ’06 — May ’06

EDITORIAL : 3

ARTICLES :

Presidential Address : The Role of Science in the

Recent Progress of Medicine

Sir U.N. Brahmachari 5

Demystifying Dyslexia

Paromita Ghosh 37

Physico- Chemical Nature of Drug-Nucleic Acid Binding

S. N. Upadhyay 41

Terminator Technology : An Ecological Disaster

B.L. Jagetiya, M.J. Kaur, Tina Choudhary, Pankaj Purohit,

Khushbu Bhatt and Neelam Acharya 47

Present Scenario of Ultrasonic Applications

Kailash and K. M. Raju 52

Twinning and Twins

A. B. Das Chaudhuri 59

SOMETHING TO THINK ABOUT

Storing Excess CO2 Underground

Prof. H.S. Ray 65

ANSWERS TO “DO YOU KNOW”? 66

SHORT COMMUNICATION

High Speed Knockout in the Brain

D. Balasubramanian 67

KNOW THY INSTITUTIONS 70

CONFERENCES / MEETINGS / SYMPOSIA / SEMINARS 73

S & T ACROSS THE WORLD 74

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EDITORIAL

SAFETY, HEALTH AND ENVIRONMENT AT WORK-PLACES

Productivity of a person working in the premisesof any organization–manufacturing or service–depends on the design, maintenance andmodification (from time to time) of the workplace.This is true for all levels of workers and for alltypes of work, though the dependence could varyin nature and extent from one category of workersto another, and from one type of work to a second.Since modifications involve some designconsiderations and maintenance has to take intoaccount the design, work-place design assumes avery important role in determining productivity–something that we all want to optimize.

Work-place (in relation to productivity) includesthe place used by a worker individually as well asthe over-all situation in which the entireorganization works. Work-place has to becomprehended in terms of physical as alsopsychographic (human) features. Physicalfeatures include considerations of adequacy (ofspace), cleanliness, safety, noise level, illuminationand ventilation, and the like besides access to safewater and pure air. Psychographic features relateto the nature and extent of interactions amongworkers, peer relations and relations betweensuperiors and sub-ordinates, and more importantlystress caused by the work as also the policy of theorganization affecting working life. Incidentally,safety is an umbrella term and has to be viewedagainst various types of exposure to unhealthy,dangerous or difficult situations faced by individualworkers e.g. radiation hazards or chemical hazardsas well as situations which affect workers in aparticular area or in the whole organization, likefire hazards. In fact, agricultural workers handlingpoisonous chemicals like pesticides or insectidesor even using chemically polluted water areexposed to serious health hazards.

Given that Industry and Agriculture have toexist and have to adopt advances in technologiesincluding those which are associated with risks andnoting that workers in other places also are

vulnerable, attempts are being made to minimizethe deleterious effects of unsafe, unhealthy andenvironmentally poor work place. Safety, Healthand Environment at work-places have to beunderstood in terms of indentifiable and measurableparameters ; permissible upper or lower limits foreach such parameters have to be developed, andaction has to be taken by organizations to ensureconformity to such standards. Apart from attemptsto conform to prescribed limits for individualparameters, usually fraught with findings of non-compliance occasionally, organizations shoulddevelop and maintain systems to ensure safety,health and friendly environment at work-places.And as is true for other systems, systems requiredto ensure these drivers of producitivity should bebased on four components, viz. organization,processes, procedures and resources.

Among the important standards which addressthese and related issues, the most well knownis the Environment Management System standardISO 14001 and the British standard BS 8800,released in 1996, relating to occupational healthand safety management system. However, unlikethe international standard ISO 14001, the Britishstandard does provide guidance in the matterand is not a standard against which certification forcompliance can be issued, helping the organizationto identify its weaknesses which could be actedupon. Several Certification bodies came up sincethen to develop an widely accepted protocol, viz.OHSAS 18001 which allows auditing andcertification. In fact, the International LabourOrganisation deplored as late as December 1998the absence of an international standard in thematter, noting that OHSAS is not an internationalstandard and lacks the edge of an ISO specification.

A meaningful and effective implementation of anystandard or protocol in this area calls for commitmenton the part of top management. Fortunately, with agrwoing consciousness all around, top managementhas been held responsible whenever standards are

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violated, particularly when such violations causecasualties in some recognizable form or the other. Infact, the number of cases where top management hasbeen booked for such violations in legal disputes hasbecome quite noticeable in some industrially advancedcountries. Of course, it is very true that peopleconsciousness at all levels is a key factor in maintaininga safe, healthy and environment-friendly work-place.Beyond consciousness, training of people in using andoperating safety devices, in observing needs ofpersonal hygiene, in maintaining cleanliness, inmeeting emergency situations, etc. are quite important.

Coming back to work-place design, besidestaking full advantage of ergonomic principles, wehave to understand and implement a few actionsscientifically and take recourse to some calculations(statistical in nature) in order to reduce risks andreview situations. Thus, we have to (1) analysetasks to be carried out by a worker ; (2) identifyhazards associated with materials to be handled oraccessed or accepted, processes to be carried out,procedures to be followed, checks to be exercised,(3) calculate risks for different types of hazardsand take actions based on these. Risk is usuallycomputed in terms of a risk priority number (RP),more or less on the lines of a Failure Mode andEffect Analysis (FMEA), based on three inputs,viz. frequency of occurrence, severity of occurrenceand impact or consequence. More often than not-and thanks God for that-adequate data do not existto allow an easy computation of risk. This is whysophisticated statistical techniques for evaluationof very small probabilities have to be used in ascientific determination of risk.

Human aspects of safety, health and environmentare gradually gaining momentum and attention is beingpaid to such matters as problems of lone or solitaryworkers, physically or mentally challenged workers,segregated workers, and so on. Studies on humanbehaviour in emergency situations and on alertness toavoid hazards etc. are being recognized as importantinputs in our efforts to ensure safety, health and goodenvironment to all our workers. Emphasis is also being

placed on emergency preparedness and on drills andmock exercises like firefighting.

All this is in relation to work-places in theorganized sector, being overseen by a number ofregulatory bodies. A lot remains to be done toimprove the situation in the relatively ignoredunorganized sectors of manufacturing or service.Of particular concern are the unhealthy environmentin which children and adolescents work or areforced to work, and even handle hazardous materialsand processes, with little provisions to take care ofassociated risks. Large numbers of male and femalechildren and adolescents are involved in the Matchand Fireworks Industry in Sivakasi, Bidi Industryin Vellore and Murshidabad, Diamond-cuttingIndustry in Surat, Glass Industry in Ferozabad,Pottery Industry in Khurja, Lock Industry in Aligarhand Carpet Industry in various parts of U. P. Inmost of these cases, whatever we are going todiscuss here are just not heard or are just not takeninto any serious concern.

It will be not merely desirable but alsoimperative for us to raise matters relating to safety,health and environment in different types ofenterprise with reference to their specific featuresand not just issues that are common to all andmostly known to all and, may be, mostly takencare of, or mostly ignored. We have to think ofresponsibilities and obligations of differentstakeholders–people who work, people who designand maintain work-places, people who decide oninvestments in health and safety, people who aremeant to act as watchdogs, people who handleemergencies and disasters, and people who designand develop methods and practices to improvework-places. A segmented approach rarely yieldsthe desired results and it may be a good idea toform a forum of representatives from the differentstakeholder groups, equip the same with somewherewithals and charge it with some specificresponsibilities.

Prof. S. P. Mukherjee

No one gossips about other people’s secret virtue

— Bertrand Russell

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PRESIDENTIAL ADDRESS

THE ROLE OF SCIENCE IN THE RECENT PROGRESS OF MEDICINE

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* General President, Twenty-third Indian Science Congress,held during 31st January to 5th February, 1936 at Indore.

Your Highness, Ladies and Gentlemen,

We happily meet this year at Indore in thefamous land of Ma–lava, watered by the beautifulSipra–. Not far from here are the sites of the sacredcities of Ma–hismati-, Ujjayiani- and Dha–ra–, whosenames conjure up glorious visions of the past. Thetown of Maheswar is connected with the hallowedmemory of the saintly Ahalya– Ba–i-, an illustriousruler of the Indore State, whose piety and generosityare even today a household word throughout India.Ujjayiani- was a famous seat of learning in theolden times.

In the fitness of things the Indian ScienceCongress has been invited to hold one of its sessionsin this historic place, thanks to the hospitality of itsmost enlightened ruler, His HighnessMaharajadhiraj Raj Rajeshwar Sawai ShreeYeshwant Rao Holkar Bahadur, Maharaja of Indore.In the annals of Indian history, the Holkars hold anhonoured place for their achievements in the fieldsof arms and of peace.

Under the able guidance of His Highness, thecity of Indore now ranks amongst the greatindustrial and highly cultured cities of India. It isan important educational centre with an excellentplant research institute, many high schools andcolleges, an excellent institution for the training ofthe sons of Chiefs and a medical school, and withpalaces and beautiful gardens. Indore must feelproud that His Highness has recently introduced so

many reforms in his State, has given her amagnificent aerodrome with a splendid landingground, and has inaugurated many beneficialschemes, such as, geological and mining surveys,vocational education and development of newindustries and encouragement of industrial research.Within a few miles of the city are the greatwaterworks of Badarkha with the largest syphonsystem in the world which, I understand, is anextraordinary feat of engineering skill. By thegenerosity of His Highness and the cooperation ofhis officers, hosts and guests have met today undera happy augury of success and we have everyreason to congratulate ourselves on his gracioushospitality and kindness.

In rising to address you at this annual meeting ofyour Congress, I feel I am hardly worthy to occupyan office which is associated with the names ofthose with whom I cannot compete in greatness. Afew years ago, Lord Rutherford stated at a meetingof medical men that the hopes of the world restedupon their successes and ever-growing usefulness.Aviation, wireless and television have now beenaccomplished, but one thing still left to wish for,Lord Rutherford very truly remarked, was long lifeand health, and it was the medical profession withwhom it lay to give that guerdon to humanity. For“Happiness lies, first of all, in health”.

“O blessed health! thou art above all gold andtreasure....

...... He that has thee has little more to wish forand he that is so wretched as to want thee, wantseverything with thee.”

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Standing here today as your president, I think Ishould show no partiality towards Science ofMedicine by choosing it for my address because Ihappen to be a medical man. As it is customary inthe annual meetings of scientific societies for thepresident to refer to the recent advances in Scienceand as the progress as well as the futureachievements of Medicine, which is concernedwith the preservation and restoration of normalacitivity of living matter in the human machine,depends to a great extent upon the help that she hashad and may yet get from the Sciences that youprofess, you would perhaps expect me, as far aspracticable within the time at my disposal and asfar as lies in my power, to give a review of theimportant contributions made by some of yourSciences in recent times towards the advancementof Medicine. I shall take cognizance of our recentknowledge of some aspects of living matter, asMedicine is intimately connected with life, and Ishall refer to some recent facts revealed by yourSciences which may apparently have no particularrelation to Medicine in the present day, but may beof medical interest in the futures.

The future happiness of mankind depends onthe solution of the problems of life. These problemsare much more complicated than those of Physicsand Chemistry, and still more is this the case withthe Science of Medicine, which deals with thepathological aspects of living matter. I shallprobably be able to say nothing that is new, butpresentation, from a different viewpoint, of thingsalready heard may perhaps be profitable.

BIOCHEMISTRY

I shall begin by saying a few words about ourpresent day conception of dietetics and nutrition.

As a matter of the most vital concern in nation-building, the problem of nutrition demands verycareful consideration by statesmen and scientistsalike, more so due to the fact, as has been recentlyobserved, that a great part of the world’s population

is not consuming the necessary food stuff. Aneminent Swiss authority predicts the decay ofcivilization unless there is a fundamental revisionof the people’s diet.

Dietetics and Nutrition—Vitamins

It has been stated that the function of nutritionis probably the centre of Medicine from a medicalpoint of view, and that the proper dietary of manis a most important subject for the maintenance ofhealth and prevention of disease. As has beenobserved by Hopkins, during the whole history theneeds of nutrition and the kind and amount of foodgeographically available have played a great partin determining the destinies of races. It has beenstated “tell me what you eat and I shall tell youwhat you are.” “Man’s place in future history willdepend in no small degree on the food he eats.”Nutrition is one the essential functions of life andits value cannot be too much emphasized.

Up to 20 years ago, the reign of calories wassupreme in the field of nutrition, and it was heldthat if the proper amount of energy required formaintaining nutritional equilibrium could be workedout in terms of calories, then the last word wouldbe said about the problem of nutrition. But it hasnow come to be recognized that certain substancesthat had eluded detection in the past, areindispensable in our dietary for the normal activityof the tissue cells and the prevention of certaindiseased conditions. Further the study of theproblem of nutrition has increased in recent timesfrom the quantitative to the qualitative standpoint,especially with respect to the proteins.

Though it was long known that diseases likeberi-beri were due to deficiency in the food ofcertain substances of unknown chemical nature, itwas Hopkins who made in 1912 the monumentaldiscovery of the value of the “accessory foodfactors”, or the “vitamines” as they were termed byCasimir Funk, in the maintenance of normalfunctional activity and growth. The progress of

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research upon the nature, distribution and functionsof vitamins has been very intense in recent days.To attempt to summarize all that is known aboutthem is beyond the limits of my lecture. Thediscovery of vitamins has led to the relief of aconsiderable amount of suffering and disablementthat is particularly true in regard to rickets. Manyof them are simple chemical substances and it ispossible that each of them possesses a strictspecificity in its action, though lack of more thanone vitamin may be responsible for the causationof the complex phenomena manifested by disease.

The function of vitamins and the pathologicallesions due to their deficiency are known to thoseamong you, who are biochemists or who belong tothe medical profession. I shall not discuss them here.

It is possible that the lack of vitamins does notplay such an important part in the causation ofdisease as has been claimed by some observers andthat the symptoms following a deficiency of certainvitamins may be attributed to a disturbance in thegastro-intestinal canal. It is realized today that theprocesses of digestion are much more complexthan was hitherto thought. The secretion of theintrinsic factor is but a case in point. It is nowknown that vitamin B1 deficiency is the cause oflack of appetite and defective movements in theelimentary canal. It requires but little imaginationto conceive that these effects must have somefundamental cause and that they could lead to anumber of abnormal sequelæ, such as, defectiveabsorption, stasis and toxæmia, to mention a few.

Requirements of Proteins, Carbohydrates andFats in A Dietary

The minimum amount of protein required forthe dietary of man has been a matter of dispute fora long time. Originally found by Voit at 119 gms,it was afterwards raised by Atwater to 125 andsubsequently lowered by Chittenden to 60. Shermanquotes it at about 44.4. It has now been recognizedthat the quest for a protein minimum is really an

illusion, as it depends not on the quantity but onthe kind of protein supplied. The work of Hopkinson the essential amino acids in connection withnutrition has come into prominence in the presentday. As has been pointed out by him, the foodproteins which can be used with the greatesteconomy in the body are those which contain allthe amino acids in such relative proportions as willcorrespond most nearly with their proportion in theliving tissues of the consumer. These are theproteins of so-called high biological value,constituting the first class proteins. It has beenobserved that the average consumption ofCambridge undergraduates, those in training beingexcepted, is about 80 gms of protein.

The Problem of Perfect Diet

There are many problems that await fullerinvestigation by physiologists and biochemists infuture before the perfect diet can be proclaimed. Afood in order to be effective, must be ingested bya body both physically and psychically sound. It ispossible to be well-nourished on the simplest ofdietaries. Who can say for certain what is theoptimum protein diet or the optimum intake of fat?What about the food of the Eskimos, the humancarnivores of the world, who live for long periodson purely animal food? Hindhede has emphasizedthe superiority of the high fat, low protein diet ofthe Danish farmers over the high protein, low fatdiet of the neighbouring Finlanders. But is thisapplicable to all mankind? There has been muchtalk about the energy value of different foodsexpressed in calories. But, as Cathcart has said, arenot these merely convenient units of measurement?How are we to explain the deleterious effects of“very high” cereal dietary and how are theycorrected by “protective” foods, such as milk andleafy vegetables? Do the cereals contain any toxins,which are neutralized by a proportional quantity ofthe protective food? What definite information isavailable as to the body needs of the differentkinds of vitamins? A further question is the problem

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of hypervitaminosis, as also the actual part playedby vitamins, and any difference which may arisefrom taking synthetic or natural vitamins.

Nearly 90 years ago, Chevers taught that thedietary of the Hindus with a very moderate quantityof animal food was the fittest for a tropical climate.Thus he wrote, “It is certain, that the law-givers,who prescribed for the people of India a dietconsisting mainly of vegetables and water, thelighter kinds of animal food, such as fish, pigeonsand goat’s flesh, being only occasionally introducedin moderate quantities, judged almost asphysiologically as they could have done, had theystudied at the feet of Liebig and Prout”. Similarlyin a discussion on the dietary of man, the meatlessdiet of some of the finest soldiers of His Majesty’sIndian Army who fought in the last great worldwar was highly extolled. This is an interestingsubject for research in the quest of minimumanimal protein required for human consumptionand the future may show that it may be influencedby climatic conditions. Recent researches of Bergtend to show that factors which determine theminimum quantity of protein necessary to preservenitrogenous equilibrium, such as, the particularprotein the subject is accustomed to taking and theratio of inorganic based to inorganic acids availableto or formed in the body of the subject.

This brings me to the question of animal versusvegetable protein. Investigators of the present-dayhold that, in general, proteins of animal origin aresuperior to the vegetable proteins for the purposesof nutrition and that the testimony of humanvegetarians is useless in determining the amount ofanimal protein requirement of man, because theywere probably not vegetarians during the first partof their lives.

Are there first class fats? At present we knowlittle about the nutritional value of different fats,but some work goes to show that certain fatty acidsof the linoleinic series may be essential. It hasbeen stated that the synthetic fat intarvin may be

used by fasting persons of normal health withoutthe development of acidosis. Do not theseadumbrate the possibility of the existence of firstclass fats? Further work is also necessary todetermine if there are essential carbohydrates.

Mineral Constituents of Diet

In recent years there has been an advance in ourknowledge of the importance of inorganicsubstances, especially minerals in our dietary. Manyof these such as calcium and phosphorus arerequired for structural purposes and their deficiencygives rise to structural diseases. There are otherswhich are required to be present in minute quantitiesin our dietary and which are perhaps concernedwith the stimulation of the active processes in thetissues. These are copper, manganese and perhapsyet other undiscovered elements. Their deficiencyis regarded to be responsible for certain forms ofanæmia, though very recently this view has beendoubted by some observers. The possibility of theexistence of undiscovered mineral deficiency indisease is for the future to reveal, and may Isuggest that certain obscure diseases of India, suchas, infantile biliary cirrhosis of children may beinvestigated from this point of view.

Complicated are the inter-relations of thevitamins, the hormones and the mineral constituentsof the tissues in the prevention of certain diseases.For instance, bio-chemistry has shown that a supplyof iron, copper, vitamin C and thyroxin are theessential factors in the formation of erythrocytesand hæmoglobin, in addition to an active bonemarrow. Deficiency of any of these may give riseto certain types of anæmia. A generous supply ofcalcium and phosphorus together with a liberalsupply of vitamin D is essential for the perfectdevelopment of the bones and teeth of the child.

Prolongation of Life and Rate of Growth

It recent times, studies in nutrition have beenconcerned chiefly with the maintenance of normalhealth and production of a rapid rate of growth. It

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has however been observed still more recently thatprolongation of life associated with a retarded rateof growth has been noted in many divergent forms,such as, rats and brook trout and that animals kepton a restricted food intake for long periods outlivedby a wide margin those that were allowed to eatfull from the time of weaning. The inverserelationship of the rate of growth and the time ofonset of senility is also apparent from otherinvestigations. Evans has noted that animals injectedchronically with preparations containing growthhormone of the hypophysis show evidence ofpremature senility. On the other hand, Lee andSchaffer have shown that administration of thepituitary growth hormone results in retention ofjuvenile chemical characteristics by the tissues.Other clues for the study of these problems arefurnished by the facts that thymus extracts greatlyincrease the rate of growth and maturity whilepineal extract seems to retard growth. Wetzel inhis work on “Motion of Growth” has shown thatexcessive rate of growth during infancy andchildhood is associated with excess of wastefulheat production and that this may have graveconsequences. It is apparent that some of the currenttenets in the field of nutrition require reconsiderationin an effort to determine the optimal rate of growthfor each period in life.

It seems, however, that the preponderance ofevidence indicates that the increased growthachieved by well-considered improvement in thediet is accompanied by general physiologicalbetterment and definite improvement of the species.By intelligent improvement of nutrition ofexperimental albino rats through successivegenerations there has been developed a new speciesof these animals.

Environment and Improved Nutrition

In the present day, physiologists realize that adiet which appears to be adequate is not invariablythe optimum diet. Better environment and improvednutrition will improve hereditary character and

bring mankind to a higher level of physicaldevelopment. Newer knowledge of nutrition maylead to the development of a larger stature, greatervigour, increased longevity and a higher level ofcultural attainment (McLester).

Indian and Indo-Javanese Dietary

In a recent investigation into the diet of the Indo-Javanese in the Dutch Indies, it has been observedthat on a diet which appeared hardly adequate from aEuropean point of view the people of the countrylived in a fairly good health, though their weight wasof a somewhat low standard. The subject requiresfurther investigation to determine what wouldconstitute a proper dietary for the Javanese.

Coming to the Indian dietary, in recent timessome interesting work has been done with thebalanced diets for Indians by Tilak and hisassistants. The dietary worked out by them is theinclusion with the staple food grains in commonuse by the people of India, of soya-beans, driedskimmed milk, rice polishing, fresh groundnut cakeand preparation of sprouted seeds. Such dietaries,if confirmed, may help in solving the problemfacing large masses of people in India, i.e., how toobtain a reasonably good diet for 5 to 7 rupees amonth. Aykroyd has found that diets which inpaper at least, adequately fulfil human requirementscan be bought in Madras for about Rs. 4/- permonth. “Cheap balanced diets” of this nature must,of course, be subjected to the test of practice.

Perhaps millions of the people of India,especially among the poorer classes, suffer fromvarious degrees of malnutrition which leads tolessened power of resistance to infection.McCarrison’s work in this field is well-known.Sanitation and nutrition must go hand in hand inall countries especially in India, where so manydiseases-epidemic and endemic-prevail.

Gastro-enterology

Alimentary auto-intoxications, allergicconditions from imperfect metabolism, and auto-

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infections from the alimentary tract play animportant part in Medicine and the gastro-enterologists are claiming today that the Scienceand practice of nutrition is becoming an independentand complete speciality, which is to be identifiedwith theirs. Perhaps the Science of Nutrition,including the problems of the dietary of the peopleof a country, will, one day, form part of thedepartment of preventive medicine of the State, asit has already begun to be in certain countries.

Dietary in Diabetes

In India where diabetes is common, the properdietary of the disease is an important subject, andI shall very briefly refer to it. Since the epoch-making discovery of insulin in the treatment ofdiabetes, the pendulum is swinging from the fatdiet of Newburgh and Marsh to “high” and “higher”carbohydrate diet of Sansum and others. Recently,it has been observed that administration ofcarbohydrate stimulates the production of anunknown insulin kinase, the insulin acting as asubstrate in the metabolism of sugar (Himsworth).On the other hand, large amounts of fat mayinhibit the action of insulin. On this view a “high”or “higher” carbohydrate diet for diabetes aided byinsulin finds a rational support and it is possiblethat, by the adoption of such a diet, the life of adiabetic may be more prolonged and death ratefrom diabetes more reduced than what has beenachieved in the present-day, in spite of theintroduction of insulin.

Hyper-vitaminosis, Hyperhormonism,Antihormones

In speaking of vitamins in connection withmaintenance of nutrition, one cannot help makinga brief reference to a condition discovered inrecent times and known as hyper-vitaminosis. Thisconsists of a series of toxic symptoms followingthe administration of excessive doses of certainvitamins such as A or D. It may be incidentallymentioned here that excessive production of theinternal secretions of the ductless glands in the

system, and administration of an excessive amountof the same may also give rise to toxic symptoms.The condition may be described as hyper-hormonism. Further it is possible that inhibitoryprinciples may be produced as a response on thepart of various hormones, and that the clinician inhis endeavour to correct a hypo-glandular statemay actually add to the gravity of the condition bycausing an overproduction of inhibitory principles,as a result of too persistent treatment with hormones(Collip). In diseases due to the deficiency ofhormones, their artificial administration musttherefore be intermittent and regulated accordingto the needs of the patient, just as they are normallymanufactured and distributed according to the needsof the body in health. Whether inhibitory principlesmay be produced by excessive use of vitamins Icannot say.

Biological Catalysts

Before I leave this portion of my address, mayI make a passing remark about the biologicalcatalysts. The catalysts of a living cell are theenzymic structures which promote reactions withinthe cells and determine their direction. Perhaps inthe maintenance of the normal reaction within theliving cells, the vitamins, the hormones and theminute mineral constituents play an important part.The action of medicines and diseased productsupon the permeability of the cells and upon theaction of enzymes within them must be an importantfield for research and may be of great value inMedicine for the study of chemotheraphy andimmunology.

PHYSIOLOGY

No one can doubt that physiology has had a greatinfluence upon the whole field of Medicine inrecent times.

Recent researches have thrown light on themechanism of the fundamental reflex reaction for

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the protection of the animals and have shown howwith the evolution of an anti-gravity mechanismand of extended movement, the brain stem hasbecome evolved to take over this increasedresponsibility. Magnus has analyzed the variousnervous stimuli from the periphery which areconcerned in this very delicately coordinatedmechanism. The new data have completelyrevolutionized our conception of the nervous stem,and signs and symptoms of disease which hithertocould not be properly understood have now becomecapable of analysis.

In more recent years Sherrington and his schoolhave worked more exactly on the relation of thenervous system to responses produced when it isactive. These fundamental studies will no doubtthrow much light on the changes so often observedin disease. His researches have shown that thecentripetal impulses do not pass straight throughthe spinal cord, but at certain stations in the cordthey are transferred into an enduring excitatorystate which may in turn set up fresh impulsesyielding the reflex discharges.

Adrian’s researches have also added greatly toour knowledge regarding the exact nature of theimpulses which pass along nerves in differentconditions. With a most admirable technique hehas studied nerve impulse and its origin withhighly profitable results. He has come to theconclusion that change of potential may be offundamental importance in the activity of nervecells. He has shown that damaged nerve fibres setup impulses at very high frequencies and theseperhaps play a part in sensation of pain, thoughsometimes impulses in the smaller, slowlyconducting nerve fibres may also be concerned inthe physical mechanism of pain. He has been ableto observe the activity of a single nerve cell andhas shown that human voluntary contractions areregulated in exactly the same way.

In Russia Pavlov and his school have elaboratedthe reflex reactions of the higher parts of the

nervous system. Their results are capable ofconsiderable application to many of the higherhuman activities.

A. V. Hill has studied the nerve impulses withexquisitely sensitive apparatus from the point ofview of thermal phenomena accompanying it andit is becoming clear that the nerve impulse consistsof a transmitted physico-chemical event, the wholecycle of event comprising activity and recovery inthe nerve being supported by the energy derivedfrom metabolic oxidative processes, associated withthe cycle.

Further it is possible to conceive “the nervousimpulse as a succession of transformation ofchemical into electrical energy, and conversely—these transformations being necessary by thestructure of the fibres.”

Haldane and his pupils have continued theirwell-known work regarding the control ofrespiration. Carbon dioxide, formerly looked uponas a product of excretion, to be got rid of as soonas possible, has been shown by them to be anessential stimulus to respiration. This discoveryhas been of immense value in modern anæsthesia.Further it has been shown by Yandell Hendersonof Yale University that carbon dioxide is alsoessential for the tone of the blood vessels. Daleand Evans have shown that carbon dioxide isessential for the activity of the vasomotor centre,just as it is responsible for the activity of therespiratory centres. Barcroft has shown theprinciples by which oxygen is transported by theblood. As a result of the work of Haldane, Barcroftand their co-workers, it is now possible to dealwith respiratory distress and failure by morescientific methods than what was possible in formerdays.

