Biotech News

Bi techVolume 6 | No.4-6 | July - Dec. 2011

N E W S

Department of BiotechnologyMinistry of Science & TechnologyGovernment of India

To the Readers

Disruptive innovation

Spider silk expressed in Bombyx mori : Can muga silk follow?

What you are holding in your hands is a special combined issue (4-6 of Volume 6, July to December 2011) of Biotech News that celebrates DBT’s Silver Jubilee (1986—2011). In this issue, we have assembled a number of articles that were invited from several distinguished people.

Science, like business, is ‘done’ through a series of sustaining and disruptive innovations. It is the disruptive innovations – often used synonymously with ‘disruptive technologies’ – that have the capacity to displace dominant existing technologies and ultimately (and unexpectedly) change the way people think and do things.

Our cover story is about one such disruptive innovation: it focuses on spider silk, which has been in the news recently. On a weight-to-weight basis, spider silk is stronger than steel. It is believed that a pencil-thick strand of spider silk could stop a Boeing-747 in mid flight and comic strip hero Spider-Man used this to snare bad guys and swing from skyscrapers. Its strength, combined with other traits such as lustre, non-allergenicity, anti-microbial property and high elasticity, makes spider silk a favoured material, put to diverse and novel uses in textiles, wound dressings, surgical sutures, bullet-proof vests, as scaffold for tissue engineering, etc. In January this year, the BBC reported that the largest piece of cloth – an elaborately embroidered cape and a 4m long scarf – both spun from the silk of more than a million spiders will go on display at the Victoria and Albert Museum, London. Shigeyoshi Osaki of Japan’s Nara University has recently twisted strands of the golden-orb spider’ s (Nephila maculata) dragline silk into violin strings (Physical Review Letters,108: 154301, 2012) that result in a “packing structure” with practically no space between any of the strands and claims that the strings have a “soft and profound timbre” vis-a-vis traditional gut or steel strings. Nevertheless, viable commercial production of spider silk has been rendered impractical by the small quantity of silk produced and the territorial and cannibalistic nature of spiders.

It would, therefore, be interesting to develop viable biotechnological approaches to produce spider silk on scale. While it has been possible to express spider silk proteins in diverse hosts (bacteria, yeast, plants, insect- and animal systems, as well as in the milk of transgenic goats), yields have been low and scale-up expensive. More importantly, none of these systems were equipped to spin silk fibres. On the other hand, the domesticated silkworms (Bombyx mori) can be cultivated en masse; it is now possible to produce transgenic silkworms with piggyBac vectors, and to target recombinant protein production to the silk gland with tissue-specific promoters. Moreover, Bombyx silk glands are naturally endowed with the ability to spin the recombinant proteins and extrude them as fibres. Hence, it would be wonderful to combine the fine qualities of silk from Bombyx mori with the strength and durability of spider silk. In a recent path breaking study, Donald Jarvis and coworkers at Wyoming University have used silkworms as surrogate hosts to express the synthetic A2S8

14 spider silk gene (Teule et al. 2012, PNAS, USA 109: 923-928).

They found that transgenic silkworms were not only able to express the recombinant protein but also spin composite silk fibres with improved mechanical properties. This, together with other earlier developments,

Cover Page Illustrations : The golden spider, Nephilia clavipes is in the act of entangling its prey, dragon fly in to its web.

102 BIOTECH NEWS VOLUME 6 | NO. 4-6102 BIOTECH NEWS

opens new possibilities for the production of novel composite biomaterials. J Nagaraju (pg. 104) has elegantly brought out an account of the biology of spider silk and the promise it holds in changing the conservative face of silk fibres – products of millions of years of evolution. Sourabh Ghosh (pg. 112) evaluates the attempts to modify the physical and chemical properties of silk fibroin proteins to develop various types of tissue engineering scaffolds.

From the Indian perspective, the successful expression of spider silk and the assembly of recombinant proteins into composite fibres in B. mori should have profound implications. We have four major marketed varieties of silk – mulberry, tasar, eri and muga – each produced by a distinct moth species that feeds on a specific plant host. According to the Central Silk Board, the country produced 20,410 MT of silk during 2010-11. While the share of mulberry silk was 16,360 MT (80.2%), the three non-mulberry silks – now rechristened Vanya silks – together made up the balance 4,550 MT(19.8%). Within the Vanya group, the golden yellow muga silk, accounted for just 124 MT (0.6%) of India’s silk production. Muga silk culture is very ancient – the pitambara worn by our gods was presumably made of this silk. The muga

silk moth (Antheraea assama) is wild and endemic to Assam and neighbouring regions. The cocoons are collected by unskilled labour from forests. Production and productivity are both low and dwindling as the silkworms are subject to the vagaries of nature; control of pests and diseases is never easy in such species. It would be highly desirable, therefore, to express the precious muga silk protein in the B. mori silk gland. Partial sequencing of the muga silk gene has already been accomplished at the Centre for DNA Fingerprinting and Diagnostics, Hyderabad. The amino

acid composition of both mulberry- and muga silk is almost similar, although organization of the amino acids in terms of repeat structures is quite

different. With the availability of requisite tools and techniques, the time is now ripe for Indian scientists to restore muga silk to its well-deserved golden glory.

There are other insightful articles in this issue on a variety of subjects: herbal drugs (pg.118), vaccines (pg. 144), food security, agriculture (pg. 120), fisheries and aquaculture (Pg.

126, 129 and 132). Several distinguished experts have recalled their fond association with DBT during these past 25 years. Gerlind Wallon writes about the opportunities for India and the

European Molecular Biology Organization to work together (pg. 122), while Chandrima Shaha has focused on the interesting relationship between biotechnology and the

visual arts, and the need to increase the dialogue between scientists and artists to explore the other’s medium (pg. 146). All these are very busy people, but agreed to write because of their commitment to science. To all of them I would like to convey heartfelt thanks and appreciation.

Dr Francis Collins, the Director of the National Institutes of Health, USA, was in India recently. We were very fortunate to get him to talk to Biotech News during his busy schedule. Dr Collin’s life demonstrates the power of imagining the future – in this case genomic medicine – and relentlessly pursuing the same to make it real. Thanks to him and others like him, genomic medicine does not appear as hazy as it was a few years ago. In an exclusive interview, he spoke on a variety of issues, including his vision for the future of medicine (P. 155).

All in all, I hope that the combined issue has been worth waiting for.

s. nateshEditor-in-Chief

[email protected]

103BIOTECH NEWSJULY - DECEMBER, 2011 103BIOTECH NEWS

Spider Silk

Promising Strands

COVER STORY

J. Nagaraju

By virtue of its unique properties, unmatched with any natural and synthetic fibres, such as lustre, high tensile strength comparable to steel and elasticity to rubber, silk fibre is finding its ever increasing variety of uses ranging from fabrics to biomaterials to use in military and medicine in the ingenious and innovative human hands.

J. Nagaraju Ph.D is Staff Scientist & Group Leader at Laboratory of Molecular Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad-550 076. Email: [email protected]

Silk, the most sought after fascinating natural fibre, is secreted by amazingly diverse

group of animals, particularly arthropods. By virtue of its unique properties (such as lustre, high tensile strength comparable to steel and elasticity comparable to rubber), unmatched with any natural and synthetic fibres, silk fibre is finding ever increasing variety of uses ranging from fabrics to use as biomaterials in military. Besides, silk fibres are relatively non-allergic, biocompatible, biodegradable and possess antimicrobial properties.

Silks are produced by 113,000 species in the insect order Lepidoptera alone which is in addition to silks produced by

members of several other insect orders and more than 34,000 known species of spiders of which about 50% use their web to catch prey. For every silk that has been characterized in any detail, over 1000 uncharacterized silks are known to exist!

More than 130 different shapes of spider webs are known. Two groups of spiders - deinopoids and araneoids – make such webs. Their use of different kinds of adhesives for the “capture spiral” tempted biologists to speculate that the two spider lineages had evolved web weaving independently. But recent studies suggest a common origin (Garb et al. 2006, Science 312, 1762).

Spider silks have evolved over millions of years. Hence, it is not surprising that spiders rank seventh among all animal species in global diversity, next only to the five largest insect orders Coleoptera, Hymenoptera, Lepidoptera, Dipteral and Hemiptera.

Silks are protein polymers synthesized by the specialized gland cells and are secreted into silk gland lumen before they are extruded out in the form of fibre. Silks produced by different species are quite different in their physico-chemical properties, and are used for different purposes which include construction of protective shelter, structural support for developing eggs and egg sacs, reproduction, foraging and dispersal.

104 BIOTECH NEWS VOLUME 6 | NO. 4-6

The most studied silks are those from the species that belong to Bombycoidea of Lepidoptera, particularly the domesticated silkmoth, Bombyx mori, the golden spider, Nephila clavipes and the garden cross-spider, Araneus diadematus. Eversince the domestication of the silkmoth, B. mori about 5000 years ago in China (Arunkumar and Nagaraju 2006, Molecular Phylogenetics and Evolution 40, 419-427) silk is associated with the cultural life of people in different parts of the world. Unlike B.mori and other commercially cultivated wild silkmoths (the Chinese oak tasar silkmoth, Antheraea pernyi; Indian tropical tasar silkmoth, A. mylitta; Indian golden silkmoth, A. assama; and eri silkmoth, Samia Cynthia ricini) which secrete silk fibre at the end of their larval life, spiders produce silk throughout their life. Depending on the species, the silkmoths produce 600 meters to 1200 meters whereas spiders produce less than 130 meters of silk from their ampullate silk glands and about 12 meters from their web. In a recent report, spiders in Madagascar have been found to spin a single thread which spans across a river with a length of 25 meters. Historically, spider silks have not found widespread use in processed textiles, because spiders are solitary and predatory and are more difficult to cultivate in large numbers to produce silk on large scale. In fact, as early as in 1709, François Xavier Bon de Saint-Hilaire, the President of the Court of Auditors of Montpellier demonstrated that spider egg sac silk could be used for fabrics (stockings and gloves) in the same way that silkworm silk is used. However, considering that several hundred thousand spiders would be needed to produce a pound of

silk it was concluded by the French Academy that spider-based silk industry could never be profitable.

The nets of orb weaving spiders (those species that weave wheel-shaped webs) of Araneidae family have been in use for a number of years due to their extraordinary mechanical and biomedical material properties. The silk fibre in the web looks very similar but is actually composed of different silk fibres. For example, female orb weaving spider can produce up to seven different silk fibres tailored for specific purposes including one special silk to use as egg case. These different silk types in the

same web show great variation in their properties such as strength, extensibility and viscoelastic behavior.

Silk glandS

In almost all the spiders and insects, silk fibre is secreted from specialized silk glands (with the exception of fecal fibres of beetles). Unlike insects where the diversity of silks is reflected in the diversity of insects that produce silk, among spiders the orb web weaving spiders are equipped with specialized silk glands in the same individual and produce different types of silks to design and engineer

Spider Silk

Promising Strands

Fig. 1 : Schematic overview of Nephila clavipes diversity of silk glands, and specific function they perform.Fritz Vollrath, Liquid crystalline spinning of spider silk. Nature 410 (2001)

105BIOTECH NEWSJULY - DECEMBER, 2011

the complicated web (Fig. 1), quite often accomplishing the process simultaneously.

In Lepidoptera, to which the domesticated silkmoth belongs, silk is secreted by the specialized ectodermal cells that constitute labial glands. These glands are made up of one cell layered glandular epithelium with three distinct compartmentalized territories each with fixed number of cells. These are designated as anterior (ASG), middle (MSG) and posterior (PSG) silkglands. One interesting feature is that the cells in PSG and MSG express specific set of genes encoding silk proteins in a highly

tissue-specific manner. In fact, this salient feature attracted scientists in early 1970s to use silkworm as a model system to characterize the silk protein-encoding genes and their tissue-specific regulation. The silk-encoding gene is one of the earliest genes to be cloned in eukaryotes. The labial glands which eventually become silkglands develop during early embryonic development and subsequent growth is accomplished during larval life without mitosis and single cells accumulate up to 400,000-800,000 haploid genomes by endomitosis at the onset of metamorphosis, the highest degree of polyploidy ever reported!

Silk is made up of two distinct families of highly specialized proteins: fibroins and sericins. Fibroin, which is the core silk fibre, is a complex of three proteins each of which is encoded by a single gene: (i) fibroin heavy chain (Fibroin-H) of 350 kDa, (ii) fibroin light chain (Fibroin-L) of 25 kDa both of which are linked by disulphide bonds, and (iii) a fibrohexamerin of 25k Da which is loosely attached to six dimers. Sericin proteins are the products of at least 4 genes of which sericin-1, sericin-2 and sericin-3 have been identified. Sericin-1 produces at least 4 or 5 messenger RNAs through alternate splicing. Fibroin secreted in the PSG cells form the core of the silk filament. Sericins produced in the MSG cells glue and ensheathe the silk filaments that come from the paired silkglands together (Fig. 2).

Unlike insect silkglands (as exemplified by Bombyx mori), spider silkglands produce multiple silks simultaneously in the same individual (Fig. 1). The glands that are dedicated to the production of silk proteins include cylindrical, pyriform and aciniform glands,

major and minor ampullate glands, aggregate glands, and flagelliform glands. Spider silk glands are modifications of some other organs and are present throughout their life. This feature emphasizes the importance of complex silk glands in the evolution of spiders. The silk proteins produced by different spider silk glands are quite different in their amino acid composition as well as in the structure of their crystalline and non-crystalline domains. Each silk gland is deployed to secrete proteins for a specific purpose. For example, proteins drawn from the cylindrical gland are used for egg

Spider Silk

Promising Strands

SpinneretsPiriformes

Aciniform

Cylindrical

Agreegate

Flagelliform

MajorAmpullate

Spinneret

anterior Silk gland

250 cellsNo Secretory function known

Middle Silk gland

300 cells

Secretes Sericins (20-320 kDa),

Secretes Seroins,

Secretes Protease

Inhibitors.

Posterior Silk gland

500 cells

Secretes Firboin Heavy chain (390 kDa)

Fibroin Light chain (25 kDa) and

Fibrohexamerin (30 kDa)

Fig. 2 : A) Silk glands of Bombyx mori showing three distinct regions, B) Magnified silkgland cells showing giant polyploidized nuclei formed due to endomitosis, C) Silk fiber cross section showing sericin layers on fibroin core and D) β-sheet forming crystalline repeat motifs of silk fibroin heavy chain (BmFhc) rich in Alanine and Glycine.

Bombyx mori cocoon Silk Fibroin{ (GAGAGS) N = 8 - 10 – [(GA) N = 1 - 3 – GY] N = 4 - 7 } N = 4 - 5 – (Spacer)

Sericin 1, Sericin 2 and

Sericin 3

Fibroin Heavy chain,Fibroin Light chain &

Fibrohexamerin

Ser R

ich

Silk

Ala-

Gly

Ric

h Si

lk

a

C

d

B


sac preparation, from ampullate glands for dragline silks, from flagelliform glands for prey capture threads, and from aciniform glands for prey wrapping, in different species of spiders. This amazing diversity of spider silks adapted to perform different functions has contributed to the evolutionary success of spiders. In fact, the two important evolutionary events – the divergence of the advanced spiders, Araneomorphae from the primitive spiders and the modern orb weaving spiders, Araeoidea coincide with the evolution of major ampullate glands and the flagelliform glands. This aptly substantiates what Catherine Craig stated in her book: Spiderwebs and Silk (Catherine L. Craig 2003, pp 256, Oxford Univ. Press) that ‘spiders are defined by their silks’.

Silk CoMPoSition

In natural protein fibres such as silk which are genetically encoded, the fibre properties are determined by their amino acid composition and the order in which they are arranged in the protein and how they are spun and drawn as fibre from the liquid form. The unique feature of any silk fibre that distinguishes it from the synthetic fibre is the presence of distinct crystalline and non crystalline regions, the amino acid sequences of which are genetically encoded. The spiders and insect silks are made up of large quantity of non-essential amino acids that include non-polar and hydrophobic amino acids like glycine and alanine (Fig. 3). The silk proteins are composed of highly repetitive sequences of these amino acids which occur as motifs each of which contains 10-15 amino acids. A single silk protein will have these motifs repeated more than hundred times (Fig. 4). These repetitive blocks form β-pleated

crystalline regions. In addition to the domains of repetitive motifs, the silk protein termini are composed of non-repetitive regions of 100-200 amino acids which are non-crystalline amorphous regions and play an important role in assembling the silk protein into fibre. These regions form well-defined secondary and tertiary structures in solution. In fully grown silkglands of 5th instar silkworm larva, silk proteins exist in a particulate fluid form in a random-coiled state. During the spinning process larvae extrude silk fluid through a special apparatus called spinnerets which have ~10

µm diameter and then deposited on a support from where it is drawn further to form a distinct fibre. In the silkworm, crystalline regions account for 70 % of the total silk fibre. The amino and corboxy termini of the predominant silk protein, the fibroin-H chain (350 kDa) of the silkworm, B. mori interacts with two other proteins produced in the posterior silk gland, fibroin–L chain (25 kDa) and fibrohexamarin (25 kDa). Interestingly, these terminal sequences are conserved across Lepidoptera. Both the termini are flanked by amphiphilic proline

Spider Silk

Promising Strands

5.7 A

5.7 A

GLyCINE

ALANINE

SERINE

3.5 A

A B

Fig. 3 : A) Illustration of how polyAlanine and polyGlycine-Alanine amino acid organization affects crystal packing in β-sheet formation B) Most abuntant amino acid residues in silk fibres, Glycine, Alanine and Proline being non-polar, they confer hydrophobicity to the silk fibres while polar residues like serine attributes the hydrophilicity of the cementing silk proteins like sericins. Catherine L. Craig, Comparative architecture of silks, fibrous proteins and their encoding genes in insects and spiders. Comparative Biochemistry & Physiology, 2002.


residues (35 residues at N terminus and 26-27 residues which include three cystine residues at the conserved region at C terminus). Disulfide linkage between fibroin-L and fibroin-H proteins and non-covalent interaction of fibrohexamerin with the N-terminus of fibroin-H ensure secretion and transportation of both these proteins.

The building blocks of fibroin protein in B. mori are hexapeptide (GAGAGS) motifs which occur in strings 8-10 blocks separated by two to six GAAS or similar tetrapeptide repeats followed 43 residues of GA dipeptides further

followed by charged amino acid residues (Fig. 2D). The 43 residues act as spacers interrupting the run of repetitive region into large modules. The number repeats per module is not fixed nor the number of motifs. Such repeat heterogeneity and crystalline motifs formed by simple amino acids or poly alanine tracks in the silk protein impart unique properties to the silk fibre.

The differences between B. mori and spider silks are striking. Unlike B. mori silk fibre, the spider silk fibre is secreted by major ampullate glands (MA) (for example, Nephila clavipes and Araneus diadematus) secrete two

different types of proteins, Ma1 and Ma2 that differ in their amino acid composition. Both these proteins are composed of short crystal domains that are formed by the repeating sequence stretches of 34 and 35 amino acid residues, respectively (Fig. 4B,C). Each of these repeats also harbors another short crystal forming domain of poly alanine block (PAB) of 8-10 residues and these make up to ~15% of the total volume of the hydrated silk. Ma2 differs from Ma1 in that it has 15-17% proline residues which are thought to affect the elasticity of the fibre (Fig. 4A). The crystal domains are interconnected by 16-20 long glycine-rich amorphous chain which is interspersed with polar glutamine residues rendering the silk fibre to supercontract on absorption of water and the rubber-like elasticity is provided by hydrated amorphous regions when the fibre is stretched. Probably this variation in the non-crystalline region in spider silk coupled with the conserved PAB have contributed to the unique features such as strong and incredibly tough and viscoelastic nature of spider silks that are quite distinct from insect silks, and has evolutionary diversification of spider silks.

The remarkable features of the spider silk such as rubber-like elasticity and steel-like strength have been imparted by the genetically encoded molecular structure and the environment in which they are spun. Its strength of 1.1 GPa approaches that of typical high textile engineering steel (1.3 GPa), but silks have a significantly lower relative density (1.3) than steel (7.8) (Gosline et al. 1999 The Journal of Experimental Biology 202, 3295–3303) (Fig.5 and table on Pg. 9). Compared on a weight basis, silk by far is the stronger material.

Spider Silk

Promising Strands

PROLINE

Fig. 4 : Major ampullate gland (MA) fibroinsNc-MA-1: AGAAAAAAAGGAGQGGYGGLGSQGAGRGGLGGQGNc-MA-2: SAAAAAAAAAGPGGYGPGQQPGGYGPGQQGPGGYGPGQQGPSGPGA) Models for the molecular architecture Araneus diadematus Major ampullate (MA) supercontracted gland silk, fibre silk with crystalline β-sheets and amorphous side chains, B) Typical structure of silk fibroin with repetitious crystalline block flanked by amorphous non-repititive C & N termini and C) β-sheet forming crystalline repeat motifs of A. diadematus MA silk; crystalline Alanine-rich block is coloured blue and the Proline residues, red in the Glycine rich amorphous block. J. M. Gosline, et al., The mechanical design of spider silks: from fibroin sequence to mechanical function. The Journal of Experimental Biology 202, 3295–3303 (1999).

Amorphousnetwork chains :

16–20 amino acidresidues long

Water : 50% oftotal volume

ß-sheet cyrstals :crosslink and reinforce the polymer network

skincore

fibril

Supercontracted MA silk : crystal volume fraction is 10-12%

Native MA silk :crystal volume fraction

is 20-25%

repeatMotif

B

A

C


Spider silk protein-encoding genes are highly repetitive in nature and are quite difficult to clone, sequence and maintain the clones in the bacterial strains. The complete sequence of major ampullate spidroins 1 and 2 (MaSp1 and MaSp2)-encoding genes from the black widow spider, Lactridectus hesperus dragline silk has been obtained. These genes are comprised of single exons with 9390 bp and 11340 bp, respectively. Molecular weight of the dragline silk proteins range from 250 to 350 kDa. On the other hand, flagelliform protein-encoding gene from Nephila clavipes is made up of 13 exons interrupted by conserved introns. As mentioned earlier, the MaSp1 and Masp2 proteins are highly repetitive in nature and are conserved in most of the ampullate spidroins of orb-weaving spiders for the last 125 million years. The preponderance of non-polar and polar amino acids, low abundance of charged acidic and basic amino acids, highly conserved nature of conserved repetitive motifs that form crystalline domains, distinguishes these proteins from any other proteins, and play key role in shaping the unique features of spider silks.

Silk aS BioMaterial

The aforementioned unique properties of silk fibres secreted by spiders and silkworms coupled with recent technological innovations have elevated these natural fibres, beyond their use in textile industry, into their use as multifunctional biomaterials for a variety of applications in medicine (as sutures for wound ligations, ocular, neural and cardiovascular surgery, as drug delivery particles and as scaffolds for tissue engineering and tissue repairs), in cosmetic industry, bullet-

proof materials for military use, and a host of other applications.(Fig. 6)

SPider Silk ProduCtion By uSing reCoMBinant dna teChnology

As mentioned earlier, large scale production of spider silks is hampered by small quantity of silk fibre they secrete and their cannibalistic behaviour. These limitations have prompted scientists to look for recombinant DNA-

based alternatives to harness this important natural fibre in a cost-effective manner. Such an effort requires cloning of spider silk protein encoding gene sequences in a vector which is propagated in an ideal host to produce silk fibre in its natural form. This is quite a challenging task considering the fact that silk encoding genes are highly repetitive in nature and are difficult to reliably amplify by polymerase chain reaction. Also,

Spider Silk

Promising Strands

Tensile mechanical properties of spider silks and other materialsStiffness, Einit Strengt, Gmax (GPa) Extensibility Emax Toughness (MJ m-3) Hysteresis (%)

MaterialAraneus MA silk 10 1.1 0.27 160 65Araneues viscid silk 0.003 0.5 2.7 150 65Bombyx mori cocoon silk 7 0.6 0.18 70Tendon collagen 1.5 0.15 0.12 7.5 7Bone 20 0.16 0.03 4Wool, 100% RH 0.5 0.2 0.5 60Elastin 0.001 0.002 1.5 2 10Resilin 0.002 0.003 1.9 4 6Synthetic rubber 0.001 0.05 8.5 100Nylon fiber 5 0.95 0.18 80Kevlar 49 fiber 130 3.6 0.027 50Carbon 300 4 0.013 25High-tensile steel 200 1.5 0.008 6

Fig. 5 : Stress–strain curves for major ampullate (MA) gland (red line) silk and viscid silks (blue line) of an orb-weaver.J. M. Gosline, et al., The mechanical design of spider silks: from fibroin sequence to mechanical function. The Journal of Experimental Biology 202, 3295–3303 (1999).

