UD Deshmukh, GV Phatarphekar, SP Dandekar
Department of Biochemistry, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai – 400 012, India., India
An open access article from: J Postgrad Med 2001;47:222.
The name Biochemistry was coined in 1903 by a German chemist named Carl
Neuber. However, work in this very living, aspect of chemistry had
started much earlier.
Claude Bernard is accredited with the
sirehood of Biochemistry. He was the first to conceive and present to
the scientific community, the idea of a ‘fixed internal milieu’. This
was as early as – or, perhaps, as late as, when seen on the backdrop of
chronology of science as a whole – the later half of the 19th century.
The
idea of Biochemistry as a distinct, well defined part of bioscience
took shape without difficulty for, where it takes place – the cell, was
already well delineated and defined.
The cell was perceived to
have a certain ‘milieu’, which was best suited to its structural and
functional needs for optimum efficiency. Chemical changes from within
and without constantly strove to destabilize this most suited
proportion of constituents in their quality and quantity.
The
cell, through mechanisms not wholly understood yet, does its best to
withstand the changes, and keeps the milieu constant. This is the best
approximation of homeostasis and what biochemistry is all about.
If
we consider chemical composition of the living and chemical processes
and reactions, which form the basis of the living matter as
biochemistry, then studies pertaining to this discipline of science
began with the early chemists like Priestley, Lavoisier, Scheel and
others. This was even before the 19th century. These studies were
confined to the fulfillment of the curiosity about the composition of
the animals and plants. Trailing these initial forays into chemistry
were studies of chemical processes involved in respiration and
fermentation; and chemical quantitative analysis of ‘organic
substances’, which necessarily meant substances made by the living
organism.
Biochemistry began as a separate discipline,
distinct from chemistry and other biological sciences under the name
‘physiological chemistry’ or sometimes also called ‘pathological
chemistry’.
The first volume of ‘Zeitschrift für Phisiologiche Chemie’ came out in 1877.
As
is commonly observed the leading edge lay in the European heads and
laboratories in the earlier period, during which time the American
quest for ‘what lay on the other side of the mountain’ was mostly
spirited away by the pioneering that they were mostly busy with. They
were not far behind. The ‘Journal of Biological Chemistry’ (JBC) came
in 1906, representing the ‘American Society of Biological Chemists’.
The
first Indian effort was there for all to see in 1930, just about 25
years behind the publication of the JBC. This was in the form of the
Journal of Indian Institute of Science. In India, at least to begin
with, Bangalore had the leading edge. Journal of Indian Institute of
Science started publishing before 1930. This was followed by the
Journal of Indian Chemical Society, in 1933.
We find a lot of
research activity in Bangalore in and around the ‘30s. Workers like BT
Narayanan and BN Pramanik, working respectively, on isolation of
‘growth promoting factor in Bios’, and reporting the growth promoting
activity of inositol. D Narayanamurti, N Narasimhamurty and M
Sreenivasaya were working on enzymatic activity of amylase and maltase.
Even earlier than this, in1927, V Subramanian has published his results
on handling of saccharic acid by Aspergillus niger.
Prakash S
and Dhar in a different work but parallel research were studying the
anticoagulant activity of fluorides, citrates and oxalates.
Many
different scientists were noted to be working in different fields
around this, starting period, without appreciable endeavor towards
coordination or any concerted activity towards a common goal.
Billimoria
HF, Banergi GG, Narayanan BT, Ghosh AK and others have worked on
different aspects of vitamin chemistry, functioning, content,
occurrence etc. Desai BL and Dastur RH were working on plant
biochemistry. They were studying the dependence of the rate of
photosynthesis on the chlorophyll content and water content. Of course
much more chemistry, metabolism and some very fundamental aspects of
enzymology were under close scrutiny at the same time. This was also
the time when Embden and Meyerhof were creating history studying the
formation of pyruvate. Elsewhere Bodansky and Somogyi were carving out
their names to be remembered for generations to come.