Areas such as the cerebral and pulmonary vessleswhich were once thought to have a poor vasomotorsupply have now been found to be much bettersupplied than had hitherto been imagined.

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With regard to the heart, the earlier studies ofcardiac distrubances by Mackenzie have played animportant part in advancing our knowledgeregarding the physiology of the heart, and the workof Starling and of Lewis has placed much of it ona strict experimental basis in more recent times. Anew interpretation of the electro-cardiogram indisease has been recently evolved.

The discovery of the function of the carotidsinus by Hering and its study by Heymans havebeen of great value to physiology and topharmacology as well. By the recognition of theactivity of this sinus and its possible variations onecan now explain many of the differences in responsewhich hitherto have been a great draw back inexperimental work. In the nerve connection of thissinus and the effect of pressure on it lies, accordingto some observers, the explanation of sudden deathunder gas anæsthesia.

One of the most important new facts discoveredin recent years regarding digestion is the relationshipof the proper functioning of the stomach to theproduction of blood, and the subsequent applicationof this to the treatment of pernicious anæmia. Thiswork had its origin in the physiological studies ofWhipple on the normal regeneration of blood afterhæmorrhage and administration of liver. Followingthe same line of research Minot and Murphy foundthat administration of fresh liver had a remarkablecurative effect on pernicous anæmia. This led to therecent liver therapeutics for treatment of the disease.

The researches of Castle, however, connectedthe etiology of pernicious anæmia with defectivegastric secretions. Recent experiments ofMeulengracht have shown that pernicious anæmiain human beings may be due to atrophy andinactivity of that part of the stomach whichcomprises the pyloric gland region and may besaid to have localized the seat of origin of perniciousanæmia in human beings. Thus stomachpreparations for the treatment of pernicious anæmiamay with advantage be producible from the pyloricgland region.

From a physiological point of view, theseexperiments give the pyloric glands a function. Aswe know, it has hitherto been difficult to ascribesuch a function to the pyloric glands and thespecial pyloric gland cells. Now it seems possiblethat the pyloric glands are the seat of specialsecretory function and secrete the substance Castle’s“intrinsic factor” that is essential to the blood andthe nervous system.

These experiments open up the theoreticalpossibility that under certain circumstancespernicious anæmia may be due to an isolatedatrophy or inactivity of the pyloric gland organwithout a simultaneous atrophy or inactivity of thefundus gland organ, i.e., without simultaneousapepsia or achlor-hydria (“dissociated achylia”)although judging from present clinical experiencethis possibility does not appear to be of muchpractical importance.

It has been shown by Loewi that the vagusnerve inhibits or checks the activity of the heart bythe liberation of a chemical substance which directlyinfluences the myocardium. This is a find of greatimportance, as there is increasing evidence that theactivity of all nerves may take place through theagency of similar chemical substances. Cannonand co-workers believe that they are capable ofappearing in two forms of combination, oneproducing only the augmentor and the other onlythe inhibitory effects of sympathetic nerves.

Extensive investigation as to the nature of theprocess by which nerve impulses influence theeffectors has been carried out by Dale and it seemsfairly established that all different messageseventually produce the desired effect by theliberation of either acetycholine or of a substancelike adrenalin. Dale distinguishes such nerve fibresas “cholinergic” or “adrenergic” according to thenature of the active substance liberated. Thepreganglionic fibres of the autonomic system, themotor nerves, and the post-ganglionic fibres of theparasympathetic belong to the ‘cholinergic’ category

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while the post-ganglionic fibres of the sympatheticusually fall under the “adrenergic” group. It hasbeen pointed out by him that Langley andAnderson’s evidence, long available, as to thekinds of peripheral different fibres which canreplace one another in regeneration, can beexpressed by the statement, that cholinergic fibrescan replace cholinergic fibres, but that nerve fibresof different chemical functions cannot replace oneanother. This discovery has no doubt an importantevidence on our new conception of the modeaction of “neuromimetic” drugs.

Certain recent experimental studies tend to showthat living tissues may be the seat of radiation ableto produce effects at a distance, and that certainactivities in one cell of a tissue may influenceactivities in a neighbouring cell and that chemicalreaction may be accompanied by radiations, andevents in one cell may thus influence other cellswithout material transmission.

The Endocrine Glands, the Glands of Destiny,the Pituitary

It has been held that the ductless glands are the“glands of our destiny” and that “these potentoverlords of our bodies are dictators of our mindsand personalities”. It may be possible that thefuture may reveal that genius, intelligence, beauty,character, morality, and other human characteristicsare dependent upon diverse combinations of thesecretions of these bodies, just as their deficiencyor excess may give rise to disease.

Insulin has completely changed the prospect ofthe treatment of diabetes. The discovery thatparathyroid extract mobilizes the calcium of thebones has revolutionized the treatment of diseasedue to calcium derangment. Our knowledge of theinteraction of endocrines has increased in recenttimes. I would just mention a remarkable fact that,as shown by Houssay and co-workers, there is noglycosuria when both the pituitary and the pancreasare removed, and further that the injection of

extract of the anterior pituitary is followed by theappearance of glycosuria.

May I end this portion of my address by makinga little more reference to the pituitary, which seemsto have a multiplicity of functions. It may beregarded as the headquarters for the hormones orthe chemical messengers which control most of theother endocrine glands and thereby probably almostevery cell of the body. The Chemistry of thepituitary is by no means closed and it may be thatthe most important discoveries in the pituitarychapter have yet to be written. It has been held that“the integration of the endocrine system is basedon the influence of the diencephalon upon theanterior pituitary, which through complex hormonesacts on the other endocrine glands, stimulating orinhibiting the production of simpler hormones inthem. These hormones are closely relatedchemically to other substances concerned in normalactivities such as, the growth of the embryo, thegrowth of bone and calcium metabolism, as well asabnormal activities such as malignant growths.”Further, “in general we can see a division of labourbetween nervous and hormonal events, andaccordingly between the respective regulators, thecentral nervous system, and the anerior pituitarylobe. The central nervous system regulatesprincipally the specific, acute functions ; thereforeit also influences those neurogenic endocrine organs,the adrenal medulla and the posterior pituitarylobe, the hormones of which cause acute changes.The regulator of the non-neurogenic hormonalsystem, the anterior pituitatry lobe, regulates mainlythe development and state, and partly also thesecretion, of the remaining endocrine organs, thehormones of which bring about longer lastingchanges of the conditions of many other organs”(Loewi).

In studying the developmental history of theremarkable endocrine gland, the pituitary, one findsthat by the seventh week of embryonic life, as thebase of the skull is being laid down between theroof of the pharynx and the floor of the fore-brain,

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the stalk of the Rathke’s pouch which forms theanterior and intermediate lobes of the pitutitarybody is drawn out and lies at the posterior borderof the nasal septum. Usually some fragments of thepituitary stalk persist in the mucous membrane ofthe roof of the nasopharynx. Cases have beenobserved in which the whole pituitary body lies inthe posterior part of the nasal septum. By the ninthweek the stalk usually disappears, but occasionallya canal in the body of the sphenoid bone of theadult—the craniopharyngeal canal—marks the siteof the embryonic stalk. Herring, very recently, hasreferred to the functions attributed by the ancientsto the pituitary. We may make here a reference tothe remarkable claims made by the ancient Yogisof India who practised what is known as KhechariMudra. They elongated the tongue slowly bypractice and manipulation aided by cutting itsfraenum, if necessary, and carefully introduced itinto the nasopharynx. The Yogis claimed to havedeveloped remarkable powers of their body andmind in this way. Did they conceive that thetongue mechanically stimulated the secretion ofthe glandular structures in the nasopharynx(pituitary?) which might be subsequently absorbedinto the system, in the same way as adrenalin isabsorbed when put under the tongue, and interactwith the secretion of other endocrine glands? Willsome future investigator test the validity of theabove claims?

Tissue Culture

May I now say a very few words about tissueculture.

“Tissues cultivated in vitro show two types ofgrowth, which are sometimes termed “somatic”and “uncontrolled” respectively.”

“In somatic growth, which is usually seen bestin cultures of early embryonic tissues, the explantedfragment behaves to some extent as if it were stillpart of the body. It may increase in size by any orall of the three methods observed in vivo, viz., bythe multiplication of cells, by the enlargement of

cells and by the formation of intercellular material,and if removed from an embryo at an early stageof development often continues to differentiateduring cultivation. For example, undifferentiatedskeletogenous mesoderm will form cartilage andbone in vitro, explants of the undifferentiated retinagive rise to nerve cells and rods and cones, and incultures of the early mesonephros typical kidneytubules may develop.”

“The second type of growth—uncontrolledgrowth, is perhaps more characteristic of tissuescultivated in vitro. Its main features are theprogressive simplification of the originalhistological structure of the explant correlated witha diffuse outgrowth of the cells multiplicationonly. Even in uncontrolled growth, however, cellsnever wholly depart from their original type, andepithelial and connective tissue cells remaindistinguishable as such even after prolongedcultivation.” (Fell and Willmer).

The Carrel strain of fibroblasts is the oldest setof cultures in existence, but there is evidence thatcertain types of epithelium and various forms ofmalignant tissue can also be made to live andmultiply indefinitely in vitro. These results suggestthat at least some types of vertebrate cells may bepotentially immortal, just as certain types ofprotozoa or the flat worm may be kept indefinitelyalive. It has been climed by Wells and co-writersthat “if Dr. Strangeways had lived in the time ofJulius Caesar and set a series of sub-culturesgrowing from a scrap of him, fragments of thateminent personage might, for all we know to thecontrary, be loving now”.

The recent invention in the Rockefeller Institutefor Medical Research jointly by Carrel andLindbergh, of a “Life Chamber”, a sort of artificialbody of “heart, lungs and bloodstream”, has enabledscientists for the first time to keep the organs alive,functioning and even growing for a long periodoutside the body. The method of Carrel-Lindbergh

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consists of the transplantation of an organ or ofany part of the body into a sterile chamber and itsartificial feeding with a nutrient fluid through thearteries. In this way the thyroids and ovaries ofanimals have been artificially cultured, and madeto grow. The perfusion fluid consists of proteinhydrolytic products, hæmin, cystein, insulin,thyroxin, glutathione, vitamins A and C, bloodserum and other substances according to thenecessities of the particular organ to be perfused.There is no doubt that tissue culture is likely to beof immense importance in the study of the humanbody and in the preventive and curative treatmentof diseases.

I have briefly outlined how the Sciences ofBiochemistry and Physiology have been laid undercontribution in the recent progress of Medicine.There are, no doubt, various other facts worthy ofnote in their application of Medicine, but I haverefrained from mentioning them for want of spaceand time.

It is pleasing to know that many of theinvestigators whose names I have just mentionedhave been Nobel laureates for researches in thesubject group of Physiology and Medicine.

Genetics

I hope it will not be regarded as transgressionof the ambit of my subject if I pay a passing tributeto the recent activities in the field of genetics.

The account of Mendel’s epoch-makingexperiments in his cloister garden, on the crossingof varieties of the common pea, somehow or othersank into oblivion for thirty-five years. But suchwas the potentiality of his work that, whenrediscovered, it not only laid the foundation butalso gave a new impetus to the study of theScience of heredity. In recent times Mendel’s theoryof what called by him factors (now known asgenes) has received confirmation in the hands ofMorgan and others. Their physical existence in thechromosomes has been proved and it is now known

that the chromosomes are indeed the bearers of thehereditary units and that to their very reliablemechanism we owe the regular behaviour of theinheritance of chracteristics from parents to children.Heredity is really a most remarkable phenomenon.The production generation after generation, ofoffspring identical in all but minor peculiaritieswith their parents is indeed one of the greatmysteries of life, and it is by the orderly divisionof the chromosomes and their contained genes lifecan be maintained. It is becoming more and moreestablished that “the general laws laid down byMendel have as wide a validity for genetics ashave Dalton’s for Chemistry”.

The practical outcome of the application of theprinciples of genetics as demonstrated by themagnificent work in research laboratories such asthose at Cambridge, Edinburgh, Aberystwyth, andAberdeen, has been of immense value in improvingcrops and live-stock. The boundless possibilities inheredity revealed by the Science of genetics haveplaced great power in the hands of breeders ofplants and animals and they can now tell withapproximate accuracy what to expect from matings.This knowledge has revolutionized breeding in alldirections, and resulted in the production of biggerand better plants and animals used for food, clothingor pleasure. In the course of time man may be ableto replace the natural selection of more fertilemediocrity and the artificial sterility of the high-grade parents by human selection and the artificialfertility of high-grade parents. Sooner or later thefrequency of the latter would increase in geometricalprogression and control and guide the qualities ofmankind in any way it desires for the good of man.The future trend of creative evolution, includingman’s own destiny, depends on his response to thenew knowledge and on his intelligent applicationof genetical discoveries, in the near as well asdistant future (Hurst). Genetics aided by betterenvironments may also be able to prevent thetransmission of hereditary weakness and hereditarydiseases, some of which are sex-linked. In this way

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it may lead to the production of better type of men,free from diseases of the mind and body that arepropagated from father or mother to their childrenand thus the difficult task of medicine for avertingor curing hereditary diseases or diathesis will bereduced to a minimum.

CHEMISTRY

It has been recently remarked by LordMoyniham that perhaps in the relation of Physicsand Chemistry to Medicine, we stand on the verythreshold. Let us see what advances have beenmade at this threshold in recent times.

I begin with the recent contributions intherapeutics due to the application of Chemistry. IfI were to attempt to enumerate the variouscompounds that are brought every day to notice ofthe medical profession in recent times, as hypnotics,anæsthetics, analgesics, antipyretics, antiseptics, orfor other threapeutic purposes, then their numberwill be legion and my task may be impossible. Ishall therefore refer briefly to a very few principletherapeutic chemicals of recent times.

How complicated is the mechanism ofchemotherapy is shown by the fact that a slightalteration in the constitution of a compound maybring about a complete change in its physiologicalproperties. This is well-exemplified in thepreparation of the various amino-quinoline derivatesfor antimalarial purposes. A slight change in theconstitution of these compounds leads to a completedisappearance of these properties. 6-amino-quinoline and 8-amino-quinoline have no action noparamoecia in strength of 1:4000. The introductionof OH into 8-amino-quinoline and quinoline-8-glycine-amide raises their toxic action onparamoecia to a remarkable degree and themethylation of 6-oxy-8-amino-quinoline byreplacement of H of OH by CH3 reduces its actionon paramoecia to nil (Brahmachari and co-workers).Diethylmonosulphone is without hypnotic action,while both dimethylsulphonediethylmethane and

the isomeric diethylsulphonedimethylmethane(sulphonal) are strongly hypnotic.

Anæsthetics and Hypnotics

Amongst the more interesting synthetic drugsintroduced in recent times are those recommendedfor producing anæthesia, when given by injection,preliminary to and partly replacing the use ofvolatile anæsthetics.

Though it may be held that inhalation anæsthesiaseems to hold its own which is, to a great extent,due to the development of the gas and oxygenmethod, yet attempts are being made to introduce,in recent times, other synthetic compounds whichmay be used for anæsthesia.

The new basal anæsthetics include tribromoethylalcohol (avertin), urethanes and some of the newersubstituted barbituric acids. Most of them aresodium compounds, such as soneryl sodium,amytalsodium, evipan sodium, pernocton, andnembutal. Among the general anæsthetics that havebeen introduced in recent times may be mentionedevipan sodium, and cyclopropane and di-vinyl ether.

To one coming from Calcutta, the history ofanæsthetics has a peculiar interest, because Waldie,who was one of the pioneers of chemical researchin India and who lived in Calcutta, was associatedwith the discovery of the anæsthetic properties ofchloroform in 1844. To his memory there is atablet in the rooms of the Asiatic Society of Bengal.To all of you, the same must also be of greatinterest because the first Chloroform Commissionwas held in India.

There is no doubt that general anæsthetics havebeen conducive to the advance of all branches ofMedicine. “The medical sciences, physiology,pharmacology, pathology and bacteriology wouldhave remained inaccurate and incomplete hand-maidens of Medicine, had it not been made possibleby the aid of anæsthesia to critically examine,corroborate or disprove the claims, hypotheses andtenets of workers of all types.” (Standar)

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Synthetic chemistry has produced numerous localanæsthetics better than cocaine. A new era has beenopened to the operating surgeon. His visitations onthe most delicate parts are performed, not onlywithout agonizing screams he has been accustomedto hear, but sometimes with a state of perfectinsensibility, and occasionally even with theexpression of pleasure on the part of the patient. Whocould have imagined that drawing the knife over thedelicate skin of the face might produce a sensation ofunmixed delight! That the turning and twisting ofinstruments in the most sensitive bladder might beaccompanied by a beautiful dream! (Warren.)

We are steadily approaching the solution of aperfect analgesia for labour.

In recent times, much work has been done inthe quest of a suitable hypnotic. The demand for agood hypnotic has grown more and more intenseof late, because due to the stress and strain ofmodern life, many ask for an ideal draught or atablet or a pill which would quickly put them inpossession of “tried nature’s sweet restorer, balmysleep”. From the hypnotics of olden times to recentones, the chemist has travelled a long way, and heis still moving further and further in the search forbetter hypnotics.

The chief advances in our knowledge of hypnoticdrugs in recent times have been

1. the discovery of many new derivatives of thebarbituric acid series ;

2. the introduction of a number of drugs otherthan alkaloids for purposes of basal anæsthesia.

The barbituric acid derivatives are perhaps themost commonly used hypnotics at the present day.Other recent hypnotics not derived from barbituricacid include avertin.

An ideal hypnotic should be free from any toxiceffects, should be quickly excreted and should give aquiet natural sleep of normal duration in a short time.Such a hypnotic has yet to come. Further the samehypnotic is not suitable for all types of cases andsometimes methods other than hypnotics are suitablefor individual persons for relief of sleeplessness.

May I now refer to the hypnotic properties ofthe extracts from the root of Rauwalfia Serpentina.As early as March 1912 the speaker read a note onits alkaloidal principles and therapeutic propertiesin a meeting of the Asiatic Society of Bengal. Theextracts have marked hypnotic properties and arespecially indicated in certain forms of insanity.Since the above paper was read, much work hasbeen done on the Chemistry of the drug and manyalkaloids have been extracted from the roots. Itshypnotic properties may be due to these alkaloids.

I now pass on to certain aspects of Chemistry inits application to a few protozoal diseases asrevealed by recent researches.

Organic Arsenicals

The best known of trivalent organic arsenicalsis salvarsan, for which the non-proprietary namearsphenamine is in common use in the BritishEmpire and the United States. The drug is nowgenerally used in the form of one of its twoprincipal derivatives. The first of these is neo-arsphenamine, the second is sulph-arsphenamine.The first pentavalent organic arsenical used in thetreatment of trypanosomiasis was atoxyl. Animportant derivative of atoxyl is tryparasmide. Ithas been found very successful in the treatment oftrypanosomiasis. Other new therapeutic organicarsenicals include stovarsol, etharsanol, proparsanoland carbarsone.

Symmetrical Ureas

The first and best known of the symmetrical ureagroup of trypanocidal drugs is Bayer 205 or germanin.In 1924 Fourneau and collaborators described theproduction of a symmetrical urea, which is nowobtainable in France under the name Fourneau 309(moranyl) and is identical with Bayer 205.

Quinoline and Acridine Antimalarial Derivatives

Schulemann and his colleagues succeeded inincreasing the antimalarial properties of methyleneblue by replacing its short side chains by a longer

3

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chain. Investigation subsequently conducted withthe quinoline nucleus led to the discovery ofbeprochin afterwards named plasmochine orplasmoquine. Similar experiments were made laterwith other heterocyclic nuclei including acridineand this led finally to the discovery of atebrin.These compounds are of great therapeutic value incertain forms of malaria. In Calcutta a number ofamino-quinoline compounds are being synthesizedunder the speaker’s direction and their antimalarialproperties tested. Some of them have already beenreported to have a marked action upon paramecia.

Leishmanocidal Organic Antimonials

One of the most terrible of tropical diseases, sofar as certain parts of India are concerned, is Kala-Azar. Antimony, which was once banned to suchan extent that the graduates in medicine of theUniversity of Heidelberg had to swear never to useit, has now been found to be its specific. By theintroduction of organic antimonials in its treatment,the mortality of this disease has been reduced from99% to about 1 or 2% in uncomplicated cases. Theterrible nature of this disease in its epidemic formwhen it ravaged Bengal in the Seventies was welldescribed by a contemporary writer as follows—“The devastation of the epidemic has a very sadtale to tell. Countries that once smiled with peace,health and prosperity, have been turned into hot-beds of disease, misery and death. Villages thatonce rang with the cheerful merry tone of healthfulinfants, now resound with loud wailings andlamentations. Huts, which offered too little spacefor their occupants are left without a tenant. Theskulls of human beings now strew the fields atevery few yard’s distance. The fell disease hasmocked every human effort, and absorbed in itspowerful grasp, day by day and inch by inch, everyblessed spot which once used to be prized for itssalubrity” (Roy).

It was doubtless a very great advance in thetreatment of the disease from massive doses ofquinine to tartar emetic which was the first antimony

compound introduced by Rogers into India for thetreatment of Kala-Azar. Soon after the introductionof the latter, the speaker conceived the idea ofusing sodium antimonyl tartrate (Plimmer’s salt)and tartar emetic was soon replaced by thiscompound.

The next step in the treatment of the diseasewas the introduction by the speaker of theintravenous administration of metallic antimony ina state of fine subdivision, which was attendedwith remarkable benefit. It was observed that wheninjected intravenously the particles of antimonyare picked up by the same cells in the spleen asthose that harbour the parasites of Kala-Azar, thatthe two contending agents thus come in closestcontact with each other in these tissue cells, andthat the fight ends most remarkably in the completedestruction of the parasites in the speediest way.

The next further advance in the treatment ofKala-Azar was the introduction of certain organiccompounds of antimony and the use of thesecompounds in Kala-Azar infection has been thesubject of the speaker’s research for many years,and in 1920 some of them were prepared for thefirst time in India in the Calcutta Campbell Hospital.

Early in 1921, the speaker discovered an ureaantimony compound for the treatment of Kala-Azar. Its introduction and his other researches onantimonial compounds opened up a new vista inthe treatment of the disease in India by means oftherapeutic organic antimonials, just as thediscovery of salvarsan led to the introduction oforganic arsenicals in the treatment of spirochætaldiseases. This urea compound was named “ureastibamine”.

I shall not detain you here with the romance ofurea stibamine, however interesting it may be. ButI recall with joy the memorable night in the CalcuttaCampbell Hospital at Sealdah when after a veryhard day’s work at about 10 P.M. in a little roomwith a smoky dimly burning kerosine lamp, thespeaker found that the experiments in the

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preparation of this compound were up to hisexpectation. The room still remains, but the signsof a laboratory in it have completely disappeared.

The first series of cases treated with thiscompound were published early in 1922. Soonafter this, most remarkable results were obtainedwith it by Shortt in Shillong to whom the compoundwas sent for trial. The value of this compound wasquickly recognized. It was introduced, soon after apreliminary experimental trial, by the Governmentof Assam for the treatment and prophylaxis ofKala-Azar.

Today urea stibamine stands pre-eminent in thetreatment of Kala-Azar in India and as a powerfulprophylactic against the disease, and it is a matterof supreme statisfaction that this treatment hasbeen the means of saving the lives of a vastpopulation of suffering humanity.

The following remarks from the Annual PublicHealth Report of the Province of Assam for theyear 1933 dated 23rd July, 1934, are worth quoting“It has to be borne in mind that, when no specificremedy was known for this disease, that 98 personsat least out of every 100 were doomed to certaindeath within a comparatively short space of time.Since 1923, when reliable figures for the diseasefirst became available to the end of the year underreport, no less than 328,591 persons have beenbrought under treatment. It is no exaggeration tosay that approximately 3.25 lacs of valuable liveshave been saved to the Province”.

Further advances have still to be made in thetreatment of infections with leishmania donovani,as there are antimony resistant cases, thoughfortunately few, and the treatment of that ugly skininfection which was first described by the speakeras a post-Kala-Azar condition and known as dermalleishmanoid is frequently unsatisfactory. Cases ofthis condition may be a menace to a community, asa possible reservoir of the parasite of Kala-Azar.

Chemical Structure and Physiological Properties

Dealing with the relationship between chemical

structure and physiological properties one meetswith a remarkable series of compounds in recenttimes having a common nucleus but possessingvaried physiological properties. I mean thecompounds having the ceondensed benezene ringsystem or phenanthrene, as well as, the reducedphenanthrene plus a fourth five-membered carbonring or cholane. The cholane nucleus is found inbile acids, cholesterol and other sterolas.

A structure of the cholane type is also found inthe sex hormones which are responsible for thesecondary sex characters of animals. Thesehormones are coestron, luteosterone and the maletesticular hormone or androsterone. They have closestructural relationships with each other and withbile acids and cholesterol which probably containtheir biological precursors.

The male sex hormone or androsterone hasbeen artificially prepared. Friedmann has pointedout that the aromatic ring, corresponding to ring Aof oestrin is not necessary for the development ofthe oestrogenetic effect as the benzene nucleus canbe replaced by the furane ring, fural-pyruvic acidbeing even more active than benzal-pyruvic acid.Recent experiments suggest the possibility of gettingoestrogenetic activity in ring-free compounds byarranging the carbon atoms 13, 14, 8, 9 of oestrinin a suitable way.

Synthetic hydrocarbons containing thephenanthrene nucleus, such as dibenzanthracene,are found to possess carcinogenic properties. Thecancer-producing action of certain tars is due tothe presence of a hydrocarbon allied todibenzanthracene. It has been synthesized and thepowerful carcinigenic action of the pure substancehas been confirmed. It is perhaps, the most potentcarcinogenic substance so far discovered.

The aglucones, that is, the non-sugar parts ofdigitoxin, strophanthin and several other closelyrelated substances are allied to the sterols as theyembody structures of four carbon rings. Bufotoxinhas a constitution closely allied to those of the

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cardiac aglucones and possesses a characteristicaction on the heart similar to that of digitalispreparations. The phenanthrene nucleus is presentin some of the most powerful alkaloids, such asmorphine and codeine of the opium group, and thecorydalis alkaloids and in colchicine.

All hormones of the secondary types containbenzene rings. In some cases the ring is a simpleone as in thyroxin, pituitrin and adrenalin. Inothers it is a complicated one, the condensedphenanthrene ring. The Needhams and Waddingtonhave observed the most remarkable phenomenathat the chemical organizer or, as they call it, theevocator which determines certain developmentsof the embryo, belongs to the same group.

Chemistry of Vitamins and Hormones

X-ray work on vitamin B1, B4 and C has beencarried out in recent times and the structural formulaof C as l-ascorbic acid has been established by aclose collaboration of crystal analysis with theordinary chemical methods.

The structure of carotene and vitamin A hasalso been established by X-ray analysis, asconsisting of cis-polyene chain which is presumablythe chain of polymerized rubber.

Vitamin B1 possesses two ring systems, oneglyoxaline or pyrimidine and the other a pyrrolecontaining a substituted sulpur. It is not allied toflavins. Vitamin B1 possesses antiberriberiproperties. The crystalline specimens of Jansenand Donath are according to most recentobservations, the pure vitamin itself with theadmixture only of a small and variable amount ofinactivated vitamin.

Vitamin B2 is a complex, containing flavin andanother factor, the absence of the latter and not offlavin being considered responsible for thesymptoms of pellagra in rats. The flavin factorexerts a growth-promoting action. A substanceidentical with lacto-falvin of milk which is alliedto vitamin B2 has been isolated and synthesized.

Examining the oxidation—reduction properties offlavin-cleavage products, Kuhn and Moruzzi wereable to sum up the relationship of the flavin groupby saying that the parent substance was a reductant;that combined with a ring system which contains asubstituted amino group it produced a colour; thatthe addition of a carbohydrate side chain yielded avitamin; and that the further addition of a proteingroup resulted in an enzyme (the yellow respirationferment of Warburg).

