birth of morden pharmacology in india

8/14/2019 birth of morden pharmacology in india

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BIRTH OF MODERN PHARMACOLOGY

B. MUKERJI*

Evolution of Indian Pharmacology

IN INDIA

Prior to 1921, pharmacology as a distinct scienti f ic . discipline wasunknown in India. Excepting the sporadic efforts made by a group of workersto study the value of some indigenous anthelmintic remedies under the guidanceof Father F. J. Caius and Dr. Mhaskar at the St. Xaviers Coll e ge and the Haff-kin e Institute in Bombay, no systematic study based on animal experimentation

and analysis was being undertaken in any of the University laboratories ormedical institutions. Pharmacology was not included as a subject of study inthe medical curriculum of Indian Universities. In 1922, the School of TropicalMedicine at Calcutta was started and for the first time a full chair in Pharma-cology was established there. The duties of the Professor included amongothers, the study of the pharmacology of Indian plant drugs claimed to beefficacious in the treatment of various tropical diseases prevalent in the country.Professor Ram N a t h Chopra , a student of the well-known British pharmacologist,W alt e r E . Dixon of Cambridge, was selected as the first professor. He initiated

systematic studies in experimental pharmacology as a post-graduate and researchdiscipline in th e School of Tropical Medicine. About the same time, Prof.Hardikar, a student of Professor Arthur R. Cushney (known as Father of BritishPharmacology,, returned to India and took up a teaching position in theOsmania Medical College, Hyderabad. He had collaborated with Prof. Cushneyin the laboratory studies, on the metabolism of Quinine in the human systemand thereby cultivated a liking for pharmacological methods of study on drugs.He introduced in Hyderabad the modern scientific concept of experimentalstudies in animals and human beings of drugs mentioned in the Indian materia

medica. Another notable name in the evolutionary history of Indian pharma-cology is that of Dr. B. N. Ghosh who received training in the subject alon g withhis post-graduate work in Medicine at Edinburgh and Glasgow and later joinedthe Carmichael Medical College (now R.G. Kar Medical College, Calcutta) as anadditional teacher in Medicine and Therapeutics. His interest in experimentalpharmacology brought him in touch with Prof. Chopra at the School of TropicalMedicine, and this association and joint effort helped a great d ea l in buildingup the first modern pharmacology laboratory at Calcutta. Prof . Chopra publi-

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shed his first paper from the newly started ,Laboratory in collaboration with Prof.B. N. Ghosh on the ' Therap eu tics of Emetine in 1922-23. This probably was thefirst paper published in India where the toxic effects of repeated doses of emetine

injections on cardiac musculature were demonstrated on experimental animalsand which incidentally served as the first note of warning in India against thedangerous practics of employing heroic doses of emetine in the treatment of alltypes of dysenteries and liver complications. Since then, a steady stream ofresearch emanat ed from Chopras laboratory as well as fr om the laboratoriesof the Haffkine Institute in Bombay which gradually helped in creating a

consciousness in the Indian medical world of the importance and potentialimpact of Pharmacology on medical studies of the future.

Early development of Indian PharmacologyPrewar and War period (1922-1943) :

Trends in medical education were fast changing in Great Britain abo u tthis time and Pharmacology as an essential part of the teaching discipline wasrecognis ed in the medical colleges there, in place of the old and time-honoureddescriptive materia medica. This new outlook on the role of Pharmacology inmedical education soon permeated the Indian scene and between 1924 to 1939(beginning of the Second World War), independent chairs in Pharmacologyand Therapeutics w e re established in all the older and the newly started Indianmedical colleges on more or less the same pattern adopted in British medicalcolleges. At the Calcutta medical college, the old chair of materia medicaand Therapeutics was converted to a chair of Pharmacology in 1923 and Prof.Chopra was appointed, in addition to his duties as Research Professor at theSchool of Tropical Medicine, to take care of undergraduate teaching there. Dueto lack of trained teachers, many other pharmacology departments in Indianmedical colleges remained attached with Physiology or Clinical Medicine forquite some time. During this period, Professor Chopra attracted a few senior and

junior medical graduates to acquire training in modern experimental pharma-cology in his laboratories, and succeeded remarkably well in developing anAll-India school of Pharmacology teachers and research workers who mannedmany of the medical colleges and research centres all over India and Burma(then wi th in British India). Noticing the new avenues and opportunities in thisfield emerging in India, several Indian students also took up advanced studiesin Pharmacology in different centres of learning in Great Britain, Germany,France, e tc. The Rockefeller Foundation also came to the help at this stage byoff ering post-graduate fellowship to one or two Indian medical doctors to pursue


