BIRTH OF MODERN PHARMACOLOGY IN INDIA

B. MUKERJI*

Evolution of Indian Pharmacology

P r i o r t o 1 9 2 1 , p h a r m a c o l o g y a s a d i s t i n c t scientific. discipline was
unknown in India. Excepting the sporadic efforts made by a group of workers
to study the value of some indigenous anthelmintic remedies under the guidance
of Father F. J. Caius and Dr. Mhaskar at the St. Xavier’s College and the Haff-
kine Institute in Bombay, no systematic study based on animal experimentation
and analysis was being undertaken in any of the University laboratories or
medical institutions. Pharmacology was not included as a subject of study in
the medical curriculum of Indian Universities. In 1922, the School of Tropical
Medicine at Calcutta was started and for the first time a full chair in Pharma-
cology was established there. The duties of the Professor included among
others, the study of the pharmacology of Indian plant drugs claimed to be
efficacious in the treatment of various tropical diseases prevalent in the country.
Professor Ram Nath Chopra, a student of the well-known British pharmacologist,
Walter E. Dixon of Cambridge, was selected as the first professor. He initiated
systematic studies in experimental pharmacology as a post-graduate and research
discipline in the School of Tropical Medicine. About the same time, Prof.
Hardikar, a student of Professor Arthur R. Cushney (known as ‘Father of British
Pharmacology’,, returned to India and took up a teaching position in the
Osmania Medical College, Hyderabad. He had collaborated with Prof. Cushney
in the laboratory studies, on the metabolism of Quinine in the human system
and thereby cultivated a liking for pharmacological methods of study on drugs.
He introduced in Hyderabad the modern scientific concept of experimental
studies 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 along with
his post-graduate work in Medicine at Edinburgh and Glasgow and later joined
the Carmichael Medical College (now R.G. Kar Medical College, Calcutta) as an
additional teacher in Medicine and Therapeutics. His interest in experimental
pharmacology brought him in touch with Prof. Chopra at the School of Tropical
Medicine, and this association and joint effort helped a great deal in building
up the first modern pharmacology laboratory at Calcutta. Prof. Chopra publi-
* Retired Director Chittaranjan Cancer Research Institute, Calcutta.
shed his first paper from the newly started ,Laboratory in collaboration with Prof.
B. N. Ghosh on the ‘' Therapeutics of Emetine’ in 1922-23. This probably was the
first paper published in India where the toxic effects of repeated doses of emetine
injections on cardiac musculature were demonstrated on experimental animals
and which incidentally served as the first note of warning in India against the
dangerous practics of employing heroic doses of emetine in the treatment of all
types of dysenteries and liver complications. Since then, a steady stream of
research emanated from Chopra’s laboratory as well as from the laboratories
of the Haffkine Institute in Bombay which gradually helped in creating a
consciousness in the Indian medical world of the importance and potential
impact of Pharmacology on medical studies of the future.

Early development of Indian Pharmacology

Prewar and War period (1922-1943) :
Trends in medical education were fast changing in Great Britain about
this time and Pharmacology as an essential part of the teaching discipline was
recognised in the medical colleges there, in place of the old and time-honoured
descriptive materia medica. This new outlook on the role of Pharmacology in
medical education soon permeated the Indian scene and between 1924 to 1939
(beginning of the Second World War), independent chairs in Pharmacology
and Therapeutics were established in all the older and the newly started Indian
medical colleges on more or less the same pattern adopted in British medical
colleges. At the Calcutta medical college, the old chair of materia medica
and Therapeutics was converted to a chair of Pharmacology in 1923 and Prof.
Chopra was appointed, in addition to his duties as Research Professor at the
School of Tropical Medicine, to take care of undergraduate teaching there. Due
to lack of trained teachers, many other pharmacology departments in Indian
medical colleges remained attached with Physiology or Clinical Medicine for
quite 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 an
All-India school of Pharmacology teachers and research workers who manned
many of the medical colleges and research centres all over India and Burma
(then within British India). Noticing the new avenues and opportunities in this
field emerging in India, several Indian students also took up advanced studies
in Pharmacology in different centres of learning in Great Britain, Germany,
France, etc. The Rockefeller Foundation also came to the help at this stage by
offering post-graduate fellowship to one or two Indian medical doctors to pursue
further studies in advanced pharmacology in America. Though a comparative
new-comer in the Indian medical world, pharmacology as an independent
subject in the medical curriculum gradually succeeded in building up a position
of prestige and status for 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 the
ancient systems of medicine (Ayurvedic, Unani, etc.) in the country and to find out
whether the claims advocated for them by- the practitioners of ancient medicines
were true. The work at the School of Tropical Medicine, Calcutta, and the
Haffkine Institute at Bombay primarily focussed attention on the following main
objectives :

(a) To make India self supporting by enabling her to utilize the

drugs produced in the country by manufacturing them in a form
suitable for administration.