Vitamin C is closely related to simpler carbo-hydrated and sugars. It is a keto-hexonic lactone.

Vitamin D can be artificially prepared fromirradiation by ultraviolet rays. It has been isolatedfrom irradiated ergosterol in a crystalline andapparently pure form, the crystalline compoundbeing known as calciferol. The production of vitaminD by the irradiation of the sterols of the skin byultraviolet rays of the sun is a most interestingchapter in the history of Medicine, reconciling, as itdoes, the dispute whether rickets is due to a deficiencyin the diet or want of proper sunlight.

Rapid progress is being made today in theisolation of hormones in a chemically purecondition. The hormone thyroxine, the activeprinciple of thyroid gland, the iodine-containingamino acid has been synthesized by Harington andhis collaborator Barger from tyrosine from whichit is probably formed in the animal body. Kendallof the Mayo Research Institute has succeeded inpreparing what appears to be the hormone of thesuprarenal cortex, which may be beneficial in thetreatment of Addison’s disease. Ephedrine andpseudo-ephedrine are alkaloids isolated from speciesof ephedra and are chemically allied to adrenalin.Physiologically epherdrine and adrenalin hehavesimilarly in many respects. Epinine, a syntheticcompound, possesses, in a marked degree, thepharmacological action of adrenalin.

The Specific Carbohydrates

The discovery of type specific carhohydrates is

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among the most remarkable triumphs of Chemistryin recent times. It has been observed that aderivative of gun arabic possesses propertiesresembling those of the specific polysaccharides ofone of the types of pneumococcus serum. Thevalue of polysaccharides possessing immunologicalfunctions, and the knowledge of their composition,properties and structure must be of great value inmedicine. The polysaccharides of the cholera becilliand of B. dysenterioe (Shiga) have been investigated.

Isotopes and Heavy Water in Relation of Life

Vernadsky has put forward a hypothesis thatthe living organisms possess a selective powerbetween isotopes of an element. Among the plants,Loring and Bruce have shown that in the potassiumof potatoes isotope of atomic weight 41predominates while in ordinary potassium the chiefisotope is of atomic weight 39. In the case of manthe future may reveal that isotopes of elementsplay in important part in the maintenance of healthand that they may vary in disease.

Barnes has suggested that the polymerizedmolecules of water are of primary importance inphysiological processes. The discovery of thehydrogen isotope (deuterium) of mass 2 and theisolation of quantities of “heavy water”, containingthis isotope have opened a new field in thephysiology of water. Gortner considers that thewater in the Medusa is as much “alive” as are theproteins, the fats, the lipids, or the carbohydrates.The water relations and different molecular formsof water in the living organism lie at the foundationof problems concerning both health and disease. Ithas been held by him and others that in lyophilichydrosols and hydrogels the water may exist intwo states, i.e., in the state of free water which ischaracteristics of water in bulk and in the state ofbound water which is characteristic of the lyophilicsystem, and that the equilibrium between free andbound water is undoubtedly of major importancein vital phenomena. Two hypotheses have been

presented as to the possible nature of bound water.

1. An oriented adsorption of the water dipolesat the interface, and

2. an oriented adsorption of hydrogen andhydroxyl ions.

The effects of the substitution of the deuteriumform of hydrogen in place of ordinary hydrogenand of the isotopes of other elements into organicmolecules may have in the future an importantapplication in Biochemistry and Medicine.

I have referred only to a very few achievementsin Medicine due to the application of Chemistry inrecent times. The advance has been so very greatthat even in snake venom has been found atherapeutic application for the relief of the terriblepain of inoperable cancer or as a systematichæmostatic in uncontrollable haemorrhage. Thesex hormones are having therapeutic applications,and the pregnant mare’s urine has been founduseful in pituitary cachexia with disturbance ofcirculatory regulation and on the metabolism ofcarbohydrate and fat. Ovarian extracts have beenused in the treatment of hemophilia.

The relaion between chemical constitution ofcompounds and their varied physiological andtherapeutic properties, though at present consistingmostly of jumble of empirical facts may one daylead to generalization of vast importance.Therapeutics is moving today from merelyqualitative to quantitative foundations. Some ofyou may live to see that remarkable results may beattained by Chemistry in the treatment of diseaselike tuberculosis or cancer for which chemicaltherapeutics has at present day only a limitedapplication in gold or selenium and leadrespectively. It may be mentioned in passing theinteresting results obtained in Berlin by Fischer oncancerous rats. By keeping these animals in pureoxygen, under a pressure of 1.5 kg. per sq. cm. for24 hours, he observed that the tumour explodedliterally outside of the body, tearing the skin, and

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was finally eliminated as sloughing tissue.Crystalline insulin free from impurities is nowavailable. Mandelic acid, phenyl hydroxy-aceticacid and its sodium salt are very recently cominginto use in the treatment of B. coli infection of theurinary tract, the principle of treatment being basedon the fact that a ketogenic diet leads to theproduction of b-hydroxybutyric acid which is theeffective agent in the urine of patients treated witha ketogenic diet and which is allied to mandelicacid. Newer treatment of epilepsy, of myastheniagravis and of agranulocytic angina are coming inthe field due to the triumphs of Chemistry. Youmay see the synthesis of other newer vitamins andinternal secretions as well as extracts from differentorgans of the body synthesized or isolated in apure state and used in medicine for the treatmentof disease. We look forward to the day whenendocrine preparations will be available for oraladministration and the dread of the needle averted.

PHYSICS

I now pass on to the contribution of Physics toMedical Science. Its application is partly for thepurpose of diagnosis of diseases and partly fortheir treatment. Further, Physics is slowly evolvingconception of living matter by X-ray analysis, byimproved methods of microscopy and by theadvancing knowledge of the constitution of matter.

It is not my intention to give here an account ofthe various apparatus that Physics has madeavailable for the diagnosis and treatment of diseaseas such an attempt will be merely cataloguing. Ishall only refer here to some of them that havebeen of striking value in Medicine or that mayprove useful in the study of the structure of organicmatter.

The Electro-cardiograph

The Electro-cardiograph is a valuable apparatusfor studuing certain diseases of the heart. A portableapparatus which can be taken to the patient’s house

and which is constructed on the principle of thestring galvanometer is now available. Anotherportable Electro-cardiograph based on the principleof the valve amplifier is also available. By meansof a special Electro-cardiograph outfit, simultaneousrecords of a heart may be obtained in the wards ofa hospital for purposes of research showing (1)heart sounds, (2) electro-cardiagram, and (3) carotidpulse by means of Hill’s wire sphygmograph. Anapparatus consisting of a Stethograph combinedwith an Electro-cardiograph may prove a valuableaid in cardiology.

The Electro-cardiograph has shown that tracingstaken of patients dying of various maladies candemonstrate that for some time after clinical deathsome cardiac activity cloud be registered theduration varying from six to twenty minutes. Theseobservations show that in cases in which there iscardiac standstill during anesthesia or in the newborn, resuscitation may be effected by timelycardiac injection or needle puncture. There may beother conditions that may be discovered in futurein which the same may be possible.

It may just be mentioned here that a convenientnew method of assay of vitamin B1, based onelectro-cardiographic measurements, has beenrecently described.

An Electro-encephalograph of the Future

One of the most recent advances in Biophysicsis the discovery of some electrical phenomena inthe human brain, which were origianlly studied byBerger and subsequently by Adrian and Matthews,the letter observers using the Matthews’Oscillograph constructed on the principle of avalve amplifier. The electrical changes consist of arhythmic oscillation of potential with a frequencyof about 10 per second appearing when the personexperimented upon lies quietly with eyes closedand dis-appearing when his attention is fullyoccupied. Non-visual activities which demand theentire attention, e.g., mental arithmetic, as well as

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sensory stimuli demanding the same, abolish thewaves.

Berger considers that this “Berger rhythm”represents the normal activity of every part of thecortex of the brain while the experiments of Adrianand Matthews point to the conclusion that theyarise from the activity of cortical cells in someparts of the optical lobe connected with vision.

I consider that future researches in this line maybe as important in studying, as pointed out byHopkins, the functions of the brain as the electricalchanges in the heart are in studying cardiac diseases.An electro-encephalograph may then be a valuableapparatus in Medicine and may be useful for thestudy of the diseases of the central nervous systemor of the mind, such as, anxiety neurosis orpsychosis as the Electro-cardiograph has been instudying the diseases of the heart. Further work inthis direction in the hands of Adrain and his co-workers is awaited with keen interest.

Ultraviolet Ultra-microscopy

One of the latest developments in microscopy isthe use of ultraviolet light with dark groundillumination.

Barnard’s technique and apparatus have madephotography with ultraviolet light as certain andreliable as ordinary photomicrography. Hismicroscope has already revealed the structure ofsome of the viruses and inclusion bodies. We arebeginning to learn that there is no clear line ofdemarcation between the ultra-microscopic virusesand the visible bacteria. I hope that further advancesin ultra-microscopy with shorter waves, aided withimproved methods of fine adjustment and electricalequipment for producing the spark source, will infuture reveal the nature of the bacteriophage, andthat of the smaller viruses which is not possible atthe present-day without the aid of biological tests.Differential centrifugalization, graded ultra-filtration, the recently developed methods ofelectron diffraction and micro-dissection may behelpful in this direction.

Thanks to the recent advances in the ultra-microscope the nature of the filterable viruses as abiological problem has assumed a new aspect inrecent days. The view that viruses are small micro-organisms similar to ordinary bacteria is beingdaily confirmed. There is reason to believe that thesize of the smallest virus which behaves like livingorganisms approaches that of the largest organicmolecule. Until recently little evidence wasavailable to suggest the existence of what may betermed saprophytic viruses except that of Riverand Tillett who demonstrated in 1923 the presencein the testicles of rabbits of a virus that is notnormally pathogenic. Barnard has howeverdemonstrated by means of refined examination ofthe deposits, which sometimes occur in mediumcontaining horse or rabbit serum, the presence ofminute bodies, which in size, shape as well asgeneral optical properties are in no way differentfrom undoubted pathogenic viruses. These bodiesincrease in number and are seen to be in process offission. They have been cultivated to the fourthsub-culture. This demonstrates the existence ofviruses which are saprophytic in habit, and tendsmore and more to lend support to the theory thatviruses are living organisms. The recentannuouncement made by Stanley of the Rockefellerinstitute however complicates our conception ofviruses. He has reported the separation, from thejuice of Turkish tobacco plants infected with themosaic disease, of a crystalline protein that has theproperties similar to tobacco-mosaic virus. It is tooearly to speculate on the eventual significance ofthis fundamental controbution, with regard to itsrelation to virus diseases in animals or to othervirus infections of plants.

There is experimental evidence in recent timesthat the casual agent of acute rheumatism isprobably a virus.

It is not my intention to continue further remarkson ultraviolet ultra-microscopy but I can foreseethat aided by X-ray analysis it will reveal in futuremore and more new facts about the viruses and the

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bacteriophage than what is known in the present-day and that the doubt very recently expressed bysome observers whether the viruses will ever beseen will cease. The association of viruses with thespecific micro-orgnisms in bacterial diseases mayin future be found to be more common than isimagined at the present-day.

Infrared Photography

Photomicrography with infrared light makes itpossible to investigate, with transmitted light, manyobjects which are black or very dark brown in colour,and which consequently absorb very strongly bothwhite light and for the most part also ultravioletlight. The infra-red rays enable one to photographthe veins of the skin or the diseased condition of itsdeeper layers or of the iris under an opaque cornea.

The Micropolychromar—Optical Staining ofColourless Objects

In studying under the microscope colourlessobejcts, medical, zoological or botanical, we meetwith difficulties, beacuse as a rule they exhibitlittle optical contrast and are barely visible. Theusual procedure of chemically staining such objectsis tedious and kills them unless they are stainedwith vital stains. They micropolychromar opens upa new avenue for scientific investigation of suchcolourless objects. It provides a means of “staining”them not chemically but optically. This opticalstaining has the effect of showing up the objectbrightly illuminated in one colour on a differentlycoloured background. The objects are not merelydifferentiated from the background by virtue oftheir relative brightness but even when thebackground is as bright as the object, the objectand background appear in contrasting colours. Bymeans of this optical contrast staining, the finestructures are revealed with remarkable distinctness,the apparatus combining in one image theadvantages of both dark field and bright fieldillumination. The value of such an apparatus instudying the structures of living cells and tissuesparicularly chromosome structrue may be great.

Ultropak

One of the recent advances in microscopy isdue, to a great extent, to changes which have takenplace in methods of producing the appropriate typeof illumination. Of special importance is thearrangement for polarized light recently evolvedfor the Ultropak. This arrangement eliminatescompletely the glare and haze which arises fromdirect reflection, so that the inner structure of theobject may be observed in every detail and with aremarkable degree of distinctness, the image of theobject may be observed in every detail and with aremarkable degree of distinctness, the image of theobject being formed only from diffused depolarizedlight reflected from its structure. It is a useful aidfor the up-to-date worker engaged in microscopicalresearch in general Biology, Zoology, Parasitologyand in Experimental Medicine, in which theobservation of living organisms under highmicroscopic magnification is involved.

X-ray Crystal Analysis—Its Aid to Organic andBiochemisty

But evidently the microscope has its limitations.Sir William Bragg’s application of X-rays has ledto the discovery of the proper structure of matterwhich is beyond the limits of the microscope. Untilquite recently, the majority of the tissues, such asthe hair and skin, were believed to be non-crystalline, but recent investigations by means ofX-rays and Crystal Physics have shown this beliefto be incorrect and it has even been held thatentirely non-crystalline materials are very difficultif not impossible to find. Minute regularities whichare beyond the range of the microscope can nowbe detected by means of the X-rays.

Speaking of the crystal structure, of the solidstate, as revealed by X-rays, Sir William Bragg hasstated that all the investigations of the solid bodiesof every form aim at finding out the connectionbetween their properties on the one hand andcomposition and arhcitecture on the other. Whilesome of these properties are directly dependent on

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the atoms of the unit cell in the crystal, there areothers which depend on atomic relations which arenot fully developed within the cell. The action ofthe atomic forces in groups of hundreds orthousands or tens of thousands of atoms must beconsidered before we can understand these otherproperties of the solid state. It is within a region ofdimension covering groups like these andsomewhere in the scale of sizes there perhapsenters, as Sir William Bragg says, the breath of lifeto control these atomic compositions which enterinto living organism. It has been stated that “instructures produced by organisms, forces are activein their formation which are not present in solutionswhen ordinary crystals are deposited. The presenceof these additional forces in living protoplasmprevents a clean-cut regularity in arrangement ofthe molecules; that is, it introduces irregulararrangement of the molecules, or a degree ofamorphousness. If this is the case, then thedetermination of the space group for a givenorganized substance will have little value”(Sponsler). But it is possible that furtherimprovements in X-rays analysis may prove oneday useful in considering the activities which occurin the protoplasmic matrix of organisms, and ofstructures which are produced through vital process.They may enable us to look into the mysteriousprotein molecule without destroying it and todiscover whether diminution of the above-mentioned forces in any tissue in disease or theircessation in death may be accompanied by a changeof the amorphousness of the aggregates of themolecules to some more or less characteristiccrystallite or crystalline state.

X-ray methos of analysis may be applied one dayin the study of the cancer cell and it is hoped that itsapplication may increase our knowledge of cellconstruction and cell growth, which helped by ourfuture knowledge of the colloidal state in living cellsmay one day strengthen out power in combating thedreadful scourge of malignant disease. The changesthat take place in the tissues in cancer and other

pathogenic conditions have been studied by thismethod By Clark and co-workers.

The animal fibres are built of stringy proteinmolecules, which are made of strings of groups ofatoms. The length of these groups which are markedby joints at regular distances is always the same buttheir breadth varies and therefore a protein chain ismore irregular than a cellulose chain. The proteinchains can be made up in many different ways. Thedifference between species of animals may be due tochanges in the order of the groups in protein chainscontained in their body. If due to an accident ordisease the order of the groups in a protein chain inthe dividing chromosomes of a fertilized ovum wasupset, the basic pattern for part of the tissues of theembryo would be changed, and as the tissues wouldsubsequently grow according to the new pattern, thefinal structure would have a new patter and differentproperties. The shuffling of the order of the unitgroup of protein chains may be a fundamentalagency in the process of evolution, normal orabnormal. It is difficult to determine the order of theunit groups in a protein chain by the methods ofOrganic Chemisty. But X-ray analysis may make theproblem easier in future. A comparative study of theorder of these groups in the proteins of animals isnow becoming possible and may one day enable oneto investigate the internal structrue of the organsmore minutely than what is possible at the presentday. There is no doubt that X-ray analysis hasopened up a new way for the study of living matter.

Electron diffraction gives information similarto that given by X-rays but with the importantdifference that a much smaller thickness of materialis effective in producting the diffraction pattern.Layers with a thickness of about 10–6 cm containingten molecular layers or thereabouts have been usedand the effective thickness can be made smallerstill by using slow-speed electrons. Another modernbranch of Physics is being developed which maybe of practical application in Crystal Physics,namely the technique of molecular rays. These

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have up to the present been used chiefly for studyingthe properties of atoms or molecules of substanceswhich can be obtained in the vaporized state, suchas the metals, the common gases, a few inorganicsalts, and some organic liquids. Such a techniqueor that of electron diffraction may one day findapplication in medical as well as in textile research.The processes of absorption of drugs and dyes inthe treatment of disease as also of antibodies aswell as many other facts in immunity might infuture be studied by these techniques.

Spectrograph

In recent years a new field has been opened upby the spectrograph in the domain of chemicalanalysis, both qualitative and quantitative. It hasnow become possible to apply spectrum analysis tobiological problems, among which are to be countedall the questions arising in theoretical and practicalmedicine regarding the metabolism of the heavymetals and its significance for the organism, whetherhealthy or diseased or the treatment of disease bythe administration of heavy metals (Gerlach andGerlach).

Until recently the only metallic elementsconsidered as playing an important part in animaland vegetable life were sodium, calcium,phosphorus and iron and, to a less degree, potassiumand magnesium and to these may be added silicon.The powerful influence sometimes exerted on lifeby very small quantities of elements, such as,copper, arsenic, mercury, iodine and boron, etc., asrevealed by recent knowledge has led to anincreasing need for improved and accurate methodsof analysis for detecting and estimating minutequantities of elements. Results obtained by theflame method of spectrographic analysis areapplicable for the purpose.

As an example of the application of thespectrograph to mdeicine, 0.1 c.c. of blood may betaken from a patient suffering from severe anæmiaevery 10 or 12 days to study the effect of treatment.

The blood is rolled up in small places of ashlessfilter paper and spectrographed on a plate andthereby changes in the various constituents of theblood, such as potassium, magnesium, calcium,iron and copper may be readily followed.

It has been shown by this method that humanhair and finger nails contain minute quantities ofcopper and silver, varying in quantities with theage of the people. By its means the routinedetermination of the vitamins may be studied. Thestudy of absorption spectrum bands given by thedifferent vitamins has helped in the work for thedetermination of the chemical nature, theconcentration and assay of vitamins. Similarmethods of hæmoglobinometry are now available.Spectrum analysis has become of great importancein pathological as well as forensic medicine fordetecting traces of metals in human organs. It hasbeen recently employed for styding the nature andthe constitution of the amino acids of the proteinmolecule as well as for their quantative analysis.

Ultracentrifuge

Studies on the size and structrue of the moleculesof proteins, as well as upon the molecular weightsof certain enzymes, carried out with the aid ofSvedberg’s ultracentrifuge, constitute a new andpromising application of Physics to medical researchand valuable work has been done with it inconnection with blood pigments and serum proteins.It may be helpful in the study of immunology andthe physical chemistry blood.

Opthalmo-eikonometer

The Opthalmo-eikonometer has been developedfor measuring the size and shape of ocular imagesand has opened up a new field in Ophthalmology,Psychology, and Neurology. It consists of the studyof image size variation in binocular vision.

A technique has been developed, “by means ofwhich the brains of mammals can be stimulated ataccurately defined points and a correlation

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established between the locus of stimulus andphysiological function”. Interesting possibilities liein the determination of the influence of certain partof the brain over some of the organs of internalsecretion and over the function of the gastro-intestinal tract, the kidneys, etc.

A method has been recently evolved whichpermits observation of the form and behaviour ofliving cells providing a valuable means for studyingnervous control of the circulation and the nature ofnerve destruction and regeneration.

Micro-manipulator and Micro-dissection

Operative work on the living cells has long beenthe aim of investigators in cytology and inexperimental embryology. By micro-dissection andinjection the physical structure of protoplasm hasbeen determined by Chambers and others. Untilrecently the results obtained by the micro-dissectionmethod related to the viscosity, the differentiation ofcortex and interior, the nature of the surface film, thenature of chromatic and achromatic structures individing nuclei, internal and surface changesinfluencing cell division, protoplasmic changesaccompanying fertilization, and the effect on theprotoplasm of the injection of certain substances.

One of the most important applications of micro-injection methods for the study of cell physiologyis the role of electrolytes in the maintenance ofprotoplasmic structure and function. K and Na arefar more toxic when applied externally then wheninjected, the order of toxicity for the immersionexperiments being K, Na, Ca, Mg. CaCl2 isconsidered to have the most marked toxic effect onthe internal protoplasm MgCl2 is considerably moretoxic to it than either KCl or NaCl. From the aboveand similar experiments, it is presumed that themaintenance of the colloidal state of livingprotoplasm depends upon the presence of definitelyproportional amounts of different electrolytes. Therelative amount of different types of salt presentmust be in such proportins that the solidifyingaction of the one is balanced by the dispersive

action of the other, K is said to be a labiliser whileCa is a stabilizer. Ca is essential for the formationand maintenance of the protoplasmic membrane.

The determination of the hydrogen ionconcentration of protoplasm has been considerablydeveloped in recent years by micrurgical technique.Both colorimetric and potentiometric methods arepossible for the determination of the pH ofprotoplasm by the use of micro-electrodes. Bymeans of this technique it is found that the livingprotoplasm of widely different types of cells has,under normal conditions, a remarkably constantpH value. The technique has also rendered possiblethe study of the oxidation—reduction potential ofprotoplasm.

The recent investigations in micro-dissection ofhuman polymorphonuclear neutrophiles show nomarked divergence from Chamber’s excellentdescription of the physical structure of cells ingeneral. It would seem, however, that the cellmembrane, in this case, is more rarely a nakedsurface film than he ascribes to most cells. Thecytoplasm is more liquid than that of the monocyteand clasmatocyte.

Observation by micro-injection method on plantnuclei show evidence of an elementary structruetogether with a fluid sap in the resting nucleus andsupports the view that, in plant cell at least, apersistent framework exists which might accountfor the genetic coutinuity of the chromosomes.

Radiology

X-ray diagnosis has improved in the present dayto an almost spectacular extent; and radiation therepyhas now established its claim to an important placein the treatment of malignant disease.

One of the recent advances in diagnosticradiology is undoubtedly the introduction ofcholecystography by Graham and Cole. Theradiologist can now visualize the biliary tract andthe gall-bladder by means of tetraiodophenol-phthalein; by the injection of air he can outline

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organs in the abdominal cavity and the sinuses ofthe brain. By the use of organic compounds ofiodine he can make visible the lungs, the airpassages, the interior of the uterus, the spinalcanal, the pelvis of the kidney and the urinarytract, and, by the use of a radioactive substancecalled thorotrast, the tissue of the reticulo-endothelial system including the spleen and theliver. Cerebral angiograms may also be taken bymeans of this substance for the prupose of localizingbrain tumours. Modern fluorescent screen enablesdigestive movements, heart beats or lungmovements to be watched or cinematographed.Placenta prævia has also been brought within thepossibilities of radiological diagnosis.

Perthes has found that the intensity of radiationfalling upon a surface perpendicularly is inverselyproportional to the square of the distance of thesurface from the focal point of the target of thetube. The cumulative effects of Roentgen rayswere also studied by him, as also the fact thatharder X-rays produce a longer latent period. Heobserved that X-rays as ordinarily used arecomposed of mixed rays and filters were firstintroduced by him to cut off softer rays.

By the standardization of physical and biologicaldoses and the proper intervention of filters thedangers of radiation therapy have been greatlyreduced in recent times. Today with the improvedtechnique and modern equipment we can safelywork with rays of much higher intensity thanbefore without the slightest danger to man, mindand machine.

X-ray and radium therapy is bidding fair todisplace the knife in the treatment of certain formsof cancer. The response of tumours to radiationdemands wide study, each type of tumour having adifferent response, both clinically and histologically.By contrasting the sensitivity of growth with thatof skin—in both cases using the minimum lethaldoes as the standard—it has been possible to placetumours in different groups—radio-sensitivetumours, epitheliomata, adenocarcinomata andradio-resistant tumours.

Views on radiation treatment have changed todayand the single massive does of X-radiation,advocated in former days, is now replaced by aseries of smaller doses spread over a period oftime. The real problem of malignant disease lies inthe treatment of glandular metastases. For deeperlesions and gland areas we turn either to

1. X-rays which, excited by very high and ever-increasing voltages, tend to approach g-rays inquality, or to

2. large quantities of radium placed at distancesremote from the skin with the object of obtainingthe large depth dases possible with X-rays.

The growing belief in the efficacy of“teleradium” is indicated by the rapidly increasingnumber of large radium units being set up in theworld. It is to be hoped that with advances in thetechnique to teleradium and deep X-rays, betterresults may be obtained in future in the treatmentof cancer.

With improvement in apparatus and techniqueit has now been possible to distinguishradiologically the softer tissues of the body formeach other and the extent of invasion of newgrowths in them.

Though the explanation of chemical, physio-logical and morphological changes in normal andpathological tissues on irradiation is very scanty in thepresent state of our knowledge, yet there is a promisingbeginning as will be seen in recent developments onthe subject, especially in great laboratories in America,such as, the Mayo Clinic, Rockefeller Institute and theforemost medical schools. Special radiosensitivenessof cells has received emphasis in the hands ofDesjardins and others.

I may just say a word about the application ofX-rays to genetics. The origin of the new genes bymutation has been shown to be speeded up at leasttwo hundred times by X-rays.

Radium and Artificial Radioactivity

Lawrence of the University of California has

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succeeded in producing a radioactive form ofsodium from common salt, having remarkableproperties. This will enable sodium to be introducedsafely into the animal system, and is likely to be ofgreat value in medicine, He has announced that itwould soon be possible to produce cheap radiumfor commercial purpose and it has been claimedthat the discovery of artificial radioactivity inelements, otherwise inactive, will be of greaterimportance in medicine than the discovery of naturalradioactivity. Proto-actinium may have valuabletherapeutic properties. The new artificially producedradioactive elements may before long replace thecostly radium for therapeutic purposes and for thestudy of many biological processes.

Light Therapy and Electro-therapy

I have already mentioned the uses of theultraviolet and infrared rays photography as an aidto Medicine. They have also had therapeuticapplications in modern times. It is generallyconsidered by many authoritative observers thatultraviolet and infrared rays modify each others’effects on the living organism, according to theirseveral proportions in combined relations.

Short-wave and ultra-short wave therapy is oneof the latest branches of physical therapy. It is notmy intention to give an account of the variousbranches of electro-magnetic wave therapy. I shallonly very briefly refer to short-wave and ultra-short wave therapy.

The better results claimed for the very powerfulshort-wave instruments may be partly explained bythe greater capacity effects obtained in the tissueas the wave-length decreases.

It has been inferred that the more delicate thestructure, either of cells or micro-organisms, thegreater would be the disruptive action of short-andultra-short electromagnetic vibrations.