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further studies in advanced pharmacology in America. Though a comparativenew-comer in the Indian medical world, pharmacology as an independentsubject in the medical curriculum gradually succeeded in building up a position

of prestige and statusfo r

itself within the period of two decades,The major interest of Pharmacologists in India during the Pre-second

World War period has been the screening of the age-old remedies known to theancient systems of medicine (Ayurvedic, Unani, etc.) in the country and to find outwhether the claims advocated for them by- the practitioners of ancient medicineswere true. The work at the School of Tropical Medicine, Calcutta, and theHaffkine Institute at Bombay primarily focussed attention on the following mainobjectives :

(a) To make India self supporting by enabling her to utilize thedrugs produced in the country by manufacturing them in a formsuitable f or administration.

(b) To discover remedies from the claims of Ayurveda, Tibbi and otherindigenous sources suitable to be employed by exponents ofwestern medicine.

( c ) To discover the means of effecting economy, so that these remediesmight be within the means of the great masses of population inIndia whose economic condition was very low; and.

(d) Eventually, to prepare an Indian Pharmacopoeia of standarddrugs and preparations for universal acceptance in drug manu-facture in the country.

During the intervening period of over 25 years between the First andthe Second World Wars, much work in this field wa s done at various centresof medical and non-medical studies in India. Many important medical plantsof the ancient Hindu materia medica have been carefully investigated from everypoint of v iew. Their chemical composition has been determined, the pharma-cological action of the active principles worked out in animal experiments andsuitable preparations from promising items tested clinically on patients in thehospitals. It was realised by the pioneer workers that, it was only by a thoroughenquiry with modern pharmacological methods, the real merits of thesedrugs could be established and a demand created for their acceptance and usein th er apeutic s not only in India but in other parts of the world. This labo-

rio us teamwork between chemists, pharmacologists and clinicians brought into


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E 11prominence the merits and qualities of several indigenous itmes such as Hola rrhenaanti-dy se nkco, M&n nzadirachta, Butea frondma, Alstonia scholaris, Caesalpinia bondu-cello, Adhntoda u&a, Bncopn herba, Dnmin exlanra, %rminalia nrjuna, Pmrnlen C O T -

yliflin, Sida cordifolia, Swertin chiretta, Andrographis paniculala, Plantago ounla, The-v&a neriiflia, Rivea cuneala, Acorus calamlrr, Berberis aristota, Nardortachys jatamami,Bnlmmodendvn mukul, etc. Unfortunately most of these items examined showeda certain amount of useful biologic activity but were not found to be superior tothe drugs of their categories already included in the pharmacopoeias of W estern

countries; in fact, these were not even nearly as efficacious. Many drugs ofquestionable value and doubtful utility apparently crept into the old Indian Sys-ter ms of medicine from folk-lore and hearsay evidence, and this might accountfor the frequent and often contradictory laboratory data obtained thereon by

the early experimenters who approached the subject analytically with real en-thusiasm and zeal. Full details of work done in this area had been publishedin Indian medical journals between 1925 and 1960 and in such books as the Indigenous Drugs of India by Chopra, the Indian Pharmacmlical Codex (Vol. I) byMukerji, the Glossary of Indian Medical planls by Nayar and Chopra, the Medici-nal and Poisonous Plants of India (Vols. I & II) by Chopra, Badhwar and Chopra,and Tmpical Therapeutics by Chopra, Mukerji and Chopra. The I. C. M. R.Monograph on pharmacology and therapeutics of Indian drugs by Chopra alsogives a good account of additional indigenous drug items studied till late fiftiesof this century.