Araneus diadematus MA silk:dragline and web frame

1.4

1.2

1.0

0.8

0.6

0.4

0.2

00 0.5 1 1.5 2 2.5 3

Araneus diadematus viscid silk :catching spiral of orb-web

Stre

ss (

GP

a)

Strain

Einit

=10GPa

Einit

=0.003 GPa


Spider Silk

Promising Strands

Expression Host Silk Spider Advantages Drawbacks

Bacteria:Escherichia coli (B and

K12 derivatives)

various engineered spider silk proteins

Nephila clavipes (Nc)

& Araneus diadematus

(Ad)

Easy to handle expression system; easy to manipulate; rapid growth; easy to upscale;

cost-efficient fermentation

Nucleotide sequences must be adapted to prokaryotic codon usage; poor production of larger spidroins; genetic instability of repetitive nucleotide sequences (deletions,

insertions); premature translation termination→product inhomogenity

Yeasts:Pichia pastoris

engineered MAS

Easy to upscale; cost-efficient fermentation; production of larger silk proteins possible in eukaryotes; no premature translation termination; post-translational modifications/

secreted production possible, enabling higher protein yields

Multiple gene insertions may occur→product inhomo-geneity; expression efficiency decreases with increasing

gene size

Plants:Arabidopsis thaliana,Solanum tuberosum &

Nicotiana tabacum

MAS and derived proteins

NcOnly 10–50 % of the cost of bacterial fermentation; easy to up-scale; stable production of larger spidroins; post-translational

modifications possible.

Genetic manipulation more complicated than for bacteria; longer generation intervals; large-scale field cultivation

may raise legal issues

Insect cells:Bombyx mori &

Spodoptera frugiperda

Flagelliform silk, MAS

(originating from cDNA) and mutated fragments

thereof

Nc & Ad

Among all used expression systems, insects are phyloge-netically closest related to spiders; production of larger silk proteins possible in eukaryotes; availability of conve-nient commercial cell-culture systems; no translational

pausing→higher product homogeneity; secreted production possible, enabling higher protein yields; post-translational

modifications possible; fermentable cell cultures→large-scale biomass production

Time-consuming owing to longer generation intervals compared to bacteria and to more complicated cloning procedures; cytosolic production of certain spider silk proteins resulted in protein aggregation→subsequent

renaturation reduces protein yields

Animal Cells:Baby Hamster Kidney

(BHK) Cells bovine mam-mary epithelial alveolar

(MAC) cells

MAS cDNA se-quences and variations

thereof

Nc & AdProduction of larger silk proteins

possible in eukaryotes; secreted production possible, enabling higher protein yields

Fast depletion of tRNA pools owing to the unique amino acid composition of spider silk proteins; translational pausing resulting in heterogenous protein expression;

time-consuming due to longer generation intervals com-pared to bacteria/more complicated cloning procedures

Transgenic animals:BELE goats, Mus muscu-

lus etc.

subunits of silk molecules

engineered MAS

Production of larger silk proteins possible in eukaryotes; post-translational modifications possible; protein is secreted to milk or urine, enabling high protein yields; constitutive production of silk proteins; production and secretion last for duration of lactation (milk) or lifetime (urine) of the transgenic animals

Creation of transgenic mammals is very time-consuming; separation of spider silk proteins and milk caseins during purification is challenging; creation of transgenic animals may raise ethical and/or legal issues; mice produce only

low amounts of milk, milking may be challenging

Organisms used for recombinant production of spider silk proteins

Markus Heim, Spider Silk : From Soluble Protein to Extraordinary Fiber, Biomimetic Polymers 3584–3596 (2009)

Mulberry silk fibreSilkworm strain (pnd-w1)

Hybrid silk fibre produced by transgenic silkworm strainsStrain 1 Strain 2

Dragline spider silk fibre

Average diameters (µm) 21.8 + 1.6 19.8 + 2.7 20.6 + 1.3 8.1 + 0.4

Mechanical properties

Maximum stress (MPa) 198.0 + 28.1 281.9 + 57.7 338.4 + 87.0 664.6 + 60.5

Maximum strain (%) 22.0 + 5.8 32.5 + 4.3 31.1 + 4.5 19.7 + 4.8

Break stress (MPa) 197.0 + 28.0 281.0 + 57.5 336.3 + 87.3 658.1 + 59.2

Toughness (MJ/m3) 32.0 + 10.0 68.9 + 16.2 77.2 + 29.5 79.6 + 25.4

Young’s modules (MPa) 3,705.0 + 999.6 4,860.9 + 1,269.2 5,498.1 + 1,181.2 8,949.2 + 2,096.2(Extracted from Teule et al (2012). Proceedings of National Academic of Sciences, USA, 109: 923-928)

The mechanical properties of the degummed hybrids silk fibre secreted by the silkworm engineered with chimeric (silkworm/mulberry spider) gene sequences.


the repetitive sequences of silk genes are difficult to propagate in the host strain without alterations. A couple of other problems to be addressed include (i) the highly overrepresented five amino acids (glycine, glutamine, alanine, serine and proline) and their tRNA population may get depleted in the host cell aborting the synthesis of silk proteins, and (ii) codon usage has to be adjusted to suit the host expression system. Efforts to overcome these hurdles, which include engineering of host strains, have already started yielding varying degree of successes (Table, above on Pg. 110). Although natural form of spider silk fibre is yet to be realized in the heterologous expression systems, protein aggregates of different shapes that have potential applications as biomaterials in various biomedical applications have been successfully obtained. These include drug delivery, wound healing, wound dressing and cosmetics. However, in a recent study, mulberry silkworm was genetically engineered to produce composite silk fibre consisting of silkworm/spider silk proteins. The hybrid silk fibre thus produced had significantly improved mechanical properties compared to native mulberry silk fibre (Table, below on Pg. 110). The toughness (measured as MJ/m3) of the hybrid fibre was similar to that of spider silk fibre (Teule et al. 2012, Proceedings of National academy of Sciences, USA, 109: 923-928). The published reports suggest that different processing methods and conditions yield different material properties depending on their molecular structures. For example, water insoluble proteins with high β-sheet content (such as spheres/hydrogels) can be obtained by slow self assembly processes or fast-

salting out whereas water soluble α–helical proteins (films or non-ovens) can be obtained by forced assembly processes. By appropriate treatments one can convert α-helical materials to take β- sheet conformations and vice versa. The mechanical properties of silk can also be maneuvered to meet the relevant needs by altering protein assembly methods.

The landmark developments

in cloning of silk genes, recombinant DNA research, protein expression systems, transgenesis, bioprocessing of silk proteins and silk biomechanics have brought silk fibres – the products of millions of years of evolution – to the forefront of research. The conservative face of silk is poised to change in the coming years through the integrative and innovative application of these epoch making findings.

Fig. 6 : Unique physico-chemical properties of silks fetch wide applications as bio-materials.Jonathan A. Kluge, Spider silks and their applications. Trends in Biotechnology, Cell Review (2008)

Spider Silk

Promising Strands


In 1543 Andreas Vesalius (1514–1564) wrote a textbook of human anatomy, named

‘De humani corporis fabrica libri septem’ (On the fabric of the human body). That beautifully illustrated book is revered as the founding stone of modern human anatomy. Did he ever think in his wildest dream that one day human tissues can be indeed replaced by textile fibres and fabrics?

During the last decade, Tissue Engineering research has made fascinating progress towards the fabrication of tissue constructs in the laboratory to repair, or replace, lost morphology and functions in diseased or damaged organs, in an attempt to meet the demand of our increasingly aging

society. Other than being highly priced textile commodity, silk fibre has emerged as a fascinating biopolymer for such challenging applications. Silk fibre can meet the growing need for highly specialized biomaterials in Tissue Engineering & Regenerative Medicine due to their biocompatibility, stability, mechanical properties, purity, ease of chemical modification and controlled degradability.

The Silk fibroin protein consists of a light chain (mol. wt ~26 kDa) and a heavy chain (mol. wt. ~390 kDa) linked by a disulfide bond. Silk fibroin is a block copolymer rich in hydrophobic beta-sheet-containing blocks, linked by small hydrophilic moieties. The crystalline regions are primarily

composed of Glycine-X repeats, where X could be alanine, serine, threonine or valine. Subdomains enriched in glycine, alanine, serine and tyrosine are placed within these domains. This arrangement results in a hydrophobic protein that self-assembles to form strong and resilient materials. This understanding enables us to develop large variety of three dimensional architectures of biomaterials, in the form of fibres, hydrogel, denatured porous geometry, fibre-hydrogel composites, textile structures and patterned film. Proper selection of the biomaterial design is an important aspect to simulate target tissue morphology and mechanical properties, incorporating physical, chemical, and biological signals to

Dr Sourabh Ghosh

During the last decade, Tissue Engineering research has made fascinating progress towards the fabrication of tissue constructs in laboratory to repair or replace lost morphology and functions in diseased or damaged organs, in an attempt to meet the demand of our increasingly aged society

FEAT URE

Silk fibre based Biomaterials

Lifesaving constructs

Sourabh Ghosh Ph.D is Assistant Professor at Department of Textile Technology, Indian Institute of Technology, Delhi. Email: [email protected]


guide cells into functional tissues via cell migration, adhesion, and differentiation.

Various groups around the world are working on silk fibre based tissue engineering. Prof.

David Kaplan’s group, from Tufts University, Boston, is a pioneer in using silk scaffolds to develop ligament, bone, cartilage tissue constructs and other innovative biomaterials. For example, Prof. Kaplan and Dr. Fiorenzo Omenetto’s groups, in collaboration with Prof. John Rogers from University of Illinois Urbana-Champaign, developed implantable flexible optical and electronic devices that can wrap around tortuous tissue contours (see figure above). MIT’s

Technology Review selected silk based brain implant as one of the top 10 emerging technologies in 2010. Such silk implants could offer a plethora of biomedical

applications, such as measuring electrical activity produced by the heart and brain, and for monitoring nerve and skeletal muscle activity, delivering drugs or electrical stimulations, on-line imaging, and continuous monitoring of health. This system offers great potential for studying cognition, and behavioral patterns when asleep. This system can even offer help in the treatment of people with muscular or neurological disorders, so that they can communicate or interface with computers.

Our group at IIT Delhi is working on physical and chemical modification of silk fibroin proteins to develop various types of scaffolds. For example, braided silk tapes replicating elastic behaviour of human rotator cuff muscle, or adaptation of cross-ply textile yarn winding strategies to develop fibrous scaffolds for tissue engineering of intervertebral disc

Implantable flexible optical and electronic devices made from Silk (Photo courtesy : Prof. David Kaplan)



Fig. 2 : Degeneration of Annulus tissue and herniation of Nucleus pulposus cause pinching on nerves

Caudaequina

Defect or ruptureIn Annulus Fibrosus

Compressednerve root

Herniation ofNucleus Pulposus


(IVD). IVD makes the spine flexible to bend and twist in all directions. Ageing process or injury to these disks lead to dehydration of inner gel. Degeneration of Annulus tissue, disorientation of collagen fibres result in protrusion of hard Nucleus Pulposus and application of pressure on spinal nerve root and/or cauda equina (see figure on pg. 13), causing chronic back pain. This problem is commonly known as “slipped disc”. The current approach for treating such degenerative disc problems is through reduction of inflammation and physiotherapy. Upon further degeneration, surgical removal of disk and fusion of the vertebrae is done. However, this results in reducing flexibility of the spine. Replacement of degenerated disc by a tissue engineered substitute could offer major advantages over arthroplasty or implantation of prosthetic disc, in terms of possibility of initial matching of biomechanical properties and

adaptive remodeling in the long term.

Several research groups around the world are attempting to develop bioengineered IVD. But none of these studies could have been able to successfully simulate the precise anatomical orientation of collagen fibres in AF tissue in criss-cross lamellar fashion. As a result, mechanical properties of most of these engineered tissues are several orders of magnitude below the stiffness of IVD, especially under tension and compression, and as such, are expected to provide insufficient mechanical support after implantation at the challenging intervertebral joint site. We have developed a silk scaffold having custom-made fiber alignment, where silk fibres are aligned at 30 degree to the scaffold axis, and in alternate directions in successive layers. This fibrous alignment allow cells to deposit fibrous extracellular matrix proteins at a desired orientation (see

figure 3) and ultimately developed optimum biomechanical functions of the IVD tissue. Furthermore, chondroitin sulfate, an important component of cartilage tissue, has been covalently attached with silk fibres to prepare chondrogenic microenvironment. Taken together, the combined effect of chemical composition and microstructural organization of scaffold gives rise to anisotropic and nonlinear mechanical behaviors replicating biomehanics of disc tissue.

Although silk fibre has been extensively used for tissue engineering, but several aspects of processing conditions still need to be optimized. For example, Prof Kaplan’s group reported that the processing modalities (e.g, time of degumming) could affect overall beta-crystal content, which in turn affects mechanical properties (such as rate of degradation) and biological functionality of silk biomaterials. Processing conditions and beta-sheet content have been shown to affect the metabolism of human mesenchymal stem cells and consequently altered the rate of differentiation.

Feasibility of generating new variety of genetically modified silk chimeric protein, or tunability of silkworm silk, or spider silk, presents opportunity to develop engineered tissues for organ replacement, as well as offer a platform for systematic study for addressing fundamental questions about in-vitro tissue engineered diseased tissue model systems. The modularity and versatility of silk protein-based biomaterials make them ideal candidates for translatable biomaterials research and offer an opportunity to design a new generation of biomaterials with exciting new functionalities.

Fig. 3 : Tissue engineered Annulus Fibrosus using scaffold having criss-cross silk fibre alignment




The general refrain in India is “it is all a drop in the ocean”. The country is big

and the issues are massive. At best we can only scratch the surface. Let us look at specifics, since one can get lost in myriads of issues. Let us pose a specific question. How can Biotechnology contribute to alleviation of human suffering? It is obvious that Biotech alone cannot provide the total solution, but is a powerful tool to be an important component. So, what have we done and where do we go from here?

No one can deny the fact that the growth of Biotechnology has been very impressive in the

country, ever since the inception of the National Biotechnology Board in 1982 and a full-fledged Department of Biotechnology (DBT) in 1986. To make the assessment dramatic one can state that from an adhoc budget of Rs 10 cr in 1982, the projected budget of DBT for 2012-2013 has risen to Rs 2000 cr! The starting of more than half a dozen R&D institutions in the last two decades, while process is still continuing, has led to the establishment of newer types of delivery institutions such as, Translational Health Sciences and Technology Institute (THSTI) with multiple extramural components,

Regional Centre for Biotechnology (RCB with UNESCO-Centre tag), Centre for Cellular and Molecular Platforms (c-CAMP , a section 25 company) to offer sophisticated analytical services and training, Stem-Cell institute (In-Stem) and National Agri-Food Biotechnology Institute (NABI). Newer modes of collaboration and resource sharing are being establsihed through the formation of City Clusters. Biotech Industry has widely welcomed the support system offered by Small Business Innovative Research Initiative (SBIRI) and Biotechnology Industry Partnership Programme (BIPP) and the entire Biotechnolgy

India has built an impressive Biotech infrastructure and delivery mechanisms. But, we need support systems to cross the last mile and we need regulatory systems to let newer products and technologies deliver on the promises. We need a political system that understands and appreciates the power of this technology, beyond treating S&T as a budget item and a show piece to send satellites up the sky.

G. Padmanaban

G. Padmanaban Ph.D is Sr. Scientist at Department of Biochemistry, Indian Institute of Science, Bangalore-560012. Email: [email protected]

FEAT URE

Indian S&T

When will the drops coalesce?


Industry Research assistance Programme (BIRAP) would soon evolve into an autonomous Council (BIRAC). Simulataneously many state governments are establishing the Biotech Parks, often with support from DBT. In the human resource development sector, there is a significant increase in post-doctoral training opportunities within and outside the country, support to post-graduate Biotech programmes, upgradation of Life Science Departments in universities and re-entry grants for NRIs. International collaborations have taken meaningful dimenions rather than representing routine baggages accompanying international relations. To just mention a couple of examples, the Biodesign programme between IIT-Delhi and Stanford University and the DBT-Finnish collaboration in supporting projects on clinical diagnostics are really models for emulation. The traditional Task-Force mechanisms to support R&D projects from Academia continue with further evolution into the setting up of Centres of Excellence (COEs). There has been considerable expansion of the Bioinformatics centres all over the country.

By any yard stick, the developments described above would qualify to be described as phenomenal. It is also a matter for introspection, since it has proven that such developments are indeed possible even within a government administrative system. This becomes important, since it is often mentioned that the IT sector is what it is today, only because of the private sector and at best an enabling role of the government. Interestingly, Biotech sector is still

predominantly developed through government initiative and industry needs hand-holding. It also needs to be recognised that Biotech sector is different from the IT sector in the sense that while private players would be needed to produce products, the government has a social commitment to health and agriculture. Affordability and access would be of prime importance in these sectors, where the concerns of millions of poor people need to be addressed.

The latest figure for Biotech turnover in the country is 4 billion US dollars, involving say 400 Biotech companies (I find this number quite flexible!). Are we still in the building phase? Has Biotech made a difference to the lives of people? It is, perhaps, too early to ask this question even by international standards. But, one thing is clear. In the absence of newer block-buster drug molecules hitting the market, the products making the waves are all Biotech products. Even drug discovery in the conventional sense has come to be heavily dependent on rational approaches based on an understanding of the biology of the system and pharmco-genomics. Major countries such as the US, Canada, China, Brazil, Argentina, and South Africa have derived benefits from Biotech developments in agriculture. But, transgenic technology in agriculture remains a contentious issue.

Where do we go from here? We need to look at two types of products in the health sector. One is products for life style diseases such as cancer and diabetes. Essentially, India is concentrating on Biogenerics and

the few innovative molecules are at the R&D stage. Biogenerics is, of course, important for the country and the whole developing world. India can be a leader. The limitations are still in terms of large scale manufacturing with GMP standards and fast-track clinical trial for such products. I do believe that the government should go beyond support upto pilot plant scale and look at financial support for manufacturing as well, perhaps with some equity participation in such companies to ensure appropriate compliance. For example, very few companies in India are in a position to make monoclonal antibodies for diagnostic and therapeutic purposes. If DBT/ICMR can influence high quality clinical trials with regulatory approvals in time, it would be a great contribution. The second type of products would be mass based such as vaccines and

Indian S&T

When would the drops coalesce?


diagnostics. Universal Immunisation of children is a laudable goal. India has 6 vaccines (Diphtheria, Pertussi, Tetanus, Polio, Measles and tuberculosis) under UIP. Easily, 6 more can be added to this list. Technology can seek to make combination vaccines. Strategies for making them stable and develop user-friendly delivery systems are challenges that are being addressed. But, all these would only address the supply side. There are huge problems in the demand side, which are beyond the realm of Biotech. Implemenation of strategies are major issues due to literacy levels, gender bias and rural/urban divide. Even so technology can influence policies and flooding the system with good quality, affordable products is one such strategy. The same applies to the availability of molecular diagnostic tools at affordable costs. There are a

couple of success stories, but the route to the Indian health delivery system seems to be through the Atlantic! The product has to sell internationally before it is accepted in India! I do feel that the Public Sector has a role, although the initial efforts in this direction failed. A major concern is the inroads being made by MNCs. Successful Indian companies are bought over or under negotiation to be sold on attractive terms. I guess India is a free country, but what happens to the societal goals, which forms the basis for governmental support to many of these companies to make competitive, but afforadable products? The companies look at short-term gains, but serious introspection is needed to examine whether these developments would deprive the country of affordable health products. Is there a mechanism to protect Indian and developing country interests in eventual pricing of drugs and diagnostics?

The embargo on Bt brinjal is a huge disappointment. Its indefinite continuation is a disaster. Here is a technology that can contribute to increased productivity and improved nutrition. There is considerable international experience in transgenic crops without any evidence of any kind of risk in the field. But anti-science and anti-MNC sentiments have actually seriously hampered the indigenous effort of Indian scientists to improve yields of a variety of grains and vegetables. It is tragic that this is happening despite the successful experience with Bt cotton in the country, which has converted India from a cotton-importing one to that of an exporting country. No

technology comes without a risk and there are challenges. Indian scientists are fully equipped to handle all the scientific challenges, but not unbridled activism. I do believe Biotech has to impact Indian agriculture, which is stagnating at half the productivity levels of China, despite all the conventional wisdom and agricultural practices. A Bt crop should be central to organic farming, if the real objective is to decrease pesticide exposure. A perceived or imagined risk distorts policies over the reality of a low human development index of the country to scuttle Biotech application to agriculture. It is agricultural productivity and nutrition that would contribute to improved health index of this country. A serious look at secondary agriculture where the residues can be converted to value-added products is receiving attention.

In the final analysis, India has built an impressive Biotech infrastructure and delivery mechanisms. But, we need support systems to cross the last mile and we need regulatory systems to let newer products and technologies deliver on the promises. We need a political system that understands and appreciates the power of this technology, beyond treating S&T as a budget item and a show piece to send satellites up the sky. No country can make real progress without exploiting its scientific strengths. It is obvious that many elements beyond laboratory research and industry support have to be in place before the numerous drops can coalesce. I am a chronic optimist and I look for the time when rivers would flow.

Indian S&T

When would the drops coalesce?


Herbal drug development includes various steps, starting from a passport

data on raw materials, correct identification, pharmacognostic and chemical quality standardization, safety and pre-clinical pharmacology, clinical pharmacology and randomized, controlled clinical trials. These extracts are usually a combination of several compounds that synergistically act together. Typical pharmacological features of herbal preparations are:

Metabolic Activators•Preventive agents against toxic •effectsImmuno-balancing/ •ImmunomodulatingAntioxidants•Rejuvenating/ Energy boosting•

All these features point toward their multi-variant nature and their pharmacological effects are due to the presence of many pharmacologically active ingredients that may affect more than a few genes. Our experience has been that very often purified active components of herbal extract, if used alone, normally are not very efficacious, however, combination of these components selectively and repeatedly interact with multiple sites and targets of a disease to achieve synergistic therapeutic responses. In order to understand the science behind herbal medicines, herbal researchers have to be looking at multiple variables simultaneously and how they interact with one another. Genetics, Bioinformatics, Computational Sciences, Medicinal

Chemistry and Pharmacology must integrate all at once. Along with the availability of superb computational techniques, high throughput screening techniques enable evaluation of thousands of plant extracts and raw materials via several test models in a relatively short period of time. Technology is also available for isolation and structure elucidation of all pharmacologically active components present in minor quantities. In addition, with techniques for bioevaluation, elucidation of mechanism of action, and optimization such as biomarkers, differential gene expression, chemical analyses of impurities (pesticides and heavy metals at part per billion level) as well as in vitro and/or in vivo

Pradip Bhatnagar Ph.D is President of Daiichi Sankyo Life Science Research Center in India Email: [email protected] Gupta, is Alliance Manager at Daiichi Sankyo Life Science Research Center in India Email: suman.gupta.mm@ dsin.co.in

Dr Pradip Bhatnagar Ms. Suman Gupta

Herbal drugs constitute a major share of all the officially recognized systems of health in India viz. Ayurveda, Yoga, Unani, Siddha, Homeopathy and Naturopathy. More than 70% of India’s population still uses these non-allopathic systems of medicine.

FEAT URE

Herbal drugs

Potent promise


toxicology, it is now possible to do well design experiments and statistical analyses for double blind clinical studies with herbal products.

More than 400 positive, placebo-controlled, randomized, double-blind studies have been completed for around 20 standardized herbal preparations. Development of well characterized and standardized phytomedicinal preparations should be of high priority for the pharma industry.

herBal drug develoPMent: ChallengeS and iSSueS

There are advantages and disadvantages of using plants as the starting point in any drug development program. Some of the challenges are : l Correct identification and

supply of raw material to avoid adulteration.

l Some botanical species might have been extinct.

l The properties of botanicals as recorded in classics may have undergone change due to time and environmental factors.

l Plants as biologic systems have inherent potential variability in their chemistry and resulting

biologic activity. Perhaps 25% of all plants showing promising biological activity in our assay systems fail to have the activity confirmed on subsequent re-collections.

l Standardization of ayurvedic botanicals and medicines is required, although one cannot readily apply the typical modern pharmaceutical pharmacopoeial standards.

There have been concerns about quality standards and safety issues of herbal medicines. The need for new regulations for botanical medicines has also been frequently stressed and some such regulations are coming into force in different parts of the world.

Department of Biotechnology (DBT) is playing a significant role in nurturing R &D activities in India. Its unstinted support to various sectors including Universities, public sector institutions and industry has led to a balanced growth and also opened up doors for healthy collaborations. We have been fortunate to be associated with DBT in several such collaborative programs like anti-

Dengue, anti-TB, anti-diabetic etc. Scientists from both sides contribute for a successful collaboration.

ConCluSion

Unmet need exists for new highly effective and causality-based treatments, to which herbal pharmaceuticals are expected to contribute. Availability of high-tech methods should allow researchers to optimize the effectiveness, standardization, and clinical testing of these traditional medicines to meet today’s international standards. May be in today’s era of “nomics” one can use a term Herbalnomic as a System Science that incorporate mechanism of action and biomarker based research on holistic herbal medicines.