Though some observers hold that there is veryslight or even total absence of appreciation of heatduring the administration of a short-wave treatment

which may be followed by most satisfactory results,yet many attribute the whole action of ultra-shortwaves to the heat action. They state that experimentswhich have been carried out in vivo and in vitroshow that they have no specific action on bacteriaor tissue-cells and they have observed that bacteriasoaked on to a piece of gauze, placed under theskin of animals and exposed to ultra-short wavesand undamaged with lethal dose of ultra-shortwaves, and there is no change in fragility,sedimentation rate, and bactericidal power of theblood following exposure in vitro. They concludethat the action of ultra-short waves appears to becoagulative necrosis and extreme vaso-dilatation,which is similar to the action of diathermy high-frequency current of about 300 metres.

Whatever may be the exact mechanism by whichshort-wave or ultra-shorts waves show theirtherapeutic effects, there is no doubt that the adventof short-wave therapy opens up a field of treatmentof great possibilities hitherto totally unexplored. Ithas been held by some that the outstandingdifference between long-wave diathermy and short-wave therapy is the peculiar effectiveness of theultra-short wave in infections and in conditions ofsuppuration, where diathermy is definitelydangerous, that this quality belongs only to theultra-short waves of from 6 to 3 meters and thatbetween 15 and 30 meters there is only heat effect.

I shall not detain you by discussing the principlesof diathermy or the various forms of light therapyas they are beyond the limits of my thesis. It maybe said in brief that the rays of different wavelengthsand frequencies have come into modern practicefor the treatment of many diseases with excellentresults.

I hope that advances in photo-dynamicsensitization may in future lead to the discovery oftherapeutic substances which will be activated bythe short infra-red, luminous, red, and orange raysand act as sensitizers in the presence of blood-serum.

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When we survey the immense development inthe use of light waves, visible, ultraviolet, X-rays,and others in the investigation of structures and thetreatment of disease, with their future potentialities,it may be said without conceit—truly we arebeginning to see through a glass less darkly.

Bragg-Paul Pulsator—Artificial Respiration

Among the many useful apparatus which Physicshas placed at the disposal of Medicine in recenttimes for therapeutic purposes, I would like tomention here as an example, one devised forprolonged artificial respiration. There has been oflate an increased scientific interest in artificialrespiration methods. The one mentioned here hasbeen designed by Bragg and Paul and is known asBragg-Paul Pulsator. It shows the triumph of aartificial apparatus in maintaining one of the mostvital functions of the body, i.e., respiration, whichit is unable to perform due to a physical disability.There are some conditions, arising both fromaccident and disease, in which long-continued andregular artificial respiration is required. Bragg-Paul Pulsator consists of a pulsator whichrhythmically inflates an air-bag encircling the bonythorax of the patient below the armpits to a definiteair pressure as indicated by a manometer. Althoughthe lengthy need of an artificial respiration apparatusis rare, still it must prove very satisfactory in caseswhere its use is indicated. In one case a patient hadartificial respiration on this principle for over twoyears with satisfactory results.

GEOLOGY

The Geologist has discovered numerous spasand springs which refresh and renovate the humansystem today. The schemes of drainage andirrigation, and of water supply in general, that arebound up fundamentally with the health of mankind,the public health departments of civilized countriesall the world over, look forward to the aid of thegeologist. It is perhaps known to you that in onesection of a town in an English county, the effects

of calcium deficiency among most of the childrenwere traced by the geologist to the poor-in-calciumdrinking water of the clay zone area of the town.In the investigation of silicosis, a disease prevalentchiefly among miners, we find the physicianworking hand in hand with the geologist who hasbeen charged with the identification of the minuteparticles of mineral matter that find their way intothe lungs of the miner. The application of thegeologist’s methods has led to the detection ofchina clay and talc in adulterated food products. Inthe investigations of the dust problems in bigcities, the aid of the geologist is indicated. Endemicgoiter has been traced to iodine deficiency indrinking water. Excess of iron may give rise to anendemic disease, the “so-called mottled enamel” inman and some animals in certain places, such asAlgiers, Tunis and others.

PSYCHOLOGY

Mental disease, before the advent of Psychologyin Medicine, was a terra incognita. Recentreasearches in psychology have thrown a flood oflight on the domain of Psychiatry. The significanceof a mental approach to the problems of psychologyhad long been misunderstood, but today not onlywe have a better understanding of mental diseasesby means of the psychological method but also weget extremely encouraging results in the treatmentof such disorders and psycho-therapeutics has founda place in the armamentarium of the medical men.

I do not know whether one would agree that theservices of Freud to knowledge have been as greatas those of Darwin, and whether Freud’s extensionof the idea of sex will stand the test of time, butthere is no doubt that one of the greatest contributionsto medical psychology in recent times is the conceptof the dynamic unconscious. To trace the genesisof mental disorders one has to dive deep intounconscious region of the mind. That the mind hasan unconscious component was not at first acceptedby physicians trained in the orthodox school.

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Awareness is not an essential characteristic ofmental process. Significant changes may go on inthe mind without our being conscious of them. It isin this unconscious region that the roots of mentaldisorder lie.

It has been recognized that the explanation ofmany fully conscious occurences — which hadprevioulsy been left unexplained as simply coming“out of the blue”—might be found in this dimmerregion. It was from this region of the mind LadyMacbeth uttered “Here is the smell of the bloodstill; all the perfumes of Arabia will not sweetenthis little hand”.

Attention has now been concentrated upon whatmight be described as the border region betweenthe psychical and the physical. In fact, some of thepsychologists—the behaviourists—might be saidto have gone over the border-line altogether andmerged the psychical in the physical, but thosemedical men who have come back again to theirown special domain via psychology of this kind,have been disposed to view the physical from thepsychological point of view. Today a firm alliancehas been concluded between Medicine andPsychology, and medical men have more and morefully recognized the necessity of studying the mentalhistory of their patients. Much work was beendone in the study of the unconscious in manyinstitutions., notably, the Nancy School. Theaftermath of the great war was seen in many casesof nervous debility which are treated in famousclinics e.g. of Hadfield and others. The power ofthe instincts and the inhibition of the latent forces,of their release, as well as the phenomena offatigue, have been thoroughly studied to the greatadvantage of medical practice and efficiency.Modern psychologist and medical men are payingmore and more attention to the aspect ofpsychological investigation of the bodymind knownas sublimation of instincts and emotions. Manymedical men at the present-day devote themselvesas specialists to the practice of psychotherapy.

It may be that the theories of genetic inheritanceperhaps apply partially at least to mental characters.It is important, as Dawson has stated, that the lattershould be distinguished and the manner of theirinheritance traced out. Much work is being done inrecent times for diagnosing and measuring unitarymental traits with the view of satisfactorily studyingthe genetic basis of mental traits. In this respect thecooperation of the medical man, the psychologistand others is imperative.

To some psychologists there is nothing morenoticeable in recent years than the rapprochementbetween Medicine and Psychology due to afundamental cause. They hold that partly thisfundamental cause is that the ultimate character ofreality is mental, and that the days of scientificmaterialism are gone which ruled over advancingthought in the last quarter of the nineteenth century,under the leadership of Huxley, Spencer and thosewho thought with them. The attempts to explain allphenomena in terms of matter, which were invogue half a century ago, have been considered tobe unsatisfactory by those who hold that mind isno longer to be either ignored or compelled to waitin the ante-chamber assigned to non-descriptcharacters called epiphenomena.

The effect of this has been seen amongst medicalmen and has made them more disposed to admit aclose association between mind and matter. It isrecognised by them that mental factors are amongstthe most important, and that these may be treatedwith a considerable prospect of success.

In the present-day, it is all to the good that manshould be treated as a unity of body and mind,instead of being handed over as it were to rivalpractitioners—to medical men on the one hand,and to the psychologists on the other. Thereforethe alliance between Medicine and Psychology isto be welcomed. It is fitting that medical men.

‘Should study passion; how else cure mankind.

‘Who come for help in passionate extremes.’

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‘Who could express with more prophetic vision

this subtle relationship

better than he who was both poet andphysician .....

for in truth the mind is undissociable for whatit contemplates.

MATHEMATICS

Bayliss once remarked that the ultimate aim ofall Sciences is to express in a mathematical formthe discoveries that have been made in them.Though it is a difficult problem to express all factsin medicine in a mathematical equation, yet theapplication of Mathematics to medicine is increasingin recent days.

Within recent times nomograms or alignmentcharts have been constructed for finding the totalnumber of calories contained in any diet of knowncomposition, for respiratory quotient, and for colourindex of blood. Observers have worked out moreor less elaborate mathematical methods for buildingup a suitable diet for any particular diabetic patient.These has been calculated on a knowledge of theso-called basal metabolism needs of the patient,his body weight, height and surface. The vitaminrequirement of man has been put in a mathematicalformula. The curve of healing of a wound wasdeveloped by Carrel and others during the war.

Various equations and curves have beenformulated in connection with disease, such as theperiodicity curves of epidemics, theory of happeningsin its application to epidemic and endemic diseases,of life tables and of carriers of disease. The latter isof special value in India. I need not dilate upon themin detail here any further.

It has to be remembered that the application ofMathematics to medicine has its limitations. Allpatients do not react in exactly the same way andsome subjects appear to be beyond the control ofmathematical formula. The various tables andcurves used in modern work are no doubt of greatscientific interest but they have their limitations.

Undetermined factors exist in more exactsciences like Physics and Chemistry. It is thereforeto be expected that the same might be still moremanifest in the Science of Medicine which has todeal with diseases of the body and mind and inwhich there are many complicated andundetermined factors to operate. In investigating aScience which deals with diseases of the mind wehave to employ our mind to tell us about itself, andthis we must do as a necessity, since we have noother instrument with which to conduct ourinvestigation. Mind is therefore both executive andjudicial, it is both judge and jury in its own cause.In such a Science there must be manyundeterminable factors.

CONCLUDING REMARKS

Forecast

From what I have stated, it is clear that thevarious Sciences can be of great service ofMEDICINE. Some of them have contributed verysubstantially to the relief of human suffering fromdisease. They can obtain valuable findings for theclinician in diseased conditions which may behelpful to him, but the responsibility finally restswith him as to how to act upon their findings. Thisshows the great importance of what is called todayClinical Science. Anatomy, the Science of structureof the body, Physiology the Science of functionand the meeting ground of Physics and Chemistryin their application to problems of health anddisease and Biochemistry the Science concernedwith the chemical processes underlying the activitiesof living matter, can be of great service to theclinician. In recent times, the need for increasedapplication of Physics and Chemistry to Medicinehas grown with tremendous rapidity.

“The aim of the medical science is to controlsuffering, to prolong life and to keep mankind in astate of vigorous health”. The science ofMEDICINE, which was once mostly limited to thestudy of disease, is now concerning herself with

33


the study of health, by the increasing knowledge ofnutrition, environment and eugenics. Though somemay say that Methamatics or Metaphysics is thequeen of sciences, yet I hold that MEDICINE isstill another or more properly speaking, she issupreme among the queens of the Sciences. I hopethat all your Sciences will serve her duly and toher best advantage, so that the person who professesher may give more and more relief to his patientsin the mitigation of their sufferings by the lightthat he gets through your agency.

The newer conceptions of life advances in recentyears have opened our minds as to the nature of theliving organism. Evolutionally, we see life adaptingitself to many varied conditions and to considerableextremes of environment. The most versatile is manwho is found from pole to equator. His capacity foradaptation has been achieved an can be maintainedonly by the possession of an almost changeless andconstant medium, the blood, which acts as the directenvironment of his most valuable possession, namely,the brain. Man’s whole body mechanism is organizedin order to preserve “La fixite de milieu interne” asit was called by Claude Bernard. One hears inPhysics of the so-called constants of nature such asspeed of light or Planck’s constant, but surely thelevel at which the essential blood constituents aremaintained may also with justice be called thesupreme constant both of and for Homo sapiens. It isno passive state; dynamic equilibrium holds itwhere it is, and preserves for us the sole conditionfor the progress of the development of man and hiscivilization. And when disease sets in, MEDICINEcomes to his aid to maintain this constant or else hemay deteriorate and die.

“Yes and how delicate. Life’s mighty mystery.... all its self propagating organisms exist onlywithin a few degrees of the long scale rangingfrom measured zero to unimagined heat ...... Norcould they endure were’t not that by a secretmiracle of chemistry they hold internal poiseupon a razor edge that many not even be blunted,lest we sicken and die.”

In million million years, the earth’s temperaturemay be reduced to such an extent it would be rashto predict how such a fall of temperature mayeffect man’s life. What then will be his bloodconstant? I can not say. If then he lives, MEDICINEwill still be called upon to mitigate the diseasesthat may attack man in the dim distant future.

It is immateral for the purpose of my thesiswhether the universe is fast proceeding todissolution and death, by the rapid increase ofentropy, according to the laws of thermodynamicsand along with which man will meet the same fate,or whether creative evolution will lead in millionsof years to the production of superman with newsuperkingdoms which are beyond the limits or ourimagination. But whatever that may be as long asman exists, MEDICINE will have to deal with theinfirmities of the degenerate man or the superman,as the case may be.

The discoveries in MEDICINE and its ancillarysciences in recent times have been phenomenal. Wedo not despair and say what Richet has said in the“Impotence of man” that “with the aid of a few drugs,we succeed in minimizing for a time a few triflingmorbid phenomena which cause us discomfort”. AsDu Nuoy has stated, a day may come when themethods of treatment generally used today, willappear to us gross as do now the methods of Mr.Purgon, of Moliere’s “Malade imaginaire”.

Who knows what the future of MEDICINEafter ten or hundred thousand years will lead to.Perhaps, in eons to come, it will be the conquest ofold age and in complete immunity from disease.Could we not dream of a day when one shall see“all disease quenched by Science, no man halt ordeaf or blind”. What sort of bodymind will then beevolved, I shall not speculate to say.

But man’s distiny may take a different anddarker turn in future. Newer diseases worse thancancer or plague or the worst virus disease oftoday may attack him in the future. Circumstances

3

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over which man may have no control, may lead tothe deterioration of his body and mind resulting inthe creation of newer maladies. These may renderthe task of MEDICINE more and more difficult.Catastorphies may occur in the world andcivilization may regress. Such a cataclysm may bea geological one or due to a devastation world warmuch more terrible than is ever known in historyor to a fatal epidemic which may spread from onepart of the world to another with terrific rapidity oras Spengler and others hold, it may be a “cyclicprocess passing through the alternate periods ofgrowth and development on the one hand anddecay on the other, as evidenced by the variousancient civilization of the world which have nowceased to exist. But whatever that may be,“MEDICINE and civilization will advance andregress together” for all times to come.

The condtribution of MEDICINE to civilizationaided by the other sciences is great. A healthybody means a healthy mind, and such minds areless likely to cause internal or external strife. Thereis no doubt that a large part of the greatly increasedcomfort and safety that we enjoy today is the resultof the phenomenal advances that have been madein the medical sciences in recent times. I wouldsay with Howard Haggard ‘And finally thephysician”. He rightly holds that “Medical historydiscloses the forces that have made our moderncivilizatoin possible.... That modern medical scienceis today one of the strongest forces operating forhuman betterment—it is the religion of healthychildhood, manhood and womanhood”.

In spite of recent occurrences, will not a dayever come when one may say that.

“The war-drum throbb’d no longer,And the battle-flags were furl’dIn the Parliament of man, the Federationof the world?”

I conceive such a day may come and thatslowly and slowly, physical warefare will giveplace to warfare of the intellect. There will be no

jealousy, and superirity or inferiority complexeswill case to exist. Slowly and slowly, man will livenot by the destruction of the lives of his neighboursand seizing their property, but by making everypart of the world healthy and habitable by improvedmethods of hygiene and thereby minimizing theneed for the control of population, the overgrowthof which has been considered to be, to a greatextent, responsible for many wars of the world.There will be no inadequacy of food supply whichhas led to many wars of aggressive in the world.

With his conception of the horrors or war, theMEDICAL man is a fit person for preaching thegospel of abhorrence of war. He can depict to youscenes in which, with the Sisters of the Red Cross,he picks up the wounded from the battlefield in themidst of most frightful agonies and tries to extracta bullet from the heart or the shattered brain or totransfuse his own and his assistant’s blood into thevein of a dying soldier when the guns are roaringin the battlefield, irrespective of whatever camp hebelongs to. I hope that in every peace league of theworld, the MEDICAL man may have somerepresentation, not as a diplomatist, but as onewhose motto is that the well being of mankindthroughout the world should be effected withoutany distruction of a life. A day may come when thewar mentality of individual statesmen, which maylead to war psychosis among the people, will beanalyzed and corrected by the psychiatrist and thepsychologist. In this connection one welcomes therecent manifesto issued by the Committee for WarProphylaxis of the Netherlands Medical Association.

Could we not dream of a day when economicdepression and unemployment will be ended, thanksto the increasing scientific development of newerindustries and newer field of frutiful work, andthere will be leisure to enjoy the beautiful fruits ofthe earth that Science may provide, and when manrelieved from toil by his mastery over the greatsources of power in Nature, will have theopportunity of being richers, happier, healthier and

35


freer than even before. I conceive that this ispossible if, as Jeans has suggested, there is aproper balance between labour-saving devices andindustry-increasing discoveries. MEDICINE, whichincludes preventive medicine may help here in itsown way be eradicating and preventing diseaseand thereby increasing man power and the capacityof the people for work, for taking part in thedevelopment of newer industries and agriculture,and for defending the country in times of need.

If one studies the evolution of man, one findsthat his intellect is growing out of proportion to hisbody. The caveman was perhaps stronger in bodilystrength than the strongest man of today. Is itpossible that man’s body may become smaller andsmaller, his fierce, destructive, and other baseinstincts and feelings may be sublimated and hismind grown more and more and in the eons tocome become independent of matter. Even thenMEDICINE will minister to the “mind diseases” inwhich perhaps Physics and Chemistry may haveno part to play. Or it is possible that after reachingits zenith of development, the mind may begin toregress and body begin to grow and thus a perpetualcycle may continue in which body and mind mayalternately undergo growth and decay for eternaltime? Or it is possible that, finally, the mind ofman may merge into the eternal and infinite Mindand feel “Soham” i.e., I am He.

If in dealing with my subject, I have sometimesdrifted to a mystic region, I would justify myselfby repeating what Einstein said “It is enough forme to contemplate the mystery conscious lifeperpetuating itself through all eternity, to reflectupon the marvelous structure of the universe whichwe can dimly perceive, and try humbly tocomprehend even an infinitesimal part of theintelligence manifested in nature.”

Some of you perhaps say that the progress ofscience does not afford any evidence that thebehaviour of living matter is governed by anyother than the laws of Physics and Chemistry

(Bertrand Russell). But who can deny whatGowland Hopkins once said that “there may be yethigher levels calling for discussion in quite differentterms”? The mechanism of life can not be explainedby the Physics and Chemistry of today, thoughperhaps some of it may be explained by some ultraphysico-chemical laws that may be discovered inthe future. Even then one may not be able to saywherein, from the radiations to the bodymind,enters the breath of life.

The bodymind of man is the finest product ofthe universe even when compared with the mostmagnificent of the stars and the nebulæ. Man’sappearance cannot be regarded purposeless oraccidental or as a sign of disease. He has discoveredthe laws of motion and relativity as well as ofradio-telegraphy, radio-telephony, aviation andtelevision. He unfolds the constitution of the starsand the nebulae, millions and millions of milesaway from the earth. He calculates the weight andtemperature of the stars and determines their ages.He finds out the constitution of the atoms anddiscovers the cosmic rays. He smashes the atomsand produces new radioactive elements. Hetransforms one element into another. He may, oneday, be able to determine the Mathematics of theatom by means of his calculator. He tries to findout when and how primordial life came intoexistence. He tells the story of the oldest man whoexisted in the earth a million years ago, and givesthe history of his evolution. He discovers thechromosomes and finds out the structures that areresponsible for heredity. He discovers and dissectsthe micro-organisms of disease, and finds thedefensive mechanism against their attacks. Hestudies the specific carbohydrates and proteins,and tries to discover the structure of the virusesand the bacteriophage. He discovers the treatmentof diseases once considered incurable. He recordsthe electric changes of the brain cortex of man invarious cerebral state, and may one day recordhuman thoughts on a sensititive plate. He studies

36


the endocrine glands, and synthesizes theirsecretions. He may one day be able to influencethe sex of the embryo at his will. He cultures theorgans of the body and studies their growth invitro. Ponce de Leon did not perhaps search for theimpossible and unattainable when he sought thefountain of eternal youth, for man may one dayconquer old age, disease and death. Though I darenot say what the “final secret” is likely to be, yetthe bodymind of man must be today theconsummation of the work of the Great Design. Inthis most complicated machine in which, it may besaid, “matter, life and mind translate roughly intoorganization, organism and organizer (Smuts)”,MEDICINE tries to give the healing balm to act asa powerful agent for the maintenance of harmonyand strength when disease sets in.

Let me now tell you what MEDICINE may doin other directions.

In the present day one cannot fail to be struckby the great increase in the varied functions thathave come to be regarded within the province ofthe MEDICAL man. “He has in large part takenthe place of the parson. He has madeencroachements on the functions of the lawyer, thelegislator and the judge, of the schoolmaster, thearchitect and the statistician. He has assumed someof the duties of the parent and guardian, while eventhe soldier and the policeman are to some degreeunder his control. In the ordering of their lives, andeven in the regulation of their vices and the reformof their shortcomings, men and women are far

more willing to seek the advice and help of themedical man than once they were. The reason is,without doubt, that his advice is much moreworth having than it once was” (Singer).

Lastly there is that wonderful influence of themind of the true PHYSICIAN upon his patient’sbody and mind. The influence has been wellexpressed in the following words “Nothing cantake his place—not propriest nor minister nor allthe clinics that Science can provide. There is arapport and as a confidence between him and hispatient which has been known to accomplishmiracles.” If this force exists, I call it “person-alitism”, the force that mind may exert upon mind,body and disease.

Thus we see that the functions of the MEDICALman are manifold. Still with all humility he says

“If I can ease on life its aching

Or brush away one pain

If I can stop one heart from breaking

I’ll not have lived in vain.

If I can help one failing brother

Into his strength again

If I can calm one fretted mother

I’ll not have lived in vain”.

I am afraid my address is “not much better-thanthat noise or sound which musicians make whilethey are tuning their instruments.... So I have beencontent to tune the instruments of the Muses, thatthey may play that have better hands” (FrancisBacon).

DOYOU KNOW ?

Q1. Where do you have four seasons, each 40 years long ?

Q2. How long did it take Victoria Memorial Hall to build?

Q3. What is the full form of A.M.?

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DEMYSTIFYING DYSLEXIA

��

Dyslexia is a major learning disability which impedes academic achievement and diminishes theself-esteem of its victims. The basic problem is trouble in reading letters, words and othersymbols. Its causes are mainly biological. However, the disorder can be managed effectively bymultisensory learning and special computer programs.

S even year old S. had a trying time at

school. His class-teacher was fed up with

his futile struggles to read and spell properly. Afterall, she was doing her best to teach. Or, shethought so. The boy’s parents were summoned tothe Principal’s office and told in no uncertainterms that the boy was mentally challenged. Theparents felt devastated. But they could sense thattheir son did not lack intelligence, the problem laysomewhere else.

Refusing to give up, they knocked at the doorsof reputed clinicians. Finally, a competent childpsychologist diagnosed dyslexia and suggestedremedial measures. So there was light at the end ofa dark tunnel for the boy in distress.

NATURE OF THE DISORDER : DYSLEXIA

Not many people know about the disordertermed as dyslexia. The word ‘dyslexia’ originatesfrom two greek words–“dus” and “lexis” which incombined form mean difficult speech. Dyslexia isjust that. It is a disorder manifested early in life inwhich reading performance is much lower thanthat expected considering the person’s level ofintelligence, age and duration of schooling1. Apartfrom severe problems in reading, there aredrawbacks in other aspects of linguistic ability as

* Human Development, Department of Home Sciences,Calcutta University, Kolkata-700027.

well. Dyslexia is, therefore, a learning disabilityas it has adverse effects on the person’s learningand achievement at school. In fact, it is the mostprominent of learning disabilities plaguing school-students. It seems to occur in equal frequencyamong boys and girls1.

CHARACTERISTICS OF DYSLEXICS

Persons suffering from dyslexia are known asdyslexics. They display the following generalcharacteristics :

(i) Possession of near-average to higher thanaverage intelligence.

(ii) Normal vision and hearing.

(iii) Trouble in processing sensory informationparticularly in making sense of printed words.Jumbling of letters of alphabet while readingwords are common e.g. reading the word“SUN” as “SNU”.

(iv) Lack of concerted effort in performingacademic tasks.

(v) Loss of concentration in studies at slightestdistraction1.

(vi) Haphazard approach towards learning tasks.

(vii) Inability to use memory strategies likemastering lengthy learning materials part bypart, revising regularly, etc.

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(viii) Weakness in memory capacity for verbalmaterials like meanings of words.

(ix) Poor performance in examinations1. Thiscomes as no surprise because at primary-school, tests of reading and writing (includingspelling)–abilities are integral parts ofassessment. Besides, poor reading skills mayimpair comprehension of what is being readthus hampering performance e.g.reading theword “GEL” as “LEG” may come in theway of understanding the properties of gel.Inability to read arithmetic problems andnumbers properly also impede performancein mathematics.

(x) In the face of bad grades, rebuke and ridicule,feelings of anxiety and guilt mount.Confidence and self-esteem go down1.

These characteristics describe dyslexics ingeneral ways. But for definite diagnosis of thedisorder, specific symptoms have to be delineated.Therfore, clinicians have agreed upon certaindistinct symptoms of dyslexia.

SYMPTOMS

(a) Speech and language difficulties beginin childhood. Inadequate phonologicalawareness is most prominent. So dyslexicsare deficient in the ability to recognizedifferent sounds in spoken language. Theknowledge about the relationship betweenwritten and spoken parts of speech is limited.Dyslexics do not realize that words consistof smaller units of sound which are denotedby printed letters.

(b) Problems occur in recall of verbal materials(e.g. words, sentences, poems, stories, etc.)after short intervals of time.

(c) Difficulties in proper ordering and sequencingof letters, numbers, words, etc2, for instance,450 may be read as 054. The sentence,

“Open your book” may be read as “Openbook your”.

(d) Clumsiness e.g. a dyslexic child may not beable to copy from the blackboard properly.He or she may start copying from the topportion of the blackboard, suddenly changehis or her mind and start to copy from thebottom of the board. In the process, much ofwhat is written on the board is missed out.

(e) Lack of consistent hand-preference. Almostall of us either exclusively use our right orleft hand for writing. But dyslexics usuallydo not have fixed hand-preferences. Theysometimes use the right hand and sometimesthe left for writing. The result is inefficiency.Their work is slow, untidy and thehandwritings are mostly illegible.

(f) Frequent reversal of letters of alphabet like bfor d, p for q etc. while reading and writing.

(g) Poor verbal fluency2. Besides being poorreaders, they suffer from halting speech,unclear pronunciations, etc.

If we consider the symptoms, we would realizethat such behavior patterns are not uncommonamong children from impoverished, educationallybackward families. But such children are notnecessarily dyslexics. They may be perfectly normalyoungsters who just need remedial training tocompensate for disadvantaged backgrounds. Butthis situation presents a curious problem-what if afew of them are actually dyslexics ? It was foundvery difficult to diagnose dyslexia amongdisadvantaged children3. However, psychologicaltests have been devised to assess the disorder asaccurately as possible.

ASSESSMENT

Two of the popular psychological tests areDyslexia Early Screening Test and DyslexiaScreening Test. Both are published by the

39


Psychological Corporation. A computerizedassessment program titled, “Cognitive ProfilingSystem” produced by Chameleon Educational isalso used.

Different assessment devices may varysuperficially but essentially each assesses the skillsconsidered important for the diagnosis of dyslexiaviz., memory, phonological awareness, auditorydiscrimination and verbal fluency3.

CAUSES

Researches are on to unearth the causes ofdyslexia so that effective remedies can be planned.There is some evidence that genetic componentsmay be involved. This is becuase frequently thedisorder runs in families. Most cases of dyslexiaare thought to result from neurological defects inprocessing of speech sounds. Important systemsfor reading alphabetic scripts are located in theleft hemisphere of the brain. In most individuals,the left hemisphere is larger in size than the rightone. But this may not be the case for mostdyslexics3. Besides, the organization of the righthemisphere is different for dyslexics4. Theseconditions may have damaging effects on readingand speech skills.