An outstanding finding of an effective Indian indigenous drug Rarrwolfin

scrpenkz, however, could be reported from the Calcutta School of TropicalMedicine during this period. Inspite o f t h e f a c t t h a t Rnuwolfia s~rpentinawas described a s the foremost and most praiseworthy Indian medicine i n1563 by a Portuguese doctor (Gracia Abort o ) in India, no substantial scientificinvestigation appears to have been carried out till two Calcutta physicians

(Dr. G. Sen and Dr. K. Bose) reported their clinical observations with crudepreparations of the drug in 1931. A Delhi physician, Hakim Ajmal Khan, hadalso been using this drug in clinical practice for sometime and he was so impressedwith its therapeutic properties that he initiated a systematic chemical ex amina-tion of the active principle of Rauwolfia through the help of an brilliant IndianChemist. (Dr. S. Siddiqui, now in Pakistan). Prof. Chopra war encouraged atthis stage by all these clinicians to initiate systematic pharmacological andclinical examination with the active alkaloidal principles isolated by Dr. Siddiqui

and extracts of crude Rauwolf

ia preparations respectively, In association


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with his colleagues, Gupta and Mukerji, the first pharmacological studies of thisdrug on modern lines were carried out and the results were published in 1933.It was found on repeated animal experiments that Rauwolfia alkaloids, as isolated

by the chemistry department of the Institute exerted pronounced sedative effectson the central nervous system and lowered blood pressure in cases of hyperten-sion. The workers anticipated from their laboratory and clinical data thatRauwolfia ' would prove to be a valuable addition to the armamentarium ofthe physicians and recommended further studier in this direction. Inspite ofintensive studies on Rauwolfia in the pharmacological laboratories of the Schoolof Tropical Medicine and the attached hospital by several ofchopra ' s co-workersand students between 1933 and 1948, the isolation of the important alkaloid,Rescrpine and the now well-recognised clinical use of Rauwolfia could only be

established in 1952 by a band of S wiss workers in the Ciba laboratories in Switzer-land. Though the Indian chemists and pharmacologists failed in their persistentattempt to characterise the unitary alkaloid responsible for Rauwolfia action, it isa matter of satisfaction to all pharmacologists and clinicians that with the help 01modern chemical and pharmacological methodology it was ultimately possible toplace Indian Rau w olfia and its alkaloid, rcserpine, on rhe scientific drug mapof the world.

From about 1925 to the beginning of 19,+0, there was hardly any highlight

in pharmacological teaching and research in India, beyond the work on Indianmedicinal plants carried out in the two post-graduate research centres atCalcutta and Bombay. Even at these two centres, except for the elaboration ofroutine screening procedures and techniques of modern pharmacology, almostno detailed experimental, analytical, biochemical, toxicological or quantitativepharmacology programmes were undertaken and pursued. In the establishedmedical colleges and in a few newer institutions that came into being, attemptsw e r e made to organise and set up modern pharmacological laboratories with

imported equipment and apparatus so that the students could train themselves inputting up animal experiments, and pharmacology teachers could hold adequatedemonstration experiments in whole animals, in perfused isolated amphibianand mammalian hearts and organs, and on smooth muscle preparations. Thishelped in consolidating the position of modern Pharmacology as an accurate andreliable experimental scien ce in teaching institutions vii-a-vis the well establishedclaims of Physiology.

IYhlrini: \2:orld \\:ar II, India was in the grip of a drug famine as a

resultOS

the almost complete clotting off of supplies from Europe and other


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countries. This focussed the attention of the Health Services of the Governmentand other adminitstrators on the pharmacologists who were in teaching andresearch establishments in the country, and they were called upon to help in the

procurement, production, quality control and development of drugs urgentlyneeded for the civilian users and the theatres of war in the South East Asia andPacific islands. The importance of pharmacology as an applied discipline and acreative subject in the medical curriculum thus came into prominence for thefirst time. It is creditable that at this juncture the Indian pharmacologists incollaboration with chemists and pharmacists, though ill-equipped and withoutproper manufacturing paraphernalia, rose 10 the occasion and succeeded inse v e ra l instances to develop import-substitutes and indigenous replacements formany of the drugs commonly used in the treatment of war injuries, and in the

amelioration and prevention of such conditions as dysenteries, leprosy, diabetes,cholera, small-pox and other commonly occuring infections and communicablediseases. The Second war, therefore, can be considered to have played a veryimportant part in the development of pharmacology teaching and indirectly,in setting into motion the Indian pharmaceutical industry.