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

(c) To discover the means of effecting economy, so that these remedies

might be within the means of the great masses of population in
India whose economic condition was very low; and.

(d) E v e n t u a l l y , to prepare an Indian Pharmacopoeia of standard

drugs and preparations for universal acceptance in drug manu-
facture in the country.

During the intervening period of over 25 years between the First and
the Second World Wars, much work in this field was done at various centres
of medical and non-medical studies in India. Many important medical plants
of the ancient Hindu materia medica have been carefully investigated from every
point of view. Their chemical composition has been determined, the pharma-
cological action of the active principles worked out in animal experiments and
suitable preparations from promising items tested clinically on patients in the
hospitals. It was realised by the pioneer workers that, it was only by a thorough
enquiry with modern pharmacological methods, the real merits of these
drugs could be established and a demand created for their acceptance and use
in therapeutics not only in India but in other parts of the world. This labo-
rious teamwork between chemists, pharmacologists and clinicians brought into
 E 11
prominence the merits and qualities of several indigenous itmes such as Holarrhena
anti-dysenkco, 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 showed
a certain amount of useful biologic activity but were not found to be superior to
the drugs of their categories already included in the pharmacopoeias of Western
countries; in fact, these were not even nearly as efficacious. Many drugs of
questionable value and doubtful utility apparently crept into the old Indian Sys-
terms of medicine from folk-lore and hearsay evidence, and this might account
for 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 published
in 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) by
Mukerji, 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 also
gives a good account of additional indigenous drug items studied till late fifties
of this century.

An outstanding finding of an effective Indian indigenous drug Rarrwolfin

scrpenkz, however, could be reported from the Calcutta School of Tropical
Medicine during this period. Inspite o f t h e f a c t t h a t Rnuwolfia s~rpentina
was described as the “foremost and most praiseworthy Indian medicine” i n
1563 by a Portuguese doctor (Gracia Aborto) in India, no substantial scientific
investigation appears to have been carried out till two Calcutta physicians
(Dr. G. Sen and Dr. K. Bose) reported their clinical observations with crude
preparations of the drug in 1931. A Delhi physician, Hakim Ajmal Khan, had
also been using this drug in clinical practice for sometime and he was so impressed
with its therapeutic properties that he initiated a systematic chemical examina-
tion of the active principle of Rauwolfia through the help of an brilliant Indian
Chemist. (Dr. S. Siddiqui, now in Pakistan). Prof. Chopra war encouraged at
this stage by all these clinicians to initiate systematic pharmacological and
clinical examination with the active alkaloidal principles isolated by Dr. Siddiqui
and extracts of crude Rauwolfia preparations respectively, In association
12 J

with his colleagues, Gupta and Mukerji, the first pharmacological studies of this
drug 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 effects
on the central nervous system and lowered blood pressure in cases of hyperten-
sion. The workers anticipated from their laboratory and clinical data that
‘Rauwolfia'’ would prove to be a valuable addition to the armamentarium of
the physicians and recommended further studier in this direction. Inspite of
intensive studies on Rauwolfia in the pharmacological laboratories of the School
of Tropical Medicine and the attached hospital by several of’chopra's co-workers
and 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 Swiss workers in the Ciba laboratories in Switzer-
land. Though the Indian chemists and pharmacologists failed in their persistent
attempt to characterise the unitary alkaloid responsible for Rauwolfia action, it is
a matter of satisfaction to all pharmacologists and clinicians that with the help 01
modern chemical and pharmacological methodology it was ultimately possible to
place Indian Rauwolfia and its alkaloid, rcserpine, on rhe scientific drug map
of 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 Indian
medicinal plants carried out in the two post-graduate research centres at
Calcutta and Bombay. Even at these two centres, except for the elaboration of
routine screening procedures and techniques of modern pharmacology, almost
no detailed experimental, analytical, biochemical, toxicological or quantitative
pharmacology programmes were undertaken and pursued. In the established
medical colleges and in a few newer institutions that came into being, attempts
were made to organise and set up modern pharmacological laboratories with
imported equipment and apparatus so that the students could train themselves in
putting up animal experiments, and pharmacology teachers could hold adequate
demonstration experiments in whole animals, in perfused isolated amphibian
and mammalian hearts and organs, and on smooth muscle preparations. This
helped in consolidating the position of modern Pharmacology as an accurate and
reliable experimental science in teaching institutions vii-a-vis the well established
claims of Physiology.

