The history of biochemistry in India.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
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 11832634
Source of Support: None, Conflict of Interest: None
Keywords: Biochemistry, history,History of Medicine, 20th Cent., India,
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 OŻ2 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.