In the
later half of the 30ies the work, elsewhere, progressed. The pioneers
of the anaerobic glycolysis continued to work and further consolidated
the foundation they had laid. Embden published more work on his own
about anaerobic pathway. A little later Cori CF continued the work that
they had started, by isolating the enzymes to catalyze the conversion
of glucose to glucose 1 phosphate and then the one which helps the next
step – the conversion of glucose 1 phosphate to glucose 6 phosphate.
Svedberg T. continued his pioneering work on centrifugation and
presented an extensive table of molecular weights of proteins.
Here,
about the same time Banergi GG and Mukerji A. were working on
deficiency of thiamin in rats and determination of thiamin,
respectively. Ganapathy CV and Damodaran M were working on Papaya and
action of papain. Bhagvat K, who had been active for many years by this
time, was working on cytochrome oxidase in plants.
The next
decade saw the three great names in analysis, Consden Gordon and
Martin, blazing their new trail, making path-breaking discoveries in
paper chromatography. It also saw the immediate application of the
technique by another heavyweight, Chargaff E., who separated adenylic,
guanylic and cydidylic acid by paper chromatography. Next he prepared
DNA from tubercle bacilli.
In India, during the same decade
Damodaran K confirmed the work elsewhere and showed that different
forms of Penicillin are formed by P. notatum from lysine and b hydroxy
valine. Damodaran M continued to make his lone furrow, and proved that
even one amino acid, missing from a diet due to delayed feeding, could
cause inefficient utilization from a mixture of amino acids.
Evident are the efforts by our scientists to test the possibilities in India which were being worked out abroad.
Thus
when Krebs and Hensleit were busy finalizing the details of urea
formation; and the illustrious Cories were breaking their heads over
lactate and pyruvate our scientists were also worried about the same
intermediates. Devdatta SC was working on the lactate and pyruvate
levels inside the erythrocytes and in the surrounding plasma. His
findings were, a higher lactate concentration in fatigued frog muscle.
He was, in fact, speculating the possibility of a lactate shift on the
same lines as those of bicarbonate shift, into and out of erythrocytes.
He had tried to establish the connection between the lactate shift and
an increase in CO2 partial pressure.
At the same time Dr. NG
Magar, that ageless Guru of biochemistry in Mumbai along with Gangal SV
were working on free amino acids in crab muscle. This octogenarian is
still active – proving the epithet ageless.
In this decade,
Baliga BR and Rajgopalan K were boosting the nutrition value of raw
soybean with supplementation with B12. Bhagvat RV and Sohonie K, -one
among very few ladies up to this time and one who went from length to
length later- were also working on B12 in rat liver.
PM
Bhargav was very active in this and the previous decade. Bhattacharya
S, Chaudhuri NK and Basu VP in one corner; while Ramasrma, GB and
Sreenivasamurthy V, Shenoy KG and Shrivastav PC have all worked on
vitamin chemistry. Vijayaraghavan PK found trypsin inhibitor in
ovomucoid. Venkataraman RR worked on hyperthyroid rats, while
Sreenivasan worked on inhibition of DNA and RNA synthesis by
antibiotics. Narayanan KM was working on vitamin A chemistry. Gupta SC
and Ganguli SS worked on unsaturated fatty acid composition of various
different sources of fat. Shrinivasan M has worked on intermediates of
carbohydrate metabolism. Ramachandran GN has proposed a helical
structure for collagen.
The post independence period, for the
first one or two decades, is mostly ruled by the illustrious alphabets
of Indian biochemistry. They were, Ambe, Bachhawat, Bagchi, Baliga,
Banerji, Burma, Belkhonde, Bhagvan, Bbattacharya, Bhide, Biswas,
Chattarjee GC, Chattarjee IB, Chaudhari, Dasgupta, Datta A, Datta DK,
Datta SP. These are then followed by Ghoses and Guhas.