IYhlrini: \2:orld \\:ar II, India was in the grip of a “drug famine” as a
result OS the almost complete clotting off of supplies from Europe and other
 [ 13

countries. This focussed the attention of the Health Services of the Government
and other adminitstrators on the pharmacologists who were in teaching and
research establishments in the country, and they were called upon to help in the
procurement, production, quality control and development of drugs urgently
needed for the civilian users and the theatres of war in the South East Asia and
Pacific islands. The importance of pharmacology as an applied discipline and a
creative subject in the medical curriculum thus came into prominence for the
first time. It is creditable that at this juncture the Indian pharmacologists in
collaboration with chemists and pharmacists, though ill-equipped and without
proper manufacturing paraphernalia, rose 10 the occasion and succeeded in
several instances to develop import-substitutes and indigenous replacements for
many 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 communicable
diseases. The Second war, therefore, can be considered to have played a very
important 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 (1943-1968)

The post-war period has seen very significant developments both in

pharmacological teaching and research all over India. The Indian Government
launched a programme of expansion OF teaching facilities in all undergraduate
medical colleges, and also established many new medical colleges to turn out
larger numbers of medical graduates to provide modern medical care to the
growing population of the country in urban and rural areas. At the turn of the
thirties, undivided India had about 20 medical colleges, and now we have
about 95 medical colleges in partitioned India. In every recognised medical
college, a chair of pharmacology with standard pharmacological equipment and
trained personnel exists to cater to the needs of undergraduate teaching. In
many centres the Indian Council of Medical Research, the Council of Scientific
and Industrial Research, and the University Grants Commission are financialIy
supporting advanced teaching in pharmacology through research grants and
fellowships. While much ground still remains to be covered in bringing Indian
Pharmacology to the same level of excellence as exists in advanced countries of
Europe and America, it is now possible to adopt an optimistic outlook on the
potential development of the subject both in its fundamental and applied
aspects in the years ahead.
 During the past 20 years, advances in Indian Pharmacology have been
so significant and comprehensive that it is not possible to review all the aspects
in 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 aspects
in medical and non-medical institutions, and in drug manufacturing establish-
ments. While many centres in medical colleges and post-graduate institutions
are specialising in gastro-intestinal, cardio-vascular, respiratory, genitourinary,
autonomic, central nervous system pharmacology, the applied and clinical aspects
pertaining to chemotherapy, endocrines, antibiotics, antihistaminics, polypeptides
and enzymes, antiseptics and disinfectants, toxicological evaluation are now being
started. Where emphasis is being given on newer methodology and elegant
techniques in quantitative pharmacology and in devising delicate operative
procedures at different levels of the CNS, sense organs, visceral organs, etc.,
attention is also being directed towards more fundamental study of drug kinetics
in absorption, metabolism and excretion processes, and in recording evidence
for an enzymatic basis for active transport of the sodium and potassium ions
across cell membranes. Clinical and human pharmacology, and experimental
and clinical therapeutics are figuring as active areas of investigation in certain
other 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-graduate
cancer research centres for understanding and explaining drug interaction with
molecules comprising the complex of living material. This approach stimulates
use of physico-chemical concepts and techniques in our effort to realise how
drugs truly act and how new chemotherapeutic agents could be synthesised
in the laboratory to selectively attack malignant cells in the human organism
leaving the normal healthy cells intact and unharmed. A broad research
area in Indian Pharmacology is now concerned with the elaboration and
mechanism of action of established or new antibiotics for local and systemic
use with particular reference to the emergence of toxic symptoms, complications
or undesirable side effects. Teratogenicity is becoming a topic of interest in
certain pharmacology laboratories. Clinical orientation is gradually being
given to post-graduate workers and approach to what is called, ‘Clinical Phar-
m a cology’ at the human level is more and more encouraged. Pharmacologists
with hospital facilities have developed ‘double-blind’ and other statistical methods
for estimating the efficacy of therapy with new drugs, in the same way as being
attempted in more advanced countries of the world.
 [ 15