Investigations reveal that alphabetic processingis generally associated with Occipital, Temporaland Parietal areas of the brain5. Dyslexic childrendisplay lower than noramal activation in Temporo-Occipital areas which may also explain their poorreading skills6. Such children with mathematics-difficulties may show neural anomalies in theactivation of the Temporo-Occipital system(specializing in alphabetic-speech linkagesnecessary for reading) but not in the activation ofthe Parietal and Premotor number systems(specializing in understanding of mathematics)7.So it seems that these children actually havepotentials to grasp mathematics but reading andlanguage difficulties of dyslexia are preventingthem from performing satisfactorily in mathematics.

Researchers have reported that persons withdamage to the Angular gyrus (a region of the brainlocated at the border of the Parietal, Occipital andTemporal lobes) may be able to communicate andunderstand speech but can not read properly. As aresult, they suffer from dyslexia8. So, currently itappears that biological factors play signifiant rolesin the causation of dyslexia. The pattern of causesprovide clinicians inklings about the kinds ofremedies which would prove effective.

REMEDIES

Dyslexia does not fade away. Remedial traininghelps to manage it so that it does not interfere withacademic performance. Such training is impartedindividually or in small groups. The venue couldbe any school or a specialist centre for dyslexics9.

Multisensory learning is the most useful remedywherein the child learns the names, sounds andshapes of letters by involving a number of sensemodalities—hearing, vision, touch and movement.For example, the child may be shown the letter‘M’ in print, taught it’s pronunciation, directed totrace it’s shape using his or her fingers,demonstrated the finger movements involvedin writing it and made to practice the same.Spellings of words, sentence constructions andtheir pronunciations are taught painstakinglyin a similar fashion. To increase children’sawareness of basic speech sounds of languages,listening and rhyming games have been includedmore in school lessons9.

Dyslexics also benefit from computer programssuch as “Texthelp !” It provides a host offacilities in several languages. As a person types,he or she receives speech feedback by letter,word, sentence or block of text. SpeakingSpellchecker and Speaking Thesaurus facilitiesrender necessary help. Even the internet pagescan be read aloud9 while the dyslexic watches thetext and listens carefully. All these activities haveto be supervised by experts in remedial learning

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so that dyslexics receive valuable phonologicaltraining from these programs.

Simultaneously, counselling of dyslexics haveto continue. It can relieve them of feelings ofanxiety and guilt, boost their confidence andenhance their self-esteem.

REFERENCES

1. D. E. Papalia, S. Wendkos Olds andR. Duskin Feldman, Human Development,8th ed., Mc Graw-Hill, Boston, pp.357-358, 2001.

2. J. Elliott and M. Place, Children inDifficulty : A Guide to Understanding andHelping, Routledge, London and New York,p. 195, 1998.

3. ibid, pp. 196-204.

4. S. Heim, C. Eulitz and T. Elbert, EurJ. Neurosci, 17, 1715-1772, 2003.

5. K. R. Pugh, W. E. Mencl, A. R. Jenner et al.J Common Disord, 34, 479-492, 2001.

6. B. Shaywitz, S. Shaywitz, K. Pugh et al.Biol Psychiat, 101-110, 2002.

7. U. Goswami, Brit J Educ Psychol, 74, 1-14,2004.

8. C. T. Morgan, R. A. King, J. R. Weiszand J. Schopler, Introduction to Psychology,7th ed., Mc Graw-Hill, Singapore. 71,1987.

9. J. Elliott and M. Place, op. cit., pp 205-211,1998.

DOYOU KNOW ?

Q4. What is the name of the first test tube baby ?

Q5. What length fo tunnel can a more dig in the earth per day ?

Q6. Which reptile can live happily with one good meal a year ?

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PHYSICO-CHEMICAL NATURE OF DRUG-NUCLEIC ACIDBINDING

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Drug-nucleic acid binding ushers a new area of research with therapeutic application. The differentsteps of drug action, principles of different techniques used earlier for minitoring drug-biopolymerinteraction, mode of binding of the drugs with nucleic acids/oligonucleotides and their mechanism ofaction with special reference to different therapeutic application have been discussed.

LINTRODUCTION

ife saving drugs of various categories (e.g.anti-cancer, anti-tumor, antiviral, anti-

pyranosomal, anti-biotic, anti-angiogenesis, anti-inflammatory, anti-coagulating, etc) have proveduseful in the treatment of a wide variety of humanmaladies and, therefore, have lengthened humanlife. In a mechanism based drug design effort, themost common targets for interrupting a diseaseprocess are enzymes, receptors, RNA, DNA andproteins. Interaction of different types of drugswith these biopolymers deserve specialconsideration for achieving the desired goals1. Thebinding of drugs with RNA, DNA or specificproteins controlling gene expression is of primaryimportance in controlling the efficacy of the drug.

MODELLING DRUG-NUCLEIC ACIDINTERACTION

A number of drugs are believed to mediatebiological effects through specific interactions atmembrane bound extra-cytosolic receptors or bydisrupting membrane fluidity in a non-specificmanner. Other drugs are known to enter the cytosoland the nucleus to exert their action by interactingwith specific macromolecular targets. Nucleic acidsand proteins are generally important targets for

such drugs. The overall action of drugs aredependent upon the following factors :

(i) interaction with macromolecular hosts,(ii) transport to the site of action, (iii) transportacross the cellular plasma membrane, (iv) absorptioninto cytosol and metabolism and (v) passing throughnucleolar membrane and interaction with genes,chromosomes and their constituents.

The different modes of binding with nucleicacids can be by intercalation, covalent and non-covalent groove binding, charge neutralization/interaction and non-specific interaction. Theintercalators are 9-Amino-acridine, Proflavin,Ethidium bromide, etc. The covalent bindersthrough minor groove are Netropsin, Mytomycin,Anthramycin, etc. Covalent and non-covalentgroove binders exhibit DNA sequence specificity.Non-specific interactions of drugs with nucleicacids usually refer to electrostatic and hydrogenbonding interactions with the backbone phosphatesand or counter-ion or solvation atmospheresurrounding them2-4.

MONITORING OF DRUG-BIOPOLYMERINTERACTION

The drug-biopolymer interaction can be detectedby the following techniques :

(i) Gel electrophoresis, (ii) Electronmicroscopy, (iii) X-ray crystallography,(iv) NMR spectroscopy, (v) Quantitative foot

* Radiation Chemistry Department, Institute of NuclearMedicine & Allied Sciences, Brig. S. K. Mazumdar Road.Delhi-110054

4

42


printing analysis and (vi) Spectro-photometry,Spectrophotofluorimetry, Conductometry, Infra-red spectroscopy, etc.

(i) Gel electrophoresis of different kinds andefficient procedures for labeling and sequencingDNA have been reported5,6. Drug’s specific bindinggenerally begins by selecting a DNA restrictionfragment and labeling it with radioactive 32P,followed by incubation of restriction fragment withdrug of interest.

(ii) Electron microscopic technique is used todetect the intercalation of drugs in the major andminor grooves of DNA. By this process DNAunwinds and hence its length increases. The drug-DNA complex is placed on an electron microscopicgrid on which formvar film and carbon coatingsare done to give support. The drug-DNA complexremains in a lengthwise straight fashion whenadsorbed on a protein film. To enhance contrast,high atomic number elements live Cr, W, Pd, etcare used. The whole drug-biopolymer assembly issuitable shadowcasted and electron micrograph istaken7.

(iii) X-ray crystallography technique requires> 95% purity of final product which is possible tobe achieved by HPLC or gel filtration columns(e.g.sephadex G 50). As crystal growth kinetics isinfluenced by pH, it should be meticulouslymonitored to get a good crystal. Many times minuteconcentration of salts of Na+, Ca++, Zn++, Co++,Ni++, Mn++ etc. are used for facilitatingcrystallization. In this process drawing out of waterfrom the crystal is normally done by vapourdiffusion method.

Bragg equation i.e. nl = 2l = 2l = 2l = 2l = 2d sin q .... (1)q .... (1)q .... (1)q .... (1)q .... (1)is used to determine the crystal structure. TheX-ray beam (of wavelength l) glances the millerplanes at an angle of qqqqq, resulting in a reflectedbeam emitting at the same angle qqqqq due toconstructive interference of the X-rays in the path.Presently, fully automated computer controlled fourcircle diffractometer, using roatating anode X-ray

generator, is utilized. Collected intensity data Ihkl

is related to structure factor Fhkl by

Ihkl = KLP. Fhkl2............(2)

Where K = correction factor for absorption,crystal decay, etc.

Lp = Geometric physical correction factor i.e.Lorenz polarization factor. The crystallographicresidual factor R is given by :

R F FF

0 C

0= −

.......... (3)

Where F0 = observed experimental structurefactor.

FC = theoretical structure factor.

For small molecules R-factor is below 5% andfor macromolecules R-factor is between 15-20%.Thus drug-biopolymer crystal is assessed finallyby X-ray crystallography8.

(iv) By NMR spectroscopy, structuredetermination involves sample preparation, datacollection, 1D and 2D NMR spectra, resonanceassignments, model building and structurerefinement. It requires superconducting high fieldNMR spectroscopy equipment with state of the artelectronics and computer. A magnetic field of9-14T (resonance frequency 400-600 MHz forproton nucleus) is required. Fourier transformedtechnology is employed for rapid data collection.

For obtaining information regarding connectivitythrough bonds, multi-dimensional NMRspectroscopy uses a number of pulse sequences.This is given by 2-dimensional J-correlatedspectroscopy (COSY) and corresponding startingpoint of connectivity pathway is shown by NOSEYspectrum. By both these spectra, all the protonresonances are identified. Then idealized DNA/RNA structures (models) are constructed. This helpsin assigning structure refinement when monitoringby an NMR discrepancy factor (R-factor) becomesnecessary.

R-factor (NMR) = [N0 – Nc]/[N0]....(4)

43


where N0 = observed off-diagonal NOE volumesof all the corss-peaks associated with a givenproton.

A reasonable model should produce an R factorof lower than 20 percent. Thus NMR spectroscopyis an excellent method for structure assignment ofdrug-biopolymer binding9,10.

(v) Quantitative foot printing analysis isessentially an auto-radiographic technique. Here aprobe or cleavage agent is used which containsradio-isotopically lebeled bases (A, T, G, C).

The basic equation for foot printing plot is :-

i(rate)i = Ki(Probe i) (1 – uuuuui) ....(5)

i(rate)i = cleavage rate at cleavage site

Ki = cleavage rate constant at the site .

(Probe i) = concentration of cleavage agent orprobe at the site.

(1 – uuuuui) = fraction of site i not blocked by drugbinding at a site near cleavage site i. The drugbinding site need not be identical to the cleavagesite.

For single hit regime the auto-radiographic spotintensity is proportional to (rate)i. Thisproportionality constant multiplied by Ki gives anew constant.

In case of an isolated drug binding site. thebinding constant Kj at the jth drug site is givenby :

Kj = Cj/(C – Cj)D0 .......(6)

Where, Cj = Concentration of sites j at whichdrug is bound

C = Total concentration of sites j

D0 = Free drug concentration.

As uuuuui = (C – Cj)/C,

1 – uuuuui = [1 + Kj D0]–1 ........(7)

If two drug sites j and k are near one another,an enzyme cleavage site i may be blocked by drugbinding at either site j or site k.

The 1 – uuuuui = (1 – Cj/C) (1 – Ck/C)

=+ +

1(1 K D )(1 K D )j 0 K 0

......(8)

Then, by this thchnique, it is possible to follow

the binding mode of drug with the biopolymerfrom experimentally determinable quantities11.

(vi) Spectrophotometry, Conductometry,Spectrophotofluorimetry, Infra-red spectroscopy.

In vitro studies have been conducted in ourlaboratory by the above mentioned techniques, the

active principles of which are well known. Thiswas to find out interaction of 5-hydroxyL-tryptophan (5HTP), a radioprotector and a drug,

bbbbb-Aminoethylisothiuronium bromide hydromide(AET)-a radioprotector and Dilitiazem-acardiovascular therapeutic drug and a radioprotector

with DNA and Nucleohistone. All three of thesecompounds have the property of binding with DNA,Nucleohistone and the bases of DNA (i.e. A, T, G,C) and some aminoacids12-15. Thus these drugsmodify their course of action physiologically inside

the body. 5HTP has been recognized as a drug intreating depression, fibromyalgia, binge eating

associated with obesity, chronic headache andinsomnia16. All of these three compounds are

capable of modifying radiation-induced damagedto different organs17-20. So, potentially these are

capable of mitigating radiation-inducedcarcinogenesis. Their radioprotecting property was

tested as anti-tumor drugs to mitigate radiationcarcinogenesis.

Table 1 enumerates in short some drugs, theirmodes of action, binding sites and techniques by

which drug-biopolymer interactions have beendetected. The binding characteristics of some of

these drugs, modeling of such drugs and theirdesigning for better efficacy have been reported in

details21.

44


TABLE–1DIFFERENT DRUGS, THEIR MODES OF ACTION, BINDING SITES

AND TECHNIQUES FOR DETECTION OF BIDING SITES

Drugs Mode of action Binding site Techniques

Mytomycin Antitumor agent Binds covalently to DNA in minor X-ray crystallographygroove and alkylate the exocyclic group ofguanines.

Anthramycin Antitumor agent Binds covalently to DNA in minor groove X-ray crystallographyand alkylate the exocyclic group of guanines

CC1065 Antitumor agent Binds covalently to DNA NMR spectroscopy

Bleomycin Antitumor, Antibiotic DNA cleavage agent at G-T Dinucleotide Electrophoresisagent for treatment ofsquamous cell tumours &malignant lymphomas

Neocarzinostatin Antitumor, Antibiotic Binds to minor groove of B form of DNA Spectrophotometry,agent Carcular dichroism

Methyl nitrosurea Anticancer agent Alkylation of DNA through N-7 position NMR spectroscopyof guanine at the major groove

Cisplatin Anticancer agent Binds to DNA in N-7 position of guanine Electrophoresis

Netropsin Antibiotic, Antiviral and Binds to double stranded B form of DNA X-ray crystallographyAntitumor agent at A-T rich site

Distamycin Antibiotic, Antiviral and Binds to minor groove at A-T rich regions X-ray crystallographyAntitumor agent of DNA in the O-2 position of thymine

and N-3 position of adenine

Berenil Antipyranosomal agent Binds to minor groove of DNA through X-ray crystallographyA-T rich regions

Adriyamycin Anticancer drug Intercalates with DNA via the minor Foot printing techniquegroove. Adjacent G-C pair are recognized

Chromomycin Antibiotic, Antiviral agent Binds to double helical DNA Foot printing technique

Mirthramycin Antibiotic, Antiviral agent Binds to double helical DNA by two Foot printing techniquecontiguous G-C pairs

Daunomycin Anticancer agent Intercaltes in the major Spectrophotometry &groove of DNA X-ray crytallography

Olivomycin Antibiotic, Antiviral agent Binds to bouble helical DNA by two Foot printing techniquecontiguous G-C pairs

Nogalamycin Antibiotic agent Binds to regions of alternaive purine- Foot printing techniquepyrimidine sequence

Actinomycin Antibiotic agent Binds to DNA through hydrogen bonding Spectrophotometryand intercalation

b-Aminoethylisothio- Radioprotector Binds DNA by charge Spectrophotometry &uronium bromide neutralization Spectrophotofluorometryhydrobromide

5-Hydroxy-L Radioprotector & drug Binds to DNA and Nucleohistone by Spectrophotometry &Tryptophan charge interaction and intercalation Spectrophotofluorometry

Diltiazem Radioprotector & drug Binds to DNA by charge neutralisation Spectrophotometry & IRSpectroscopy

45


MECHANISM OF ACTION OF DRUGSBOUND TO OLIGONUCLEOTIDES

It was suggested in 1980 that RNA ligandsmight be useful for therapeutic ends. These werenamed ‘Aptamers’ by Ellington and Szostak22. In1990, it was demonstrated23 that large libraries ofRNAs could be screened in vitro for RNA ligandsthat bind T4 DNA polymerase and a variety oforganic dyes. This ‘systematic evolution of ligandsby exponential enrichment (SELEX) starts bygenerating a large library of randomized RNAsequences. This library containing 1014 to 1015

different RNA species fold into different structuresdepending on their particular sequence. The libraryis incubated with the target protein of interestand those RNAs present in the library, thatbind with the protein, are separated from thosethat do not. Different analytical techniques likeaffinity chromatography, immuno-precipitation,electrophoretic mobility shift or filter bindingtechiniques are used for separating the highestaffinity molecules from the pools. The retainedRNAs are then amplified by RT-PCR and in vitrotranscribed to generate a pool of RNAs that havebeen enriched for those that bind the target ofinterest. This process is repeated 8 to 12 times toget the RNA ligands with the highest affinity forthe target protein isolated. The winning ‘Aptamers’are then cloned and sequenced.

‘Aptamers’ act as attractive therapeutic agentsby folding into a three-dimensional structure basedon their nucleic acid sequence to find to theirtargets. Binding of an ‘Aptamer’ is a highly specificinteraction with the ability to discriminate betweenrelated proteins that share common sets of structuraldomains24-27. Some of the important properties of‘Aptamers’ are :

(i) Binding affinity in nanomolar to picomolarrange ; (ii) Entire selection is a chemical processand can therefore targtet any protein ; (iii) It canselect for ligands under a variety of conditions forin-vitro diagnostics ; (iv) Uniform activityregardless of batch synthesis ; (v) It returns to

original conformation after temperature insult ;(vi) Unlimited shelf life ; (vii) No evidence ofimmuno-genicity ; (viii) Cross reactive compoundscan be isolated to facilitate preclincial studies and(ix) ‘Aptamer’ specific antidote can be developedto reverse the inhibitory activity of the drug28.

Pharmacokinetic manipulation of ‘Aptamers’rely on the efficacy of the clearance mechanism.To render ‘Aptamer’ activity independent ofbiological clearance, base pairing between the‘Aptamer’ and the oligonucleotide antidote occurs.This alters the shape of the ‘Aptamer’ therebypreventing it from binding to its target. The abilityto develop ‘Aptamers’ that retain activity in multipleorganisms facilitates preclinical development.Antidote control of ‘Aptamer’ activity enables safe,tightly controlled therapeutics.

‘Aptamers’ may prove useful in the treatementof infectious diseases, cancer and cardiovasculardisease. Optimally stabilized and formulated‘Aptamers’ are now available as intravenous orsubcutaneous injectables with blood half-lives inthe 6 to 12 hour range29, 30. New oligonucleotidestabilization chemistries continue, therebyproducing injectable ‘Aptamer’ formulations withlonger blood half-lives (e.g. > 24 hours) seemsfeasible in future. Immune-modulated aptamers asadjuvants to cancer and other vaccine strategies arebeing developed31. So, ‘Aptamers’ may prove usefulto a large extent in the clinics.

ACKNOWLEDGEMENT

Author is thankful of Dr. T. Lazar Mathew,Dr. T. Ravindranath, Ex-Directors and to Dr. R. P.Tripathy, DIRECTOR, INMAS for suggestions,inspiration and permission for publishing this paper.

REFERENCE

1. C. L. Propst, S. M. News 41, 5-7, 1991.

2. K. Appet, J. Med. Chem 34, 1925-1934, 1991.

3. L. H. Hurley and F. L. Boyd—Annual Reportsin Medical Chemistry. Editor— D. Bailey,

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Chapter 26, pp 259-268, Acadimic Press,New York, 1987

4. R. C. Huang, J. Bonner and K. Murray,J. Mol. Biol, 8. 54-59, 1964.

5. D. Blocher and M. Kunhi,—Int. J. Radiat.Biol. 58, 23-34, 1990.

6. D. M. Smith, G. P. Raapshort—Int. J. Radiat.Biol. 79(5), 333-339, 2003.

7. A. Mookerjee and S. N. Upadhyay—TheNucleus 19(3), 172-182, 1976.

8. H. W. Wyeoff, C. H. W. Hirs and S. N.Timasheff (Editors)—Methods inEnzymology, 1985, 114-115. Academic Press,New York.

9. A. H. J. Wang and H. Robinson-Nucleicacid targetted drug design, T. J. Perum andC. L. Propst (Eds) pp 17-64, Marcell DekkerInc. New York. 1992.

10. A. Pullman and J. Jortner CRS.—Molecularbasis of specificity in nucleic acid—druginteraction 123-131, Kluwer PublicationsDordecht, 1990.

11. J. E. Beuzit, M. S. Maurizot, R. Sabatier,B.B. Baydras and M. Charlier—Biochemistry32, 2104-2110, 1993.

12. S. N. Upadhyay, Radiation Protection &Environment. Bull Radiation Protection 71,1 45-53, 1998.

13. S. N. Upadhyay, Ram Pal Singh andA. Ghose J. Surface Sci. & Technol. 9. 67-79, 1993.

14. S. N. Upadhyay, J. Surface Sci. & Technol.15, 3-4, 137-146, 1999.

15. S. N. Upadhyay, J. Surface Sci. & Technol.,17 3-4, 157-167, 2001.

16. T. C. Birdsall, Alternative Med. Rev. Aug 34, 271-280, 1998.

17. S. N. Upadhyay, J. Ind. Chem Soc. 80, 619-621, 2003.

18. S. N. Upadhyay, Ind. J. of Nuclear Medicine18 1 & 2, 1-11, 2003.

19. S. N. Upadhyay, S. Singh, R. Bhardwaj,N. K. Chaudhury and T. Lazar Mathew, J.Ind. Chem. Sco. 80, 33-35, 2003.

20. T. B. Dey, S. N. Upadhyay and A. Ghose,Indian Photobiology Society, News LetterNo 42, 63-66, 2003.

21. T. J. Perum and C. L. Propst, “Nucleic acidtargeted drug design” pp1-16, Marcel DekkerInc., New York, 1992.

22. A. D. Ellington and J. W. Szostak, Nature346, 818-22, 1990.

23. C. Tuerk L. Gold, Science 249, 505-510,1990.

24. J. A. Joudna, T. R. Cech and B. A. Sullenger,Proc. Natl, Acad.Sci. USA. 92, 2355-2359,1995.

25. S. W. Lee and B. A. Sullenger, NatureBiotechnol, 15, 41-45, 1997.

26. C. P. Ruskoni, E. Seardino and J. Layzer,Nature 419, 90-94, 2002.

27. C. P. Rusconi, A. Yeh and H. K. Lyerly,Thromb. Heamostasis 84 , 841-848,2000.

28. S. M. Nimjee, C. P. Rusconi and B. A.Sullenger, Ann. Rev. Med. 56, 555-583,2005.

29. C. E. Tucker, L. S. Chem and M. B. Judkins,Chromatogr. Biomed. Sci.. Appl. 732,203-12, 1999.

30. S. R. Watson, Y. F. Chang and D. O.’Connell, Antisense Nucleic Acid Drug. Dev.10, 63-75, 2000.

31. S. S. Marotto, S. K. Nair and C. Rusconi,Cancer Res. 63, 7483-89, 2003.

47


TERMINATOR TECHNOLOGY : AN ECOLOGICAL DISASTER

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The paper deals with terminator seeds and the technology to produce them as well as theirhazardous effects on farmers, food security, agricultural biodiversity and ineffectiveness forpreventing gene flow.

* Laboratory of Plant Physiology and Biotechnology,Department of Botany, M.L.V. Government College,Bhilwara (Rajasthan)-311001

IINTRODUCTION

n 1998, for the first time the Delta and PineLand Company, working with the U.S.

Department of Agriculture [USDA] acquired U.S.patent for Technology Protection System [TPS].Within days the rest of world knew TPS as terminatortechnology. In Terminator Technology certain genesare inserted into seeds that ensure that resultingplants will produce self terminating offspring ‘Suicideseeds’. This genetic technology is designated toprevent unauthorized seed saving by farmers. Theutility of this technology to an agrobiotech company,marketing these crops would be to prevent farmersfrom cheating by breaking their agreement andsaving seeds anyway. For this reson the seed killingstrategy was later named “Genetic Use RestrictionTechnology” [GURT]. GURT is a system, which hasthe purpose to protect the financial interest of thedevelopers that means the multinational companies.In this case there is absolutely no agronomic benefitfor farmers. The sole purpose is to faciilitate monopolycontrol and the sole benefificary in this case isagribusiness community.

The terminator technology is used to control theplant gene expression in two major ways. Theterminator consists of a set of three novel genesinserted into one plant. In another technique, two orthree genes are present on two different plants, whichare later to be cross-pollinated. The end result isalways a dead seed in the following generation. The

three genes required are : a ‘terminator gene’ thatstops seed development, a ‘repressor gene’ thatrepresses the terminator gene and an ‘activator gene’that activates the terminator gene by preventing therepressor gene from working. Controlled expressionof these genes results, sterile off prings of anengineered plant.

These genetically modified crops have someagronomic advantages like increased yield,nutritional quality, flavour, disease and droughtresistance and processing characteristics, but theseseeds hold farmers back from their tradional savingof seeds for future generations and utilization ofbreeding technique. The terminator technology withits terminator seeds force farmers back to themarket every season. They also scuttle communityconservation of agricultural biodiversity. Thistechnology, therefore, is called “Neutron Bomb” ofagriculture. Civil society and many governmentshave called for a ban on the technology2.

THE HISTORY

In the history of plant breeding, Mendel pubishedhis work on the genetics of pea in 1865. He laiddown genetical rules of plant crossing for the firsttime. He is known as “Father of Genetics”. In1860, Major Hallett discovered a modern plantbreeding concept “Pedigree method”, for cereals.3

In this method farmers brought seeds, sowed them,selected the best seeds for the next season and bredtheir own varieties. The advantage of this methodwas that the varieties uniquely adapted themselvesto local soil, weather and environment.

In 1908 George Shull introduced ‘hybridizaton’,

48


a wonderful euphemistic term. These discoveries ledfarmers to save and develop their own seeds forgenerations. In hybridization, two distant plantrelatives were corssed, that create a ‘hybrid vigour’.

Dr. Melvin Oliver, a scientist at the USDAlaboratory, developed a strategy to allow a plant todevelop from a seed but produces non-viableoffsprings. His approach was to utilize normalgrowth process in all plant and place it under adifferent genetic control switch. The normal processis called ‘programmed cell death’ and is used byplants to fight off pathogens. For example, when aplant leaf is damaged or infected, the cells around theaffected region immediately go for self destructionby making a protein that arrests their cell machineryfor producing proteins. Genes control the productionof proteins and Dr. Oliver put the gene responsbilefor this process under the control of another genewhich is active only as a seed reaches full maturity.The presence of the active inhibitor gene prevents theseed from germinating.

The terminator crops have been field tested inEurope since 1990 and in United States since1992, where several have already been releasedcommercially. There are more than 150 US patentslisting for the terminator technology.4 The firstterminator patents to catch public attention werethose jointly owned by USDA and Delta and PineLand Company, which they acquired in March1998. The novelty fo those patents lies in the factthat the company gained complete control over thehybrids as well as proprietary chemicals that controlgene expression. These patents, being contrary tobasic human rights, met with universalcondemnation world wide.

THE TECHNOLOGY

There are three key components of terminatortechnology :

(i) Terminator or Barnase gene, (ii) BlockingSequence or Repressor gene and (iii) Activator orRecombianse gene.

Terminator gene : This gene halts seeddevelopment and produces Barnase enzyme, whichbreaks down RNA. RNA is an intermediate in theexpression of all genes. So barnase gene is leathalto all the cells, in which it expresses. When barstaris present (specific inhibitor of barnase), it formsone to one complex with barnase, in this waybarstar blcoks the lethality of barnase gene. Bothbarnase and barstar are the products, of bacteriumBacillus amyloliquefaciens, In the bacterium cellboth of thse bind with each other and show noharmful effects. When barnase is secreted outside,it is harmful to other cells.