Powerful new technologies such as HTS and combinatorial chemistry are revolutionizing drug discovery. But natural products still offer unmatched structural variety, especially as new environmental niches are explored, and their usefulness can be further extended by engineering the proteins that produce them and using them to probe biological pathways.

Herbal drugs

Potent promise


Health is the most important indicator of development, and nutrition is one of the

most important determinants of health. Nutrition security implies awareness and access at affordable cost to a) food security (an age-appropriate balanced diet), b) safe drinking water, c) disease- free environment and d) health care outreach. Biotechnology with a vast canvass of knowledge and tools can contribute to all of these. This write-up, however, focuses on food security.

the Challenge of MiCronutrient defiCienCy in indian dietS

Diet surveys in India show that being cereal-based, Indian diets are qualitatively very deficient in

micronutrients, particularly iron, vitamin A, and some B-vitamins. Following strategies can address the problem. a) Dietary diversification to enrich diet with micronutrient-dense foods, b) Micronutrient supplements; c) Food fortification and d) Bio-fortification.

dietary diverSifiCation to enhanCe MiCronutrient SeCurity

The best and sustainable way to enrich diets with micronutrients is to promote decentralised, nutritionally- oriented, integrated farming (including horticulture, legumes, millets and livestock), using green methods of farming like use of organic fertilisers and pesticides. Such a strategy enhances household access to

nutrient- dense foods, protects environment and saves water and is very suitable for dry land areas. The Societal Programme of DBT has made a big contribution to food and environment security, by promoting farm technologies mentioned above. It is the only programme which reaches out to the remotest villages from Kashmir to Kanyakumari through a network of NGOs. However, some stock- taking to assess its impact is needed. Nutrition and health education has to be an important component of such a strategy to ensure that the food produced is used for the family, and all is not sold for income.

food fortifiCation

Food fortification programme demands that the item chosen

For ensuring nutritional adequacy for a population more than six billion it is required to deploy all possible scientific tools that can enhance the quality of our diet. Biotechnology offers new opportunities in this context.

Mahtab S. Bamji

Mahtab S. Bamji Ph.D is INSA Hon. Scientist at Dangoria Charitable trust, 211, Sri Dattasai Apartments, RTC Cross Rds - 500 020, Hyderabad. Email: [email protected]

FEAT URE

Biotechnology

Food Security and Society


should be consumed by the poorest of the poor, and centrally produced. Salt is one such commodity. Iodised salt to prevent goitre is one success story in India. Very recently government has given permission to produce and market iron- fortified, iodised salt (double fortified salt) to address the dual problem of iodine and iron deficiency. Double fortified salt has been developed by the National Institute of Nutrition, Hyderabad and hopefully will go a long way in preventing anaemia. However, it should be remembered that food fortification only prevents deficiency. It cannot cure moderate and severe anaemia, and has to be an adjunct to other strategies. Fortification of cereals like wheat and rice with micronutrients like iron etc. is still in trial stages in India. Fortification of foods used for supplementary feeding in programmes like ICDS and Mid- day meal, has been suggested. Low-cost, micronutrient-fortified, ready- to- cook cereal –pulse-based

foods can help to reduce the labour of meal preparation, and also meet the court directive of serving hot- cooked food to ICDS/School children. Selection and dose of micronutrients has to be carefully done.

BiofortifiCation

Biofortification is a seed-based approach, where plant foods are enriched with specific nutrients, whose deficiency is a problem. It can be done through conventional cross breeding or marker –driven crossing, in plants where there are naturally occurring micronutrient-rich varieties. Where appropriately endowed varieties are not available, genetic engineering involving transfer of genes from other sources is done. Indian scientists with financial support from DBT, and other agencies have developed promising products, but their field testing is delayed due to health and environment safety concerns and in some cases ill –informed activism. A

robust, independent regulatory and monitoring mechanism may tide over this problem.

theMatiC net-work PrograMMeS

Following natural disasters like earthquake (north India) and Tsunami (south India), DBT has designed multi-centric network programmes to reduce the adverse effects on livelihood of people and environment of affected regions. These have had very good impact and brought succour to lacs of people, through application of science and technology.

An interesting and very successful network project for income generation through Prasad (offerings) at holy places like Hindu and Buddhist temples, churches and durgahs using local food grains and non-food, bio-resource has helped to generate employment for lakhs of women, and in some cases convert waste to wealth, example rose water from waste rose petals. Hyderabad

Biotechnology

Food Security and Society

Contd. on page 210


The impressive rise and development of science in India in recent years presents

many opportunities for cooperation and collaboration between India and Europe. The most effective ways for building long-term connections is by training scientists in the laboratory also bringing them together to discuss research at scientific meetings. Collaboration yields many benefits, including sharing and transfer of knowledge and skills, access to specialists and scientists from other disciplines, cross-fertilization of ideas and containment of escalating costs by broadening access to resources.

Almost 50 years ago, the founders of European Molecular Biology Organisation (EMBO)

envisioned fostering research environments where scientific knowledge and researchers move freely across borders. Today, the position of EMBO in Europe is firmly established in the life science community via its competitively elected members, with a reputation for excellence and supported by funding from 27 member states. EMBO supports more than 500 fellowships per year, is the largest fund provider for scientific meetings in Europe, organizes 80 events annually, and publishes four internationally renowned scientific journals. “Taking the vision of EMBO’s founders beyond Europe is the logical next step,” says EMBO Director Maria Leptin. EMBO recently signed co-operation

India’s rise as a country of significant scientific potential requires cooperation and collaboration with other countries. EMBo’S initiatives focussing on India are helping to strengthen the bonds between Indian and European scientific institutions.

Gerlind Wallon

FEAT URE

EMBO - India

Window of opportunity

Gerlind Wallon Ph.D is Deputy Director at EMBO Young Investigator Programme, Meyerhofstr. 1, D-69117 Heidelberg, Germany. Email: [email protected]


agreements with the governments of the Republics of South Africa and Singapore.

EMBO has actively sought to increase contacts with the Indian life science community, starting with the election of K. Vijayraghavan from the National Centre for Biological Sciences (NCBS) in Bangalore as an Associate Member of EMBO in 2007. This is an honour that has so far only been bestowed upon 107 scientists from outside Europe. The contact process culminated in a visit of an EMBO delegation in January 2011. The delegation, headed by Nobel Laureate Tim Hunt and EMBO Director Maria Leptin, visited nine academic institutes across India. A meeting with representatives of the Indian Government including M.K. Bhan and S. Natesh from DBT and the Honourable Minister Shri Kapil Sibal, laid the foundation for

discussions about a co-operation agreement.

Vijayraghavan told an audience of scientists at a special symposium highlighting Life Science Research in India: “These are exciting times in India, in particular with the speed of development and levels of financial investment into the life sciences. Opportunities for research are arising all over the place. But we have to play it right, so that Indian science will thrive. We need to more than match this growth in funding with growth in quality science. There is no doubt that this can be done” The symposium, a satellite to The EMBO Meeting 2010, was co-organized by EMBO and the Wellcome Trust/DBT-India Alliance to inform expatriate Indians in Europe of the latest development and opportunities back home and included a keynote lecture by Nobel Laureate Venki Ramakrishnan.

“High level, intense and small conferences in India are important for the development of Indian life science culture,” says Vijayraghavan. “EMBO Courses and Workshops have been extremely important for the development of the scientific landscape in Europe over the past decades, bringing together top scientists and catalyzing change in a cooperative manner. They are admired the world over. We need to create this buzz of interactivity in India and bring the best courses and workshops here. Working with EMBO is the way to get such activities rapidly in place in India.”

EMBO has funded several courses and workshops in India over the past years. In 2012, three events will be supported by EMBO and held in Vellore, Khajuraho and Hyderabad respectively.

Inder Verma, Professor

at the Salk Institute in San Diego, EMBO Associate Member and member of the Science Advisory Council Overseas to the Department of Biotechnology (DBT) of the Government of India, is organizing site reviews of leading institutes in India at the request of the DBT. Verma says: “It is only right that the top Indian institutes should aspire to play in the top league world-wide. Advice on how to get there should and can be sought from leaders in the field.” Eero Vuorio, President of EMBL Council and Director of Biocenter Finland, reports that a review of Finnish molecular biology research carried out by an expert panel of life scientists put together by EMBO has significantly influenced science spending and funding in Finland (Nature, Vol 394 (1998), pg 820). “Getting impartial, outside advice from science experts is tremendously helpful,” says Vuorio, “you must also have an administration that is willing to act on the advice.” Piet Borst, former Director of the Netherlands Cancer Institute in Amsterdam, EMBO Member and part of the review panel led by Verma expressed confidence that the advice from the delegation will be implemented: “The review was requested by the DBT and I have confidence in its leadership.”

Thomas Lecuit, EMBO Member from Marseille, recently spent a year on sabbatical at the NCBS. “I was very impressed by the high-level research environment that I encountered and enjoyed my stay tremendously. I wish there were more opportunities for researcher-driven exchange.” Leptin adds “On my visits to India, it has been wonderful to see the enthusiasm of Indian doctoral students for pursuing their further

EMBO - India

Window of opportunity

Contd. on page 163


Agriculture biotechnology has come a long way in the last 25 years. During my

Ph. D. days biotechnology meant tissue culture and somaclonal variation. Very quickly we started using PCR based methods for fingerprinting, marker assisted selection, gene discovery and the rest is history. The large genome sequencing projects added yet another dimension to our basic understanding but also highlighted the need for data analysis and bioinformatics capabilities.

The initial successes in agricultural sector were the introduction of tissue culture banana followed by other ornamental crops. The Department

of Biotechnology was instrumental in setting up such labs around the country which provided disease free planting materials as well as creating jobs for semi-skilled workers in the tissue culture labs. This technology is still being used at large scale by private and public sector institutes. From its very inception, DBT has been supporting various programs in the public institutions, creating facilities training and capacity building. A number of programs with other countries have provided a learning opportunity for Indian scientists as well as allowed access to technologies through these collaborations.

The biosafety guidelines for recombinant DNA research

including GM were put in place by DBT. Bollgard cotton was the first GM product to be cleared for commercialization after completing the biosafety requirements. The success of this technology alone, followed by the two- gene stacked version highlighted the benefits some of the technologies bring to Indian agriculture. The level of support and investments by DBT as well as the private sector increased.

With new innovations, the need to have intellectual property protection in place is extremely important. To be able to protect our innovation, incentives are required for increased investments. These have also progressed with our ability to patent or protect materials under various Acts.

Usha Barwale Zehr is Chief Technology Officer at MAHYCO Seeds Ltd., Resham Bhavan, 4th Floor, 78 Veer Nariman Road, Mumbai 400 020. Email: [email protected]

Usha Barwale Zehr

While Science provides us opportunity to accelerate the speed at which products can be delivered to farmers to improve on our competitiveness, the policy environment continues to challenge us and is an area in need of immediate attention otherwise all the investments we make collectively for agri-biotech research will not come to completion.

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Agri-biotech in 2025

Need to match policy with science


Looking at the progress being made in gene discovery, it is essential to have downstream capabilities in place which permit us to look at these genes for their utility. For instance, if in the past we would look to generate 10 events for a gene, now we are looking at hundreds of events to be able to generate the one or two events which could be commercialized. This implies that the transformation protocols will have to be that much more efficient to be able to generate the required numbers in the same or shorter time. Once the genes are available and the protocols are developed, it becomes a numbers game to produce a marketable event.

Similarly in molecular markers, we have moved from RFLPs to RAPD markers, to SSRs, and AFLPs, to now on to SNPs. Each one of these progressions have meant a reduction in time to complete the experiments, smaller amount of starting materials, lower costs in general. While the amount of academic information available

from public institutions has been growing, the concern of it getting translated on the farm remains. Adoption of these tools requires that they be made so simple and cost effective that there is universal acceptance. This means setting up high through put labs which bring the cost per data point to Rs. 5 instead of Rs 50 which is the current costs. The time factor is also addressed with these high-throughput systems where by data is available in shorter time. In the case of rice and some vegetables for instance, if the data is available prior to transplanting, only the selected plants have to be transplanted. The amount of data being generated in various labs need better coordination and availability and leads to a discussion on how Public-Private partnerships can be formed which create a win-win situation for both parties.

The DBT has been very active in creating environment for Public Private partnerships. With growing investments by private

sector and increased support for public institutions, this presents tremendous leveraging power to combine the strengths of the parties. The most recent programs of BIPP and BIRAP further encourage such relationships.

Over the next 15 years, agribiotech in farming systems is likely to play an increasing role. Already we see that in nations where agriculture plays a dominant role in the economy, conscious decisions to adopt biotech crops have been taken to different degrees. This trend will most likely continue as multiple pressures on agriculture (land and water availability, population pressure) drives the need for greater sustainability yet at the same time meeting nutritional needs. We see by 2002 at a minimum water use efficient crops, fertilizer use efficient crops, molecular breeding tools which enhance precision thus shortening the development cycle. As of now we have primarily focused on input traits or abiotic and biotic stresses.


Need to match policy with science

Contd. on page 163


During the year 2008 capture fisheries and aquaculture together supplied the world

with about 142 million tonnes of fish of which a quantity of 115 million tonnes was used as human food, providing an estimated apparent per capita supply of about 17kg, an all time high. To this contribution aquaculture accounted for 46% of total food fish supply. Globally fish provides more than 1.5 billion people with almost 20% of their average per capita intake of animal protein. China remains by far the largest fish producing country. World capture fisheries production has been relatively stable in the past decade with the exception of marked fluctuation driven by catches of anchoveta- a

species extremely susceptible to oceanographic condition determined by El Nino. Meanwhile, aquaculture continues to be a fast growing animal food producing sector. To outpace population growth, an average annual growth rate of 6.6 % is required. Aquaculture is set to overtake capture fisheries as a source of food fish. World aquaculture is heavily dominated by the Asia pacific region which accounts for 89% of production in terms of quantity and 79% in terms of value. This dominance is mainly because of enormous production by China which accounts for 62% of global production in terms of quantity and 51% in terms of global value. Meanwhile it is surprising to note

that the growth rate of aquaculture production was slowing down due to various reasons.

The fish sector is the source of income and livelihood for millions of people around the world. It is estimated that in 2008, 44.9 million people were directly engaged full time or, more frequently, part time and 12% of them were women. On an average, each job holder provides for 3 dependents of family members and thus the primary and secondary sector together support the livelihood of a total of about 540 million people or 8.0% of the world population. Marine and inland capture fisheries put together in million tonnes, the top 10 producer countries in 2008 were 1. China (14.8), 2. Peru (5), 3. Indonesia (5),

Prof. I. S. Bright Singh is Coordinator at National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Lakeside Campus, Fine Arts Avenue, Cochin – 628016. Email : [email protected]

Prof. I. S. Bright Singh

The fish sector is the source of income and livelihood for millions of people around the world. Asia accounted for 2/3rd of the world production. To maintain 6.6% growth in fish production several challenges need to be addressed.

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Fisheries Biotech in 2025

Need for a technological push


4. United States of America (4.3), 5. Japan (4.2), 6. India (4.2), 7. Chile (3.6), 8. Russian federation (3.4), 9. Philippines (2.6), 10. Myanmar (2.5). Global inland capture fisheries production was fairly stable between 2000 and 2004 at about 8.6 million tonnes but during the following four years it showed an overall increase of 1.6 million tonnes reaching 10.2 million tonnes in 2008. Asia accounted for 2/3rd of the world production.

To maintain 6.6% growth in fish production several challenges need to be addressed.

SPeCieS diverSifiCation

More than 360 species are produced in aquaculture worldwide, 25 of these are of high value and traded globally. But in India hardly around 6 species are widely cultured suggesting the scope and need of adding more species in to the group of cultivable. While doing so much, basic information on biology of the species which includes food and

feeding habits, habitat requirement, breeding and larval production, diseases and disease management have to be generated. An adaptation trial to suit to the region is of paramount importance.

Brood StoCk develoPMent – Pathogen free and Pathogen reSiStant

There has been negligence from the part of the country in brood stock development for the species being cultured. If India had continued the tempo which it had in the nineteen eighties in developing Fenneropenaeus indicus, the Indian white shrimp, as the species of choice for India, by this time we would have domesticated pathogen free and pathogen resistant brood stock of the species to be used in the wake of the white spot virus disease. Today we run from pillar to post to have White spot syndrome virus (WSSV) free Penaeus monodon and Litopenaeus vannamei to sustain the shrimp industry. This has added more oil

to the fire by inviting more exotic pathogens to our waters. It has to be made a part of the National policy in aquaculture development to domesticate all cultivable species with the genomics being worked out with the ultimate objective of full genome sequencing.

Marker aSSiSted SeleCtion and MoleCular Breeding

Transgenesis has almost proved non viable as it invites more criticism on release of genetically modified organisms to culture environment as the feral population might interfere with the population diversity and upset the ecosystem. In this context, marker assisted selection and molecular breeding have emerged as the viable option in the improvement of stocks. DBT has been focusing during the past one decade on the development of molecular markers to pave way for marker assisted selection and molecular breeding through its task force on Aquaculture and Marine Biotechnology. This activity has to




be intensified, spreading to more species and also supporting more projects in the application of the markers.

Maintaining Bio-SeCurity in aquaCulture

When done in an unorganized manner species movement for aquaculture can be one of the many sources of biological threats to the well being of farmed aquatic animals as well as humans and ecosystems. As aquaculture intensifies and diversifies, biological hazards and risk to farmed animals, people and ecosystems also increase in number and diversity with potentially serious consequences. Some of these hazards are infectious diseases, pests of public health concerns, residues of chemotherapeutics and resistance to anti microbial agents, zoonosis, invasive alien species and release of genetically modified organisms. The growing number,

complexity and seriousness of these risks have driven the development of the concept of bio-security and its increasing applications. An integrated strategy to manage bio-security, business, environmental and social risk will better promote sustainable growth of the aquaculture sector. A serious threat in the intensification of aquaculture is the trans - boundary movement of aquatic animal diseases which can spread rapidly. Examples are epzootic ulcerative syndrome, White spot disease and Koi herpes virus.

raPid and SenSitive diagnoStiCS

One of the most important requirements of establishing a powerful bio-security measure is to have sensitive and rapid diagnostics as micro arrays as the number of pathogens to be screened is high and the time available is limited, an area in which DBT can think of investing. The OIE manual of

diagnostic tests for aquatic animals provides a standardized approach to the diagnosis of the diseases listed in the aquatic code to facilitate health certification of trade in aquatic animals. However, the requirement is to build a viable platform for each fish species for the detection of all the pathogens at one go.

reCirCulating aquaCulture SySteMS (raS) and zero water exChange SySteMS

Increase in fish production in limited space and with limited quantity of water has become inevitable as part of intensification of aquaculture. In this context, recirculating aquaculture systems and zero water exchange systems offer unlimited scope for biosecured fish biomass production and protection of the environment as well. Realizing this requirement in advance DBT has developed the required nitrifying bioreactors for the establishment of RAS and assisted for

Packed bed nitrifying bioreactor for establishing Recirculating aquaculture system, developed with the funding by DBT



Contd. on Page 163


Fisheries and aquaculture supplied India with over 8.3 million tonnes of food fish

in 2011. The country also has an important role in global fisheries as the second largest producer of fish in the world and higher enhancement levels as compared to world fish production levels. Increase in production of finfish and shellfish, from 0.75 million tonnes in 1950-’51 to 8.3 million tonnes during 2010-’11, demonstrating over 11 times growth in the last

six decades, is a testimony to the contributions of the sector. While the marine sector is almost constituted by capture fisheries, aquaculture currently accounts for nearly 78% in inland fisheries sector. The sector has also been one of the major foreign exchange earners, with revenue reaching Rs. 12,901 crores in 2010-’11 accounting for about 18% of the agricultural export. The contribution of fisheries sector, at an overall annual growth rate of 4.5% during the previous

five year plans is estimated around 1.10% to the GDP and 5.3% to the agricultural GDP. With its continued growth, it is expected that the fish requirement by 2025 would be of the order of 16 million tonnes and in the near future, aquaculture will produce more fish for direct human consumption than capture fisheries. The rapid growth of Indian aquaculture sector has significantly benefited both from conventional technologies and modern biotechnological tools, and

S. Ayyappan Ph.D is Director General, Indian Council for Agricultural Research, New Delhi. Email : [email protected]. Gopalakrishnan Ph.D is Principal Scientist at NBFGR, Cochin Unit, CMFRI Campus, Cochin. Email : [email protected]

The rapid growth of Indian aquaculture sector has significantly benefited both from conventional technologies and modern biotechnological tools, and it is expected that the latter will further help the sector in meeting the ever growing demand for aquatic food in the coming decades.

S. Ayyappan A. Gopalakrishnan

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Fisheries biotech in 2025

Requiring a multipronged approach


it is expected that the latter will further help the sector in meeting the ever growing demand for aquatic food in the coming decades.

genoMiCS and genetiC iMProveMent:

Development of genetically improved strain of Labeo rohita, CIFA IR 1 (Jayanti rohu) through selective breeding, demonstrating over 17% higher growth efficiency per generation, is a landmark in the Indian aquaculture sector. However, the availability of genomic tools for production of improved strains of farmed fish and quality fish seed is still scarce. Functional genomic approaches to study the variation and differential expression of candidate genes of economic importance among populations of cultured species will be of immense help in marker assisted selection (MAS) programmes. For example, such a study can be used for assessing the effect of white spot syndrome virus (WSSV) or virulent strains of Aeromonas hydrophila on different genes in order to investigate the disease resistance mechanisms in wild populations of Penaeus monodon and Indian major carps respectively. Accordingly, there is large interest growing in demonstrating adaptive population divergence at the molecular level, as well as in identifying the genetic architecture of local adaptive fitness traits of species that are in aquaculture. Efforts have been initiated in India also in a consortium mode to decipher the whole genome sequence information of Labeo rohita, Clarias batrachus and Penaeus monodon; and population genomic approaches to identify the outlier loci in the genes associated with production traits in prioritized cultivable

species. Such projects would also provide the required genomic resources for developing single nucleotide polymorphism (SNP) microchips helpful in selection programmes of cultivable species.

dna BarCoding:

The lack of a proper database on our aquatic biodiversity is one of the greatest impediments for proper utilization of resources and safeguarding of our interests. DNA barcoding has been attracting international attention for its application in accurately identifying fishes, fish eggs and larvae; fish product/meat sample of a species (thus helping in curtailing illegal trade of the endangered organisms) and in resolving taxonomic ambiguity including discovery of new species. The technique has become a reality in the biodiversity rich country like India for advancing taxonomic knowledge and digitizing the identity of species. DNA barcodes of more than 500 finfish species reported from Indian waters have been prepared so far by different agencies. Reliable barcodes are yet to be developed for many other commercially important aquatic groups and this calls for concerted, joint efforts of molecular biologists and traditional taxonomists to generate accurate baseline information. However, the protocol/software to convert the DNA sequence information into digital vertical barcodes is still not available in public domain and this can lead to innovations in bioinformatics, electronics and devices such as handheld bar coders. Another option is to utilize the DNA barcode data for identification of species-specific SNPs that can lead to development of DNA chip for much faster and

precise identification of many species and hybrids and detection of fish product adulteration.

BioSeCurity and diSeaSe Control:

Aquatic animal diseases, mostly caused by viruses, bacteria, fungi and other undiagnosed and emerging pathogens have become the primary constraint to the culture of several aquatic species causing huge economic losses. Movement of live aquatic animals, within and between countries, for aquaculture and the ornamental trade, is an important route of trans-boundary aquatic animal disease (TAAD) spread. Control of WSSV, high infestation of viral infection in broodstock of tiger shrimp and identification of newer




pathogens remain major challenges for shrimp aquaculture industry in India. Accurate and rapid detection and identification of potential pathogens using morphological and molecular diagnostic tools are very important in disease management. The wide use of diagnostic kits developed by various organizations has helped the Indian aquaculture industry and farmers to take timely preventive measures to control viral diseases such as WSSV in shrimps. The country has also developed the rapid diagnostic capability for detecting the eleven fish OIE listed pathogens using molecular and immunological tools. In the absence of true adaptive immune system in shrimps, an alternative and target oriented approach against crustacean viral infections is RNA

interference (RNAi). However, there is an urgent need to develop simple and effective methods including the use of nanotechnology for delivery of accurate dose of si/ds RNA into target cells and increasing their stability in shrimp cells.

vaCCineS:

As high safety measures now exist against the uncontrolled use of antibiotics in aquaculture, research focus is now shifted to use of vaccines as alternate for disease prevention. A wide range of commercial vaccines is available against bacterial and viral pathogens and the use of vaccine is now a routine and well established practice in finfish aquaculture sector in European countries, especially to control the spread of bacterial diseases. This has also been found to be cost-effective and has led to considerable reduction in usage of antibiotics and other chemicals, used to control the spread of aquaculture diseases. Recombinant DNA technology as a biotechnological tool helped to develop protein vaccines which are economical and safe compared to the traditional vaccines. However, monovalent vaccines are not always practical as many strains and varieties of a single pathogen are generally reported in tropical countries like India. Due to such difficulties; coupled with the lack of concerted efforts and efficient vaccine delivery mechanisms, commercial production of fish vaccines is yet to become a reality in India. Another potential researchable area is improving the performance of vaccines with regard to its stability and efficacy. Efforts are also required to develop and large scale production of effective parasitic vaccines of Indian fish species.

fiSh gerM Cell tranSPlantation:

Cryo-storage of fish spermatozoa, eggs and embryos without loss of viability is of considerable value in aquaculture and conservation. Species-specific sperm cryopreservation protocols have been developed for nearly 30 Indian freshwater fishes. Fish gamete cryopreservation research still faces an important challenge in the form of long-term storage of fish eggs and embryos. Development of fish cell lines, pluripotent embryonic stem (ES) cells and germ cells from fishes and transplantation/cloning as an alternative to long term storage of finfish eggs and embryos has been emphasized for rehabilitation of endangered species. This opens new vista for multidisciplinary approaches in the field of germ cells transplantation techniques and steps have been initiated in India in these lines especially in major carps and catfishes to achieve germline chimeras, where the donor cell enters germline development and result in fertilizable gametes.