Development of Pharmacology in the Post-war period (1943-196 8 )

The post-war period has seen very significant developments both inpharmacological teaching and research all over India. The Indian Governmentlaunched a programme of expansion OF teaching facilities in all undergraduatemedical colleges, and also established many new medical colleges to turn outlarger numbers of medical graduates to provide modern medical care to thegrowing population of the country in urban and rural areas. At the turn of thethirties, undivided India had about 20 medical colleges, and now we haveabout 95 medical colleges in partitioned India. In every recognised medica lcollege, a chair of pharmacology with standard pharmacological equipment andtrained personnel exists to cater to the needs of undergraduate teaching. Inmany centres the Indian Council of Medical Research, the Council of Scientificand Industrial Research, and the University Grants Commission are f inancialIysupporting advanced teaching in pharmacology through research grants andfellowships. While much ground still remains to be covered in bringing IndianPharmacology to the same level of excellence as exists in advanced countries ofEurope and America, it is now possible to adopt an optimistic outlook on thepotential development of the subject both in its fundamental and applied

aspects in the years ahead.


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During the past 20 years, advances in Indian Pharmacology have beenso significant and comprehensive that it is not possible to review all the aspectsin a few pages of this article. A happy feature of this Indian pharmacological

scene is its broad-spectrum growth in both its laboratory and clinical aspectsin medical and non-medical institutions, and in drug manufacturing establish-ments. While many centres in medical colleges and post-graduate institutionsare specialising in gastro-intestinal, cardio-vascular, respiratory, genitourinary,autonomic, central nervous system pharmacology, the applied and clinical aspectspertaining to chemotherapy, endocrines, antibiotics, antihistaminics, polypeptidesand enzymes, antiseptics and disinfectants, toxicological evaluation are now beingstarted. Where emphasis is being given on newer methodology and eleganttechniques in quantitative pharmacology and in devising delicate operativeprocedures at different levels of the CNS, sense organs, visceral organs, etc.,attention is also being directed towards more fundamental study of drug kineticsin absorption, metabolism and excretion processes, and in recording evidencefor an enzymatic basis for active transport of the sodium and potassium ionsacross cell membranes. Clinical and human pharmacology, and experimentaland clinical therapeutics are figuring as active areas of investigation in certainother Indian centres. Considerable interest is now centering around the question

of drugs for the mentally ill, antifertility, anti-virus and anti-cancer drugs.

Molecular pharmacology is currently becoming popular in some post-graduatec ancer research centres for understanding and explaining drug interaction withmolecules comprising the complex of living material. This approach stimulatesu se of physico-chemical concepts and techniques in our effort to realise howdrugs truly act and how new chemotherapeutic agents could be synthesisedin the laboratory to selectively attack malignant cells in the human organism

leaving the normal healthy cells intact and unharmed. A broad researcharea in Indian Pharmacology is now concerned with the elaboration andmechanism of action of established or new antibiotics for local and systemic

use with particular reference to the emergence of toxic symptoms, complicationsor undesirable side effects. Teratogenicity is becoming a topic of interest incertain pharmacology laboratories. Clinical orientation is gradually being

given to post-graduate workers and approach to what is called, Clinical Phar-

ma cology at the human level is more and more encouraged. Pharmacologists

with hospital facilities have developed double-blind and other statistical methodsfor estimating the efficacy of therapy with new drugs, in the same way as beingattempted in more advanced countries of the world.


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Status of Modern Pharmacology in India

Space will not permit a more detailed account of all asp e cts of theover-all development of Pharmacology in India. From what has been already

recorded, it will be apparent to the readers that modern pharmacology, as dis-tinguished from the descriptive, is a discipline of comparatively recent origin inIndia, limited to the second and third quarters of this century. Considering itsyouthfulness, the development of the field has been fairly rapid as a teachingdiscipline in the medical, and later, in pharmacy, dental, nursing and veterinaryinstitutions. As a basic medical science, pharmacology is now taught in 95medical institutions in India, and also forms a part of the curriculum in severalpharmacy, veterinary and other schools of study concerned with the healthprofessions. Pharmacologists in India are being increasingly called upon toapply their knowledge and skill in pharmaceutical industries interested in thedevelopment of new drugs for medical and veterinary uses, for the control ofpests, and promotion of plant growth. Research institutes are needing theservices of pharmacologists to study the action of poisons and to find out suitableantidotes, to study radiation damage and its prevention, to probe into the secretsof life processes operating at the cellular and molecular level, to maintain qualitycontrol of drugs and to devise newer, cheaper and better substitutes for importedspecialities for combating infective conditions and metabolic disorders ofunknown etiologies,