Repressor gene : It is DNA sequence thatkeeps the teminator gene ‘turned off’ until theseeds are sold to farmers, This gene would beprogrammed to stay ‘on’ all the time to keepterminator gene ‘turned off’.

Activator gene : This is a recombinase genethat produces recombinase enzyme. This enzymeis responsible to splice out the blocking sequenceso that the terminator or barnase gene can expressitself. The recombinase gene is placed under thecontrol of a promotor that responds to an externalchemical, say the antibiotic tetracycline.Cre recombinase and RAG recombinase aresome examples of recombination system.Cre/lox P system was originally isolated frombacteriophage P1. Cre catalyses recombinationbetween two lox P sites, splicing out any stretch ofDNA in between. This system is useful both inplants and animals. RAG recombinase is usefulonly in animals.

There are many ways to engineer sterility butlittle is published for field trials. Two systems arediscussed below :

(A) Barnase Recombinase system and (B)Barnase Barstar system.

Barnase Recombinase system : In this system,to engineer pollen/ovule sterility barnase is placedunder the anther/ovule specific promoter that allowsthe gene to be expressed only during anther/ovule

49


development. A blocking sequence (repressor gene)is also engineered between promoter and barnsegene.

Anther/ovule Blocking Barnasespecific promoter sequence gene

Recombinase gene with its tetracycline specificpromoter, is engineered first to barnase gene or itcan be introduced by crossing the GM linecontaining recombinase with another, that containsbarnase to give a hybrid.

Tetracycline Recombinase Anther— Blocking Barnasespecific gene ovule sequence gene

promoter specificpromoter

Tansgene of interest (like as in herbicidetolerance) with its own promoter is stitched next tobarnase.

Tetracycline Recombinase Anther— Blocking Barnase Transgenespecific gene ovule sequence gene of

promoter specific interestpromoter

In the absence of external chemical, thetetracycline, the activator gene or recombinse genedoes not produce the recombinase enzyme. At thistime the blocking sequence is programmed to stay‘on’ to keep the terminator gene turned ‘off’. In thepresence of tetracycline the recombinse gene isexpressed and produces ecombinase enzyme whichsplices out blocking sequence in the barnase promotorand barnase gene is expressed in male/female part ofthe plant. Theoretically, there will be no fertilepollen/ovule from this transgenic crop.

When the seed company is ready to sell seedsto growers, it first treats the seeds with tetracycline,

Tetracyclinespecific

promotor

RecombinaseGene

Antherspecific

promotor

BlockingSequence

TerminatorGene

(Barnase Gene)

ForeignGene ofInterest


promotor

RecombinaseGene

Ovulespecific

promotor

BlockingSequence

TerminatorGene

(Barnase Gene)


m RNA forRecombinase enzyme

Recombinase enzyme


promotor

RecombinaseGene

Antherspecific

promotor

TerminatorGene

(Barnase Gene)


m RNA forRecombinase enzyme

Recombinase enzyme


promotor

RecombinaseGene

Ovulespecific

promotor

TerminatorGene

(Barnase Gene)



promotor

RecombinaseGene

Antherspecific

promotor

TerminatorGene

(Barnase Gene)



promotor

RecombinaseGene

Ovulespecific

promotor

TerminatorGene

(Barnase Gene)


m RNA for Barnase enzyme

Barnase enzyme

Degrades RNA of the cell

m RNA for Barnase enzyme

Barnase enzyme

Degrades RNA of the cell

Fig. 1A and 1B : Terminator Technology to produce male / female sterility

which turns ‘on’ the recombinase gene. Thisrecombinase gene produces recombinase enzyme.This enzyme binds to the blocking sequence andsplices out this blocking sequence so that terminator

gene becomes active and produces barnase, whichbreaks down the m RNA, and becomes lethal tothe cells. In self fertilized crops, there will be noseed set (Figures 1A and 1B).

50


In other cases, a recombinse gene may beengineered in to a GM line with a barstar gene.This line, when crossed to a GM line (male sterile)containing barnase gene, will give a hybrid which,when treated with tetracycline will produce plantsthat will set seed at least theoretically becausebarstar neutralizes barnase. If the harvested seedsare grown again, only 7/16 of the seeds will befertile with same characteristics as those of originaland 3/16 seeds will be sterile. Two seeds out ofsixteen will be partially sterile.

Barnase Barstar system (Male sterility systemof Bayers Crop Sciences) :-In AgEvo’s (nowBayer Crop Science) application for field trials,only two lines are mentioned. These are :

Male sterile oil seed rape line : This line ismaintained in a hemizygone state. i.e. with onlyone copy of the male sterility gene barnese underthe anther specific promotor and a gene forphosphinothricin tolerance (glufosinate tolerancegene, H).

Male restorer oil seed rape line : This line ismaintained in homozygous state i.e. with two copiesof the restorer gene barstar under the control ofanther specific promotor linked to glufosinatetolerance gene H.

Barstar and barnase genes are on differentchromosomes and each is linked to a glufosinatetolerance gen H. Cross of Male sterile and Malerestorer lines produces F1 hybrid containing twokinds of plants. (a) Plants with H-barnase &H-barstar transgene in hemizygous state. Barnasein such plants is neutralised by barstar, so, plantsare male fertile and produce pollen and areglufosinate tolerant. (b) Plants with H-barstar inhemizygous state which are male fertile as well asglufosinate tolerant.

As H-barnase and H-barstar are on differentchromosomes, they assort independently of eachother. Two kinds of F1 hybrid plants producedifferent kinds of pollen. The plants with H-barnaseand H-barstar (both in a hemizygous state) producefour kinds of pollen in equal proportions, three of

which carry the glufosinate-tolerance gene. Theplants with only H-barstar in hemizygous stateproduce two kinds of pollen in equal proportions,those with the glufosinate-tolerance gene and thosewithout. Thus, 5/8 of the pollen produced by the F1

hybrid plants will spread the glufosinate-tolerancegene and 2/8 of the pollen will spread the male-sterility gene barnase, half of them carrying themale-sterility restorer gene barstar, and half without(Figure 2)

Female

H Barnase

H Barnase ×

Female

H Barasat

H Barasat

Male sterile line Male restorer line

H Barnase H Barasat H Barasat

F1 hybrid

H Barnase H Barasat H Barasat

Fertile Fertile

H Barnase

Sterile Fertile

H Barnase

Fertile

Pollen

Fertile

Fig. 2 : Reconstruction of the male sterile system(devised by Bayer Crop Science)

HAZARDOUS EFFECT OF TERMINATORTECHNOLOGY

The terminator technology is supposed to givethe plant higher yields, drought and insect resistanceability etc., but the results are disappointing. Someof hazards are as follows :

Misfortune of farmers : The 12,000 years oldpractice in which farm families save their best seedfrom one year’s harvest for the next season’splanting, may be coming to an end if terminatortechnology will be approved all over the world.Critics say that it could spell disaster for world’sfood supply, since more than one billion farmers,primarily small farmers in Africa, Asia and LatinAmerica depend on saved farmed seeds.

Threat to food security : The second reason for

51


criticizing the terminator technology is the absenceof adequate biosafety legislation. Countries mightbe induced to accept the terminator on theassumption that the technology is safe and thetransgenic traits can not survive to a secondgeneration, even by cross pollination. Thisassumption is ill founded. As with all geneticengineering, its direct effect and its side effects areunpredicatable and carry all the risks inherent inthis technology. The gene cocktail of the terminatorincreases the risks that new toxins and allergenswill show up in out food and animal fodder. So itshould be banned unless “it is too late to lock thestable door when the steed is stolen”.

Destruction of agricultural biodiversity : Theterminator genes themselves could infect theagricultural gene pool of the neighbouring cropsand of wild and weedy relatives, placing a timebomb. Temporary gene silencing of the poisongene or failed activation of this countdown enablesuch infection. Molecular biologists have mixedviews on the potential ecological hazards of thesterility trait. From first generation seed mightspread via pollen to neighbouring crops or wildrelatives growing nearby. The danger is thatneighbouring crops could be rendered sterile dueto cross pollination wreaking havoc on thesurrounding ecosystem. So biosafety issues remainan important concern.

Ineffectivity for preventing gene flow :Terminator crop system is ineffective for preventinggene flow, because this gene control system isleaky, in the sense of not being 100% accurate assome fertile pollen/seeds are likely to be produced.Male sterile terminator plants can still be fertilizedby non terminator pollen, just as terminated pollenfrom ovule sterile plants can cross with nonterminated plants, thus enabling gene escape.Horizontal gene transfer is also possible in thissytem. It is the process whereby the GM DNA istaken up directly in to cells of unrelated speciesand incorporated into the cell’s genome. Bacteriaviruses, plant residues, dust pollen, insect pollinatoract as vector of horizontal gene transfer.5

Lethal effects of barnase gene and recombinasegene : The gene involved in terminator crops ispotentially fatal.6 Barnase is an universal poison. Itis a poten RNAse that breaks dow RNAindiscriminately and is known to be harmful toanimals and humans. When perfused into ratkidney’s, barnase causes kidney damage.7 The sitespecific recombinase is not specific. There is alreadyevidence suggesting that genome can be scrambledby the recombinase. Transfer of both the terminatorgene barnase and the recombinase will have drastic,potentially fatal effects on health.

Both the patent and the technology should berejected on the basis of common sense, food securityand agricultural biodiversity. The terminatortechnology has absolutely zero agronomic benefit,there is no reason to jeopardize the food security ofthe poor by gambling with genetic engineering inthe field. Whether the terminator works immediatelyor later, in either instance it is biological warfareon farmers and food security. So these killingcrops must be stopped once and for all.

REFERENCES

1. R.A. Steinbrecher and P.R. Mooney. TheEcologis, 28, 5, 1998.

2. www.etcgroup.org 17 April 2003.

3. J.P. Berlan and R.C. Lewontin. “AgriculturalGenetics and Sterifix Breeding”. Unpublishedmanuscript pp. 5-6. 1998.

4. “USD – Delta & Pine Land Commercia-lization Agreement Reched, PollenTransformation System”. Jan 2001, SCOOT.

5. M. Giovannetti. The ecological risks oftransgenic plants, Riv. Biol. 96(2), 207-223,2003.

6. ISIS News ‘Killing Fields Near You’Terminator Crops at large.Ed. Mas – Wan Ho, Institute of Science inSociety.www.isis.org.uk, ISSN : 1474 – 1814 (online), 2001.

7. O. Ilinskaya and S. Vamvakas. Toxicology.120, 55-63, 1997.

52


PRESENT SCENARIO OF ULTRASONIC APPLICATIONS

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In this article, some recent developments and applications of ultrasonics are presented. It includeslaser ultrasonics, acoustic microscopy, ultrasonic stimulated vibro-acoustography, accousticemission, saser and medical ultrasonics.

* Dept. of Physics, B. N. V. P. G. College, Rath, Hamirpur-210 431, U. P.

RINTRODUCTION

esearch and development in the field ofultrasonics is growing steadily. Some latest

topics and applications such as laser ultrasonics,acoustic microscopy, ultrasonic-stimulated vibro-acoustography, acoustic emission, saser and medicalultrasonics are discussed in this paper.

Ultrasound is playing an important role in ourdaily life. It is finding applications in variousbranches of science, engineering and medicine. Aslate as in 1900, only the ultrasound whistle wasused. The interesting observation of the relaxationphenomena in gases and liquids towards the latetwenties and the observation of diffraction of lightby ultrasonic waves in the mid thirties greatlyincreased the interest in physical ultrasonic waves.By 1930, it had become an interesting but smallresearch area of physics. In the 1960s and 70s,however, it became an important research tool inphysics, a far ranging instrument for flaw detectionin engineering, in medicine and a reliable methodof underwater signalling. One could for example,study phonons using ultrasonic techniques. Otherapplications in solid-state studies and in materialsscience phenomena have made the subject an activeone.

The range of frequencies available has beenextended to mega hertz (MHz) and even giga hertz(GHz). Ultrasonics is a powerful technique for

inspecting and characterizing materials. It can beused not only to detect bulk and surface flaws butobtain information of material microstructure alsowhich determines the engineering properties suchas elastic mudulii and ultimate strength. Ultrasoundtechniques use the interaction of high frequencysound waves with matter, in order to generateinformation about the physico-chemical properties.Such measurements have been established innumerous areas like medicine, oceanography andmaterial sciences. All these developments haveincreased the range of ultrasonic applicationsmanyfold. There appears to be no area today whereultrasonics does not find an application. There arenumerous applications such as fluid flowmeasurement, liquid level measurement, gas sensorsetc. In fact, the uses of ultrasonics are increasingevery day with research and development workkeeping right pace with each other.

LASER ULTRASONICS

The method of generation, detection andcoupling of ultrasound may be called conventionalultrasonics. Such a technique cannot obviously beapplied at elevated temperatures, because it requiresfluid coupling and most fluids vaporize above afew hundred degrees Celsius. Also, if thetemperature exceeds the limit of the transducermaterial, the transducer ceases to be piezoelectricand to be operational. On the other hand, beingable to use ultrasound at elevated temperaturescould be of far-reaching importance, since all metalsand ceramics are processed at elevated temperatures.

53


In this case, ultrasound could not only provideinformation on the thickness of the part beingprocessed but also on its microstructure, whichdetermine many engineering properties. Such alimitation could be circumvented by usinglasers for generation and detection of ultrasound.This technique is called laser ultrasonics1, 2.Laser techniques use one laser for generation andanother for detection. In this case, there is no needof fluid contact and transduction can even beperformed in vacuum. Laser ultrasonics alsoprovides a solution to limitation of conventionalultrasonics which is less obvious and prevents itsuse in so many cases of industrial interest.Conventional ultrasonics requires a manipulator tomake the transducer to follow the curved surfaceand eventually, especially for small radius pipes,the addition to the transducer of an acoustic lensfor acoustic wave-front matching. In the case oflaser ultrasonics there is no need of such addedgel and the beams are simply scanned over thesurface. The experimental studies show that Laserultrasonics is, in general, less sensitive thanpiezoelectric transduction and considerable researchand technological development was needed toprovide useful signals.

An important application of laser ultrasonics isto measure the strength and flexibility of paperwithout touching it and even when it is moving at30 meters per second. Paul Ridgway and RickRusso are developing a laser-based ultrasonictechnique to measure paper’s mechanical propertiesnon-destructively while it is on the paper-makingmachine or ‘Web’. Laser ultrasonic is a non-contractand non-destructive method to analyze paper’smechanical properties. A short pulse of laser lightless than micro second generates ultrasonic wavesby either a thermal expansion or an ablationshockwave or both. The ultrasonic wave propagatesalong the paper sheet and is detected at knowndistance (several millimeters) using a non-contactinterferometric technique. The time of flight of the

wave over the known distance gives the propagationvelocity of the wave. The wave velocity istheoretically related to elastic properties, which isempirically related to strength properties.

ACOUSTIC MICROSCOPY

For imaging the variations of the mechanicalproperties of materials, acoustic microscopy ismaturing into a very useful technology. Quantitativemeasurements are possible in the field of biologicalapplications, material characterization anddiagnostic medicines. There are several types ofacoustic microscopy, which are as follows :

(a) Scanning acoustic microscopy.

(b) Scanning electron acoustic microscopy.

(c) Scanning laser acoustic microscopy.

(d) Near-field scanning acoustic microscopy.

(e) Line focus beam acoustic microscopy.

Scanning acoustic microscopy is a reflection-imaging instrument, which images the surface andnear surface variation of the mechanical propertiesof the sample. The major applications of scanningacoustic microscopy are in the examination ofstructural materials3. In scanning electron acousticmicroscopy (SEAM), the focused elctron beamgenerates acoustic signals by periodic or pulsedheating of a solid and acoustic signals are detectedby piezoelectric transducers in contact with thesolid, as shown in Fig. 1. The electron beam scansthe surface of the solid and the transducer output isused to form a magnified scanned image. Thesensitivity to semiconductor doping and itssubsurface imaging capabilities make the techniqueuseful in microelectronics. Resolution and depthprobing on the micron scale are well suited tomany integrated circuit devices. The other usefulapplications of SEAM are imaging grain structurein polycrystalline solids, imaging acousticvibrational modes in plates, foils and wires imagingnear surface and subsurface cracks. Scanning laseracoustic microscopy is a transmission-imaging

54


instrument which images the interior of samplesby visualizing the shadow cast by material propertyvariations in the path of the acoustic beam. This

field scanning acoustic microscopy is similar toscanning laser acoustic microscopy except that thesound field on the surface of a sample is detectedwith a tip or a pin hole that is much smaller thanthe wave length. The images obtained by the near-field scanning acoustic microscopy representvariations in the mechanical properties of the samplewith a spatial resolution equal to the size of thepinhole or tip. Line focus beam acoustic microscopyis useful to study a material’s propagationcharacteristics and these measurements have beenfound to be very speedy and accurate.

ULTRASONIC STIMULATED VIBRO-ACOUSTOGRAPHY

Palpation is routinely used for the evaluation ofthe mechanical properties of tissues in regions thatare accessible to touch. These means of detectingpathology using the stiffness of the tissues aremore than two millenia old. Even today, it iscommon for surgeons to feel lesions during surgerythat have been missed by advanced imagingmethods. Palpation is subjective and limited toindividual experience and to the accessibility ofthe tissues to touch. It appears that some means ofnon-invasively imaging elastic modules may beuseful to distinguish the tissues and pathologicprocesses based on a mechanical property such aselastic modulus. To this end, many approacheshave been developed over the years. These havebeen used in conventional imaging methods tomeasure the mechanical response and mechanicalstress of tissues. Static, quasi-static or cyclic streseshave been applied. The resulting stress has beenmeasured using ultrasound and the related elasticmodulii has been computed from visco-elasticmodels of tissue mechanics. A new ultrasonictechnique has been developed that produces speckle-free images related to both tissues stiffness andreflectivity. The method, ultrasound stimulatedvibro-acoustography6,7 uses ultrasound radiationpressure to produce sound vibration from a smallregion of the tissue that depends on the elastic

Modified ScanningElectron Microscope

Scan Control andCRT Drive Circuitry

CRT

Electron BeamScanning

Coils

Sample

Stage

Sound waves

ReceiverAmplifier

PiezoelectricTransducerReceiver

Fig. 1 : Scanning Eelctron Acoustic Microscope

provides a new capability for visualizing thestructural characteristics of living tissues. The mostpopular industrial application of the scanning laseracoustic microscopy is bond evaluation. Thescanning laser acoustic microscopy can distinguishbetween bonded and unbonded ribs and can measurethe percentage of bond for partially bonded ribs aswell. Scanning laser acoustic microscopy providesthe means to visualize the grain structure, grainboundaries and impurities in the metal specimens.Photo-acoustic microscopy, scanning electronacoustic microscopy and scanning laser acousticmicroscopy technique, theory of acoustic imaging,schematic diagram and their industrial applicationhave been reviewed by few workers4. Someinvestigators5 have reported line focus beamaccustic microscopy and found these measurementsbe very accurate non-destructive. Near-field scanningacoustic microscopy can be either a reflection or atransmission-mode instrument. Transmission near-

55


characteristics of the tissue. With this method, onecan detect micro-calcification within breasts andthis technique promises to provide high qualityimages of calcification within the arteries. Thismethod may also be used in non-destructiveevaluation and for underwater communication.

ACOUSTIC EMISSION

The emission of elastic waves, as a result ofrapid release of strain energy caused by a structuralalteration in solids, is called acoustic emission. Inconventional engineering materials, acousticemission has been correlated with various types ofdislocation motions such as crack-growth, movingdislocations, slip, twinning, grain boundary slidingand fracture. Acoustic emission sources range fromatomic size lattice defects to macroscopic sizeearth-quakes and rock burst in mines. Generally,an acoustic emission source behaves like a pointsource and radiates energy in the shape of sphericalwavefront. Acoustic emission studies are extremelyinteresting and have great potential in theunderstanding of mechanical properties of solids.Practical applications of acoustic emission techniqueare in determining the approach to failure in largepressure vessels in the nuclear, aerospace, bridges,cranes, chemical industry, etc. The acousticemission method has many distinct advantagesover other non-destructing testing methods8.

SASER

The abbreviation of “Sound Amplification byStimulated Emission of Radiation” is SASER. Thereare many types of laser devices generating coherentelectromagnetic waves, but creation of an ‘acousticlaser’ i.e. SASER is of great interest because of avariety of potential applications of such devices.Some researches9 have reported about a SASER,which is made from a 5mm long rectangular crystalof ruby. The ruby block is kept into liquid heliumbath to cool it to 3.8K to freeze out unwantedsound waves. When a laser beam is focused on thecrystal, electrons on the chromium ions absorb the

light energy, jump to a higher energy level andthen drop back to a lower level, giving out theirexcess energy as light. To create phonons ratherthan photons, a strong magnetic field is applied.When the field is switched on, the eletrons absorblight but lose their energy in small steps ratherthan a single leap. These steps are too small to givea photon but just enough to create vibrations in thecrystal lattice. These phonons travel the length ofthe crystal and reflect from the walls, making fiveor six passes in all. Each time, they whiz throughthe region where the laser light is focused, theystimulate excited electrons on the chromium ionsto lose their energy and give out more phonons.This process is known as stimulated emission,which is the basic ingredient of the SASER. Someinvestigators10 have studied phonon emission dueto transition in a two-level system well known inglasses. This SASER has a pair of tiny piezoeletrictransducers mounted on opposite ends of a smallblock of glass just 2 cm. long. Recently someworkers11 have reported a resonant tendency in adouble layer heterostructure designed in order toproduce intense terahertz coherent phonons. ThisSASER is based on a quantum well, an artificialatom made from layers of semiconductors such asGaAs that can trap an electron in quantized energylevels. When an electron is injected into the wellwith a small voltage, it jumps between these energylevels, blasting out a stream of phonons at ultrahigh frequencies. Some12 have reported the theoryof sound SASER with consideration for coagulation.Their device is based on a cylindrical vessel filledwith water containing thousands of tiny gas bubbles,which are produced by electrolysis. If these bubblesare squeezed by varying electric field, they willresonate. If a sound pulse is injected now, it willgather energy from the vibrating bubbles. Thus,finally a powerful, highly directional narrow beamof low frequency sound waves emerges from theend of the container, as shown in Fig. 2.

The applications of the SASER are many withimmediate use in acoustic microscopes and sensors.

56


A tunable SASER could discover exactly howelectrons vary their energy when a material heatsup or cools down. This could reveal the insidestory of things like heat dissipation, electrical

place along with X-rays and nuclear medicine as adiagnostic tool. Its main attraction in imaging liesin its non-invasive character and ability todistinguish interfaces between soft tissues. Incontrast, X-rays only respond to atomic weightdifferences and often require injection of a densercontrast medium for visualization of non-bonytissues. Similarly, nuclear medicine techniquesmeasure the selective uptake of radioactive isotopesin specific organs to produce informationconcerning organ function. Radioactive isotopesand X-rays are clearly invasive. Ultrasound isnot only non-invasive, externally applied andnon-traumatic but also apparently safe at theacoustical intensities and duty cycles presentlyused in diagnostic equipment. The main limitationof ultrasound, however, is that it is almostcompletely reflected at boundaries with a gas whichis a serious restriction in investigation of andthrough gas-containing structures. The frequencyshift caused by the reflection of sound from movingobjects (Acoustic Doppler effect) is used to imageflow in medicine. Blood flow in vessels can beimaged within the body in real time without theuse of radioactive tracers.17

Ultrasound through tissue medium :

Density and compressibility fluctuations in atissue medium act as the scattering centers for anincoming ultrasound wave. As a result of thisscattering, the scattered wave carries a significantamount of information about the tissue medium.Thus, in principle, it is possible to characterize thetissue medium by analyzing the scattered componentof the wave, in particular the back scatteringcomponent18. Due to the non-invasive nature,ultrasonic medical imaging currently draws attentionfrom scientific community worldwide, although itsuffers inherently from poor resolution. However,with the developments in transducer technology, itis possible today to investigate the velocity andattenuation of ultrasound propagating through tissuemedia with greater details useful for pathological

D

A

C

B

Fig. 2 : SASER (A. suspended tiny bubbles of gas,B. set of bubbles runging, C. pass sound waves &

D. sound waves emerge)

resistance and conductivity. The powerful anddirectional sources of sound could be used fortasks such as detonating explosives from afar, or asa weapon, to immobilize terrorists by stunningthem with a blast of sound. The amplitude of thephonon beam can be easily modified.

MEDICAL ULTRASONICS

Ultrasound finds extensive applications in themedical field13-16. It has made an outstandingcontribution in imaging and has become anindispensable tool in various specialities such asobsteterics, cardiology and internal medicine. Atpresent, ultrasonics has brought about a revolutionin the medical sciences.

The use of ultrasound in the medical fieldcan be divided in two major areas—the therapeuticand the diagnostic. The major difference betweenthe two applications is in the ultrasonic powerlevel at which the equipment operates. In therapeuticapplictions, the system operates at ultrasonic powerlevels of up to several watts/cm2 while diagnosticequipment operates at power levels below 100mW/cm2. Therapeutic equipment is designedto agitate the tissue to the level where thermalheating occurs and has been found to be quitesuccessful in its effects for the treatment of muscularailments such as lumbago. Ultrasound has taken its

57


interpretation. It is, generally, observed that thepressure amplitude as launched by transducer fallsoff exponentially with distance and attenuationbecomes frequency dependent19.

Ultrasonic lithotripsy :

An acoustic lithotripter is a device for destroyingstones in the kidney or gallbladder by focusedultrasound of very high amplitude. Extra-corporealshock lithotripters20 generate pulses in water inwhich peak positive pressures extend up about 100MPa and peak negative pressures to 10 MPa.These pulses are less than a microsecond induration. In clinical practices, they are delivered atpulse repetition frequencies up to 40 Hz. A singlepulse may contain only a half cycle, or severalcycles ; taking the frequency to be the rate atwhich zero crossing occurs, this varies from 150kHz to 700 kHz. In a surgical procedure fordestroying kidney stones, it is typical to apply1000 shocks or more. This has become a verypopular method of treatment. A special advantageof focused high intensity ultrasound signals is thatdeep-seated diseased tissues like tumours can beaccurately destroyed in the body without damagingthe surrounding tissues between the surface andthe lesion21.

Medical diagnosis :

Acoustic sonograms have become an importantmedical diagnostic tool, which is widely used nowa days22, 23. An acoustic wave propagates casilythrough biological tissues. The scatterings fromthe discontinuities in the system are detected bythe receiver as in SONAR. Knowledge of thevelocities and attenuation in the various tissuesthen enable one to have an acoustical image insideof the human body, for instance, the abdomen.Several imaging processes are used to get additionalinformation. It is becoming a common practicefor pregnant women to have a sonogram of thebaby to be sure that all is well. The eye and theheart are also studied under some conditions usingthese techniques. Tumours, cysts, abscesses and

any other disorders can be recognized in manyorgans.

With the increasing demand for rapid and moreaccurate ultrasound diagnosis, it is importantthat the ultrasound systems deliver high qualityand reliable images and with minimal effort.For high quality imaging, transducers withmulti-directional focusing allow unparalleled imageresolution and clarity. These transducers enable usto achieve exceptional special resolution throughout the depth of the field with fine control ofthe beam pattern. Also, as compared to theconventional ultrasound systems using multiplexingtechniques in array transducers, each transducerelement has its own dedicated channel, thuscontributing to the formation of an individualpixel in the image, and, therfore, providing a highsignal to noise ratio. Digital technology hasgreatly helped to improve the image quality.With the availability of high-speed data converters,analog processing of the signals is minimized.With the development of high frequency transducersand electronics, an era of micron imaging hasopened up24.