BioreMediation:

Intensive aquaculture produces large amount of effluents with harmful substances such as residues and metabolites. Application of bioremediation is a promising biotechnological approach to remove nitrogenous and other organic wastes, thereby increasing the survival and growth of cultured species. Various bioremediation preparations have also been developed in India such as nitrifying bacterial consortia using a strain of Bacillus sp and use of agro waste products, biofilms, biofilters etc., with a view to remove nitrogenous and organic wastes in aquaculture system. However, a thorough



Contd. on Page 210


Food and nutritional security is being addressed at the global level through

aquaculture in both cold and warm waters. Aquaculture is considered one of the most rapidly growing food producing sectors in the world since capture fishery has stagnated. According to FAO global statistics (FAO, 2010), close to 90% of aquaculture takes place in Asia, China being the leader, followed by India. The major problem faced by aquaculture globally is the mass mortalities due to diseases. In spite of this, it may sound strange that with the exception of Japan, there are no commercial fish vaccines produced

in Asia, while the European and American aquaculture has at least a dozen commercial vaccines to prevent disease. One of the consequences of lack of vaccines in Asian aquaculture has been the indiscriminate use of antimicrobial agents leading to unacceptable levels of residues and emergence of antibiotic resistant bacteria.

The need for supporting research that can lead to development of vaccines for aquaculture was recognized by the Department of Biotechnology (DBT), Government of India a decade ago and DBT rightly considered collaboration with Norway that has the experience of

minimizing antibiotic use in salmon aquaculture through vaccination. India-Norway Platform on Fish Vaccines was developed after a series of discussions between Indian and Norwegian scientists who met in Delhi first and then in Oslo to develop this collaborative program. To improve the chances of success and move towards commercial vaccines, Pharmaq, the Norwegian company that has experience in vaccine development and commercialization is involved as a partner in this platform. Research on vaccine development for cultivable freshwater and marine finfish species to protect them against major aquaculture pathogens

Indrani Karunasagar

The major problem faced by aquaculture globally is the mass mortality due to disease. Close to 90% of aquaculture takes place in Asia, China being the leader, followed by India. Vaccination using recombinant proteins is being increasingly recognized as useful to protect aquatic animals against infectious agents.

Bacterial diseases in fishes

Exploring new solutions

Indrani Karunasagar Ph.D is Professor & Head at Department of Fishery Microbiology & Director, UNESCO MIRCEN for Marine Biotechnology, Karnataka Veterinary, Animal and Fisheries Sciences University, College of Fisheries, Mangalore- 575 002. E-mail : [email protected]

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is also funded through programme support to the Centre of Excellence in Aquaculture and Marine Biotechnology a project awarded to the Department of Microbiology at the College of Fisheries, Mangalore.

Carps are not only the most common cultured species in the world but also the most widely cultured freshwater fish in India. In addition there are giant strides being taken by the Marine and Brackish Water Fisheries Institute (Indian Council of Agricultural Research) and the Marine Products Export Development Authority to promote culture of marine fish such as the Asian Seabass, Groupers, Pearl Spot, Cobia and others. The important warm water bacterial pathogens that threaten the freshwater aquaculture industry are Aeromonas and Edwardsiella species while the major bacterial pathogen of marine fish is the Vibrio species. Hence the major goal is to develop effective vaccines for Indian major carps and marine cultivable fish like Asian seabass to protect them against these pathogens. Aeromonads are autochthonous inhabitants of freshwater aquatic environments and infections caused by these (see picture above, left) are referred to by different names such as motile aeromonad septicemia, hemorrhagic septicemia, red pest, red sore, ulcerative disease and

furunculosis. Another important fish pathogen, Edwardsiella is ubiquitous in the aquatic environment and is responsible for mass mortality in several commercially important fish such as tilapia, eel, catfish, mullet, salmon, trout and flounder with the disease being referred to as edwardsiellosis (see picture above, right). Vibriosis is the most common disease affecting marine finfish grow-out system in the Asian region, leading to catastrophic economic losses with the most commonly encountered fish pathogenic Vibrio species being Vibrio anguillarum. It constitutes the normal microflora of the aquatic environment.

why are outer MeMBrane ProteinS (oMPS) Potential vaCCine CandidateS?

Vaccination using recombinant protein is being increasingly recognized as a powerful tool useful to protect aquatic animals against infectious agents. The OMPs are important molecules of cell envelope of Gram negative bacteria as they play various roles in bacterial adaptation including pathogenesis of bacterium. They have gained importance as new generation vaccine molecules. They are present in large amount on the bacterial surface and are essential for maintaining the integrity and selective permeability of

Common carp infected with A. hydrophila Catfish infected with E. tarda



Vaccine being injected during trials


bacterial membrane. The unique characteristic of these OMPs is that they are relatively conserved, highly immunogenic in nature as they have epitopes exposed to the environment and therefore offer themselves as excellent candidates for vaccine development. Studies carried out by our and other groups reveal that total OMPs and/or any specific OMP are potent immunogenic molecules and provide significant

protection to fish challenged with pathogenic bacteria. The lab studies involved in vaccine design is highly

tedious, time consuming and cost intensive. In silico studies using bioinformatics tools provide very valuable information in prediction of protein model, active epitopes, stability, immunogenicity etc which has been possible in all of our research, thanks to the Bioinformatics Centre (sub-DIC) set up by the DBT thus enabling dry and wet lab to come together for fish vaccine development.

Predicted 2 D (figure below), and 3 D structure of OmpW protein of showing four exposed loops

in outside of the membrane. The protein has β-barrel in architecture, possess 4 β-strands which is antiparallel to each other and tilted strongly with respect to the barrel axis.

Vaccination trials carried out with OMPs in the ongoing DBT projects appear promising. Trials conducted with specific recombinant OMP such as OmpA, OmpW, OmpTS, OmpF2 of Aeromonas and Edwardsiella have been found to be highly immunogenic and protective to finfish. Recombinant OmpK, OmpU and OmpV are being seen as potential vaccine candidates against Vibrio infections of marine fish. Studies clearly demonstrate the potential of the specific recombinant OMP’s as promising vaccine candidates for aquaculture.

Vaccines alone cannot solve disease problems in aquaculture. Excellent husbandry, including good biosecurity and genetics, optimal nutrition, appropriate densities, life stage considerations, and system management (including water quality/chemistry) are all important for minimizing disease in general, and for maximizing vaccine effectiveness.



Predicted 2D structure of OmpW protein of A. hydrophila

DBT invites the concept notes in the various identified area of bioremediation for basic and applied research interventions. The priority areas include but not limited to: • Development of biological treatment process for the industrial (textile, leather, paper etc.) effluent.• Development of bioremediation technologies for soil, groundwater and wastewater.• Waste and natural resource management.• Bioremediation of xenobiotic compounds.• Bio-restoration technologies for restoration of degraded habitats.

Last date for submission of concept notes is 31st July 2012.

For more details please visit DBT website: http://dbtindia.nic.in/index.asp

Call for proposal in Bioremediation Technology


Molecular breeding involves indirect marker-assisted selection (MAS)

during a plant breeding exercise, thus providing a means for crop improvement. MAS is particularly useful for improvement of those simple or complex traits for which phenotypic selection is difficult or labor intensive. The approach also helps in cases, where the trait has a low heritability that makes phenotypic selection ineffective. However, the genetic variability for the trait of interest should be available within the primary or secondary gene pool of the crop, so that the gene(s) may be easily transferred by hybridization (sometimes involving embryo rescue), and no genetic engineering is required.

Marker-trait aSSoCiationS: a Pre-requiSite for MaS

MAS for a specific trait in a crop involves indirect selection of desirable plants in a segregating population on the basis of one or more DNA-based markers that are known to be associated with the gene(s) controlling the trait of interest. Therefore, generally marker trait associations (MTA) for the trait of interest should be known and also need to be validated for the parents used in a breeding program. Only rarely, information on MTA may not be required, as in case of genome wide selection (GWS), which is also described as genomic selection (GS) and is a relatively newer method that is based on the assumption that the trait of interest

is controlled by few major genes and hundreds of minor genes that are distributed throughout the genome, thus making every mapped marker important for the selection. In some cases, marker assisted recurrent selection (MARS) is recommended, when the trait is controlled by many genes, so that the selection for all the genes in a segregating population becomes prohibitive. This approach involves intercrossing of selected individuals in each round of selection cycle.

advantageS of uSing MaS over Conventional Plant Breeding

The advantages of using MAS include the following: (i) no phenotypic data need to be recorded; (ii) selection can be

Pushpendra Gupta Ph.D is Honorary Emeritus Professor at Department of Genetics & Plant Breeding & NASI Senior Scientist at Chaudhary Charan Singh University, Meerut – 200 005. E-mail : [email protected]

Pushpendra Gupta

Molecular breeding has opened new vistas for enhancing agricultural productivity. This is important for a country like India where future growht in agricultural output will not come by bringing more acerage under cultivation, but by tweeking yields with in the same.

Molecular Breeding for Crop Improvement

Harnessing the genes

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undertaken at the seedling stage, and the undesirable plants need not be maintained till maturity; (iii) selection is neither influenced by genotype x environment interactions, nor by low heritability of a trait, these features being not uncommon for complex traits; (iv) pyramiding of genes for traits like disease resistance is possible, which is difficult if not impossible through conventional plant breeding, since selection for an additional resistance gene in the presence of an existing resistance gene is not possible.

different Plant Breeding MethodS involving MaS

MAS can be effectively used as a part of any of the several methods of plant breeding, which

have been described in sufficient details in a recent review (Gupta et al., 2010a). Among these methods, marker-assisted backcrossing (MABC) is the most commonly used method for simply inherited traits. In this method, often both foreground selection (for selection of the trait of interest) and background selection (for reconstitution of the parent) are used, since the objective is to transfer a desirable gene without disturbing the genotype of a well known superior recipient parent. However, there are situations, where either foreground selection or the background selection can be dispensed with. For instance, if the donor parent carrying the desirable

Crop and cultivar gene targeted for MAs Trait improvedCountry of

origin

Wheat

Patwin yr17, Lr37 Resistance to stripe and leaf rusts USA

Lassik GluA11, GluD1 5+10, GpcB1, yr36, Lr37/yr17/Sr38

Stronger gluten, higher protein content, resistance to stripe/leaf rust

USA

Farnum yr36, Gpc-B1 Resistance to stripe rust & high grain protein content

USA

rice

Swarna-Sub1A Sub-1A Tolerance to submergence India

Imp. PB1 xa13, Xa21 Resistance to bacterial blight India

Imp. Samba

Mahsuri

xa5, xa13, Xa21 Resistance to bacterial blight India

Birsa Vikas

Dhan 111

(Py84)

Multiple QTL for improved root growth

Early maturity, drought tolerance and high yield

India

pearl-millet

HHB 67-2 Unknown gene? Resistance to downy mildew India

Maize

VivekQPM9 Opaque-2 Higher lysine & tryptophan India

Downy mildew is the single most destructive pearl millet disease (ICRISAT)




1. Gupta, P.K, J. Kumar, R.R. Mir, A. Kumar (2010a). Marker-assisted selection as a component of conventional plant breeding. Plant Breed. Reviews 33: 145-217.

2. Gupta, P.K, P. Langridge and R.R Mir (2010b). Marker-assisted wheat breeding: present status and future possibilities. Molecular Breeding 26: 145-161.3. Singh, A.K., S. Gopalakrishnan, V. P. Singh, K. V. Prabhu, T. Mohapatra, N. K. Singh, T. R. Sharma, M. Nagarajan, K. K. Vinod, Devinder Singh, U. D. Singh,

Subhash Chander, S. S. Atwal, Rakesh Seth, Vikas K. Singh, Ranjith K. Ellur, Atul Singh, Deepti Anand, Apurva Khanna, Sheel Yadav, Nitika Goel, Ashutosh Singh, Asif B. Shikari, Anita Singh, Balram Marathi (2011). Marker assisted selection: a paradigm shift in Basmati breeding. 71: 120-128.

trait is also a high yielding superior genotype, one may like to obtain a genotype, which is superior to each of the two parents. This is possible only if selection is exercised not only for the trait of interest using foreground selection, but also for the overall performance evaluated through phenotypic selection that is used in conventional plant breeding. Similarly, there may be situations, where selection of the trait can be exercised on the basis of phenotype, but the reconstitution of the genotype takes time, so that in such cases, one may exercise only background selection to speed up the process of breeding without using MAS for any foreground selection.

PyraMiding of geneS uSing MaS

Pyramiding of genes for disease resistance or genes for more than one traits of interest is another area,

where MAS provides a definite advantage over conventional plant breeding. Examples of successful pyramiding for genes for bacterial leaf blight (BLB) and those for blast disease are available in rice. Similarly,

examples of pyramiding genes for rust resistance, and those for multiple desirable traits like grain hardness, high grain protein content and bread making quality are available in wheat. Some of these examples are described in recent reviews (Gupta et al., 2010a, Gupta et al., 2010b; Ashok K Singh et al., 2011).

CultivarS derived through Breeding involving MaS

A large number of genes in a number of crops have been used for crop improvement involving MAS. For instance, in wheat alone, >60 genes have been used for MAS (Gupta et al., 2010b), some of them resulting in cultivars. Most of these cultivars resulted from MABC. The most important examples of cultivars produced through MAS in India include the following: Swarna-Sub1A, Improved Pusa Basmati-1 (PB-1), Improved Samba Mahsuri

and Birsa Vikas Dhan 111 (Py 84) in rice, Vivek QPM-9 in maize and HHB-67-2 in pearl millet (Table 1).

dBt PrograMS for MoleCular Breeding

Keeping in view the importance of molecular breeding for crop improvement through biotechnology, recently the Department of Biotechnology, Government of India initiated a new Task Force for Accelerated Crop Improvement Program (ACIP), in addition to its existing Task Force in Agricultural biotechnology. A number of research programs on MAS have been funded by DBT, which should lead to the development of superior cultivars in several crops in due course of time.

an integrated aPProaCh of CroP Breeding

It is anticipated that biotechnological approaches for crop improvement including MAS and GM crops will help in meeting the challenges of food and nutritional security not only in India, but globally. Hopefully MAS and GM approaches will lead to enrichment of the genetic resources available with the plant breeders, so that eventually, the plant breeders will utilize these biotechnological approaches as an essential component of conventional plant breeding to speed up the programs of crop improvement, utilizing not only the genetic variability available in the primary and secondary gene pools, but also that available any where else including artificially synthesized genes.

Farmers viewing HHB 67 Improved seed multiplication plots (ICRISAT)




In India, large numbers of people suffer heart valve damage as a result of rheumatic heart

disease. This condition is produced when a bacterial throat infection, especially in children, evokes a severe immune response. The body’s immune system may then turn on its own tissues, including the heart. Rheumatic heart disease can affect the valves of the heart, which are then unable to function properly. Without valve replacement, these people risk heart failure and death. In India, the majority of valve replacements occur in those less than 30 years of age. The most commonly replaced valves are the aortic and mitral valves.

Four Heart valves maintain unidirectional movement of blood (see figure on page 91). The tricuspid and pulmonary valves (on the right side of the heart) control the deoxygenated blood from the systemic venous part of the circulation to the lung .The mitral and aortic valves guard the left side of the heart as the oxygenated blood from the lungs courses to the supply the rest of the body.

When these valves require to be replaced the choice is either a biological or mechanical valve. The rest of this article will confine its focus to the evaluation of mechanical heart valves. The artificial valve must withstand

the stress of opening and closing some 40 million times a year. The materials used for the valve have to be compatible with blood and human tissues. When open, the valve should allow the blood to flow smoothly through. Once closed, the back flow of blood should to be minimal. Several designs of mechanical valve are available, like, the single tilting disc, caged ball and the bi-leaflet valves (Sadhana Vol. 28, Parts 3 & 4, June/August 2003, pp. 575–587). In India, tilting disc mechanical heart valves are made by Sree Chitra Tirunal Institute for Medical Sciences, & Technology, Thiruvananthapuram (under the leadership of Dr Bhuvaneswar).

A. Subrahmanyam

Failure of mechanical heart valves can create serious, often life threatening complications among cardiac patients as post implantation the mechanical valve can run into complications characterized by the time frame of occurrence into early and late. Early identification can reduce if not eliminate some of the mortality and morbidity associated with the complications of mechanical valves.

Mechanical Heart Valves

Anticipating the glitches

P. Ramesh Thangaraj A.C. Ganapathy

A. Subrahmanyam Ph.D is Professor at Department of Physics, IIT, Madras, Chennai 600036. E-mail : [email protected] Ramesh Thangaraj Ph.D and A.C. Ganapathy Ph.D are Senior Cardiothoracic Surgeons at Department of Cardiothoracic Surgery. Apollo Hospital, Greams Road, Chennai 600024 E-mail : [email protected]

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Currently the bileaflet design (see figure on the right) is more commonly employed. They are made from pyrolytic carbon of varying purity and combinations.

The essential components of a typical bileaflet valve are the sewing ring, the hinge mechanism and the leaflets themselves.

The mechanical valve has a variety of complex problems: during insertion and during the valve operation. Heart valve diseases fall into two categories: Stenosis and Incompetence. The stenotic heart valve prevents the valve from opening fully, due to stiffened valve tissue. Hence, there is more work required to push blood through the valve. Whereas, the incompetent valves cause inefficient blood circulation and cause backflow of blood in the heart, called as regurgitation (excessive backward flow). A variety of diseases both inflammatory and degenerative can cause valves dysfunction. Broadly

the hemo-dynamic dysfunction of any heart valve could be either obstruction to forward flow or regurgitation or a combination of both. Although the prosthetic valves themselves may have problems of stenosis and regurgitation much like a native valve, the clinical implications may be different.

Post implantation the mechanical valve can run into complications characterized by the time frame of occurrence into early and late.

The commonest problem include a mismatch between patient size and valve size leading to an increased gradient across the valve. Dehiscence of the valve can occur due to technical issues at the time of the operation or infection. Thrombosis can occur as an early or usually as a late complication and pannus formation which is in growth of tissue into the valve can result in valve dysfunction.

Endocarditis of the implanted valve is infection of the valve and it carries a poor prognosis when it does not respond to antibiotics. It may require an urgent re-operation to replace the infected valve. Hemolysis of blood commonly occurs when a jet of blood has to squeeze through a narrow space like a paravalvular defect.

Evaluation of me-chanical valves has been done by Echocardiography, cinefluoroscopy, CT scans and angiography. Echo cardiography (pulsed, continuous wave, colour (both 2D and 3D) us-ing both the trans- thoracic) probe over chest and transesophageal (probe through the food pipe) is the preeminent method of evalu-ation. The easiest estimation with echo cardiography is the gradient, but this value alone can be mis-leading. The effective orifice area (EOA) which when indexed to the body surface area is a very useful measurement to detect a patient

prosthesis mismatch. In general if the EOA is <0.85cm2/m2 for aortic and 1.2cm2/m2 for mitral a signifi-cant mismatch exists. The param-eters evaluated are qualitative, semi


Anticipating the glitches

Valvulapulmonar

Valvulatricuspide

Valvula aortica

Valvula mitral

Contd. on page 142


Nature is a perfect ecosystem caressing its numerous constituents within a

constant state of equilibrium. In this home to the many, interdependency and crosstalk within the constituents plays a major role. One organism feeding on the other and itself being fed by another in this balanced ecosystem gave the first clue of artificially controlling the agricultural pests as early as 300AD when Chinese first observed the insects being attacked by the predatory ants. Agricultural pests have been a problem ever since the start of crop husbandry. Human intervention in identification of their natural enemies and realigning their balance in the pest infested areas led to the development of the

phenomenon of biological control. Although synthetic pesticides ruled for quiet some years, the wheel is now turning back to evolving mechanism of biological control in view of their target specificity and environmental safety.

A broad spectrum of biocontrol agents have been identified globally and are being investigated for deployment in strategies to minimize predation of crops by insects. India being economically dependent to a large extent on agriculture, is also investing a lot in efficient use of these biocontrol agents which belong to different taxonomic groups.

Government of India has invested aggressively in biological

pest control system through Department of Biotechnology and Indian Council of Agricultural Research. These agencies have invested substantial resources to identify, develop and commercialise biocontrol agents. In pursuit of such application the work has progressed in deployment of whole organism or its metabolite as biological control agent.

Entomopathogenic fungi like Metarhizium anisopliae, Beauvaria bassiana, Nomuraea rileyi, Trichoderma viride, Verticillium lecanii etc. infect insects at different developmental stages and their spores/conidia have been formulated for use as insect control agents. When the fungal spores come in contact with the insect cuticle, they germinate,

Raj K Bhatnagar Ph.D is Group Leader & K. Sowjanya Sree Ph.D and Bindiya Sachdev Ph.D are Group Members at Insect Resistance Group, ICGEB, Aruna Asaf Ali Marg, New Delhi- 110 067. E-mail : [email protected]

Raj K Bhatnagar K. Sowjanya Sree Bindiya Sachdev

Using natures on mechanisms to counter pests for enhancing agricultural productivity allows increased production without polluting the environment which is inevitable in case of chemical pesticides.

Biological control of crop pests

Going full circle

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penetrate and proliferate in the insect tissue sucking up all its nutrients and finally sporulating from the cadavers. Formulations containing some of these fungi have been effective against insect pests. These have been commercialised and sold under different names such as Bio-Power, Bio-Catch and Bio-Magic1. The viruses like the Nucleopolyhedrosis viruses of Helicoverpa armigera, Spodoptera litura, Hyblaea puera and Granuloviruses of Chilo infuscatellus and Plutella xylostella infect the respective larval hosts, lyse the cells which leads to the death of the infected larvae. These viruses have also been formulated and are being deployed commercially in agricultural fields. Parasitoids like Trichogramma chilonis and entomopathogenic nematodes (Steinernema carpocapsae, S. biocornutum and Heterorhabditis indica) are also powerful insecticidal agents. A gammaproteobacterium, Photorhabdus luminescence, which harbours in the gut of the entomopathogenic nematode,

Heterorhabditis indica, produces insecticidal toxin complex A (TcA). Our lab at ICGEB, New Delhi has successfully evaluated, registered and commercialised a liquid formulation of Photorhabdus luminescence under the trade name Bioprahar.

In addition to formulating the whole organisms for biocontrol of insect pests, their metabolites, macromolecules are also being employed in control of phytophagous pests. Among various macromolecules, the insecticidal crystal proteins (cry) of Bacillus thuringiensis have been successfully deployed through transgenic route. The first crop being commercialised expressing cry1Ac in cotton has been accepted and cultivated under large acreage. Cultivation of transgenic cotton has offered documented economic and environmental benefits to growers. In addition to insecticidal proteins, the RNAi pathway based strategies in control of specific insects have also

shown immense promise. Cotton boll worm larvae fed on plants expressing double-stranded RNA of a cytochrome P450 gene showed retarded growth2. Plant mediated RNAi employing critical insect proteins is being explored further for evolving efficient biocontrol strategies. The fungal toxin from M. anisopliae, Destruxin, has also been demonstrated to be insecticidal and its potential to evolve as an efficient insecticidal formulation is underway. Plant extract from Azadirachta indica (Neem oil) containing Azadirachtin and other limonoids has been successfully used against Whiteflies, Thrips and Aphids. It is being marketed by different agro-industries with the names Nimbecidine EC and Margosom EC.