Ambe KS
has worked on the action of cytochrome oxidase on reduced cytochrome C
and the relevance of phospatidyl inositol to this reaction. Bachhawat
BK had aroused a lot of interest among the biochemical circle by
describing an unusual enzyme activation of CO2 during his work on lipid
metabolism. Banerjee S. Kawishwar and Biswas DK studied the effect of
insulin on the enzymes of TCA cycle. Belkhonde ML and Nath MC studied
the biosynthesis of vitamin C in germinating mung seeds. Bhattacharya G
postulated two different processes of uptake of glucose, only one of
which is insulin dependent. Burma DP, Chakravarti and Chakravarti
isolated and studied the enzyme phosphatase in photosynthesis.
Chatterjee
GC,Ghosh GC, Ghosh NC and Guha BC identified that 2 keto L
gluconolactone is an intermediate in the biosynthesis of ascorbic acid.
Chaudhari NK had research interest in biochemistry of cancer and anti
cancer agents. He specially worked on 5 fluoropyrimidines. Dasgupta PR
studied the chemistry of protein hormones and showed the existence of a
precursor of corticotropin called precorticotropin.
Datta DK
studied the reaction between oxalic acid and oxygen to give CO2 and
water. He isolated a flavin containing oxalic acid oxidase, which
catalyzes the reaction while Datta SP measured the stability and
reactivity of metal complexes of amino acids and peptides. Ghosh JJ and
Guha SR worked on ammonia formation in the brain.
The
contributions of Guha BC are particularly noteworthy. He had diverse
interests. He worked on carbohydrate metabolism; he also proved that L
ascorbic acid is synthesized in the kidneys of birds, reptiles and
amphibians instead of the liver, like in most mammals. With Bagchi SP
he worked on the synthesis of aminoacetone from threonine and glycine.
The scheme provided a new path for the oxidation of threonine.
The
contribution of Thakur V was important in that the work provided a
method to locate the serine residue in proteins like insulin,
ribonuclease, glucagon, serum albumin and lysozymes.
The
Indian Journal of Biochemistry and Biophysics (IJBB) started publishing
in 1964. This was the period that the whole atmosphere in the world
scientific community had suddenly become surcharged with a new
enthusiasm. Many scientists full of vigour were switching over to
biochemistry. And many an old head were taking stock and were being
dragged into the strong, surging torrent, to join the deluge of papers
which had started pouring in by now.
Indian Journal of
Biochemistry (this was the name to start with) had the patronage of
luminaries like Prof. PS Sarma, Prof. GP Talwar, Prof. BK Bachhawat,
Prof. DP Burma, Dr. V Jagnnathathan, Dr. C Gopalan, Dr. A Sreenivasan,
Dr. PM Bhargav, Prof. LK Ramachandran, Prof. RK Misra, Dr. CR Krishna
Murti and Prof. KN Radhakrishnan.
The collaboration for this
effort by the Society of Biological Chemists of India shows an
exemplary spirit of mutuality. The chief editor of the Indian Journal
of Biochemistry has gone on record expressing his gratitude for sharing
the experience and expertice of the Society of Biological Chemists of
India in the publication of the Journal of Biochemistry and Biophysics.
In
less than five years the IJBB had lured the Biophysicists led by Prof.
GN Ramachandran and it was through his insistence that the word
‘Biophysics’ was later added to the name. The cause of biochemistry in
India got a great boost through the initial spadework done by Prof. PS
Sarma and Shri. A Krishnamurthy, for it is their effort, which finally
convinced CSIR for the need of such a venture. Biochemistry in India
will be forever indebted to them.
A very special and
noteworthy development in 1974 was the foundation of the prestigious
‘Association of Clinical Biochemists of India’. The first annual
conference was held at Patna, and the honor of being the organizing
secretary was very aptly given to Dr. KP Sinha. This opened a new
chapter in the history of biochemistry, and this development created an
opportunity for all the research workers in the subject to congregate
and exchange ideas every year. This also made possible, a new approach
to research in the country, and an era of integration which was the
need of the hour, and which makes the impact of new, path-breaking
research more tangible.
The recent technique of recombinant DNA
and gene cloning became available to the Indian biochemists around the
same time and the first Indian work in this area was published in IJBB
in1983. The IJBB celebrated its silver jubilee in the year 1989.