Ultrasonic imaging and therapy :

Ultrasonic imaging and therapy of thebrain using concepts derived from time reversalmirrors, a technique is developed for focusingultrasonic waves through the cranial wall, permittingto obtain focal spots as delicate as in the absenceof the skull. This research aims to develop ultrasonicimaging of the brain and a system, which willdestroy brain tumours by ‘hyperthermia’. Thistechnique takes an ultra fast ultrasonic imagingsystem which captures several thousandultrasonic speckle images per second. An‘Ultrasonic Pistol’, which will measure therheologic properties of soft materials, is underdevelopment.25

CONCLUSIONS

From the above discussion, one can,undoubtedly, say that ultrasound finds extensive

58


applications in different aspects of modern life.The latest developments have greatly increased theinterest in ultrasonics and have made the subject tobe an active one. The study of ultrasonics, atpresent, extends an unlimited field of acivity forinvestigators and it opens up immense opportunitiesfor their applications.

REFERENCES

1. C. B. Sruby and L. B. Drain, LaserUltrasonics, Adam Hilger, UK, 1990.

2. D. O. Thompson and D. E. Chementi, Reviewof progress in quantitative Non-destructiveevaluation, 12, 495, 1993.

3. G. Golan and C. W. Pitt. Appl. Surface Sci.,106, 491, 1996.

4. R. S. Gilmore, J. Appl. Phys., 29, 1389,1996.

5. J. K.ushibiki, T. Okuzawa and Y. Ohashi,J. Appl. Phys. 87, 4395, 2000.

6. J. F. Green leaf, Science, 280, 82-85, 1998.

7. J. F. Green leaf, Pro. Natl. Acad. Sci., USA.96, 6603, 1999.

8. K. Pradbhakar and S. P. M. Rao, IAPTBulletin, 20, 113, 2003.

9. P. A. Fokker, J. I. Dijkhuis and H. W.Dewijin, Phys. Rev., B55, 2925, 1997.

10. J. Y. Prieur et al, Physica B., 219-220, 235,1996.

11. S. S. Makker et al, J. Phys. Condens. Matter,10, 5905, 1998.

12. I. V. Volkov, S. T. Zavtrak and I. S. Kutten,Phys. Rev., 56, 1097, 1997.

13. P.N.T. Wells, Biomedical Ultrasonics,Academic Press, London, 1977.

14. W. L. Nyborg, Ultrasound : Medical Appl.,Biological effecs and Hazard Potential,Plenum, N. Y., 1987.

15. S. K. Shrivastava and Kailash, J. Biosc., 30,269, 2005.

16. S. K. Shrivastava and Kailash, Bull. Mater.Sci., 27, 383, 2004.

17. M. P. Kapoor, J. Pure Appl. Ultra., 19, 104,1997.

18. R. K. Saha. S. K. Sen., S. K. Sharma andB. D. Roy, Abstracts, XII-NSU, Amritsar,43, 2003.

19. S. Saha, S. Karmakar, R. K. Saha, M. Roy,S. Sarkar and S. K. Sen, Abstracts,XII-NSU, Amritsar, 44, 2003.

20. S. Chiled, C. L. Hartman, L. A. ScheryandE. L. Carstenson, Ultr. Med. Bio. 16, 817,1990.

21. B. B. Goldbergand P. N. T. Walls (Eds),Ultrasonics in clinical diagnosis, ChurchillLivingstone, Edinburgh, 1983.

22. L. A. Frizzel, Encyclopedia of AppliedPhysics, VCH Pub., New York, 22, 475,1998.

23. P. N. T. Wells, Rep. Prog. Phys., 62, 671,1999.

24. R. S. Khandpur, Abstracts, XII-NSU,Amritsar, 41, 2003.

25. A. J. Colemon and J. E. Saunders, Ultra.Med. Bio., 15, 213, 1980.

59


TWINNING AND TWINS

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Methodologically twins render valuable service to the science of human genetics. Researches ontwins in India done by the scientists of different disciplines appear to be still in a formative period.In this paper the biology of twins is briefly described along with relevant twin researches inIndia ; moreover, researches in our laboratory conducted in the area of twins specially relatedto human genetics are presented. Interdisciplinary researches on various problems of twins arerequired and the knowledge thus achieved could be used for the development of human geneticsand biomedical sciences.

* Human Genetics Laboratory, Department of Anthropology,University of Calcutta. 35 Ballygunge Circular Road,Kolkata-700 019. e-mail : [email protected]

AINTRODUCTION

lthough research investigations havecontinued in different branches of biological

sciences in the area of twin studies, the issue is yetto be resolved convincingly so that it mayopen new vistas in development of human geneticsand biomedical sciences in India. An attempt hasbeen made in this paper to assess the extent ofresearches on twins in India including works in ourlaboratory.

OCCURRENCE OF TWIN BIRTHS,ETIOLOGY, ESTIMATION AND ETHNICDIFFERENCE OF TWINNING ANDZYGOSITY DIAGNOSIS OF TWINS

The interest and curiosity involving twins maybe found in ancient mythology where twins wereconsidered to be supernatural. The commoner hasthe notion that the twin birth is an accidental andrare phenomenon. In reality it follows a quantitativerhythm which recurs worldwide among all groupsof populations. It is, therefore, not an accidentalphenomenon but is determined by certain lawsgoverning generation in human species. The use oftwins as a research tool in service of man was firstproposed by Sir Francis Galton with a great

foresight in the second half of the nineteenthcentury.

Regarding occurence of multiple births in humanspecies Hellin put forward a mathematicalproposition which is now known as Hellin’s Law.According to this law in human species an averagenumber of one twin birth is found in every 89single births, one triplet birth in every 892 singlebirths and so on. Thus, within the limits ofprobability, one X multiple birth would be seen inevery 89(x-1) single births.

It is now known and generally acceptedthat identical/monozygotic (MZ) twins arederived from a single fertilized egg whereas non-identical/dizygotic (DZ) twins developed fromfertilization of double eggs by double spermsseparately. The two members of MZ twin pair willbe always of same sex i.e., male-male or female-female. On the other hand, two members of DZtwin pair may be male-male, female-female ormale-female.

For estimation of proportion of MZ and DZtwins in a population a statistical method wasdeveloped by Weinberg1. In a population in which

secondary sex ratio is 1 : 1, DZ twins of ;

and ... types should occur according to

= Male, = Female

60


the chance frequencies 14

12

14

: : . This means that

the number of same-sex DZ male and female twin

pair 14

14

+ would be same as that of opposite-sex

twins, 12

or the total number of DZ twins would

be twice that of the observed number of opposite-sex twins. Therfore, the number of MZ twins isobtained simply by subtracting the number ofdizygotics from the total number of all twins.

On a racial basis the declining rate of twinningfrom highest to lowest is found among Negroes,Caucasians (Whites) and Mongolians. The Africantribe, Yorubas from Nigeria is reported to be havingthe highest average of one twin pair in 22pregnancies. On the other extreme, the Japaneseaverage only one pair in about 160 births and evenlower rates have been reported for other Mongoloidgroups.

The most important aspect of use of twin methodof study in human genetics is to diagnose thezygosity of twins, i.e., whether they are MZ orDZ twins. Therefore, classifying a set of twinsaccording to zygosity is a prior task before usingthem in human genetical research work. Theuniqueness of twin study in human genetics is thatit offers to determine the relative role of heredityand environment and their interactions in respectof qualitative and quantiative traits of man whichmay be morpho-metrical, physiological, bio-chemical and behavioural in nature. The identicalor MZ twins with the vital function of theirgenotypes remain similar or concordant throughouttheir lives, even in widely different environments.Methodologically, therefore, twins render valuableservice to the science of human genetics.

The reliability of determination of zygosity oftwins improved gradually by using efficient methodsviz. :

1. Fetal membrane method

2. Similarity method

3. Weinberg’s differential rule

4. Mailed questionnaire

5. Genetic markers, and

6. DNA finger printing.

In fetal membrane method, the physicians havefrequently tried to judge whether a twin birth isMZ or DZ by means of analysis of the afterbirthof twins i.e., amnion, chorion (germinal discs ofthe fetus) and placenta (germinal disc attached tothe ulterus by placenta). All twins enclosed in asingle chorion are indeed sure test of monozygosity.

Earlier, in most twin studies the similaritymethod of diagnosis was based on a multitude oftraits. Concordance or similarity and discordanceor dissimilarity of hair and facial traits were usuallyconsidered in similarity method for zygositydiagnosis of a member of a twin pair.

The Weinberg’s differential rule is alreadydescribed in the text earlier. In this methodindividual twin pair is not subjected to zygositydiagnosis but MZ and DZ twin pairs are statisticallyestimated from total twin population.

Psychologists developed this twin zygositymethod by mailed questionnaire. In this method aset of well designed seventeen questions(approximately) are mailed to parents of twins oradult twin pairs and are asked to fill up thequestionnaire. By scoring the rating of concordanceor discordance of question answers the pairs werediagnosed as MZ or DZ twins.

In the method of twin zygosity by geneticmarkers, single locus traits such as blood groups,red-cell enzyme systems, serum proteins, etc. whichfollow Mendelian inheritance are taken intoconsideration. Concordance in respect to numberof genetic markers increases the probability oftwin pair being monozygotic whereas singledifference in any system immediately recorded thepair under study as dizygotic twins.

In the method of twin zygosity by DNA fingerprinting, DNA analysis with multilocus minisatelliteDNA probes has been used for zygosity

61


determination of twins. The international status ofresearch in use of microsatellites in zygositydiagnosis of a twin pair is most reliable anddependable since its efficiency is claimed to be at99.97% level of probability.

BRIEF DESCRIPTION OF TWIN RESEARCHIN INDIA

A recent exhaustive review on Twin Researchin India2, covering most of the works availablefrom the existing literature, clearly showed thatscientific workers explored twin study in Indiamainly on the following lines (a) twinning rate,(b) maternal age and twinning, (c) mortality rate intwins and (d) zygosity determination of twins andestimation of role of heredity and environment inrespect of particular trait.

On the basis of an arbitrary sample size of 3000births covering various regions of India, the reportedrates fluctuate between 2.7 per thousand in Ludhiana(Punjab) and 21.8 per thousand in Srinagar (Jammuand Kashmir). The MZ twinning rate varies between1.42 per thousand in Mysore (Karnataka) and 7.90per thousand in Lucknow (Uttar Pradesh) whereasDZ twinning rate varies between 2.94 per thousandin Howrah (West Bengal) and 13.8 per thousand inNagpur (Maharastra).

The effect of maternal age on twinning wasinvestigated by a number of workers. The maximumincidence of twinning in the age groups 35-44,25-34 and 15-24 years was found to be 62.4%,59.9% and 37.5% respectively. Guha observedhigher trend of twinning rate with advancing ageof the mother. The gradual increase of twinningrate from the age group 30-34 years and upwardsis due to increase of DZ twinning whereas MZtwinning rate did not show a clear trend of increaseof decrease.

The literature on perinatal mortality rate oftwins available in India show a wide variationranging from 0.104 to 0.344 (Trivedi andMatashaw4 and Srivastava et al.5).

The first attempt to estimate twin zygosity usingWeinberg’s differential rule was made by Sarkar6

in the All India Survey. The proportion of MZ andDZ twins in percentages in differential racial andgenetic heterogeneity of Indian populations wasfound to be 34.5 : 63.6. Further works with samemethod were done by Goswami and Wagh7 inMadhya Pradesh and Guha3 in West Bengal.Srivastava et al.5 and Sharma8 made efforts todetermine zygosity of twins in precise way withthe help of both morphological traits such assomatoscopy, somatometry, dermatogiyphics,pattern of placentation etc. and genetic traits suchas PTC taste sensitivity, secretor factors, bloodgrouping, colour blindness, G6PD etc. It wasSharma9 who for the first time used adequatenumber of standard genetic markers such asA1A2BO, CcDEe, MN, Kell, Duffy, ABH secretorfactor etc. for proper diagnosis of 48 pairs ofPunjabi twins in Chandigarh. The relativecontributions of genetic and environmentalcomponents in the variability of lung functionvariables were determined based on 54 pairs ofzygosity diagnosed Bengalee twins with blood types(ABO, Rh, MN), finger prints, physical appearancesand parental history10.

TWIN RESEARCH CONDUCTED BY THEAUTHOR AND COWORKERS ; ITSIMPLICATION IN HUMAN GENETICS

An attempt has been made to throw some lighton the question of hereditary nature of twinningwith Bengalee twin materials. For the purpose 77pedigrees, each with four generations, werecollected from rural Bengalee population inhabitingvillages surrounding Habra township in North 24Parganas district, West Bengal. The incidence ofoccurrence of twins was first detected in a particularfamily and then considering twins as probandthe pedigree was constructed upto fourgenerations. Two important pedigrees are presentedin Appendix-1. The occurrence of twins in thegenerations of pedigrees is due to genetic factors.

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It can be deduced that twinning is familial traitwhich fits the hypothesis of genetic control11.

In our laboratory data on hair variables such asincidence of medulla, diameter, area of cross-section and weight were collected from 48 pairs ofzygosity diagnosed German twins with 11 geneticmarkers. With some limitations heritability or h2

statistic has been estimated using formulah DZ Mz Dz2 2 2 2= −σ σ σb g/ . Here h2 is theproportion of variability in twins attributable to

genetic variation and σDz2 and σMz2 are theintrapair variances of the DZ and MZ twin pairsrespectively. The incidence of medullary structure,diameter, area of cross-section and weight of hairheritabilities have been found to be 0.96, 0.92,0.87 and 0.59 respectively12. Further, heritabilitiesof some important parameters of antioxidant defensesystem like glucose-6-phosphate dehydrogenase(0.93), catalase (0.72), glutathione peroxidase (0.60)and lipid peroxidation (0.50) are estimated in redblood cells by twin study.

Pedigree 1. (i) With one pair of twins both females.(ii) With another wife, son has two pairs of twins one same sexed females and the other

unlike sex.(iii) Two pairs of twins in a family.

[NB : = Male, = Female, = Proband]

APPENDIX-I

Pedigree 7. Twnning in families in successive generations.(i) With one pair of twins both females.

(ii) With another wife, son has two pairs of twins one same sexed females and the otherunlike sex.

(iii) Two pairs of twins in a family.

[NB : = Male, = Female, = Proband]

63


As mentioned earlier, in human genetics zygositydiagnosis of MZ and DZ twins using blood groupsand other genetic markers is prior task in order todetermine the relative role of heredity andenvironment and their interactions with respect toany trait in man. Significant contribution has beenmade on the methodology for diagnosis of twinzygosity by pointing out that the indiscriminate useof several conventional genetic markers indetermination of zygosity of twins from a particularpopulation should be discontinued. This is becauseefficient sequential search procedure for twindiagnosis utilizing frequency of genetic markers ina population has been developed in our laboratoryand demonstrated in the German population.Efficient genetic markers have to be selectedconsidering the gene frequencies in the populationconcerned. Moreover, large number of geneticmarkers must usually be investigated because oflow mean heterozygosity of proteins and antigen.It is hoped that this method will be helpful in theefficient application of genetic markers to zygositydetermination in any population. The formulaedeveloped are quite general and procedure explainedcan easily be generalized to other situation13.

Assuming twinning as a recessive trait the higherincidence of twinning rate in the Bengalee Muslimpopulation than in the Bengalee Hindu populationis attributed to inbreeding14. The Bengalee Muslimpopulation practise consanguineous marriageleading to inbreeding where the triat concerningrecessive genes escalates.

Zygosity of 15 pairs of Bengalee twins wasdiagnosed using genetic markers like ABO, Rh,MN, Hp and PTC in our laboratory. Of these MZand DZ twins were found to be 7 and 8 pairsrespectively. The zygosity diagnosed set of twinswere utilized to investigate the genetic influence indetermining the effect of cadmium on glutathionecontent of red blood corpuscles. The results clearlyshow that genetic endowment is an importantdeterminant of reduction in glutathione content of

human red blood corpuscles after treatment withtoxic element, cadmium15.

CONCLUSION

Noting the absence of any nationwide Registerfor twin birth, it appears that accurate assessing ofrates in the diversity of social and biologicalbackground in populations in India is nearlyimpossible and attempts to estimate them mightlead to confusion. On the other hand, the variationin twinning frequencies in different populations ofIndia offers a unique opportunity to investigatefactors responsible for this variation. InIndian population, besides considering well knownfactors such as birth order, maternal age, etc.affecting multiple births specially of twins, the roleof socio-economic, rural-urban differences andinbreeding effect (like in Muslim community)affecting twinning rates may well be examined.It appears that an active centre involving twinresearch is a dire need in a country like India.In the last decade the development of molculartechnique and its applications in biologyhave opened new avenues of research previouslyunavailable. Emphasis should be given on moleculartechnique specially use of microsatellitesfor determination of twin zygosity. These diagnosedsets of twins could be utilized for multiplepurpose in researches on human geneticalproblems.

It appears that research on twins is notconsidered seriously as it ought to be among thescientific workers of different disciplines in India.Fortunately, importance of twin research is nowrealized. What is needed most in the Indian contextis interdisciplinary work on various problems oftwin study so that knowledge achieved therefromcan be utilized not only for benefit and welfare oftwins but also for development of human geneticsand biomedical science in general.

64


ACKNOWLEDGEMENT

The author acknowledges cooperation fromDr. Indrajit Dasgupta, Fellow, DST (Governmentof West Bengal) and Mr. Somnath Basu, M. Sc.who have given their able assistance in variousways during preparation of the manuscript ofthe paper.

REFERENCES

1. W. Weinberg Arch. f. Ges. Physiol. 88 ;346-430, 1901.

2. A. B. Das Chaudhuri and S. BasuBio-Cultural Frontiers of Man (Eds. K. C.Tripathy and N. K. Behura), 25-38, UtkalUniversity, Bhubaneswar, 2001.

3. A. Guha J. Ind. Anthrop. Soc. 17 ; 61-68,1982.

4. R. R. Trivedi and N. D. Matashaw J. Obstet.Gynecol. Ind. 15 ; 591-598, 1966.

5. J. R. Srivastava, M. Bhalla and J. N. BhallaInd. Pediat. 14 ; 121-127, 1977.

6. S. S. Sarkar Trans. Bose. Res. Inst. 30 ; 235-238, 1967.

7. H. K. Goswami and K. V. Wagh Acta Genet.Med. Gemellol. 24 ; 347-350, 1975.

8. K. Sharma Acta Genet. Med. Gemellol. 29 ;157-163, 1980.

9. J. C. Sharma Ann. Hum. Biol. 10 ; 163-171,1983.

10. S. Chatterjee and N. Das. Ann. Hum. Biol.22, 289-303, 1995.

11. A. B. Das Chaudhuri and S. Basu J. Dept.Anthrop 1; 5-10, 1993.

12. A. B. Das Chaudhuri Progress in Clinicaland Biological Research (Ed. W. E. Nance),261-268, Alan R. Liss, Inc., New York,1978.

13. A. B. Das Chaudhuri Acta Genet. Med.Gemellol. 40 ; 159-164, 1991.

14. A. B. Das Chaudhuri, S. Basu andS. Chakrabarty Acta Genet. Med. Gemellol.42 ; 35-39, 1993.

15. A. B. Das Chaudhuri, S. Chakrabarty andT. Bandhopadhyay Acta Genet. Med.Gemellol. 48 ; 45-50, 2000.

DOYOU KNOW ?

Q7. Which thing lives for 17 years but is active only for 5 weeks, spending the rest of its lifesleeping ?

Q8. A normal human needs about 3300 cal/day for his daily survival. How much does a full growncrocodile need?

65


SOMETHING TO THINK ABOUT

STORING EXCESS CO2 UNDERGROUND

��(�� )� �� &��

N uclear wastes need to be stored in specialcontainers to avoid contamination of the

environment which will be lethal. It may be timeto seriously devise CO2 storage schemes too becausevast amounts of CO2 coming out of gasoline drivenvehicles and thermal power plants are now wellbeyond the assimilative capacity of nature.

CO2 level is rising in the atmosphere at a rateof about 2 molecules per million. A recent articlepublished in Scientific American, (July 2005, p 49)says that when William Shakespeare took a breath,his lungs received 280 molecules of CO2 per millionmolecules of atmosphere. Now he would breath in380 molecules.

CO2 emitted by vehicles is scattered andtherefore, it posed difficulties of collection andstorage but that from thermal power plants throughchimneys should be more amenable for storage. Amedium size car going 10,000 miles consuming 1ton of gasoline will release about 3 ton of CO2 outof the tail pipes. A large (1000 mega watt) coalfired thermal power plant would produce some 6million tones of CO2 annually, roughly equivalentto 2 million cars. Today some 25 percent of totalworld wide CO2 emission is due to thermal powerplants equivalent to 1000 big plants. The number isexpected to double in the next decade. India andChina will be main contributors to enhanced CO2

emission.

The consequences of this CO2 in the atmospherewill be global warming, gradual increase of sealevel, CO2 absorption in the sea acidifying thewater etc. Consequences of these changes may be

devastating. In the past there was an equilibrium inthe CO2 cycle where CO2 was absorbed in sea,where it went in skeletons of sea animals, and byplants on land which produced CO2 absorbingcarbon to grow. However, there is not enoughgreen cover now and photosynthesis being a slowprocess, there is just not enough land mass to growall the excess CO2 in the atmosphere. One theorysays that global warming will bring in climatechange and melting of polar ice and warming ofthe northern areas of the globe will create newgreen cover to restore ecological balance. This,however will destroy the civilization that we havenow. There will be catastrophic changes unless wedevelop new technologies with priority to store theexcess CO2 being emitted to air.

At the same time mankind has to concentrateon energy more efficiently and substitutingnoncarbon, renewable or nuclear energy sourcesrather than fossil fuels (coal, oil and natural gas)which are primary sources of man madeatmospheric CO2.

The strategy that is recommended for battlingthe CO2 menace in the first phase envisages captureof CO2 emissions from power plants and subsequentinjection into geological underground formationsfor long term storage. This is contributingsignificantly towards slowing down the rise of CO2

concentrations in the atmosphere.

There are essentially three kinds of power plants.The traditional plants burn coal fully in one step inair, converts water to system at high pressure thatturns a turbine to generate electricity. In theimproved process, coal gasification is done in

66


steps, the first, burns coal partially in presence ofoxygen to produce a synthetic gas, ’syngas’containing hydrogen and CO2. It then removessulphur and burns Syngas in air in gas turbine. Inthe third kind under development, only oxygen isused.

The CO2 emission from these plants first needsa treatment for sulphur removal after which the gascan be injected into a solution of brine in sand ina geological formation deep down in a way thatthis will not affect the aquifer. The layer targetedis salt-water formation more that 2 km below thesurface in sedimentary rock. At such depth, becauseof the pressure that is many times the atmospheric

pressure, CO2 will go into a ‘super critical-phase’one that is nearly as dense as the brine it replacesin the geological formation.

Other schemes envisaged include storage indeplected oil and gas reservoirs, in coal seames, inminerals (e.g. serpentine) that form stablecarbonates and, of course, will be more controversialbecause nobody is sure whether this CO2 will gointo the bodies of animals more efficiently orwhether it will be counter productive.

What is no longer debatable is that somethingneeds to be done on a massive scale when mankindis still fit enough to think, plan and act.

ANSWERS TO “DO YOU KNOW?”

A1. In planet Neptune.

A2. 21 years.

A3. Ante Meridiem.

A4. Louise Brown.

A5. About 220 feet.

A6. The python.

A7. A type of Grasshopper called Cicada.

A8. Only about 200 cal/day.

67


E

SHORT COMMUNICATION

HIGH SPEED KNOCKOUT IN THE BRAIN

'�� #��"��

very time we think of the brain we arefilled with wonder. It is an exquisitely

made organ, neatly packed and protected by asturdy and robust skull within which it sits packagedin a skin that allows things to enter and exit in aselective and planned manner. The more we learnabout it, the more it defies easy categorisation. It isalso the bugbear of reductionists, people who liketo say things like “the heart is nothing but apump”, “the kidney is nothing but a filter” or,more to the point, “the brain is nothing but acomputer”. The answer, of course, is that it is andit is not. The mechanisms of operation can turn outto be fundamentally different. The acquisition ofinformation, addressing and storing it and recallare only formally similar but the way some ofthese are handled by the brain and by the computerare different indeed.

Yet, what draws people to make such “nothingbut” statements ? I believe it is this formalsimilarity, or a study of only a part of the whole,which leads to this—quite like the famous case ofthe six blindfolded people where, each in his ownway, was describing the elephant by feeling butone part of it. The brain operates on the basis ofmeasured transport of specific chemical substancesacross cells and the consequent triggering ofelectrical signals. Basic perception in the brain andin the central nervous system itself, uses both thesemodes. When you feel something, it is a

consequence of these primary events.Neurophysiology describes the actual way the nervecells are arranged and connected for their function.Neurochemistry discusses the chemical aspects ofthe matter while electrophysiology attempts toprovide the details of the electrical activities ofthese cells and tissues.

Here too, an understanding to the brain isattempted at two levels ; one at the molecular,cellular and tissue level which is what much oftoday’s molecular and cell biologists do. The otherlevel is to approach it as a whole system in itscomplexity and analyze it, the way a systemsengineer or a computer hardware person does.

The molecular and cellular level approach is thebottom-up approach while the systems approach istop-down. It is clear that the two approachescomplement one another and that a total under-standing will come about only when we combinethe two. Today, we are yet to understand in detailindividual processes and responses in the brain,such as what causes pleasure, what causes pain, orwhat the detailed steps are when we react orrespond to a stimulus. The molecular biologistwould say that since many of these are hardwiredand genetically determined through genes and theDNA molecule, it is worthwhile to identify theactual chemical molecules involved and thebiological steps that lead to some of these aspectsof brain function.

We seem to be doing a lot of things by instinct,many through experience and quite a few bylearning from examples. Some of the tastes that we

* L. V. Prasad Eye Institute, LV Prasad Marg, Banjara Hills,Hyderabad 500034, e-mail : dbala@lubly:itph.net. Articlepublished earlier in The Hindu, Reproduced with permission.

68


acquire or experiences that we enjoy are reallythat—acquired, meaning that we learn to derivepleasure or enjoyment even from substance orstimuli that are not necessarily immediatelyacceptable. The use of mood-altering drugs forenjoyment is one such. Likewise, to enjoy alcoholis to acquire a taste for it, by first overcoming theinitial negative response. Tobacco chewing orsmoking is another such example. The first reactionis of distaste or even pain. It is the aftertaste whenthe nicotine hits the brain cells that the tobaccouser starts to enjoy.

PLEASURE CENTRES

What are these pleasure centres or pain centresin the brain ? On the anatomical or large-scalelevel physiologists have identified zones, regionsor parts of the brain which are largely concernedwith feeling, response, activity or the other. Hence,it is said that one hemisphere is the intellectualpart while the other hemisphere is the aestheticpart. The processing of signals that reaches fromthe eye to the brain occurs in the visual cortex andthe final result is the perceiving of the object.

One can go further down into the cell andmolecular level. Specific molecules and substancesare used to tickle the pleasure centres in our brain.This is something that mankind has known sincethe dawn of civilization. Hemp or bhang, charas orcannabis, as they are called, have been known inHindu mythology. Persian and Arabic scholarshave written about it. Shaik Tafar Shirazi of Irantalks at length about them. The Maratha kingShivaji went a step further and used the tincturedhemp leaf in wine for his enjoyment. The betelnutis hallowed in Hindu, Parsi and Jain scriptures,Social grace demanded that the host offers hisguests a few betel leaves and a couple of betelnuts. Likewise is a third narcotic substance whichcomes from calatropis, called akra or mandara (ormadar as the Hindu physician Susruta called it).Legend has it that Emperor Akbar was so namedas he was born under an Ak bush.

Then there was this wily custom recorded incolonial books about Indian Ayahs or nannies, whowould feed a crying infant a bit of opium so thatthe child is comforted and goes to sleep. Cocainecomes from Latin America and is perhaps one ofthe most sought after drugs that soothes the tensemind and dulls one into a sense of relaxation,peace and satisfaction. Modern chemistry andmedicine have given us molecules such asamphetamine which acts even faster than cocaine(hence the slang “speed” for this drug).