In addition, careful observation of crop associated insect fauna led to the discovery of predatory insects that are natural enemies to important agricultural pests. Chrysoperla carnea (lacewing) is


Going full circle


1 T. Stanes & Company Limited, www.tstanes.com2 Mao Y-B., Cai W-J., Wang J-W., Hong G-J., Tao X-Y, Wang L-J., Huang Y-P., Chen X-Y. 2007. Silencing a cotton bollworm P450 monooxygenase gene by

plant-mediated RNAi impairs larval tolerance of gossypol. Nature Biotechnology, 25 (11): 1307-1313.3 Cummins J. 2007. Parasitic fungus and Honey bee decline. Institution of Science in Society Report. http://www.i-sis.org.uk/PFHB.php 4 Shah S. 2010. As Pharmaceutical use soars, drugs taint water and wildlife. Yale Environment 360 Report. http://e360.yale.edu/content/feature.msp?id=2263

one such predator feeding efficiently on aphids. This strategy has been greatly explored in the classical biocontrol as a part of integrated pest management programme. Normally native predatory insects are amplified in field for targeting pests, however, sometimes such insects are brought in from other equivalent geographical niches to reduce incidence of local insect populace. Preliminary lead in this strategy started as early as 1920s when an exotic coccinellid beetle, Rodolia cardinalis, was introduced to India from USA for the control of Icerya purchasi, cottony cushion scale on citrus trees. Since then many other exotic natural enemies have been introduced to India from the place of origin of the exotic pest

species. This strategy to multiply exotic insects as predators tends to be so simple and straight forward but is actually loaded with threat to imbalance local ecosystem due to skewed distribution and change in genetic makeup of native species via hybridisation with closely related exotics. The exotics might also sometimes be vectors for harmful pathogens to native species. Hence, extreme care should be practised in the choice and implementation of exotic species as biocontrol agents.

While last decade’s economic and environmental concerns about chemical pesticides opened up avenues for discovery of novel organisms or their macromolecules for control of crop pests, care should be exercised

in implementing such measures. No doubt, these biocontrol agents present immense repertoire of insecticidal organisms/ molecules but they need to be critically evaluated before integrating them into pest management strategies. The way we manage our natural assets will define our collective future. The decline of honey bees, the most important pollinators, in nature due to reduced tolerance to the pathogenic fungus, Nosema ceranae, as a result of increased use of chemical insecticides3 and the eroding population of vultures due to the biomagnification of declofenac4, a pain killer given to livestock, in the food chain is an alarming signal to apply technology judiciously.


Going full circle

quantitative and quantitative in nature. Over the years reproduc-ibility of the diagnostic data are high but inter-observer differences still persist.

The evaluation using Doppler Echocardiography includes peak velocity/gradient, mean gradient contour of the jet velocity, doppler velocity index and the presence, location, severity of regurgitation

The challenges that remain in evaluation of mechanical valves are the early identification of thrombosis before significant changes in

gradient or visual confirmation occur, as both these reflect a later stage in the disease process.

The accurate observer independent quantification of regurgitation, especially paravalvular regurgitation would be very useful clinically.

Early diagnosis of pannus formation and surveillance remains elusive.

Magnetic assessment as a concept in the evaluation of prosthetic valves has been explored in the context of MRI evaluation of prosthetic valves.

The use of thin film

magnetic sensors incorporated in the structure of the valve itself and the information that it may provide in a real time basis could be a potential new way of solving some of the challenges in the evaluation of mechanical valves. This task is undertaken with INDIGO initiative of Department of Biotechnology in cooperation with European Union (EU).

The hope is that early identification can reduce if not eliminate some of the mortality and morbidity associated with the complications of mechanical valves.


Anticipating the glitchesContd. from page 139


After pneumonia, diarrhoea is the major cause of childhood deaths in India.

In 2008, 18% of the global child deaths and 77% of child deaths in Southeast Asia were from India. Diarrhoea continues to remain a formidable killer in our country. Africa and Asia bear the brunt of childhood diarrhoea when territories are resized by the concentration of childhood diarrhoea using the size of the land area in proportion to absolute numbers of diarrhoeas by a technique known as ‘density cartography’ (see figure on Pg. 42).

Among the several interventions that are available, provision of safe water and sanitation is unquestionably the best solution to reduce diarrhoeal

deaths. The feasibility of providing safe water and sanitation across the country is a daunting task and despite efforts is still a distant dream. Besides, diarrhoea caused by viral enteric pathogens like rotavirus will occur regardless of socioeconomic level, improvements in water and sanitation and geographic location. A vaccine against targeted diarrhoeal etiologies represents a tangible intervention strategy to reduce the overall burden of diarrhoeal diseases. But unlike other diseases like tuberculosis, malaria or HIV which are caused by one causative agent, there are more than 30 different established etiologies for diarrhoea ranging the entire spectrum of bacterial, viral and parasitic pathogens.

These etiologies have their own epidemiology, transmission patterns and pathogen biology. Choosing the diarrhoeal etiology to develop a robust vaccine is therefore essential to the success of a vaccine program against diarrhoeal diseases in a given setting or a country.

A substantial burden of diarrhoea in India is due to Rotavirus disease and cholera. Both are characterized by acute watery diarrhoea and vomiting with diarrhoea caused by rotavirus often accompanied by fever. Acute watery diarrhoea rapidly leads to loss of body fluids resulting in dehydration, and death if not corrected. Rotavirus is a childhood disease, with the incidence of infection peaking in infants aged 6-12 months

Diarrhoea continues to kill a large number of children across the world. India accounts for a significant proportion of these fatalities and has a special interest in efforts aimed at developing vaccine for diarrhea.

G. Balakrish Nair

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Vaccines against diarrheal diseases

Where do we stand?

G.Balakrish Nair Ph.D is Executive Director of Translational Health Science and Technology Institute, 496, Phase-III, Udyog Vihar, Gurgaon 122016, Haryana. Email: [email protected]


in India while cholera can affect any age group although recent trends show a disproportionate shift in incidence to children below 5 years in several cholera endemic areas. Rotavirus disease is associated with significant mortality especially in developing countries that account for 85% of the rotavirus deaths. Estimates show that about 123,000 deaths occur every year in India among children aged less than 5 years due to rotavirus diarrhoea. Likewise cholera has also significant mortality especially when it occurs as an epidemic as seen in the recent devastating cholera outbreak in the Caribbean country of Haiti.

Licensed global enteric vaccines against these two significant causes of diarrhoea are available in the past two years to the public health program in India. Two rotavirus vaccines namely Rotarix® and RotaTeq® are licensed in India while a bivalent oral killed cholera vaccine Shanchol® is licensed and manufactured by an Indian vaccine manufacturing company. Shanchol was licensed in December 2009 in India and was WHO prequalified in September 2011 thus making it a

global vaccine. The universal usage of the licensed rotavirus vaccines in India is stymied by affordability while the target group to be vaccinated for cholera is still under debate.

To make these vaccines affordable, the Department of Biotechnology (DBT) is spearheading the indigenous development of enteric vaccines. A rotavirus vaccine that has evolved out of programs funded by DBT includes a naturally occurring bovine-human reassortant, 116E. Another vaccine in development by a program supported by DBT is the recombinant live oral cholera vaccine strain VA1.3/VA1.4. The rotavirus and cholera vaccines were found to be safe and generated robust immune responses in limited human trials and have the potential to be efficacious vaccines. Both the rotavirus and cholera vaccines are being developed by Indian manufacturing companies. Randomized double blinded placebo controlled trials are still under progress.

The time has come to introduce the rotavirus and

cholera vaccines into the national immunization program. These vaccines are available for use in the private sector but are expensive and children who are in most need are deprived of access to these vaccines. The addition of new vaccines to immunization programs could substantially reduce child deaths in India. The emphasis on discovery of new vaccines or better versions of existing vaccines must continue but what really needs to be propelled are policy and programmatic issues that decide on the introduction of these vaccines. The emphasis must clearly shift from the discovery mode to translation for public good. Otherwise, we will have the disreputable situation of being unable to control diseases despite having vaccines to prevent them. The DBT has recognized this hiatus and has created a new Institute known as the Translational Health Science and Technology Institute which will play a central role in taking such issues to the forefront and translate basic research findings into applied tools to prevent, control or treat human diseases.

Vaccines against diarrheal diseases

Where do we stand?

Territory size shows the proportion of worldwide cases of diarrhea found in children aged 0-4 living there (source: http://www.worldmapper.org).


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I remember reading two novels in school that left a profound influence on my mind as to

how the world would look like in future, They were ‘Men Like Gods’ by H.G. Wells and ‘Brave New World’ by Aldous Huxley. While Wells projected a better future as a utopian society, Huxley predicted a frightening vision of the future. Although divergent in views, both books were of much interest to the readers and influenced the intellectual mind over a great period of time as to what science and technology could do. In modern times, in addition to books, visual arts are a great communicating medium for providing transforming thoughts to the public. Articulation

of information from visual media imparts deep influence in shaping of thoughts in our psyche that can eventually result in policy decisions affecting human society. This is interesting to us as scientists because it provides clues to how society is interpreting the biotechnological revolution as we see it happening.

Green fluorescent protein has been a brilliant tool for biotechnologists. In the late nineties, it is this very molecule that inspired imaginations of one individual named Eduardo Kac who started a project on creation of Alba, a‘GFP BUNNy’ rabbit whose birth was interpreted as a complex social event that started with the creation of a chimerical animal that does not

exist in nature (http://www.ekac.org/; Berra, Y, PNAS, 106: 10073-10080, 2009). This event was actually the dawn of a novel dialogue between artists and biotechnologists dubbed as “bio-art” that attempted to understand the complex relationships between genetics, organism, the environment and the notions of normalcy, heterogeneity, purity, hybridity, and otherness.

Creation of Alba triggered much interest in bio-art post year 2000. While a variety of interesting expressions were taking shape in paintings, installations in art became an important component to articulate progress in biotechnology. Particularly, the ability of biotechnological tools to harness the

Chandrima Shaha Ph.D is Director of the National Institute of Immunology, New Delhi E-mail : [email protected]

Chandrima Shaha

Articulation of information from visual media imparts deep influence in shaping of thoughts in our psyche that can eventually result in policy decisions affecting human society. This is interesting to us as scientists because it provides clues to how society is interpreting the biotechnological revolution as we see it happening.

Biotechnology and Art

Creative Connections


power of the living tissue outside the body in addressing human health problems fired curiosity in artists of different genre. As a consequence, we see an exciting array of works emerging out of interesting collaborations. University of Dublin along with Wellcome Trust as a co-founder, runs a ‘Science Gallery’ in Australia to provide a platform for artistic expressions of science that could generate significant public interest. In early 2011, this gallery showcased an exhibition by ‘SymbioticA’, a centre of excellence in biological arts at the University of Western Australia Perth, where artists and scientists participate to produce artworks. This exhibition called ‘Visceral: the living art experiment’, explored the idea of using living tissue to create innovative artworks. For example, one of the artworks in the exhibition showed novel book covers derived by tissue engineering from a combination of pig and human skin cells where animal sacrifice

was not involved. This work with dead cells was accompanied by exhibits created with viable cells like ‘Vision Splendid’ where a nutrient bath had a small figure seeded with human cells that continuously multiplied during the exhibition to help people to consider the meaning of immortality as to indicate that life can be lived beyond the life of the donor (http://www.sciencegallery.com/visceral/). The Museum of Modern Art in New york City in 2008 presented an exhibition called “Design and the Elastic Mind” where genetic engineering, nanotechnology and biomimicry were shown almost in poetic dimension. Embryonic stem cells from mouse were used to create a designer garment like a coat that kept growing during the exhibition demonstrating the power of science, design and art and how biological engineering can be used for art (artists, Oron Catts and Lonat Zurr). Eventually, the coat grew so big in the installation culture that it

clogged its own nutrition system and the curator had to make a decision to euthanize the coat making big news in the art world. Another exhibit was termed as ‘Steak of the Future’ that was based on cells growing on an abdominal scan made from a cow, suggesting that in future it may not require animal sacrifice to produce steak (http://www.moma.org/ explore/ multimedia/ videos/12).

Traditionally, the tree of life represents the Darwinian view of evolution, however, artists’ perceived creation of different life forms through biotechnology as a taxonomic crisis. ‘NoArk’, a research project during 2007-8 explored this supposed crisis (http://tcaproject.org/projects/noark).The artists took cellular stocks from tissue banks, laboratories, museums and other collections and made a techno-scientific body in a chimerical blob growing in a single vessel. In a sense they were making a unified body of suborganisms that were


Creative connections

CanCer genoMiCS

Dr. Hunter Cole is an internationally renowned artist and a geneticist who uses various forms of visual art like abstractions, digital art and installations. She holds a Ph.D. and Master’s degree in Genetics from the University of Wisconsin-Madison, and a Bachelor of Science from the University of California-Berkeley. She teaches biology and art at Loyola University Chicago. She created a course, Biology Through Art, where students have the opportunity to create innovative artworks in a biology laboratory. This painting has been reproduced with Dr. Cole’s kind permission.

microarray

DNA binding proteinsDNA

female figure

short DNA fragmentsfor shotgun sequencing

cancer cellsfemale figurefemale figure

DNA mutation


unclassifiable, suggesting the work as a symbolic precursor to manmade nature. Perhaps one of the most striking images of the 20th century was the picture of a mouse with a human ear growing out of its back. Scientists using a biodegradable ear-shaped mold grew human cartilage cells and introduced it into the body of a mouse (J. Vacanti at the Tissue Engineering and Organ Fabrication Laboratory at Massachusetts General Hospital in Boston). Although this picture created a furore amongst pro-living groups, the image inspired many artists because of the possibilities of engaging with life in a sculptural way. ‘One of the powerful artists in this field of bioart is Patricia Piccinini (http://patriciapiccinini.net/archive/) who has made many contributions in the form of artworks. Excited by visualizing stem cells in a petri-dish, she thought that these cells formed the basic format of the organic world because they were intrinsically nothing but can become anything, alluding to the pluripotent power of these cells. She came up with

an installation ‘Still life with Stem Cells’ that can be interpreted as an artist’s vision of a variety of life forms stem cells can create. In a way she presented creatures that defied classification with babies ageing before their times and vehicles in the shape of a baby, expressing her anxiety on what biotechnology can do to society. Artists with scientific training however look at advances in biotechnology in a more positive perspective where artists like Dr. Hunter Cole represent biotechnological advances as a promise for the future. Her painting like the ‘Cancer Genomics’ now in the collections of NIH is an evidence of how biotechnology can be interpreted by abstract art (http:// www. huntercole. org/ artgallery/ biologypaintings/ cancergenomics.html).

Biotechnology has changed the pace of the society and as a strong communicating medium, art has exerted profound influence on the public mind in the West. Nationally, the Department of Science and Technology has created the National Council for Science and Technology Communication

that aims to create excitement concerning advances in science and technology. That the enthusiasm is generated is palpable from the images from a national science photography contest organized by the National Council for Science and Technology Communication. There are many individual efforts to discuss and blend scientific observations in an art form, however, to the best of my knowledge, there is no significant platform in our country for visual arts to attempt to interpret scientific advances.

Evocative art forms pertaining to biotechnology has to be created with great sense of responsibility as that fuels public psyche. Very much like the two opposite novels that I quoted in the beginning, some views will be of optimism while some will be about the things that can go wrong. Therefore, it is perhaps worthwhile to increase the dialogue between scientists and artists to explore each other’s medium to create a beautiful collaboration of expression for societal benefit.


Creative connections

Moving on !!!Moving on !!!

Please write to: The Circulation Manager (Biotech News) Communication and Outreach Division Aravali Foundation for Education Aravali House, 431/D-22, Chhattarpur Hills, New Delhi-110 074 Email: [email protected] | Fax: +91-11-26301016


In 2047 India shall reach a milestone : 100 years of development free from the

colonial yoke. We, and the world at large, like to prophesize the rise of India as a global power with envious economic clout. For meaningful pivotal role in world affairs, educational, socio-cultural and technological ascendancy are also essential corollaries to economic might. In other words, all round development of the one key element in human societies, the human resource needs to be cultivated and developed with no holds barred. State of the art and future concept education for the proliferation of knowledge and skills in the humanities as well as science and technology (S&T) are essential for

enriching our large human resource, second only to China in numbers. We have to exploit this stupendous wealth of ours for embarking purposefully on the creation of a modern state of high importance and consequence on the world stage.

Since education and knowledge are the foundation of transcension of available human resource, let us examine our current status in these fields, and future plans/options for taking up the mantle of leadership along with the few other major players in the International arena.

India is described today not as an emerging, but emerged economy. But in other allied important fields mentioned above,

our position is highly tenuous. The basic parameters-economic, social, cultural and technological excellence, derive from a robust and progressive education system. Cutting edge S&T contributes to the innate, manifest and futuristic strength and potential of people. These can be realized only through a working and visionary education system. Let us therefore focus on the current status, potential and future of the Indian education system and its role in advancing the frontiers of knowledge and capability in all fields, particularly in S&T.

It may be appropriate here to begin by reflecting first on the limitations and fundamental requirements of our educational

G. C. Mishra

For any nation to harness its full potential in science and technology, fostering and nurturing human talent is of critical importance. G C Mishra examines where we are and what we need to do to get us where we wish to go.

Human Resource Development in Science

An India perspective

G. C. Mishra Ph.D is Eminent Scientist at National Centre for Cell Sciences, Pune. E-mail : [email protected]

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systems with particular attention to its role in the strengthening and development of innovative S&T.

One of the basic needs of engaging purposefully with the daunting task of human resource development in science is to structure the scaffolds of human development from the very beginnings of education. The inability of our institutes of higher learning to measure up to global excellence in research percolates down inevitably to a similar drought of independent, original, innovative and path breaking work in our professional S&T institutes. Also, when bright young minds begin choosing their careers, they prefer other options, mainly because they see science as offering fewer opportunities in terms of economic gain. A mechanism needs to be evolved to infuse enthusiasm in young minds for quality learning, independent and innovative thinking. It becomes apparent that our first focus in undertaking human resource development has to be on a critical assessment of our education systems, and find ways of modifying these to bring them in line with modern global thought and practice.

Before taking up the nitty-gritty of Indian Education systems, let us first dwell upon certain statistics. We are a billion plus nation that is likely to overtake China in population numbers in a decade or less. We currently have about 300 universities of different qualities, but none of these measure up to the best 10, or 20 or even 50 in the world ranking. The youth of the country are dominant numerically, and its characteristic of India that most of them, irrespective of social or economic strata, hanker for education. Conservative estimates put the minimum numbers of

schools and universities required by 2047 at 200,000 and 1550-2000 respectively. Considering the inputs of teaching staff, equipment, other infrastructures for these, it would be very difficult to meet such a goal. However, India has the talent to find alternatives. The digital revolution has placed a priceless tool in our hands. Already, efforts to enlarge and enhance digital connectivity to include small towns and even the rural hinterland are under way. At the higher levels, cloud computing would have to be used extensively. Fortunately, India has the capability to excel in these fields. The recent development of the cheapest tablet in the world, the Akash, is an example. It would, of course require generous inputs of finance to undertake various ventures which are needed to enable us to impart quality education at all levels without the accouterments of formal education as we know them today. But we should not be disheartened. Let us remember that the USA replaced Germany as the numero uno in S&T only after massive inputs in its education system. China is not in any kind of slumber either. The Chinese are going all out for education, and this includes widespread and mandatory learning and acquisition of fluency in english…an asset which Indians already have. Our scientists have demonstrated ability, competence and excellence by some of them publishing original research in the most highly rated scientific journals. However, regrettably, this nation of a billion plus has not been able to produce a single path-breaking research, idea or innovation in the past 50 years. Apart from some of the faults and shortcomings of our systems which will be briefly outlined below, we must try

to understand and analyze why creativity and innovation seem to get stifled, maimed and stymied at all, but especially the higher levels of education and research in our country. Why are we not able to get out of the rut of plodding on the beaten track. As we will see below, much of this would appear to be a consequence of archaic and frozen mindsets of the education and research regulators-bodies or individuals, who seem unable even to remould and overhaul the systems, let alone taking risks in terms of supporting what may even seem to be outlandish and impossible ideas.

The shortcomings in our education systems and philosophy briefly outlined in this article have a snowballing effect on the quality of research our universities and institutions produce. We know that few, if any, of these compare well with the daily outpourings of new, original and innovative ideas in other parts of the world. This is especially true of our S&T research. Some institutes may be able to show high impact or citation indices of their published researches. However, we keep falling short of real breakthroughs which would impact the world, rather than impressing just a specialized coterie of experts. On the other hand, sometimes brilliant ideas and work have emerged even from Ph.D. students in the west. Obviously our education and research systems, especially in S&T need a complete, comprehensive and imaginative systemic overhaul.

Given the present trend of rooting for technology among both the teachers and the taught, we need to understand that we have to pay equal attention to both basic endeavors and the interface




between these, and technological innovations. The latter flow from the former. But without excellence in and of the former, the latter will dry up. Its not enough to work hard at continuing the patterns of yesteryear : we have to be on our toes, ever alert and always enterprising, seeking new paths, and innovative strategies to produce and cultivate the dreamers and help take their dreams to fruition. That is the only way to achieve excellence-perhaps even supremacy in Science and Technology.

Coming now to some specifics of the Indian education systems, let us highlight a few areas needing immediate overhaul.

First, we have to break shackles of the rote system of learning and examinations where ‘merit’ is determined on the basis of memorizing abilities. Our examination systems reward only the rote learners with little or no scope for any acknowledgement, recognition or reward for original, creative or innovative ability.

Next, it is important to infuse more flexibility in choosing the subjects at different levels of education, whether undergraduate or graduate classes, so as to generate personnel with unique capabilities and combination of expertise. Indian students should be able to dream of, for example, doing courses in ornithology and coupling them with quantum physics. These kind of unthinkable choices are made everyday and everywhere in the western world. These forms of rare mixtures of talents are needed for emergence of all round knowledge which is the real producer of original and innovative ideas.

Creating awareness of the excitement of pursuing science

should be given added special importance at the school level to enthuse young minds to the wonders, charm and potential of taking up science as a career. Realizing this, the Government of India has initiated a battery of programs. These include Innovation in Science Pursuit for Inspired Research (INSPIRE), instituted by Department of Science and Technology and Biotechnology Entrepreneurship Teams Program (BEST), by Association of Biotechnology Led Enterprises, and supported by DBT. In addition to having more such initiatives, we also should aim at rigorously training the teachers to help student exposure to science, not only as a tool to quench the natural hunger of curious human minds, but also become the breeding ground to innovations which would eventually impact the country’s economy and well being.

A variety of ongoing efforts are in place in terms of providing fellowships and conducting programs for getting the best minds to do scientific research. The dwindling of numbers in our S&T streams is, however, an unfortunate fact which has to be faced and mechanisms of amelioration found. This bleak scenario for the Sciences is mainly due to migration of our most talented students to commerce

streams. Many seats in Engineering colleges are already going unutilized. Lure of the lucre, or at least security in shortest possible time are the most obvious reasons. This trend is likely to continue, if not aggravate, unless a palpable bright future is projected and ensured for a science graduate. The best way to convince the talented lot to take up science and generate innovative ideas and products, is to assure greater financial benefits, as well as conditions that liberate the aspiring scientists from the many bureaucratic controls and interventions that infringe on their freedom of work.




Many universities / institutes try to attract scientists from outside. The Ministry of Science and Technology has initiated various programs like young Investigators Meet, Ramalingaswamy Fellowships, Ramanujan Fellowships, ICMR Talent Search Scheme, DBT-Wellcome Trust Fellowships, etc., where a handful of chosen people are given a five-year fellowship, along with contingency to work in their chosen institute/university. One of the major lacuna in this model is that these people are neither treated as scientific faculty nor as non-scientific faculty of

the institutes they belong to. Also, the position being temporary in nature, they are not recognized by universities as Ph.D. supervisors; the result is that they have to work all by themselves, which necessarily imposes limitations on their performance. Such people should be provided with additional technical help to get optimal performance from them. At best, these fellowships have become as good as the old scheme of CSIR offering pool officer position to scientists returning from the foreign countries. As these positions are temporary, their incumbents are always looking for a regular

position. Such uncertainty reduces concentration and dedication, restricting both the time spent in the host institute as well as meaningful scientific work.

Hiring competent individuals is just the beginning. It’s perhaps more important to retain, and get the best out of them. The critical role of Heads of Institutions should be emphasized here. The budding scientists should be allowed to think and work independently in their chosen area, and provided with all necessary infrastructure and other supports. The practice of hiring people to work as associates

of head of the departments/ institutions curtails the full blossoming of young talents. It is also important to build institutions for higher education and research in geographic locations that cater to the interests of the scientist’s family members such as schooling and socio-cultural activities. Availability of newer job opportunities must also be desirable option for change. Science is driven by individual commitment, brilliance, and ability to think independently. A certain amount of peer pressure, demanding but not stifling, also helps.

One emerging concern which may be mentioned here is that many of the Ph.D. students pursuing research in modern biology from Indian institutes / universities end up migrating to foreign countries. This creates a tendency in research institutions to often hiring less trained people. Major programme should be in place to upgrade the knowledge and technical skills of such personnel. The focus should also include exposure of scientists to research endeavours involving multi-faceted disciplines of science. DBT Overseas Associateship Program has been playing a major role in achieving this goal to some extent. Unfortunately, very often on returning to their alma-mater after training and working abroad, they find themselves unable to utilize their new skills/exposure mainly because of lack of appropriate infrastructure and support. Therefore, linking of the DBT/other associate-ships to a support grant to establish the required infrastructure in the home institute/university by the funding agency would be a better idea. Alternatively, DBT and other S&T apex bodies could encourage such incumbents to write



Contd. on page 158

Photo : Manoj Dabas


Human Resource Development was one of the major activities

initiated by the Department of Biotechnology (DBT) soon after it was established by the Government of India in 1986.