All these developments followed in the wake of the humblebeginning of pharmacology at Calcutta only about 40 years ago with anintervening static 8-year period of Second World War. This shows, in no uncer-tain terms, the vitality and promise of modern Pharmacology in India.

The Future

Compared to its importance as a scientific discipline and in considera-tion of the many goods that it can deliver if properly cultivated, the recognitionof pharmacology in India, is still unsatisfactory. This is reflected both in the

indifferent quality of teaching of the subject in many medical institutions and inthe overall amount and comparative substandard quality of research output.This is , in a way, not quite unexpected. Pharmacolog y 's rightful place in medi-cal education was generally accepted in India only after post world-war reorga-nisation of medical curriculum around I5 y ears ago. Though much ground hasbeen covered by Pharmacology in the medical education area, a negative app-roach to the further development of this key-subject is still apparent, in that, faci-lities offered and grants giv en to Pharmacolog y departments are usually on a muchinferior Ie v el than to other sister pre-clinical departments in the same institution.


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The same neglect of pharmacology is seen in the field of medical andpharmaceutical research in India. Ou s tide the medical colleges, there are only4 or 5 centres of applied pharmacological research of the post-graduate level. All

these are comparatively small organisations where funds, facilities and personnelengaged in pharmacological investigations as a full-time work are extremelylimited. This step-motherly attitude has naturally done much to discouragebright young graduates from taking up pharmacology as an academic career andhas further forced many beginners of promising background and inquisitive men-tal make-up to leave pharmacology for better prospects in clinical specialities.

The writer has had the unique privilege of not only seeing the rudimenteryseed of pharmacology being first planted on the Calcutta soilas a student of

Professor Chopra, but has lived throughout its lifehistory to watch the slow butsteady growth and development of the subject in teaching, research and indus-trial applications. Longstanding neglect of pharmacology in India, both pureand applied, has had its serious repercussions already on medical research anddrug industry, the two most important and fruitful avenues of its expandingendeavours. In the elaboration of new chemotherapeutic agents from naturaland synthetic sources on which Indias drug industry of the future will have tofocus its attention, Pharmacologys contribution is expected to be most conspi-

cuous. Along with the inevitable collateral developments in other technologicalfields during the third and last quarter of the 20th century, pharmacology,hand-in-hand with Botany, Chemistry, Pharmacy and Medicine, holds themaster-key to the gradual transformation of India from an importing to aproducing and possibly, an exporting country in the matter of drugs, pharma-ceuticals, chemicals, insecticides, cosmetics, toilet products and miscellaneousitems. Pharmacologists in India have the wonderful chance of effectively con-tributing to the storehouse of world knowledge in drugs. The ancient Indianmateria medica of 2000 years provides a rich mine of knowledge and is an openchallenge to Indian Pharmacologists to probe into it scientifically with an openand unbiased mind. With modern pharmacological methodology now beingappropriately pursued by many of our promising pharmacology teachers andresearchers, a new and reorientated, analytical study of Indias century-oldempirical materia medica is called for. Such evaluation by new standards andnew measurement techniques, now being elaborated so satisfactorily both at thelaboratory level (animal experimentation) and at the level of humal pharma.cology at the bedside, might yet yield further interesting new knowledge and

bring to world medicine perhaps fresh life-prolonging and life saving drugs.


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The first teething trouble of pharmacology in India is happily overcometo a significant extent and the road towards its onward march for worthwhileprogress appears to be invitingly free from many obstacles and insurmountable

hurdles. The establishment of the independent Indian Pharmacological Societyis a happy augury, and is a pointer towards a brighter and more glorious futurefor Indian Pharmacology.

birth of morden pharmacology in india

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