Indian
scientists are seen working on more subtle aspects of biochemistry
around this time as laboratories tended to be more and more
sophisticated. Amit AG studied the crystal structure of protein antigen
antibody complexes and the conformational changes in either the
antibody or the antigen after the formation of the complex. Batch IC
studied the cAMP dependent generation of active enzyme by protein
kinase and the role of calmoduline in bringing about the conformational
change.
In August 1990 SR Kasturi and GK Jarori from TIFR
collaborated with SB Iyer from the department of pharmaceutical
chemistry, University of California and UW Kenkre from the national
tissue culture facility, Univesity of Pune. All these specialists from
various fields worked on one of the most powerful techniques currently
available for eliciting structural information about enzyme bound
substrate complexs. This was nuclear magnetic resonance relaxation
methodology as applied to working enzyme system.
This ambitious
project holds enormous potential and is slated to make hitherto
unimaginable inroads in the field of enzymology and give an immense
boost to our understanding about enzyme kinetics.
Some more
pioneering work in the period just before the last decade of the 20th
century was by Indrani Mitra and Chatterjee BP; Department of
Biological Chemistry, Indian association for The Cultivation of
Sciences; Calcutta. House dust is one of the major allergens causing
respiratory lesions in humans. This was at the beginning of the current
hot topic for discussion – the dust mite ranging from region to region
and changing from season to season.
Another hot topic of today
is free radicals and antioxidants. Interest has already picked up from
as early as 1987 in our country as evidenced from the initial work in
this field by Misra, HP and Fridovich I. They have shown that O¯2 can
act as univalent oxidant or reductant, and that it is capable of
oxidizing epinephrine.
More recently Bhaskar L and
Balasubramanian KA have published in 1995 their work on the effect of
oxidants on colonic membrane and lipid peroxidation. More recent work
is in1993 – in the field dealing with the intricacies in the DNA
structure. Rao TS, Hogan ME and Revankar GR have dealt with intricacies
of non-natural nitrogenous bases like 2‘deoxynebularine or
2‘deoxyformycin A, forming stable triads with cytosine and thymine.
Mukherjee
U and Chatterjee SN have studied oxidative damage of DNA and benzoic
acid by chelated and nonchelated Cu in presence of H2O2.
Burma
DP from Banaras Hindu University, the father figure in the Indian scene
right from1960 continues to work tirelessly and continues to publish
quality work likewise. He has tried to get an insight into the long
unanswered questions viz. ‘How do the two ribosomal subunits recognize
each other?’ and ‘How does translocation occur?’
1998 saw the
silver jubilee of IJBB. From 1978 this torch bearer of biochemical
advances in India which has contributors from allover the world, has
started publishing bimonthly instead of quarterly – and this is also
falling short, looking at the present rate of contributions. Interest
in the prevention of myocardial infarction and the role of vitamin E as
an antioxidant has led to various different projects being undertaken
in different parts of the country.
In the Department of
Biochemistry, University of Madras, the effect of µ- tocopherol on the
mitochondrial electron transport chain in experimental myocardial
infarction is under study.
Integration is the need of the hour
and this doctrine seems well entrenched for, efforts are on as seen
from the concerted project being worked out with participation by a
diverse group, viz. Physics Department of Gorakhpur University,
Chemical Physics Group from Tata Institute of Fundatmental Research,
Mumbai and Bombay College of Pharmacy, Mumbai. This is to design
techniques to use NMR and molecular dynamics simulations to elucidate
the structure of protein through sequential assignments of peptides.
Thus
the march goes on. Sciences progresses. First the inter-state
boundaries and then the international boundaries collapse. This is true
for space research and it is true for all faculties of scientific
research in general. The quest for knowledge about the human genome
knows no boundaries. Hopefully the end, if it is ever in sight, will
bring a lot of good for the entire mankind. This goes to show that
Biochemitry has had a chequered history in India. Indians from all
corners of India are involved in quality research and shall help place
Biochemistry on the world map.