Status of Modern Pharmacology in India

Space will not permit a more detailed account of all aspects of the
over-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 in
India, limited to the second and third quarters of this century. Considering its
youthfulness, the development of the field has been fairly rapid as a teaching
discipline in the medical, and later, in pharmacy, dental, nursing and veterinary
institutions. As a basic medical science, pharmacology is now taught in 95
medical institutions in India, and also forms a part of the curriculum in several
pharmacy, veterinary and other schools of study concerned with the health
professions. Pharmacologists in India are being increasingly called upon to
apply their knowledge and skill in pharmaceutical industries interested in the
development new drugs of
for medical and veterinary uses, for the control of
pests, and promotion of plant growth. Research institutes are needing the
services of pharmacologists to study the action of poisons and to find out suitable
antidotes, to study radiation damage and its prevention, to probe into the secrets
of life processes operating at the cellular and molecular level, to maintain quality
control of drugs and to devise newer, cheaper and better substitutes for imported
specialities for combating infective conditions and metabolic disorders of
unknown etiologies, All these developments followed in the wake of the humble
beginning of pharmacology at Calcutta only about 40 years ago with an
intervening 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 recognition
of pharmacology in India, is still unsatisfactory. This is reflected both in the
indifferent quality of teaching of the subject in many medical institutions and in
the overall amount and comparative ‘substandard’ quality of research output.
This is, in a way, not quite unexpected. Pharmacology's rightful place in medi-
cal education was generally accepted in India only after post world-war reorga-
nisation of medical curriculum around I5 years ago. Though much ground has
been 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 g i v e n to Pharmacology departments are usually on a much
inferior Ievel than to other sister pre-clinical departments in the same institution.
 1
The same neglect of pharmacology is seen in the field of medical and
pharmaceutical research in India. Oustide the medical colleges, there are only
4 or 5 centres of applied pharmacological research of the post-graduate level. All
these are comparatively small organisations where funds, facilities and personnel
engaged in pharmacological investigations as a full-time work are extremely
limited. This step-motherly attitude has naturally done much to discourage
bright young graduates from taking up pharmacology as an academic career and
has 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 rudimentery
seed of pharmacology being first planted on the Calcutta soil’as a student of
Professor Chopra, but has lived throughout its lifehistory to watch the slow but
steady growth and development of the subject in teaching, research and indus-
trial applications. Longstanding neglect of pharmacology in India, both pure
and applied, has had its serious repercussions already on medical research and
drug industry, the two most important and fruitful avenues of its expanding
endeavours. In the elaboration of new chemotherapeutic agents from natural
and synthetic sources on which India’s drug industry of the future will have to
focus its attention, Pharmacology’s contribution is expected to be most conspi-
cuous. Along with the inevitable collateral developments in other technological
fields during the third and last quarter of the 20th century, pharmacology,
hand-in-hand with Botany, Chemistry, Pharmacy and Medicine, holds the
master-key to the gradual transformation of India from an ‘importing’ to a
‘producing’ and possibly, an ‘exporting’ country in the matter of drugs, pharma-
ceuticals, chemicals, insecticides, cosmetics, toilet products and miscellaneous
items. Pharmacologists in India have the wonderful chance of effectively con-
tributing to the storehouse of world knowledge in drugs. The ancient Indian
materia medica of 2000 years provides a rich mine of knowledge and is an open
challenge to Indian Pharmacologists to probe into it scientifically with an open
and unbiased mind. With modern pharmacological methodology now being
appropriately pursued by many of our promising pharmacology teachers and
researchers, a new and reorientated, analytical study of India’s century-old
empirical materia medica is called for. Such evaluation by new standards and
new measurement techniques, now being elaborated so satisfactorily both at the
laboratory 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.
 [ 17

The first “teething trouble” of pharmacology in India is happily overcome

to a significant extent and the road towards its onward march for worthwhile
progress appears to be invitingly free from many obstacles and insurmountable
hurdles. The establishment of the independent Indian Pharmacological Society
is a happy augury, and is a pointer towards a brighter and more glorious future
for Indian Pharmacology.