The Maharaja Sayajirao University (M.S. University) of Baroda was one of the five universities that were identified for offering an M.Sc. course in Biotechnology. I joined M.S. University shortly before the first batch of students was admitted. We looked forward with anticipation to what was a bold new experiment in Biology education in the country. The course was, and continues to be, open to graduates in Science, Engineering and Medicine. This marked a departure from the

traditional approach that would not allow non-biology students to study Biology at the master’s level, thus making much larger pool of talent available to us. This visionary decision of the DBT made it possible for a large number of motivated students from the physical sciences background to pursue their interests in Biology. In retrospect this decision has had a very positive impact. Several students who came from non-Biology background and went through the course at Baroda and elsewhere have gone on to study in some of the best places around the country and abroad and several of them have matured into excellent scientists.

As a teacher, no reward can rival the joy that you derive from noticing your students who studied

under this programme over the years now publishing in top journals like Science, Nature, Cell and so on. It is a matter of even greater satisfaction that many of them acknowledge that they were motivated to pursue a career in science during their master’s training.

The Biotechnology Teaching Programme brought together students from all over the country drawn from different disciplines. This seeming disadvantage of taking students without previous training in biological sciences, turned out to be an advantage since many students from Biology backgrounds shared their knowledge with students from non-Biology backgrounds and students with competence in Physics and Maths were able to help

Bharat B Chattoo is Director at Department of Microbiology and Biotechnology Centre, M.S.University of Baroda, Vadodara -390002, Gujarat. Email: [email protected]

Bharat B Chattoo

Cultivating new talent was one of the major activities initiated by the Department of Biotechnology soon after it was established by the Government of India in 1986. DBT made it possible for a large number of motivated students from the physical sciences background to pursue their interests in Biology

FEAT URE

DBT and Human Resource Development

A view from the stands


others with quantitative analysis in some courses. Challenge for us as teachers was to ensure that the students remain interested in Biology and were motivated to take up careers in Biology after they finish the course. It is a matter of satisfaction that we have largely succeeded in this task. yes, a few students were lost to other pursuits like the civil service or to holy matrimony, but that was indeed a very small number. However, we could not have succeeded without DBT support liberal, by university standards, equipment and consumables, and for supplementing our libraries and supporting visiting faculty. The course offered another attraction to the students by way of studentships. Although the amount of the studentships was rather modest, it was recognition of one’s success in a national competitive examination that made it significant. This was also the first time that such studentships were offered for pursuing studies in basic sciences. I recall the excitement in the eyes of the students when they did their first plasmid preps or obtained their first clones. On several occasions, the students would call me late at night to have a look at a gel or some such experimental result. The ability to do an experiment or use a technique that they had read about was a source of great motivation. It was a very welcome departure for most students who did not have an opportunity to plan or carry out a laboratory experiment during their undergraduate years.

The availability of appropriate equipment and reagents greatly helped to reduce the gap between theory and practice. We were still in the pre-internet era and the availability of some key journals provided a window to the world of contemporary science. At MSU, we followed a very rigorous schedule of continuous assessment with examinations held once a week. The answer scripts were returned to students and they could discuss their performance with the concerned teachers or fellow students. The

students initiated their research projects soon after joining the course and continued it over two academic years. They also were encouraged to write independent project proposals and present contemporary research in seminars and term papers. Several students were not very happy with the rigorous routine and what appeared to be never- ending demands of the course. However, practically all of them would write to us later after they joined elsewhere that they were able to do well because of their robust training. Perhaps, the feeling was summed up

best by a former student who joined Harvard Medical School after his master’s in our programme. When I asked him how was he coping up with his work at Harvard, he said that the journey from Bombay to Baroda was hard, but Baroda to Boston was easy. What more can a teacher ask for! He is now a tenured faculty at a leading US university, like several others who trained in the early years of the teaching programme.

Many students succeeded in competing internationally and

found places in some of the best Universities in the US like Harvard, Carniege-Mellon, UCLA, Scripps, Salk, Dartmouth, Baylor and at various Max Planck Institutes, NUS, etc. At the national level, many students joined the Indian Institute of Science, Bangalore; Centre for Cellular and Molecular Biology, Hyderabad; Tata Institute of Fundamental Research, Mumbai and National Centre for Biological Sciences, Bengaluru.

Practically all our students also successfully cleared the UGC-CSIR national entrance tests, with several making it among the first hundred ranks of merit and a few could also make it through the Dr. Shyama Prasad Mukherjee fellowships after they were introduced in 2000. These indicators gave us sufficient confidence that we must be doing something right as far as student training was concerned. One concern that has remained is that nearly two thirds of the students have pursued a career in research or teaching (the figure) and

Human Resource Development



comparatively fewer students have joined the industry. While many companies have been visiting us regularly for campus placement, industry has not been the first choice of most students. It emerges that the primary reasons are that students do not see growth opportunities in R&D laboratories where a Ph.D is very often a basic requirement. In addition, the expectations of the students are to work in cutting edge technologies and the Indian biotech industry, at least during the early years, did not venture into areas of contemporary research. Often, the students felt that after joining the industry they were not working on challenging problems.

The situation has changed recently after the new IPR regime and as the confidence levels of Indian industry improved after some initial market successes. Industry now also shows a higher risk appetite thanks to some new initiatives of the DBT under Small Business Innovation Research Initiative and Biotechnology Industry Partnership Programme. Our interaction with industry has helped us to define gap areas in training and also understand their requirements. Responding to these expectations, DBT supported two new post-M.Sc. one year diploma programmes at MSU; “Genetic Engineering and Bioprocess Development”, and “Intellectual Property Rights, Biosafety and Regulatory Affairs”. The latter programme was taken up in partnership with our Law

faculty and co-operation with local pharmaceutical industry and has attracted the attention of industry, patent firms and consulting groups. However, students by and large still prefer the traditional route of going for a Ph.D followed by post-doctoral work before they start looking for a job. While jobs in research institutes and academia are still preferred, several students are now willing to join the industry because they see an opportunity to innovate. Since Biotech industry is research intensive, most jobs

available for our graduates have been in the R&D sector. However, as the industry grows and matures, and India becomes a preferred location for discovery research we also see opportunities in areas like IP management, Regulatory affairs, Science communication and some of the other emerging areas of technology management.

As we look to the future, it is a time of enormous opportunities for the Indian Biotech community. The many exciting new frontiers

that are opening up not only in biological sciences, but at the interface of biology with medicine, engineering and the physical sciences offer us novel opportunities for making our learning and training process more responsive to these new developments. This also means that we need to revisit the human resource development scenario in the country and work on new long term strategies to meet the demands of these emerging areas that hold promise for not only pushing the boundaries of biological

research, but also for providing effective solutions to our many problems. Training human resource that is internationally competitive and is highly entrepreneurial continues to remain a major challenge. The higher education system in the country, particularly the state universities that train the vast majority of our students, is facing many challenges in providing quality training largely because of constraints in faculty recruitment and retention, infrastructure

and governance systems that need to be more responsive to the contemporary demands. DBT shall have to continue to play a leading role in human resource development for the Biotech sector since it not only has a long experience in this area, but it also monitors how the world of Biotech is changing both within and outside the country and can, therefore, offer strategies and solutions that can make India the preferred destination for the Biotech enterprise.

Human Resource Development


36%

30%

18%

8%8%

Research in India

Teaching

Research Abroad

Industry

other

Student Placement after M.Sc. MSu : 1986-2010

total number of Students : 423


Shahid Jameel Ph.D is a Senior Scientist and Group Leader in Virology Group of International Centre for Genetic Engineering and Biotechnology, New Delhi; E-mail : [email protected]

Shahid Jameel

Viral infections and diseases are responsible for significant morbidity and mortality in plants, humans and animals. overcoming viral diseases needs a focused approach and sustained effort. DBT is faciltating just that and has emerged as a major catalyst for virology research in India.

DBT in Virology Research

Raising the pitch

Viral infections and diseases are a major cause of morbidity and mortality in

humans and animals, and result in large losses to crop plants. With a temperate climate, high population density and frequent animal-human interactions, India is especially prone to the emergence, re-emergence and sustenance of viral diseases. It is suggested to be one of the likeliest places in the world for the emergence of new infectious diseases (1). Are we ready for it? Will our infrastructure, research and funding environment allow us to face those challenges?

Department of Biotechnology has emerged as the largest funding agency for modern

biology in India, and this is true to virology research as well. As DBT completes 25 years, I review the state of virology in India and take stock of the good and bad, with the hope that introspection and critical evaluation today might pave the way for a better future. This article will focus on human virology since I am most familiar with that area of work in India.

virology in india

Virology is practiced in India in different settings. Within academia animal, human and plant virology are segregated to medical, veterinary and agricultural institutes and universities, and rarely cross paths. There is Clinical

Virology in hospitals and medical colleges, which is aimed at diagnosis and patient care. Virus-related work in the private sector is limited to pharmaceutical and vaccine companies that develop and manufacture antiviral drugs and vaccines. While research in this sector is minimal and rarely original, the focus being generic or out-of-patent products, this goal is not without its merits. Indian pharmaceutical and vaccine companies are major global suppliers of generic anti-retroviral drugs and viral vaccines against measles and hepatitis B. These have made a major impact in resource-limited countries for preventing and treating viral infections.

FEAT URE


Organized virology research in India dates back to 1952 when the Indian Council of Medical Research (ICMR) and the Rockefeller Foundation set up the Virus Research Centre in Pune to work on insect-borne viruses. With an expanded scope, this became the National Institute of Virology (NIV) in 1978. Though NIV is credited with some important achievements, such as the discovery of Kyasanur Forest Disease, hepatitis E and Chandipura viruses, and development of the C6/36 insect cell line (2), it has not made the kind of international impact that it should have. The ICMR also manages three other virus research centres – Enterovirus Research Centre (ERC), Mumbai, established in 1981; ICMR Virus Unit, Kolkata, established in 1986; and National AIDS Research Institute (NARI), Pune, established in 1992. Outside of the ICMR system, various DBT, CSIR and state-level institutions and universities also have virology research

programmes.

funding for virology

The DBT and ICMR remain the two main agencies that support research, training and infrastructure development in human virology in India. An analysis of DBT’s funding over the past decade reveals interesting patterns. About half of the funded grants have a viral biology and pathogenesis focus while work on antiviral therapies, diagnostics and viral vaccines together account for the rest (Fig. 1). When classified by viruses, HIV research has attracted about half of the research funds. Other notable mentions are influenza, hepatitis E, chikungunya, dengue, Japanese encephalitis, rota, polio and human papilloma viruses, but acute respiratory viral infections have attracted little attention (Fig. 2).

Is this funding pattern in line with national needs? While there are an estimated 2.5 million cases of HIV infection in India,

data on other viral diseases is hard to find. According to WHO (3), the major causes of mortality in Indian children below 5 years of age that also have a viral etiology are pneumonia (20%), diarrhea (13%) and measles (4%). In 2010 there were a reported 48,176 cases of chikungunya, 28,292 cases of dengue, 5149 cases of acute encephalitis syndrome, about 20,000 deaths due to rabies and 46,575 cumulative cases of pandemic influenza (4).

What might be the reasons for such a funding bias? In the absence of good quality disease burden data, funding agencies set priorities based on imported data. Most funded projects originate from investigators, who are also biased in favour of the internationally more visible diseases. The need therefore is to have reliable disease burden data and for funding agencies such as DBT to then support a mixture of investigator-generated and need-


Raising the pitch

61 5 23 11

61% 5%

23% 11%

Chart Title 1 2 3 4

46 3 38 14

46%

3%

38%

14%

Chart Title 1 2 3 4

Area A. Number B. Funding (lakhs)

Antivirals 14 1400

Diagnostics 07 266

Vaccines 30 3931

Viral Biology 81 4771

Total 132 9968

A B

Figure 1. (A) Number of grants funded and (B) funds distributed by DBT on virus-related research for the period 2001-2011.


based grants. To some extent this is already happening but statistics suggest that better planning and more focus is needed.

ProBleMS and SolutionS

One of the foremost problems in virology as well as other infectious disease research in India is the lack of good quality disease burden data. The Department of Health Research (DHR) and ICMR were recently advised to focus on this for the 12th Five year Plan, and appear warm to the idea.

The next big problem is clinical research, which can itself be broken up into smaller problems, each with a unique solution. Infection and disease cohorts are almost never available, making it difficult for researchers to ask important questions. The research environment at medical colleges is poor and interactions between basic and clinical researchers are minimal. The DHR/ICMR is addressing this through increasing

research capacity in clinical settings and DBT is encouraging the partnership through its Glue Grants scheme.

Interactions between academia and industry are also not optimal. The DBT supports this with focused funding through its Biotechnology Industry Partnership Programme (BIPP). Though most grants coming to DBT on viral biology and pathogenesis claim new targets and therapeutic approaches as their end-points, there is hardly any translational research on antivirals. This is also apparent from the low levels of funding for antiviral development and there is hardly any success story.

One big problem facing virology research in India is its scattered nature and very little inter-group or inter-institutional collaboration. Despite ~60% of emerging viral infections estimated to be zoonotic there is tight compartmentalization into agencies

looking after human and animal virology. The bird flu outbreak and the subsequent pandemic flu outbreak and the Indian response to it are good examples of why better management is required. DBT can play a significant role in promoting cross-platform research through focused funding of “Virtual Virology” centres that are built around specific infection/disease themes and which bring together basic, clinical and industry researchers. The establishment of a Translational Health Science and Technology Institute (THSTI) by DBT to focus on infectious (including viral) disease, and its proposed partnership with the International AIDS Vaccine Initiative (IAVI) are steps in the right direction.

The development of an indigenous rotavirus vaccine is a good example of such a partnership and there is much to learn from that model. It also makes sense from an economic and public health perspective. It is estimated


Raising the pitch

Figure 2. Virus-based funding. The funds distributed through DBT grants for the period 2001-2011 are classified based on the viral infection/disease.

HIV 50% 50Influenza 4% 3HEV 5% 4Chikungunya Virus 4% 3Chandipura Virus 1% 1RSV 1% 1HBV 3% 2HCV 3% 3Rota Virus 7% 6SARS Virus 0% 1Polio Virus 5% 5Pox Virus 0% 1Adeno & Adeno Associated Virus 2% 2Dengue Virus 6% 6HSV 0% 1JEV 2% 2Vaccinia Virus 1% 1Enterovirus 0% 1HPV 7% 7

1

2

3

4

5

6

7

8

9

10

HIV 50%

Influenza 4%HEV 5%Chikungunya Virus 4%Chandipura Virus 1%

RSV 1%HBV 3%

HCV 3%

Rota Virus 7%

SARS Virus 0%Polio Virus 5%

Pox Virus 0%

Adeno & Adeno Associated Virus 2%

Dengue Virus 6%HSV 0%

JEV 2%Vaccinia Virus 1%

Enterovirus 0%

HPV 7%


that a national rotavirus vaccine programme would prevent 44,000 deaths, 293,000 hospitalizations and 328,000 outpatient visits each year, and save US$ 20.6 million per year for the healthcare system.

ConCluSion

Over the past 25 years DBT has been a good partner for virology research in India, but much more needs to be done. While an estimated Rs. 100 crores was spent by DBT over the past decade on virology research, it amounts to only about US$ 20 million or

US$ 2 million per year. This must increase if India is to match leading knowledge economies and prepare itself seriously for emerging viruses. The silver lining is that DBT’s annual budget is increasing and recent viral outbreaks have focused agency and investigator attention on the problems. This is an opportunity to do more focused, collaborative and translational research on the viral disease needs of India.

aCknowledgeMentI am grateful to Dr. S. Sinha, Dr. T.S. Rao and Dr. Bindu Dey at DBT for providing

the funding data, and Mr. Imran Ahmad for analyzing the data.

diSClaiMer

The views expressed in this article are the author’s own and not of his employing organization.

referenCeS

Jones KE, Patel N, Levy MA, Storeygard A, Balk D, Gittleman JL and Darzak P. 2008. Global trends in emerging infectious diseases. Nature 451:990-993.

http://www.niv.co.in

http://www.who.int/gho/countries/ind.pdf

Planning Commission, Government of India. Report of the Working Group on Disease Burden for the 12th Five-Year Plan. WG-3(1):

Communicable Diseases.


Raising the pitch

a proposal, during, or at the end of availing the fellowship, for funding their specialized research upon their return.

So far, biological research in India has not been successful in giving any tangible results in terms of human health / medicines in India. This is high time that we analyze why it is so. Science is changing, and far from being individualistic in approach; it is becoming a more multidisciplinary endeavor. Efforts should be made to address few major issues facing this country in terms of affordability of medicines, vaccines, or understanding of basic biology to the fullest, by inviting experts in various disciplines, to perform as a team. The need of the hour is to evolve a system that encourages innovation, which may require multidisciplinary and often

collaborative efforts. The present evaluation system of scientific productivity is largely individual achievement based. This needs to be revisited to catalyze multi-collaborative ventures on addressing complex challenging problems.

Pressure to publish in high impact journals could be an institutional desideratum, but must not become a mandate or policy. Any worker worth his salt would naturally try his best to publish in the best journals. But peer or institutional pressure for this must be minimal, and subtle. In other words, for real, original thought to flower, the fertilizer of generous and compassionate indulgence is the first sine qua non. Consummation, if achieved, would necessarily entail appreciation. But failure need not earn censure or scorn. In summation, we have to focus

on the human element to achieve excellence in any field - more so in the highly challenging ones of Science and Technology.

Financial security, higher and uniform salary, good, time bound and assured promotions to deserving individuals, better retirement packages etc., are some other concerns that need to be addressed if India is to attract better talented and highly trained minds to devote themselves to scientific innovations and technology development. That, and overhauling our archaic mindsets and outmoded systems of education and research administration to let scientific talent emerge and bloom, are the primary requisites for fulfilling the dream of becoming a world leader in science and economy.


An India perspectiveContd. from page 151


Dr. Francis Sellers Collins (born April 14, 1950), is an American physician-geneticist, noted for his discoveries of disease genes and his leadership of the Human Genome Project.

Dr. Collins received a Ph.D. in 1981 from the University of Connecticut. He conducted post doctoral research at the University of North Carolina from 1981 to 1984. At that time, he joined the Laboratory of Infectious Diseases, where he received tenure in 1990. He serves on the editorial boards of the Journal of Virology, Virology, and Virus Research.

He currently serves as Director of the National Institutes of Health, USA. Prior to being appointed Director, he founded and was president of the BioLogos Foundation. Great leaders have the ablitity to envision the future and work tirelessly to realize that vision. In that sense Dr. Collins is a born leader. In an exclusive interview to Biotech News, Dr. Collins outlined his vision for the future of medicine.

Francis Collins

Medicine gets personal

HORSE’S MOUTH

Photo : Manoj Dabas


BioteCh newS (Btn) : though there is a lot of excitement about it, how useful is personalized genomic medicine, especially in a country like india in which a vast section of population has limited access to resources?

PETER COLLINS (PC): I think full flowering of personalized medicine in any country it is going to take some time. It will certainly take a little longer where resources are limited. The good news is that science is moving very fast, and technology is advancing rapidly, both in terms of accuracy and lowering of the costs. I should point out that personalized medicine is not entirely a new thing. There is personalized medicine going on right now in India! For instance when you have an accident and suffer blood loss, you have to have blood transfusion. you want that transfusion to be personalized in terms of matching it to your blood type. This is an example of the kind of personalized medicine that has become a standard of care for a long time and which is very beneficial. But what is exciting is to expand those kinds of approaches on a much broader canvas. I would guess that one of the first newer areas where personalized medicine will become available, at least in some instances, will be cancer therapy. Already we know that certain types of cancers respond better to certain types of therapies than others. And we are going to be doing a better job of that in the individual case. It would be possible because cancer is a disease of the DNA, and it would be possible to identify whether a particular person’s cancer will respond better to Drug “A” or Drug “B” and to take advantage of that in making a choice about the treatment plan. That will come

about somewhat gradually for some cancers, and may be more quickly for some other cancers. Another area which is probably not too far off is the ability to use DNA analysis to identify what’s the right drug for the right person at the right dose. We all know that when we get sick and are given a drug which is supposed to be the right thing, it usually works, but not 100% of the time. Sometimes you don’t get the benefit and sometimes you get a undesirable side effect. If this was predictable and you could use this information prospectively, you could make a better choice. Take the example of some of our most potent anti-retroviral used in treating HIV AIDS. About 6% of people who are given the drug develop a severe hyper-sensitive reaction to the drug. We now know exactly how to predict which individuals would have that reaction. And the test is pretty straightforward as it is just a single gene. So in many parts of the world it is now possible to give that drug safely as long you do the test and make sure that somebody who’s not able to handle it, is not given that drug. While things are coming along, I think there may be a bit too much of hype about personalized medicine being here “today”. And then it makes some people think it is never going to be there. But the reality is somewhere in the middle. It is going to be a major advance in medicine but it will take a little while.

Btn : is genomics enough for amelioration of disease burden on human society?

PC : Absolutely not. I am as excited, as many others are, about the potential of the study of genomics to shine a new light on why diseases strike people, and what we can do

about it. However, there are many other aspects of public health and environment that are as crucial, if not more, when it comes to conditions that affect people. We want to be sure that our attention to infectious diseases is high on the list. Especially the development of new vaccines as exemplified by the

Peter Collins

Medicinal gets personal


Rotavirus vaccine which is coming along in a very exciting way. That is a very high priority. There is a genomic connection there but it is not particularly a strong one.

We need to know the genome of a virus to identify its biology. There are other things, like tobacco use

which are terribly important causes of unnecessary risk. While it is important to say that nobody should be addicted to this carcinogen, it also indicates that we have a lot of other priorities, beyond Genomics, to improve human health.

Btn : for common diseases of public health importance, a large number of genomic markers are found to be associated with them, each of which explains only a small fraction of overall risk of disease. how can then such findings be used for prediction, diagnosis or drug discovery?

PC : For prediction its true that most of the variations that we have discovered for common diseases like diabetes, or heart disease, are not individually very strong. In fact, it is possible to offer people that kind of information if they are interested. In the US there have been companies that have been marketing this directly to consumers. It will skew your odds a bit, up or down, for some of these diseases but not so much that it can be considered in most people’s minds as highly predictive. Frankly, I think that particular ability to make predictions about future risk right now is not the major opportunity although it will get better over time. I think the major opportunity is that these discoveries point us to a new pathway involved in the disease that, in turn, suggests a new idea in therapy that we would have never come up with otherwise. So if you look up at a disease like diabetes, where we need new interventions, we have discovered more in the last four years about the molecular causes of diabetes then in all of human history. Use of these genomic approaches is surely pointing us to some pretty powerful new approaches to therapy. We have to sort it out and make sure

that we are choosing the right ones that have the biggest potential for success. We are in the best place we have been in almost many decades to come up with the two new strategies for the treatment of this terrible disease.

Btn : diifferent sets of genomic markers are found to be associated with same disease in different populations. what is then the generalisability and utility of such genomic association results?

PC : Actually the common variance that have been studied to play a role in determining the risk of common disease, again if you would talk about diabetes or breast cancer or hypertension, does tend to be universal. you do find some variance almost anywhere you look in the world perhaps with different frequency. So if there is a variation in gene A that happens to be present in 60% of people in Finland, and plays a role in hypertension, one will find that very quickly if you were studying hypertension. But if the same variant has the same risk for somebody in India, but it is present in only 2 or 3 % of population, you might not find it here. So it’s clear that the nature of humanity is such that we have all descended from this common founder pool. So the common variants were already there and have been distributed around the world but they have arrived in different frequencies depending on history of the founders.

Btn : what kind of human resource and infrastructure is required for translating the knowledge that emerges out of the genomics studies?

PC : The most important human resource are the scientists and their creative instincts, efforts and hard

Peter Collins


Photo : Manoj Dabas


work to try and make sense out of what is admittedly very complex data. I think there are lots of young scientists who are striving to make those insights come true. They need support and encouragement as they devote their working life to pursue a career in science. While there are infrastructure needs in terms of facilities and hardware, a lot of the insights that are particularly important to derive from study of genomics need computational skills. I would strongly encourage young scientists interested in genomics to invest in learning computer skills including programming abilities and the ability to work with large data sets. This will help them to utilize the phenomenal resources that are available on the internet for free in terms of access to data, and access to software programs. If I was starting out right now as a graduate student in human biology, in all likelihood I will go into computational biology, an area of exceptional importance and with exciting opportunities.

Btn : you have visited several institutions in india in the last week. what were you most impressed with? where are the great opportunities?