How do these psychoactive drugs act ? We arelearning more about it now and an importantadvance has been made by two groups of scientistsworking at the Duke University Medical Centreand in North Carolina University, both in the stateof North Carolina in the US. Mark Wightman ofthe University of North Carolina and Marc Caronof the Duke University Medical Centre, along withthree other associates, have published an interestingpaper in the 15th February 1996 issue of Natureon this subject.

DAT’S THE WAY IT WORKS !

This group built on the already known fact thatthe cocaine-amphetamine class of antidepressantsand drugs of abuse cross the blood-brain barrierand interact in the brain with a protein called thedopamine transporter or DAT. Dopamine is animportant molecule that acts as a neurotransmitter;it is a chemical in the brain that modulatesinteraction between neurons or nerve cells. Itsaccumulation and transport across neurons isimportant, both in the control of limb movementand in the response to stimuli that offer pleasure oraversion. You can neither have too much ofdopamine in a neuron nor too little of it ; the levelhas to be regulated so that neuronal activity andbrain response are appropriately controlled. Thisprotein called DAT does precisely that. It is able tobind to dopamine and control the amount ofavailable or free dopamine over a function of timeand across the tissue. Too much of dopamine can

69


make you hyperactive while too little of it canresult in uncoordinate movement of limbs. TheNorth Carolina scientists argued that if we were toremove the dopamine transporter protein completelyfrom the brain cells—would the brain then becomehyperactive forever ? The argument is that controlin the level of dopamine would then be gone ; thisneurotransmitter would then not be carted off butwould be available all the time and the individualwould be on a constant “high”. To test this idea,they chose to work with the mouse as anexperimental animal and resorted to a technologythat is referred to as gene knockout. It was possiblefor them to breed mice which lack DAT byartificially disrupting the gene that produces DATin the mouse. Lo and behold, these mutant micewhich lacked the DAT protein were hyperactive,as if they were under the influence of cocaine oramphetamine all the time. In addition even whenthese mice were given doses of cocaine they showedno further response.

HELP FOR PARKINSON’S PATIENTS ?

There is an important corollary to this work ; ifone were to block DAT by specific chemicals andinhibitors, that could become an importantpharmaceutical way to handle illnesses such asPartkinson’s disease. In this illness, the effectivelevels of the neurotransmitter dopamine aresignificantly reduced compared to the normalindividual. It is this lack of dopamine that lends aParkinsonian to suffer from motor disability. Hence,this is why the patient is given the drug L-Dopa,which increases the levels of dopamine in the brainand CNS. The present research suggests thealternative, namely blocking the pathway by whichdopamine is carried away from the neurons, orinhibiting DAT. The use of DAT inhibitors wouldthus have beneficial effects on Parkinson’s patients.

Not only does this research point to specificregions of activity in the brain, namely where andhow pleasure centres are activated, but it also hasan immediate end use. Interestingly such an

experiment could not have been done with suchelegance and ease until about ten years ago. It hasbeen made possible thanks to gene knockouttechnology. What one does here is knock out ordisrupt one particular gene and then study theeffect or what happens in the whole animal. Thisis not a random or shotgun approach but a precise,molecular surgical one, addressing itself to aparticular gene in the cells. In principle, a simpleway to know the function of a single gene is tobreed an animal lacking that particular gene andthen look for the effects of this change on theanatomy or the physiology of the animal. In geneknock-out technology what one does is to choosenot the adult animal cells but those from the earlyembryo of the animal, called the embryonic stemcells or the ES cells. One knocks out a gene in twosteps. First, one makes a functionally disabled or adamaged copy of the gene under study andintroduces it physically into the ES cells. What thisdefective gene would do when it is introduced intothe ES is look for and home in on its healthycousin, namely, the same gene inside the cellwhich is not disabled. This process of pairing-upof the two similar genes is referred to as genetargeting. The result of this doubling up is to alsotransfer the disability of the introduced gene intothe “native” gene, which also gets disrupted. Notethe surgical precision and specificity of this process.The knock-out gene looks for, recombines anddisables this partner gene and none else. All theother genes in the cells remain unaltered.

Now comes the next step. Here, we pick up thegenetically modified ES cells where the gene isdisrupted, put them in the womb of a fertile motheranimal and generate a live animal. The noveloffspring thus born will be different from its parentsonly in a single gene. All other genes are identical.Thus, we have a specifically disabled gene and ananimal with a precisely disabled trait. A sort ofbottom-up approach, wherein the effect of amolecular change on the whole grown animal isstudied.

70


��

Lac, a natural resin, is a minor forest produce,cultivated and collected by tribals inhabitingthe sub-hilly tracts of Jharkhand, Chattisgarh,West Bengal, Madhya Pradesh, Maharashtra,Orissa and Uttar Pradesh. Before the advent ofsynthetic plastics and resins, lac was invaluablein moulding and insulating industries. India,then under British rule, had an unparallelglobal monopoly over the lac trade. Lac is used inpaints and varnishes, adhesives, food andpharmaceuticals, cosmetics and ethnic jewellery,electrical and leather industries, besides lac dye.

Realising the strategic importance of thiscommodity, the then Imperial Govt. of Indiaconstituted the Lindsay-Harlow Committee in 1920,

to look into all aspects of the country’s lac tradeand its development. On the suggestions of thisCommittee, lac merchants organised the IndianLac Association for Research, under the aegis ofwhich, the foundation stone of the India LacResearch Institute (ILRI) was laid on 20September, 1924, at Ranchi. It started functioningunder the founder Director Mrs. Dorothy Noris.Subsequently, on the recommendations of theRoyal Commission of Agriculture, the Indian LacCess Committee (ILCC) was constituted, whichtook over the reigns of the ILRI in 1931. TheILCC also organised and maintained liaison withLondon Shellac Research Bureau, UK and ShellacResearch Bureau, Polytechnique Institute ofBrooklyn, USA. As a result of reorganisation of

INDIAN LAC RESEARCH INSTITUTE, NAMKUM, RANCHI

71


agricultural research and education within thecountry, the ICAR took over the administrativecontrol of the ILRI from 1st April 1966. ThisInstitute is thus, one of the oldest, within theICAR system, having completed 80 years offruitful service to the nation.

A Unique Institute

The ILRI is unique and only one of its kind inthe world, being devoted exclusively to all aspectsof lac cultivation, processing and utilisation. Itfollows a multidisciplinary approach in carryingout researches on beneficial insects (lac insectsand predators / parasites of lac insect pests), forestbased lac host trees as well as bushy / shrubhosts, for a wide range of target beneficiaries-from tribal farmers, craftsmen / artisans to high-tech industrial houses, for applications in surfacecoatings, fine chemicals, electrical insulation, etc.ILRI has the world’s richest and oldest books andliterature on lac, a well organised lac museumdepicting all aspects of lac and a collection of awide range of lac host plants.

Location and Agro-Climate

The Institute is located 9 km. South-east ofRanchi city, on the Ranchi-Jamshedpur highway(NH 33), at an altitude of 650m above meansea level, 23°23' N latitude and 85°23' Elongitude. The soil status of the Institute indicatesadvance weathering on granitic gneiss. The soilof the experimental farm is of lateritic type. Thearea experiences mild, salubrious climate, with arather heavy rainfall pattern of about 1,400 mmaverage, of which, about 1,250 mm is during themonsoon.

Mandate

ILRI is a nodal Institute at national level, forresearch and development on all aspects of lacproduction, processing, product development,training, information repository, technologydissemination and national / international

cooperation. It is mandated to :

● Develop lac culture technologies, adoptingexisting or genetically improved lac insectsand hosts.

● Develop lac processing techniques for theindustry.

● Conduct research for diversification oflac utilisation, leading to pilot plantdemonstration.

● Act as a repository of information on lacproduction, processing and utilisation.

● Transfer technologies to farmers andentrepreneurs.

Organisational Structure

Headed by a Director, the Institute hasthree Research Divisions viz. (i) Lac Production,(ii) Lac Processing and Product Development and(iii) Transfer of Technology. The Divisions addresstheir identified mandates through core programmes.Presently, the entire research programme of theInstitute is divided into 6 thematic areas, calledCore Programme, listed below :

Core Programmes

1. Productivity and Quality Improvement

2. Production Improvement and CropManagement

3. Processing and Value Addition

4. Product Development and Use Diversification

5. Technology Assessment, Refinement andDissemination

6. HRD for Capacity Buildings in LacProduction, Processing and Value Addition.

Infrastructure

Manned by a strong band of dedicated scientists

72


from various disciplines including entomology,organic chemistry, physics, engineering, bio-technology, etc., the Institute has about 207 staffin scientific, technical, administrative andsupporting categories. There are several well-organised and equipped service sections to supportresearch management of the Institute. Some ofthese Sections are : Administration, Audits &Accounts, Library, Farm, Estate, Dispensary, ARIS,Product Demonstration Unit, Guest House etc. TheInsitute is responsible for the collection andmaintenance of germplasm of lac insect lines aswell as lac host trees. Presently, the ILRI ismaintaining 7 distinct strains of the lac insect, onecross, one in-bred line, as well as 9 insect stocks,collected from various parts of the country. Theexperimental farm area spread over 36 hectareshas all conventional and cultivated lac host plantsand the farm has 1,540 nos. host trees ofSchleichera oleosa (kusum), 2,480 nos. trees ofButea monosperma (palas), 1,351 nos. Zizyphusmauritiana (ber) and 8,695 nos. of minor hosttrees. The field gene bank of the Institute has thefollowing genotypes in stock : palas (13), kusum(4), ber (7), Dalbergia szemaoensis (2), Eriolaenaspectabilis (1) and Albizia saman (2). The Institutehas several prestigious laboratories, viz. HighVoltage Laboratory, Bio-technology and Bio-control Laboratories, Quality Evaluation Laboratoryetc. Besides these, the DTP and publicationfacilities are also available. A number of modernand sophisticated laboratory equipment, includingDSC, FT-IR etc. are available for research on allaspects of lac production, processing and productdevelopment. The ILRI Library has holding ofmore than 50,000 volumes of scientific journals,2,000 rare books, including back volumes ofresearch periodicals in the field of lac and surfacecoatings. Since the holdings of back volumes ofcertain journals date back to circa 1760, the libraryhas been catering to the documentary supplyservices of INSDOC, New Delhi. Besides catering

to the scientists and staff of the Institute, thelibrary also attracts researchers of neighboringeductional and research institutional, including BIT,RU, BAU and HARP, Ranchi, IIT, Kharagpur,RAU, Samastipur, PU, Patna, NIT, Jamshedpuretc. The Institute website, available atwww.icar.org.in/ilri/default.htm, developed andmaintained in-house, is a valuable source ofinformation on ILRI as well as lac. The QualityEvaluation Laboratory of the Institute caters tothe quality control needs of lac processing / lacproduct industries as well as exporters of lac / lacproducts. This QE lab analyses about 150 samples,on an average, per annum. The lab has facilitiesfor carrying out testing of lac / lac products as perBIS requirements. Over the years, the Institute hasconsistently maintained close collaboration withother ICAR Institutes, State Agricultural and otherUnviersities, and national agencies like ShellacExport Promotion Council (SEPC), Indian Councilof Forestry Research and Education (ICFRE),Bureau of Indian Standards (BIS), TribalCooperative Marketing Development Federation(TRIFED), etc. A number of external projects,funded by agencies such as Department ofBiotechnology, Technology Mission on Cotton,AP Cess Fund and Jharkhand State Govenementare concurrently operational at the Institute. TheILRI has responded to the globalization of lacindustries and agricultural enterprises of the countryas well as structural and functional reorganizationof ICAR. The Institute also has undergonestructural changes and the priorities redefined inthe past to suit R & D needs of the times.

The Institute is confident of addressingchallenging research needs on lac during 21stcentury.

Contact :Indian Lac Research Institute, Namkum,Ranchi-834010Website : www.icar.org.in/ilri/default.htm

73


Conferences /Meetings / Symposia / Seminars Date Topic Contact

8-9 August National Seminar on Organic. Kantharaja2006 Farming for Alleviation of Rural Secretary

Poverty, Association for Promotion of OrganicBangalore. Farming (APOF) APOF, UAS Alumni

Association Building, Bellary RoadHebbal, Bangalore-24Email : [email protected]

18-19 August Emerging Principles & Practices Dr. S.B. Singh2006 of Computer Information Guru Nanak Dev Science and

Technology Engineering College,Ludhiana Gill Park Ludhiana 141006

Email : [email protected]

23-25 September Algal Biodiversity and its Dr. Sivasubramanian2006 Role in Bioremediation Krishnamurthy Institute of Algology

Chennai 9, Lady Madhavan I cross streetMahalingapuram, Chennai-600034Email : [email protected]

9-11 October International Conference on Sangeeta Shukla2006 Toxicology, Toxicogenomics and School of Studies in Zoology

Occupational health & 26th Annual Jiwaji University, Gwalior-474011meeting of Society of Toxicology, Email : [email protected](STOX) Gwalior

25-27 November International Conference on Dr. Ravindra Reddy2006 Natural Hazards and Disasters : Department of Geography

Local to Global Perspectives, Sri Krishnadevaraya UniversityAnantapur Anantapur, Andhra Pradesh-515003

Email : [email protected]

30 November- International Conference on Dr. Debnarayan Jana2 December Lasers and Nanomaterials Convener (ICLAN)2006 Kolkata Department of Physics

University of Calcutta92, A P C Road, Kolkata-700009Email : [email protected]

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Scientists at the US Department of Energy’sBrookhaven National Laboratory have developed anew method for identifying different species ofmicroorganisms living in an unknown “microbialcommunity.”

The method has many applications ranging fromassessing the microbes present in environmentalsamples and identifying species useful for cleaningup contamination, to identfying pathogens anddistinguishing harmless bacteria from potentialbioterror weapons.

The technique which is called “single pointgenome signature tagging” uses enzymes thatrecognize specific sequences in the genetic code.These enzymes chop the, microbial genomes intosmall segments that contain identifier genescommon to all microbial species, plus enoughgenetic information to tell the microbes apart. Asgrowing cultures of microbes to identify species isslow and error prone, scientists have been searchingfor a way to identify key segments in the geneticcode that are short enough to be sequenced rapidlyand they hit upon this method.

(www.bnl.gov, Mar 8, 2006)

ANTI-MALARIA DRUG DEVELOPSRESISTANCE

Malaria which used to decimate entirepopulations in the tropics, largely came to becontrolled in the 1950’s with the use of chloroquinetill people began to develop resistance to it. It wasreplaced by artemisinin, which had been developedfrom a chinese herb and for the last few decades ithas been widely in use. Studies now indicate thatit might meet the same fate as chloroquine, unlessits use is strictly regulated.

S & T ACROSS THE WORLD

IDENTIFYING MICROBES

Scientists from the Pasteur Institute took bloodsamples from hundreds of patients in South-EastAsia, and treated the samples containing the parasitePlasmodium falsiparum to a variety of anti malariadrugs, including artemisinin. The results were thencompared with a similar exercise carried out inrespect of malaria patients in French Guiana. Itwas found that the patients of French Guiana,where the use of artemisinin was not regulated,had developed resistance to the drug unlike thosein Cambodia and other South-eastern countrieswhere there was no resistance to the treatment,because the use of the drug was regulated.

These findings underscore a warning by WHOon the need for extreme all round vigilance whileprescribing artemisinin-based drugs and for its useto be carefully regulated.

(PTI Science Service, Dec. 16-31, 2005)

ARTEMIS TECHNOLOGY

Many objects today have computers ormicroprocessors embedded in them that cannot bemodified by the consumer. For instance, in theautomobile industry embedded systems operate inthe car engein to improve efficiency, operatesatellite navigation, air conditioning etc. A wholeindustry has grown around these embedded systemsand now the Advanced Research and Technologyfor Embedded Intelligence and Systems(ARTEMIS) provides a platform which bringstogether the major companies in this industry.

There are belived to be more objects containingembedded systems than there are human beings onthe earth and by 2020 the capability exists for suchembedded systems to occupy much of our naturalenvironment and react to our preferencesautomatically. To make this a reality the gulfbetween architecture and physics will have to bebridged speedily and while ARTEMIS is seeking

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to do this from the software side, the nano-technology platform ENIAC is trying to do thesame thing from the nano-architecture side.

The embedded systems industry is growing atthe rate of 10% annually, and ARTEMIS which isa public-private partnership that is open for anyorganisation to join has ambitious plans for thefuture.

(CORDIS Tech. Marketplace, March 8, 2006)

IMPROVED WHEAT STRAINS

Australian scientists are developing strains ofwheat that contain a higher proportion of amylose,a particular form of resistant starch for incorporationinto breads, cereals, and other foods to meet thedeficiency caused by the excessive intake ofprocessed and refined food by a majority ofAustralians.

Nowadays one of the most serious health issuesin the developed world is the rise of diet-related

non-infectious diseases, such as cardiac heartdisease, obesity, diabetes, and colorectal cancers.The resistant starch which contains high levels ofamylose, is not digested in the small intestine andpasses into the colon where it is broken down bythe resident bacteria, releasing short chains of fattyacids which is believed to promote bowel healthand reduce the risk of colon cancer.

The inclusion of additional fibre in breads isnow a routine practice, but scientists say that thebenefit of using high amylose wheat in products,such as bread, avoids the need to add supplementaryfibre.

Trials on animals have shown that wheat withhigh amylose levels had significant health benefits,owing to the presence of short chain fatty acids intheir bowels.

In this connection, gene technology has provedparticularly useful in pinpointing the geneticchanges in wheat that are required to create thisnew type of wheat.

(National Academy of Sciences, Feb 27, 2006)

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General PresidentProf. Harsh Gupta, Hyderabad

Immediate Past General PresidentDr. I.V. Subba Rao, Secunderabad

General President-ElectProf. R. Ramamurthi, Tirupati

General Secretary (Headquarters)Prof. Avijit Banerji, Kolkata

General Secretary (Outstation)Prof. S.P. Singh, Kurukshetra

TreasurerProf. A.B. Banerjee, Kolkata

Elected Members of the Executive CommitteeProf. P.N. Srivastava, GurgaonDr. Ashok K. Saxena, KanpurDr. M. Sudarshan Reddy, HyderabadProf. B. Satyanarayana, HyderabadProf. Uma Kant, JaipurDr. Geetha Bali, BangaloreProf. Ranjit K. Verma, Bodh GayaProf. Nirupama Agrawal, LucknowProf. K.C. Pandey, LucknowProf. Col. Dr. Ranajit Sen, Kolkata

Representative of the Department of Science &Technology, Government of India

Prof. V.S. Ramamurthy, New Delhi

Local SecretariesProf. Ajit Verma, NoidaDr. R. P. Singh, Noida

Past General Presidents /Secretaries/TreasurerProf. (Mrs.) Asima Chatterjee, KolkataProf. M. S. Swaminathan, ChennaiDr. H. N. Sethna, MumbaiProf. A.K. Sharma, KolkataProf. M.G.K. Menon, New DelhiProf. R.P. Bambah, ChandigarhProf. (Mrs.) Archana Sharma, KolkataProf. C.N.R. Rao, BangaloreDr. A.P. Mitra, New DelhiProf. Yash Pal, NoidaProf. D.K. Sinha, KolkataDr. Vasant Gowariker, PuneDr. S.Z. Qasim, New DelhiDr. S.C. Pakrashi, KolkataProf. U.R. Rao, BangaloreProf. S. K. Joshi, New Delhi

��

Dr. P. Rama Rao, HyderabadDr. (Mrs.) Manju Sharma, New DelhiDr. R. A. Mashelkar, New DelhiDr. R. S. Paroda, Tashkent, UzbekistanProf. S.S. Katiyar, KanpurDr. K. Kasturirangan, BangaloreProf. Asis Datta, New DelhiProf. N.K. Ganguly, New DelhiProf. M. K. Singal, DelhiDr. (Miss) S.P. Arya, New DelhiProf. H.P. Tiwari, AllahabadProf. S.P. Mukherjee, KolkataDr. (Mrs.) Yogini Pathak, VadodaraProf. B.P. Chatterjee, KolkataDr. S.B. Mahato, Kolkata

Sectional PresidentsDr. M. S. Sachdev, New DelhiProf. U.C. Goswami, GuwahatiProf. Kisore K. Basa, BhopalProf. Anil K. Singh, MumbaiProf. M.P. Singh, LucknowMr. Sujit Kumar Mitra, KolkataProf. P. C. Pandey, KharagpurProf. M. Surendra Prasad Babu, VisakhapatnamDr. Rakesh Chandra Agrawal, RaipurProf. J.C. Misra, KharagpurDr. Amal Roy Chowdhury, KolkataDr. Rakha Hari Das, DelhiDr. R.N. Singh, Dehra DunProf. S.M. Reddy, Warangal

Elected Members of the CouncilDr. (Mrs.) Vijay Laxmi Saxena, KanpurMr. Gauravendra Swarup, KanpurProf. V.K. Verma, New DelhiDr. Dhyanendra Kumar, Arrah.Prof. Santosh Kumar, BhopalProf. P.V. Arunachalam, Tirupati.Dr. K. Jeevan Rao, Hyderabad

Representatives/Co-opted MembersMr. Nilangshu Bhusan Basu, KolkataDr. H.S. Maiti, KolkataProf. S.P. Mukherjee, KolkataProf. Col. Dr. Ranajit Sen, KolkataProf. Anupam Varma, New Delhi

Editor-in-Chief of Everyman’s ScienceProf. S.P. Mukherjee, Kolkata

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THE INDIAN SCIENCE CONGRESS ASSOCIATION14, Dr. Biresh Guha Street, Kolkata-700 017, INDIA

Telegram : SCICONG : CALCUTTA Fax : 91-33-2240-2551Telephone : 2247-4530, 2281-5323 E-mail : [email protected] : http://sciencecongress.org [email protected]

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14, 700 017,

Terms of Membership and Privileges of Members :

Membership of the Association is open to persons with Graduate or equivalent academic qualification and

interested in the advancement of science in India.

1. Member : A person willing to be enrolled as new Member has to pay an annual subscription of Rs. 200/-

along with an admission fee of Rs. 50/-* (for foreign U.S. $70) only. The annual subscription of a Member

shall become due on the 1st April of each year. Anyone who fails to pay the subscription on or before the

15th July in any year shall lose the right of voting and / or holding any office of the Association for that

year. A Member failing to pay the annual subscription by the end of March of the following year shall cease

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Members may contribute papers for presentation at the Science Congress. They will receive, free of cost,

reprint of the Proceedings to Session of any one section of their interest and also the bi-monthly journal of

the Association “Everyman’s Science”.

2. Sessional Member : Sessional members are those who join the Association for the Session only. They may

contribute papers for presentation at the Science Congress and receive, free of cost, reprint of the Proceedings

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Rs. 250/- (for foreign U.S. $60) only.

3. Student Member : A person studying at the undergraduate / post graduate level may be enrolled as a Student

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4. Life Member : A Member may compound all future annual subscriptions by paying a single sum of

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*Admission fee of Rs. 50/- is needed only for becoming a new annual member and not for sessional member / life member /

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5. Institutional Member : An Institution paying a subscription of Rs. 5,000/- (for foreign U.S. $ 2,500) only,

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as also a copy of the Association’s journal “Everyman’s Science”.

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INSTITUTIONAL DONOR of the Association, which shall have the right to nominate one person as its

representative to attend Annual Session of the Science Congress. An Institutional / Individual Donor shall

be eligible to receive, free of cost, a copy of the complete set of Proceedings of the Annual Science Congress

as also the Association’s journal “Everyman’s Science”.

A) Presentation of Papers : A copy of complete paper accompanied by an abstract in triplicate not exceeding

one hundred words and not containing any diagram or formula, must reach the Sectional President General

Secretary (Hqrs) Latest by September 15, each year.

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conditions as may be laid down by the Railway Board for travel to attend the Science Congress Session

provided that their travelling expenses are not borne, even partly, by the Government (Central or State),

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Association from time to time.

Note : All Money Orders, Bank Drafts etc. should be drawn in favour of “Treasurer, The Indian ScienceCongress Association”. Members are requested to mention their Card No. while making anycorrespondence to ISCA office.

* (A Foreign Member means one who is normally resident outside India.)

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THE INDIAN SCIENCE CONGRESS ASSOCIATION14, Dr. Biresh Guha Street, Kolkata-700 017, INDIA

Telegram : SCICONG : CALCUTTA Fax : 91-33-2240-2551Telephone : 2247-4530, 2281-5323 E-mail : [email protected] : http://sciencecongress.org [email protected]

http://sciencecongress.nic.in

APPLICATION FORM FOR MEMBERSHIPToThe General SecretaryThe Indian Science Congress Association14, Dr. Biresh Guha Street,Kolkata-700 017

Dear Sir,

I like to be enrolled as a Member / Life Member / Donor / Sessional Member / Student Member / of The

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I am sending herewith an amount of Rs. ............... in payment of my subscription by Bank Draft / Money

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(including Archaeology and Psychology &Educational Sciences)

4. Chemical Sciences5. Earth System Sciences6. Engineering Sciences7. Environmental Sciences

8. Information and Communication Science &Technology (including Computer Sciences)

9. Materials Science.10. Mathematical Sciences (including Statistics)11. Medical Sciences (including Physiology)12. New Biology (including Bio-Chemistry,

Biophysics & Molecular Biology andBiotechnology)

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14, 700 017,

StampSize

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(including State, City/Town and Pin code)

Phone No. & e-mail

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Yours faithfully

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● As per resolution of Executive Committee in its meeting held on October 10, 2004 application formembership of ISCA in ‘Care of’ of some other person is generally discouraged. However, if in theapplication form “care of” address is given then there should be also signature of the person in whosename “care of” is given.

● Admission fee of Rs. 50/- is needed only for becoming a new annual member and not for sessional member/ life member / Institutional member / student member / donor.

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Everyman’s Science VOL. XLI NO. 1, April ’06 — May ’06THE INDIAN SCIENCE CONGRESS ASSOCIATION14, Dr. Biresh Guha Street, Kolkata-700 017

INSTRUCTION TO AUTHORS FOR PAPER PRESENTATION AT THE 94TH INDIAN SCIENCECONGRESS TO BE HELD AT AMITY UNIVERSITY, NOIDA DURING JANUARY 3 TO 7, 2007.

A. PAPER PRESENTATION (ORAL/POSTER)

1. All papers to be submitted for presentation at the 94th Science Congress must be sent to theConcerned Sectional Presidents. Each paper must be accompanied by three copies of abstracts(within 100 words, without any sketches, tables, etc.) and a copy of the full paper. The name ofthe Section where the paper is to be pressented should be indicated. The model format for abstractis given below. The addresses of Sectional Presidents are given in the website :http:www.sciencecongress.nic.in

2. Each author is entitled to submit only two papers.

3. All authors must be members of ISCA. Corresponding author must give a declaration thatauthors/co-authors are members of ISCA.

4. Papers should reach on or before September 15, 2006. The abstracts of these papers if approvedwill be printed in Part II of the Proceedings of the 94th Indian Science Congress. Papers (alongwith abstracts) received after September 15, 2006 will not be considered.

5. Contributed papers would be presented primarily by way of posters. Authors of the acceptedpapers will be advised by the concerned Sectional Presidents about preparation of posters. Sizeof each poster should be 1 meter × 1 meter and should be neatly prepared which can be read froma distance of 3 feet.

6. To encourage scientists, the Indian Science Congress Association has introduced a number ofprizes for Best Poster presentation in January, 1999. A maximum of Two prizes of Rs. 5000/-in cash along with a certificate will be awarded to the best presentations in each Section duringthe valedictory function of the 94th Indian Science Congress.

MODEL FORMAT FOR ABSTRACT

NAME OF THE SECTION

TITLE OF THE PAPER

AUTHOR’S NAME (S)

&

AFFILIATION

KEY WORDS :

ABSTRACT

For details please contact :

General Secretary (Headquarters), The Indian Science Congress Association, 14, Dr. Biresh Guha Street,Kolkata - 700 017. Phone : 033-2247 4530, Fax No. ; 0091-2240 2551, E-mail : [email protected] /[email protected] Website : http://sciencecongress.nic.in

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