PC : I have had a chance to visit several institutions in Bangalore, and in Delhi. I have been here for only five days; I am sure I have just scratched the surface of the kind of scientific activities that are going on. Some of those research institutions have been very much focused on basic science, some other on translation work- things like vaccine development, some even on clinical research where physicians are working in hospitals doing research protocols and understanding how to better treat a disease for which we don’t have a

good answer for. So there is a broad and rich array of scientific activities that are going on here and I have been very impressed with that. It is clear that science in India is on this very dramatic upswing in terms of the resources going into it, the talent that is involved, particularly very significant number of young scientists who are winding up in trying to play a very significant role in next revolutions. Perhaps the thing I was most impressed with was the people and the leadership of some of the big thinkers who have helped line up resources to make all this possible. I have also enjoyed talking to some of the established investigators who are doing cutting edge research in areas that I was not aware of. India has great strength especially in terms of talented graduate students in great numbers who seem interested in not just tackling obvious problems but are really trying to take on things that are risky but potentially very important.

Btn : a large proportion of young people in india are not keen on pursuing a career in science. what should one do to get the best minds to come to science?

PC : Certainly India does have a phenomenal environment for recruiting people in IT, into business, but I think the scientific opportunities may not be as obviously lucrative. However, in providing a young person with a professional experience, a career in science is almost unmatched. I think that, in the long run, people link their happiness levels not to an exceptionally high salary but to a reasonable good and stable professional life.

Science offers a very stable

opportunity to not only make a good living, may be not a very profoundly high income, but also to have the experience of being able to discover things that nobody knew before. There are few things you would compare with that in human experience, and if one has a chance as a scientist to play a role in that historical experience of discovery, that is something almost unbeatable. So I would encourage anybody who reads these words, has a leaning towards science but fears that it is not going to be as profitable to comsider what really matters in life- the highest possible income or the satisfaction of that you have dedicated your life to something that has permanent value, something that is going to help people who need answers to illnesses that the whole scientific enterprise now has a chance to resolve.

Btn : Biotech news has a large number of young readers. any special message for them?

PC : Scientific research is probably not for everybody. It is for those who have curiosity and a desire to discover something that nobody knew before. you have a desire to help people, you are willing to work hard, but you also have to be willing to accept the idea that doing really important work does not always lead to immediate success the first time you try something. And if you are interested in having a life experience where you work together with other incredibly bright and inquisitive people both as peers and mentors, then you should go into science. you should join a community that is out to change the world and change the world they will. Here in India and across the world.

Peter Collins



EMBO - India

Window of opportunityContd. from page 123

training in an international setting. In many cases, this is an essential step before returning back home to India. But many do not know the best approaches, who to contact, what is expected of them and how best to phrase their applications.” Leptin says: “ Not all laboratories in Europe are equally well suited to supervise students, and we need a system to guide the best students to the best laboratories. EMBO is willing and able to provide help with both of these challenges.”

The recent experience of Lolitika Mandal, a Wellcome Trust/DBT India Alliance fellow from the IISER in Mohali, illustrates the global nature of research. Mandal recently attended a meeting of EMBO young Investigators at the EMBL in Heidelberg, Germany, where she met 52 young group leaders from different countries in Europe. She has also started to collaborate with one of the programme members in Italy. “I wish there were more possibilities to

interact with young group leaders. We all face similar challenges at the start of our careers. It is tremendously helpful to have a network of support of scientists who are in a similar situation.”

EMBO is working to strengthen interactions between European and Indian life scientists. The long-term goal is to provide new scientific opportunities and deliver further benefits to the research performed in Europe and India.

Looking ahead we will be focused much more on the quality aspects. Golden rice and similar products would be a reality. The promise of science is limitless. Agriculture must also be a profitable livelihood

for it to be sustainable, and benefits of the technology present opportunities that must not be ignored.

While Science provides us opportunity to accelerate the

speed at which products can be delivered to farmers to improve on our competitiveness, the policy environment continues to challenge us and is an area in need to immediate attention otherwise all the investments we make collectively for agri-biotech research will not come to completion.


Need to match policy with science Contd. from page 125

its commercialization (see figure on page 36).

ProBiotiCS/iMMunoStiMulantS/vaCCineS/novel antiMiCroBialS

Aquaculture medicine has yet to be developed as full-fledged biotechnology tools for aquatic animal health management. In the light of the ban of human and veterinary medicines for aquaculture application a new series of medicines/drugs have

to be brought out under the category of probiotics/immunostimulants/ vaccines and novel antimicrobials from the environment. This has to be oriented towards each species of the fish cultured and the pathogens confronted.

ConCluSion

While we look forward to fisheries biotech 2025 there are more challenges as the world population

will be 7.9 billion from 6.1 billion as on today and the Indian population from 1.21 to 1.5 billion. To satisfy the protein requirement of this population aquaculture production will have to be increased by 350%, a target to be attained with shrinking water spread areas and increasing pollution threats. What have been pointed above are a few key areas where thrust has to be given in biotechnology.


Need for a technological pushContd. from page 128


In the somewhat dark and dusty corners of the Technology Bhavan housing

DST (Department of Science & Technology, Govt. of India) was born a new baby, the NBTB (National Biotechnology Board) in the early-mid 1980’s. Later rechristened as the Department of Biotechnology (DBT), this government department has transformed itself to be the life and soul of the Indian Biology community. Today DBT has almost become a household name in the country and touches all spheres of developments in biology, both basic and applied. Perhaps much to the envy of the other scientific disciplines, with the generous financial support and overall guidance to progress, DBT occupies

a prime position amongst all scientific departments in India.

Dr. S Ramachandran, the visionary who adorned the top position as the Secretary initially for the NBTB and later for DBT on its genesis, has been one of the master architects of what DBT is today. Starting with a modest annual budget of Rs.5-6 crores in the mid 1980’s, currently DBT has an annual budget of more than Rs.1200 crores. Some of us have fond memories of having closely associated with Ramachandran who sought our advice and suggestions on all matters and carefully implemented them. He was indeed a visionary and way ahead of times. Ram recognized the importance of setting up of “oligonucleotide synthesis” facilities and “bioinformatic

centres” at multiple locations much before most of us had realized their importance. At a personal level my association with Dr. Ramachandran started in 1982 itself, as the convenor of the interdisciplinary programme for the DST unit on Genetic Engineering at IISc. On completion of 5 years tenure our unit was upgraded into a full- fledged “Centre for Genetic Engineering” at IISc with financial support from DBT, including tenured faculty positions.

Personally, my own research group has been immensely benefitted by the generous funding from DBT. The standards of our research publications reached much higher levels due to the inputs from DBT, for which I am ever grateful. My group was the first one in India

Prof. K.P. Gopinathan Ph.D is INSA Honorary Professor at Department of Microbiology and Cell Biolgy Indian Institute of Science, Bangalore 560 012 Email: [email protected]

Prof. K.P. Gopinathan

DBT, the triplet code of Indian bilogists

MeMory lane25 YEARS oF DBT

DBT has come out with a clear blue print of what next, a well thought out plan. We have been successful in generating highly skilled man power resource through the agies of DBT and now is the time to seriously consider how to absorb and utilize this resource by creating better opportunities. In India, the most frequently used triplet code to translate biology undoubtedly is DBT.


to initiate Molecular Biology and Biotechnolgy research on silkworms. Silk production being an important agro-based cottage industry provides employment for nearly six million people in India. In order to bring the developments and advances in Biotechnolgy to the silk industry, the DBT introduced a separate Task Force on “Silk Biotechnology” to address the concerned issues, realizing the importance of the field. I have been closely associated with this Task Force right from its inception as a member and currently as the Chairman for the last few terms. Under this Task Force, we could successfully bring various Governmental and nongovernmental institutions including the “Central Silk Board” institutions under an umbrella to foster research in the area of Silk Biotechnology. Apart from the extensively exploited mulberry silk, which accounts for 90% of the silk production, India has four other varieties of silk, including the “Muga Silk” which is exclusive to Assam and involves a lot of tribal people. With the help of this Task force in Seri-Biotechnology, we could extend financial and academic support to the remote North Eastern regions of the country. This certainly is a feather in the cap of DBT.

I am proud to state that Dr. Ramachandran was very happy with our centre, especially because of the intense scientific participation by several senior faculty from across the departments at IISc and its track record of high quality research publications. We in turn, have been proud of our association with DBT. Rightly and most deservedly, Dr. Ramachandran was honoured with the Padma Bhushan Award this

year by the Government of India. Believe it Ram, all of us are most happy and proud of you and the DBT on this coveted honour. you deserve it, on every count.

Dr. Manju Sharma, who succeeded Drs. Ramachandran and Bhatia raised DBT to higher plateaus. The scope and support by DBT expanded tremendously during her long tenure as the DBT Secretary. Manju Sharma’s pleasant disposition and positive attitudes have played a crucial role to make what DBT is today. We need such leaderships to nurture and care to conquer the peaks. The visits of the “Monitoring Committee” headed by Dr. Manju Sharma and some of the senior most and reputed scientists of India, to oversee the “Umbrella Programme” ( a mega programme covering a variety of activities at IISc) was always an event to remember. The monitoring was strict but the atmosphere was pleasant and congenial.

Dr. Ramachandran, never hesitated to call us, the practicing scientists to seek advice whenever he started a new venture, whether it was the setting up of the ICGEB (between UNIDO and DBT) or initiating new manpower training programmes at universities and institutes or opening up of entirely newer areas of modern biology. I recall the day when he called me (on behalf of IISc) to New Delhi to discuss about the prospects of starting a new Master’s degree programme at the Institute, in the back drop of the success of many of the DBT-sponsored M.Sc programmes at universities. It did not take me much efforts to convince Dr. Ramachandran about commencing a formal post doctoral research programme

instead, since many universities were already doing well with their assigned Master’s programme. A major lacunae in our country had been the lack of support for post doctoral research, which perhaps is the back bone to US, UK, or European scientific establishments. Ram readily bought my arguments and a new post-doctoral research programme for young Ph.Ds from different parts of the country for about 2 years at IISc was immediately initiated. With an intake of up to 30 PDFs for a two year tenure, the programme was later extended to CCMB, Hyderabad and Bose Institute, Kolkata. The IARI, New Delhi, soon followed our footsteps and converted their master’s degree programme to the PDF scheme. This has turned out to be the first major fillip for the long coveted desire of Indian Scientists to have research support at the post doctoral level. I ran the show for nearly 10 years at IISc and cooperated with CCMB and Bose Institute. Currently this programme supports more than 100 young research fellows every year, with a fellowship that is tenable at any institution in the country. A success story of the DBT in its creation of trained manpower at advanced levels.

Today, whether it is support to basic or applied research, the generation of trained manpower or setting up collaborative progressive industrial entrepreneurships, DBT is the force behind and the strength that we need. Besides making penetrating presence at the Universities in giving biology education a new face, DBT has established several National Institutes to foster research and development in the frontier areas




of biology. The creation of Biotech India Consortium that facilitates industrial training in Biotechnology, and providing start up funds through SIBRI, and the BIPP (Biotechnology Industries Partnership Programme) have certainly been positive steps. The establishment of Institutional Biosafety committees (IBSCs) and a national level Recombinant DNA Advisory Committee that formulated the guidelines for Recombinant DNA Research in India as well as the active involvement at the Genetic Engineering Advisory Council are some of the other notable contributions of DBT.

The DBT mode of funding research projects through dedicated task forces and a reasonable peer review system to monitor the project progress has been an effective catalyst for the growth of Biology in India. Considerate geographic distribution for project funding and identifying problems and resources unique to India while choosing

research projects for support have been a hallmark of DBT. The timely release of sanctioned grants to the investigators has also helped in overall progress although there is still scope for improvement. Walking through the corridors of the CGO Complex BlockII and greeted by smiling faces of the scientific staff of DBT has always been a pleasant experience. The initial priorities of the Department, when newly started, were three fold : (i) to create trained human resources in the emerging areas of biotechnology, (ii) to ensure adequate infrastructural support to serve as the strong base for R&D, and (iii) to support research in basic and applied areas. We can proudly declare that all these objectives have been met and we are aiming at superior goals. With all the generous financial inputs from DBT and the setting up of advanced centres and COEs, it is time to ponder whether we are doing well enough? No doubt, the quality and quantity of scientific papers

published from the country have gone up. Publications in J.Biol. Chem, J. Mol. Biol. or Nucleic Acids Research have become common. But is that enough? We have not yet reached the levels of publishing regularly in Nature, Science or Cell. That will be the day of our arrival.

In this silver jubilee year, DBT has come out with a clear blue print of what next, a well thought out plan. We have been successful in generating highly skilled man (woman) power through the aegis of DBT. It is time to seriously consider how to absorb and utilize these personnel by creating better opportunities.

Do keep up the good job DBT. We the scientific community need you for giving proper support and directions. In India, the most frequently used triplet code to translate biology undoubtedly, is DBT.

All my best wishes for many more successful years to follow.

develoPMental Patterning of Silk glandS

Embryonic or early larval silk glands showing the different functional compartments.

Canonical WNT signaling operates in mid silk gland subcompartment specification


Following a successful joint bioenergy workshop, held in New Delhi in October 2011, BBSRC and DBT are pleased to announce that a joint call for proposals in anticipated during April 2012 with an anticipated closing date in July 2012.

The purpose of this pre-announcement is to allow eligible investigators within the UK and India to begin the process of identifying potertial project partners with a view to assembling multi-disciplinary teams comprising project partners from both countries.

A further announcement will be published on the BBSRC and DBT web-sites once the call has been launched.

Scope of the Call

The call for proposals will be focused around the 3 key areas which were agreed by workshop participants to be priorities:1. Identification, characterization and improvement of novel biomass (including algal biomass) processing enzymes. 2. Application for systems and synthetic biology approaches for the development of microbial strains for the production of advanced biofules and

capable of using all of the sugars derived from lignocelluloses or algal biomass. 3. The improvement of algal strains suitable for biofuel applications including genomics approaches.

However, other areas will not be excluded, providing that the project uses biological feedstocks and relevant biological conversion processes to underpin research that works towards the production of sustainable bioenergy / biofuels.

Eligibility

Standard BBSRC and DBT eligibility guidelines will apply, any potential applicants who are unsure whether they and/or their institution meets the relevant eligibility criteria are encouraged to contact the BBSRC or DBT office using the contact information below.

For more inFormation please contact :

BBSRC : DBT: DR ViCky JaCkSon DR ShailJa GupTa

[email protected] [email protected]

PRE-ANNOUNCEMENT OF JOINT BILATERAL CALL FOR PROPOSALS IN BIOENERgY RESEARCH

Indians have high prevalence of cardiovascular diseases, type-II diabetes and earlier onset of coronary heart diseases (CHD), despite a normal body mass index (BMI) by international standard. The premise that this population is more susceptible to chronic diseases and that these conditions are linked with inflammation is plausible. Dietary changes and lifestyle modifications will have a sustained effect on reducing incidence of diabetes and CHD and there by reduced relative risk of mortality. However, it is still unclear if high calorie/high fat/high carbohydrate diet or fewer intakes of micronutrients (fresh vegetables and fruits) are linked with inflammation. Moreover, there is a need to substantiate scientifically the beneficial or anti-inflammation claims of our traditional diets.R & D Proposals are invited in the following thrust areas:

The link between inflammation and dietary carbohydrates / fats / micronutrients• Formulation and Characterisation of anti-inflammatory diets and supplements (traditional and novel)•

The proposal is to be aimed at inflammatory conditions associated with diabetes mellitus, cardiovascular diseases, arthritis, obesity, insulin resistance, aging, stress and neurodegenerative disorders.Expected outcome and deliverables:

Basic science studies aimed at improving understanding of patho-physiology of the disease concerned• Clinical studies at impacting clinical practice.• Population studies aimed at generating India specific data on links between inflammation, diet and disease. The research should be hypothesis driven, • with clinical/biological/mechanistic componentsProvide evidence based data for the use of traditional foods/anti-inflammatory diets•

Submission of Proposal: Proposals can be submitted online http://dbtepromis.nic.in/login.aspx) or by email to [email protected].

Last date for Submission of Proposals : 30th June 2012

For more details (rationale, scope, eligibility, thrust areas, submission instructions etc.) please visit www.dbt.nic.in

Call for R &D Proposals on- Foods and InflammationMeMory lane25 YEARS oF DBT

BBSRCBIOTECHNOLOgY AND BIOLOgICAL

SCIENCES RESEARCH COUNCIL

DBTDEPARTMENT OF BIOTECHNOLOgY

gOVT. OF INDIA


In pre-DBT era, most research laboratories engaged in biological science had limited

resources. As a Ph.D. student, when I sent a manuscript for publication, the only query that the reviewer had was why did we use odd 89ul as our reaction mix in our experiments. We replied that we were using a broken 100ul lambda-pipet. It was normal practice that our Ph.D. supervisors would bring broken and discarded pipets from US laboratories and we would recalibrate and reuse in our lab in India. Later, we were sharing a single pipetman between > 20 students. We had a system of booking to use this pipetman.

During my first postdoctoral training in a Canadian laboratory, it was a common practice to use and throw glass pipets and test tubes after single use. I would collect and ship them to India for my juniors to use. Fortunately, when I returned to India, I was pleasantly surprised to

see how research funding by DBT had transformed the infrastructure of Indian laboratories. Research support from DBT has not only brought back several Indian scientists from abroad, but also empowered them to make an impact on public health at large.

DBT is continuously empowering all of us to change the face of biotechnology in India with bold and liberal research support that has instilled the much needed public-good factor in our thought process. DBT is indeed the lifeline of this new mood of translating science for public good.

I can recall several occasions on which, sustained research support from DBT, has provided me with the courage to think differently and dare to commercialize our research findings.

With support from DBT’s bilateral programs and DBT’s

Indo-German programs we have been able to collaborate with several distinguished international experts as well as achieve the highest expression levels of Hepatitis B Surface Antigen and and recombinant which is more than 7 g/L and 3g/L respectively. Biotechnology companies are using these high expressing clones for the commercial production of these proteins.

DBT has been very proactive in bringing like-minded international experts to visit several research institutes in India, as well as provided timely support for their research endeavors. It is through DBT’s Indo-Finnish collaborative programs, that we at ICGEB, have been introduced to Professor Kim Pettersson from the University of Turku, Finland. Our research interactions with Kim resulted in the availability of several affordable diagnostic kits

Navin Khanna Ph.D is Sr. Scientist at International Centre for Genetic Engineering and Biotechnology, New Delhi Email: [email protected]

New pride to Indian science

Navin Khanna




in India. These kits, for the detection of Hepatitis B, Hepatitis C, HIV and Dengue infections, at the point-of-care, have made a significant impact on public health. The kits are being manufactured in India from our “Know-how” and are being sold in more than 40 countries.

The DBT supported research efforts have made diagnostic kits highly affordable and have made India not only self-sufficient, but also an exporter of these kits. Due to DBT’s support, several diagnostics kits from other countries have been replaced with Indigenous ones.

Post launching of an Indian dengue kit developed with DBT support in 2010, all imported dengue kits from USA, Australia and South Korea are disappearing from India. With the “Know-how”, supported by DBT, the production cost of a Hepatitis B point-of care test is just Rs. 6.00. This low cost of production has prevented the entry of several Chinese diagnostic kits into the Indian market. The World Health Organization purchases these Indian diagnostics kits, for their programs in several developing countries. Thus, the DBT directed research efforts are making a worldwide difference in public heath.

DBT’s proactive Secretary, Professor Bhan is directly responsible for timely intervention for helping Dengue Vaccine efforts at ICGEB. With his contacts, we were able to bring world-class dengue vaccine experts to

ICGEB, Who over the period of 2 days went through our data and approach in minute details and provided us with valuable insights and guidance. Such independent reassurance on our dengue vaccine approach from international dengue experts brought forward renewed enthusiasm in us. With his efforts, our dengue vaccine program has been brought into the domain of Indo-US-Vaccine Action Program.

DBT has actively supported several public-private partnerships. DBT provided its unconditional support to our collaboration with Ranbaxy/Daichi, on the development of anti dengue herbal preparation. This is a unique effort wherein Ayurveda knowledge was combined with modern science to search for an affordable preparation for fighting the deadly dengue virus. India has the biggest load of dengue disease in the world and an affordable anti-dengue herbal preparation will have a significant impact on public health.

DBT has initiated several innovative programs, which have become international models of cooperation. Some of these include Stanford India Bio-design program, Biotechnology Industry Research Assistance Program, Translational Health Sciences and Technology cluster, National Bio-design Alliance and more.

In brief, DBT remains the lifeline of biotechnological innovations in India and it is ensuring the long-term sustainable impact of Indian science on public health. We are privileged to experience the invaluable guidance of the Secretary of DBT, Professor M.K.Bhan. He is a true leader, who cares more about the success and happiness of other than his own. His invaluable support has encouraged us to take on new initiatives in Biotechnology for increasing the socio-economic impact of our science. DBT has brought new pride to Indian science.




In the life of a scientific institution, 25 years is too short a period, for judging

its relevance in the service of a nation. If we go by the pace and magnitude of growth and the role it has played in building the kind of institutional infrastructure and human resource required for taking full advantage of the new bioscience for our well being during so short a period, the Department of Biotechnology (DBT) has more than justified its existence, with a resolve to contribute a lot more. I am all the more happy, that DBT is commemorating its Silver Jubilee by getting itself assessed of its performance by the scientific community associated or acquainted with it. This exercise, I believe, would help it know the impact of what it has achieved vis a vis its mission and mandate, where it has failed during the milestone period and what the nation expects of it in future. My association with the DBT

is as old as its inception and what I intend to share here, are some of the worth recalling instances relating to its agribiotechnology research and development initiatives.

riCe BioteChnology network, the forerunner to the Country’S CroP BioteChnology reSearCh

It was in 1987, when I assumed the charge of Project Director, Directorate of Rice Research (DRR) at Hyderabad that Dr. Gary Toennison, of the Rockefeller Foundation (RF) met me and discussed the prospects of developing and utilizing molecular tools for the improvement of rice in India with assistance from RF. The outcome of this meet was the launch of the RF-aided, Indian Rice Biotechnology Network (IRBN), involving as many as 10 traditional and State Agricultural Universities, ICAR Institutes and the International Centre for Genetic Engineering and Biotechnology

(ICGEB). The novel strategy of bringing together institutions of applied and basic research to address problems impeding the growth of rice in the most focused manner, laid the foundation for crop oriented biotechnology research. As the convenor, the project coordinated by me for 10 years, enabled the country to develop relevant scientific manpower through short and long term training of Indian scientists in advanced laboratories in the USA and elsewhere and build the needed research infrastructure facilities to pursue targeted research. Of many research leads obtained through this network strategy, I must mention here, the first ever molecular mapping of rice gallmidge resistance gene by the joint effort of ICGEB and the DRR.

CPMBS:

The First Flagship Laboratories for Addressing Crop Related

E.A. Siddiq Ph.D is Honorary Director at Institute of Biotechnology, Acharya NG Ranga Agricultural University,Rajednaranagar, HYDERABAD-500030 Email: [email protected]

Nurturing agri-biotechnology

E.A. Siddiq




Problems By Molecular Breeding: It was the concept of Centres for Plant Molecular Biology (CPMB), conceived by Dr. Ramachandran, the Founder Secretary, that brought together the Indian Council of Agricultural Research (ICAR) and the Department of Biotechnology, to identify as many as eight Universities and National Laboratories, to undertake crop oriented biotechnology research. Representing ICAR, Dr. R.S. Paroda and I played constructive role in identifying the institutions and crop species that needed priority biotechnology intervention. The first flagship laboratories further nurtured and strengthened by the successive Secretaries, Dr. C.R. Bhatia and Dr. Manju Sharma, in a way, removed the obsession of

agricultural scientists, that crop related problems could be addressed only by agricultural research institutes. Convinced of their continued excellent performance, while the centre at Jawaharlal Nehru University has been developed into the National Institute for Plant Genome Research (NIPGR), others have grown over the years, as strong and competent research laboratories, which are sustaining themselves now by attracting substantial support from DBT and various other sources.

india, the only Country froM the develoPing world to Partner in the international riCe genoMe SequenCing ProjeCt (irgSP)

The above goes to the credit of Dr. Manju Sharma, who took the

bold decision on India’s joining the international initiative on sequencing of rice genome, despite discouraging response from a section of scientists on the ground, that it would be an exercise of no research interest and that once the job was done under the global initiative, the entire sequence information would be in the public domain for all to access and use. It was her conviction, that our participation would provide an excellent opportunity for our scientists to get acquainted with the sequencing techniques and the experience thus gained, would enable us to sequence other crop genomes of interest to India, that enabled us be a key player in the global efforts on rice functional genomics that followed. But, for

Fig. 1 : Grain traits of Pusa Basmati-1(Evolved Basmati) and Basmati370 (Traditional Basmati) varieties

Basmati 370

Pusa Basmati




Dr. Sharma’s foresight and decision making in taking along ICAR and to meet wholly the expenses on rice genomics, India would not have joined the elite group of countries in this frontier area of research. The impact of this participation is visible in its finding a place of importance in yet another global initiative - the Tomato Genomics and the successful sequencing of pigeonpea genome by India, just weeks ago.

in SuCCeSSfully exPloiting the firSt ever gM CroP

It was the intensive and extensive study based conviction, that led the country to deregulate the Mansanto-Mahyco developed Bt cotton hybrids

nine years ago, for commercial planting. As the most effective and ecofriendly strategy against the killer insect pest ‘Bollworm Complex’, the GM cotton has put an end to the serious crop losses year after year, driving farmers to commit suicide. Accounting for over 80 percent of the country’s cotton area today, it has more than doubled the production and productivity, resulting in sizeable surplus for export. In convincing the Genetic Engineering Approval Committee (GEAC) to go for the technology, my role as the GM Monitoring Committee Chairman had been crucial, especially in the absence of an institutional

mechanism either under GEAC or the DBT, then to more effectively assess its efficacy and biosafety under field condition. I still recall the day, when I had to spend nearly the entire night with the Mansanto-Mahyco representatives, in studying all the biosaftey related documents provided by them, in my capacity as the DDG (Crop Science) in the Council and the days, when the Monitoring Team, extensively travelled to assess the performance of field tested Bt cotton hybrids. Then, along with the detailed Monitoring Team report submitted to the GEAC and a more precise one page write-up prepared by me, as desired by Shri.



Variety RM171 RM55 RM202 RM72 RM348 RM241 RM44 RM1Basmati370 B C B D B B B A

Dehradun Basmati B C B D B B B ARanbir Basmati B C B D B C B ATaraori Basmati B A B D B A C A

Basmati386 B A B D B A C ABasmati217 C B B B A A A B

Kernel Basmati C A B D B B B ABasmati385 B C A D B B C B

Super Basmati C A B D B B B CBasmati198 B C A D B B B C

Pusa Basmati C B B B A A C APunjab Basmati C A A A B B A A

Kasturi C B B B A A A AMahi Sugandha C B A A B B A B

Haryana Basmati C B A B A A A DSharbati A B A B A A A C

IR64 D B C C A A A CJaya A D A B A A A C

Allele code RM171 RM55 RM202 RM72 RM348 RM241 RM44 RM1A 322 220 160 148 131 128 103 73B 336 230 182 158 140 140 109 100C 344 235 186 164 143 113 106D 348 237 173 108

A. Identity CodesAllele code

B. Code keyAllele size in base pairs

Fig. 2 : A. Specific allele profiles of Basmati rice varieties and putative adulterants at eight microsatellite loci. B. Based on the allele size of each locus code ws assigned.


Gokale, the Additional Secretary MOEF and Chairman, GEAC, despite reservations from the Green Peace and other anti GM factions on biosaftey related issues, our observations finally convinced the GEAC to approve its commercial release in 2002.

outStanding ContriButionS of two inStitutionS

As Hon. Chair Distinguished, Centre for DNA Fingerprinting and Diagnostics (CDFD) and Member, Scientific Advisory Committee and Governing Body, National Institute of Plant Genome Research (NIPGR), since their inception, I have been acquainted with some of the molecular marker aided products of economic significance that they have brought out. Two elite silkworm hybrids developed by CDFD jointly with the Andhra Pradesh Sericulture Research and Development Institute, are the first of their kind produced of parental lines evolved through molecular marker assisted breedug. By virtue of its higher productivity, reelability

and superior quality of silk, in terms of international silk grade as compared to the traditional strains, the hybrid Swarnandhra is highly popular in the states of Karnataka and Andhra Pradesh. Outcome of the research, now underway there to make the hybrid resistant to the killer viral disease ‘grassery’ by transgenic approach, is expected soon to add further strength to the silk industry. yet, another piece of work that is sustaining the country’s basmati export is the development of molecular marker based ‘Basmati Verifiler Kit’, which not only distinguishes the highly priced traditional basmati rices from the low priced look-alike non-basmati rices but also detects the extent of adulteration of basmati rices with non-basmati types by unscrupulous traders. Significantly, CDFD is the APEDA recognized nodal institute for certifying to the authenticity and genetic purity of traditional basmati rice consignments meant for export. (Figs 1 & 2)

When the country’s crop

related transgenic research had been wholly dependant on transgenes/constructs developed and owned by the developed world, it was NIPGR, which came up with nutritively rich potato transgenics, engineered using the quality protein gene (AmA 1) cloned from the leafy vegetable Amaranlhus. The gene, possibly a transcription factor, found to enhance protein content and protein quality, in terms of many folds increased essential amino acid profile and tuber yield in potato, has now been transferred to rice, where low protein content is its major nutritional limitation (Fig.3). The quality protein transgenic potato, now in the advanced stages of field evaluation and high protein transgenic rice, in advanced stages of development are expected to contribute substantially to the country’s nutrition security. The institute, also aggressively engaged in mining novel genes from various sources, has added to its repository many more genes of commercial value, which include

Fig. 3 (1) : Transgenic potato expressing AmA1. (a) pSB8G plasmid with full length AmA1 cDNA under the control of GBSS promoter. (b) Field trial of transgenic potato. Transgenic plants from size normalized seed-tubers were grown alongside wild-type plants in randomized replicated plots

Fig. 3 (2) Transgenic rice expressing AmA1. (a) pSB8N plasmid with full length AmA1 cDNA under the control of prolamin promoter. (b) Green-house grown transgenic rice.

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genes (α – mannosidase & β-D-N-acetylhexosaminidase) that help prolong the shelf-life of perishable fruits and vegetables and the one (Oxalate decarboxylase) that interferes with the causal factor(s) of kidney stone formation, lathyrism etc. (Fig.4)

ProBleM SPeCifiC network Mode ProjeCtS:

Learning from the experience gained at different phases of its growth, the DBT placed emphasis on and encouraged product oriented translational research along with knowledge generating basic research projects in network modes. Among many such projects, those aiming at tolerance to crop specific biotic and abiotic stresses, with which I was associated, as Chairman, Project Monitoring Committee, are important. Although still no immediately transferable transgenic could come out of such efforts, considering their application value sooner or later, due credit should be given to the transgenes of relevance to salinity tolerance (Glyoxylases and Helicases) by ICGEB and many unique genes of mangrove origin by M S Swaminathan Research Foundation (MSSRF). As for basic research, progress being made in understanding the molecular basis of yield heterosis aiming at directed and predicted hybrid vigour in rice by NIPGR-Mahyco and the phenomenon of apomixis towards exploring the prospects of development of true breeding hybrids in crop plants by the Centre for Celluar and Molecular Biology (CCMB), are worth mentioning.

eStaBliShMent of the national inStitute of aniMal BioteChnology: Building need based new institutions

has been one of the priorities of the DBT since beginning and particularly during the last six years, under the stewardship of Dr.M.K. Bhan. Of the many institutions now coming up, the one being established at Hyderabad, exclusively for animal genomics, is the National Institute of Animal Biotechnology. Despite enjoying the distinction of being one of the few countries in the world with the largest livestock population, no precise information is available yet on the population structure of native breeds of different livestock species. While the need is there to improve the productivity of inherently low productive indigenous breeds, otherwise well adapted to tropical stress conditions, considering their still underexploited vast genetic potential, conservation of them should receive priority attention. Also, the fact that future demand projections of milk and other dairy products cannot be met through the large but low productive native breeds and very low proportion of crossbred animals of high productivity, a multipronged strategy, taking advantage of a wide range of innovative tools that the new biosciences offer today, is urgent. Keeping in view the foregoing and the urgency of the nation to become nutrition and livelihood secure, the Institute of Animal Biotechnology was conceived by me, when I was a Member of the Scientific Advisory Council to the Prime Minister during 2004-07. The institute, fashioned in a three-tier mode, is now being established in the campus of the University of Hyderabad. It is hoped that its early and effective functioning would change the livestock scenario, for the nation to benefit from.

reaChing out the target Clientele with ProduCtS of BioteChnology

The country’s advance in the field of crop biotechnology during the last 25 years has been enviably progressive and phenomenal. Sadly, however, we have failed in shaping many a research lead into transferable technologies. It is largely on account of our not having an institutional mechanism to bridge the gap widely referred to as ‘the valley of death’ between research products on the shelves of scientists and shaping research products into commercializable technologies. The new strategy of fashioning the upcoming research institutions in 3-tier mode, integrating under one roof, the research laboratory to develop products/processes of value, the unit for scaling up them into transferable technologies and the business component for test marketing and commercialization, should help bridge the gap and ensure thereby, a research lead of promise reaches the user clientele early, as adoptable technology.

In transgenic research, event selection for desired level of efficacy and generation of data on biosafety of so selected event(s) under field condition, are two crucial steps. They require sizeable budget, which neither the research laboratory/institute that develops the transgenic, nor the private seed industry that is interested in acquiring the same for commercialization, can bear. In such a situation, death of technologies of value to mankind, is inevitable. Sadly, there is no mechanism today to save and benefit from such research products. Even public-private-partnership models being tried to rescue valuable




research leads, do not seem to be effective enough. It is, therefore, urgent that the Department of Biotechnology develops a strong and financially viable tripartite institutional mechanism, involving itself as a party representing the government, along with the public research institute that owns the research product and the private sector, which is interested in commercializing the product as other partners with precise understanding on cost sharing for the research product to cross the ‘valley of death’ and benefit the user clientele.

Adoption of a GM crop by farmers and acceptability of the produce therefrom by consumers would not be easy unless they

are told all about the technology development and testing, for biosafety giving emphasis to advantages out weighing risks if any, in the most transparent manner respecting ‘consumer right’ prior to its commercialization.

The kind of hassels we had passed through, in reaching out the BT cotton to farmers, should be a lesson and help us in identifying and correcting the procedural hurdles enabling speedy deregulation and extensive adoption of transgenics now in the pipeline. Aside the need for awareness creation among user clientele, prior to commercialization of transgenics, two more important requirements are crucial to benefit early from biotech products. Establishment of very much

needed Biotechnology Regulatory Authority (BRA) empowered to deal with and decide on all aspects of transgenic development, testing and deregulation of transgenics, should not be delayed. The present system involving several ministries, in the absence of BRA would continue to slow down the deregulation process. Lack of clarity on the Act relating to field testing and release of transgenics in states is the other problem. Agriculture being the state subject, due consideration be given to involve the states, by way of obtaining their concurrence well in advance, for choosing test locations for field testing and the regions for introduction of transgenic crops.

Fig. 4 : Enhancement of fruit shelf life in α-mannosidase or β-D-N-acetylhexosaminidase silenced tomato plants. Fruits from RNAi and wild type plants were harvested at pink stage and stored at room temperature (22-24oC in 55-60% relative humidity). The progression of fruit deterioration was recorded by time lapse photography. Time after harvest is specified by days.

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It is, indeed, an occasion of great joy and pride for all of us, that Department of Biotechnology

has successfully completed 25 years. Today, India has made tremendous progress in the field of Biotechnology, particularly in the areas of agriculture, human health & nutrition, animal sciences and environment. DBT’s active support and involvement have played a crucial role in helping India make this progress. It is worth mentioning that during the last decade, many international delegations, including many from the developed countries, have been visiting India to familiarize themselves with the biotechnology research activities being carried out here. They have even shown keen interest to partner in this area of research. Many of these remarkable research activities are being conducted under the auspices of DBT.

I have had the good fortune of being closely associated with DBT since its inception. Over the years, I have served as chairman of several task forces of DBT, such as RCGM and Selection Committee for National Bioscience Award. I have also been a Member of SAC (O) and several other DBT Committees.

DBT gained its initial momentum under the dynamic leadership of its first Secretary, Dr. S. Ramachandran, who initiated various programs and introduced and implemented numerous schemes. During his tenure in 1992-93, I was fortunate enough to get approval for the DBT-sponsored Centre for Plant Molecular Biology (CPMB) at JNU. Establishment of CPMB is a milestone in my scientific career. Intensive research was done at CPMB on various facets of both fundamental as well as

applied aspects of plant molecular biology.

In 1991, I was awarded a US Patent for the gene Oxalate decarboxylase which was the first US patent of a gene by an India-based scientist. In 1992, I also patented AmA1 gene isolated from Amaranthus and the research for this patent was funded by DBT. I fully acknowledge the support received from the then Secretary, Dr. C.R. Bhatia to patent AmA1 gene.

The contributions of Dr. (Mrs.) Manju Sharma are remarkable. She led the DBT to the centre stage, laid the foundations of many new DBT funded centers and institutions, which have now established themselves on the scientific map of the world. National Institute of Plant Genome Research (formerly known as NCPGR) is one of them. The blueprint of the Centre was

Asis Datta Ph.D is Professor of Eminence (NIPGR), President, National Academy of Sciences, India (NASI)Email: [email protected]

Setting the pace

Asis Datta




developed by me and submitted to DBT. Its approval by DBT resulted in the establishment of NIPGR, to coincide with the 50th anniversary of India’s Independence as well as the birth anniversary of Prof. (Dr.) J.C. Bose. The announcement was made on November 30, 1997 and the foundation stone was laid on 30th November, 1999 by Dr. Murli Manohar Joshi, the then Union Minister of Human Resource Development and Science & Technology. With full support and help from Dr. (Mrs.) Manju Sharma, I developed a comprehensive plan for the development of the centre and construction of the building to house it. Initially, it was started in a small laboratory at JNU and later moved to its own campus, having state-of-the-art facilities. His Excellency, Dr. A.P.J. Abdul Kalam, the then President of India dedicated the Institute to the nation on November 28, 2005. NIPGR is a premier institution for Plant Genomic Research, which aims to contribute to the understanding of the structure, expression, arrangement and function of the genes; and manipulation of

plant genes/genomes to improve varieties of food and industrial crops for better yield and quality. A marked achievement in recent years has been in the area of nutritional genomics in India, involving isolation, identification, sequencing and successful transfer of AmA1 protein gene from Amaranthus to Potato (solanum) and production of transgenic potato for use in agriculture. Similar possibilities have opened up for oxalate decarboxylase (OxDC) gene to tomato, leading to dissolution of oxalic acid crystals, with tremendous impact on agriculture and medicine. NIPGR has generated a lot of new knowledge and materials, to advance both basic and applied research in the area of plant genomics. I remember that Dr. M.S. Swaminathan, during the peer review of NIPGR, recorded that, it is India’s first and only research institute of its kind. I would also like to add that with the help and full support of Dr. Bhan, Secretary, DBT, the name of National Centre for Plant Genome Research was changed to National Institute of Plant Genome Research.

With generous support from the 11th Plan, the campus has further developed its own students’ hostel and a Plant Growth Facility.

The efforts of Dr. M.K. Bhan who stressed on the need of public-private partnership in biotechnology are highly acclaimed. In the recent past, a number of unique institutions and organizations have been created under his able leadership. These are National Agri-Food Biotechnology Institute, Mohali, which would act as a biotechnology hub; Translational Health Science & Technology Institute; and Regional Centre for Biotechnology, which will be a part of Biotech Science Cluster at Faridabad.

I join all of you in thanking DBT, for its support to the scientific community in India and whole-heartedly appreciate the impact DBT has had on Indian Biotechnology research. I congratulate all the Scientists and staff of DBT on this special occasion and I hope, that the Department would continue to deliver its best to the service of the nation.




The completion of 25 years of service to the nation by DBT is an occasion of great

satisfaction. The contribution of DBT towards advancement of policy, R&D, regulation, education, and entrepreneurship in biotechnology is indeed laudatory. My association with the department goes back to 1988 when I joined the National Bureau of Plant Genetic Resources, New Delhi (NBPGR) in the DBT supported project, National Facility for Plant Tissue Repository. It was the first initiative of NBPGR towards application of tissue culture and related biotechnology tools, for conservation of plant germplasm. One of the objectives of the project was to unravel the biosystematic relationships of crop species and related germplasm, using modern tools of molecular biology. Over the years, the tissue culture conservation facility has grown into the country’s

largest in vitro and cryopreservation genebank while the molecular characterization unit enlarged to become the National Research Centre on DNA Fingerprinting, which now has the added mandate of crop genomics. There are several other DBT initiatives in the diverse areas of biotechnology, as understood in its broadest sense, that have produced very impressive results. Some of these are mentioned in other articles of this issue.

While taking pride in these achievements, it is appropriate to reassess the evolving agriculture related R&D needs of the country and adopt appropriate strategies and midcourse corrections, wherever necessary, to fulfill these. While we have been experiencing good crop production over the last couple of years, the projected population of 2025 would require substantially more food and nutrition for a

healthy living. Below, are some of my thoughts as to how we could better utilize biotechnology to achieve the desired goals in crop production.

Adoption of tissue culture technology for mass propagation of high quality planting material has been commercially successful in several ornamentals. However, as far as high volume low-cost propagating materials required by farmers for cultivation over large field areas are concerned, the adoption level has so far been low. For example, though several companies produce 2-5 million banana plantlets annually, these meet not more than 5% of the annual need of fresh planting material. In ginger, citrus, grapes, apple, almond, and peach where micropropagation technologies for direct propagation/root stock have been successfully adopted at field level elsewhere, there is need

J. L. Karihaloo Ph.D, is Coordinator at Asia-Pacific Consortium on Agricultural Biotechnology, New Delhi -110012 Email: [email protected]

J. L. Karihaloo

Enhancing Yields




to adopt and adapt these to our situations for the much needed mass scale, high quality disease free planting material. The factors that seem to be impeding large scale adoption of tissue culture based propagation technology include, high production cost, lack of production capacities to scale, gaps in field level adaptation, and limited technology transfer and stewardship mechanisms. These constraints need to be addressed, to make effective use of this relatively low-tech yet highly relevant technology, to improve the productivity and quality of farm produce, especially in vegetatively propagated crops.

The resounding success of Bt cotton is a proof that farmers

are more than willing to adopt technologies that benefit them, irrespective of whether these are GM or non-GM. While there are a number of public sector developed GM products in pipeline, it is time that some of these reach the farmers. This will inculcate much needed confidence in the capacity of Indian scientists to deliver on the promises of biotechnology. To accelerate GM product development and delivery process, it may be desirable to revisit the crops and traits that need to be improved through genetic modification route, also taking into account alternative options. Besides technological constraints, regulatory compliance costs and uncertainties necessitate

a very focused GM programme, integrating all the necessary elements required for timely deliver of products.

To meet the biosafety requirements of the crops currently under genetic modification, there is an urgent need to develop exhaustive scientific information on their biology, particularly, reproductive mechanisms, weediness, crossability with related local forms, and ecological impact of pollen flow. Interdisciplinary projects aimed to develop such information in the context of biosafety should be encouraged through special grants schemes.

With the twists and turns

witnessed in the environmental release of Bt brinjal, regulatory management is becoming an area of concern. It is unfortunate that while India has one of the first and most well established biosafety regulatory systems, the decision making process should go through so much uncertainty, that in the long run, it discourages investment and research in a very powerful and promising technology. While decision making has to be based on internationally accepted scientific procedures and protocols, the need to inform and educate public, so that it trusts scientific evidence and decision making process, cannot be overemphasized. In my opinion, there is a crying need for a highly visible and efficient communication system, to reach out and provide unbiased information to people at various levels, about the pros and cons of GM technology.

The efforts of DBT to intensively document, map, characterize and utilize the vast wealth of Indian bioresources are admirable. Now, is the stage to validate the information, both taxonomic and value based, and make it available to bonafide users in the most efficient and usable form. There are a number of international web based bioresources portals and databases that could serve as models in terms of design as well as content. Such information source will be extremely useful to students, researchers and entrepreneurs, who most often have limited access to well stocked libraries and herbaria.

These are a few suggestions which I believe will add strength to agri-biotechnology, for making a greater impact on Indian agriculture.




Only 25 years young, and yet so many achievements to boast of! The DBT

is indeed one of those rare governmental initiatives that has had – and continues to have – a radicalizing impact on Indian science. When I returned to India to take up my current position at ICGEB, my first exposure to the recently christened Department of Biotechnology (formerly known as the National Biotechnology Board) was through interactions with the then Secretary, Dr. S. Ramachandran. Armed as I was, with the superciliousness that is typical of a US-returned native, and harboring a disdain for existing ‘systems’ (remnants of a left-leaning past), the interactions – albeit brief – with Dr. Ramachandran, was like experiencing shellshock. The clarity of his thought process, which combined youthful energy and a determined sense of purpose,

seemed incongruous at first - mired as we were in a system where even purchasing sodium chloride required an inordinate amount of paperwork and took several months to finally arrive. An ambition that was completely out of sync with reality? That was my first, knee-jerk response to his views on the future of biological science in India. But perhaps his logic was persuasive, and also perhaps his optimism was infectious. Because gradually the layers of cynicism began to peel away; being replaced by a sense of hope that things may turn out to be better after all. And if one takes stock of the situation today, one cannot but help view this as an enduring vindication of the foresight and vision that Dr. Ramachandran professed over two decades ago.

Typically, institutions waver through phases of growth and stultification as leadership

changes from one hand to another. Fortuitously though, the DBT has proved to be immune to such vagaries. Rather it has always aggressively capitalized on its core attributes, and seized enabling opportunities to pro-actively expand the base of biological research in India. Although I did not get many opportunities to interact with Dr. C.R. Bhatia, who succeeded Dr. Ramachandran as the Secretary of DBT, it was a privilege for me to become more closely connected to DBT during the tenure of Dr. Manju Sharma. In this period, I also got exposed to the workings of Task Forces and other such review committees (or, irrational black boxes of uncertainty, as described by the hapless victims). In addition to the persisting qualities of vision, and enthusiasm for driving that vision, yet another invaluable trait was added to the attributes of DBT under her stewardship. And that

Kanury V.S. Rao

Leading from the front

Kanury V.S. Rao, is Group Leader, Mammalian Biology: Immunology at International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi - 110067 E-mail : [email protected]




was generosity. This was the period of schizoid inclinations where although the economy had begun to grow, the majority of us remained ensconced in the pecuniary mindset of the past; continuing to enforce – as project review committee members - fiscally frugal standards while approving budgets for project funding. But thanks to the foresight and determination of Dr. Manju Sharma, who believed that the time had come to take bigger strides forward, we also witnessed the beginning of the era of big budget projects. On the one hand the scale of individual projects increased substantially, thus also allowing for upgradation/acquisition of the necessary infrastructure. In addition, network programs with more ambitious goals were also actively encouraged and promoted

(the Indian participation in the rice genome sequencing project being a notable example). Another particularly noteworthy feature of this period, was the addition of several new institutes (such as NCCS, CDFD, NBRC etc) to the portfolio of DBT institutes. That is, in one fairly short sweep, biological research in India gained comprehensively both in scope and depth. And, as a natural corollary, a scientific community that was better positioned to deal with new challenges emerging in the post-genomic era of biology. An excellent example of this is the investments that were made, at that time, to promote manpower generation in the field of Bioinformatics. The dividends that this is paying today - both in terms of providing ‘bench-strength’ for large-scale

data analysis, and the industries that it has spawned – stands proud testimony to the forward-looking policy of DBT.

From giant strides to ambitious leaps! That is perhaps what best characterizes the subsequent evolution of the operating philosophy of DBT, under the leadership of the current Secretary, Dr. M.K. Bhan. Many new and bold initiatives have clearly been launched during his tenure. However, more telling - at least to me - is the underlying character of these initiatives, and the transformation that this is enforcing on the manner in which biological research is conducted in India. Driving DBTs current ventures is the spirit of consolidation, and consequent integration. That is, to consolidate on the gains

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made so far, in order to achieve an integration that can synergize a new phase of exponential growth. This has not been easy, given the starkly defined inter-institutional boundaries that exist. However, through sheer strength of personality, and an unassailable logic that has the uncanny ability to strike at the core of even the most recalcitrant of mindsets, DBT is successfully whittling away at such boundaries. I have always found one-on-one conversations with Dr. Bhan to be disconcerting. On the one hand, the scope and breadth of his thought process has frequently left me gasping for breath, as I confronted my own limited intellect. And more often than not, I have been left with an uneasy feeling that what I had hitherto held dear as deep conviction may – after all – be nothing more that narrow dogma. It is rather unsettling to realize how plastic the distinction between conviction and dogma in fact is. Perhaps the most notable

achievement in this connection, has been the successful dissolution of the barrier that had divided research scientists and translational researchers (formerly, product development-wallahs) into two separate, and mutually exclusive, castes. Persistent efforts by the DBT have led to both sides gaining a healthy respect for each other and, more importantly, the recognition that the basic and the translational aspects of science, in fact, constitute seamlessly integrated units of a common endeavor. Because of this success, even the most redoubtable academic can today look a peer squarely in the eye and confess – without flinching – to being engaged in translational research. And testimony to this is the fact that virtually any biologist in the country would be proud to associate with either the upcoming THSTI cluster in Faridabad, or any such translation-oriented venture that DBT is seeding in various parts of the country. This

paradigm shift represents a singular accomplishment of DBT, and it is certain to bear rich fruit in the years to come. It is also an apt example of the pro-active leadership that DBT has provided over the years.

In view of the prevailing scenario, it is truly remarkable that DBT has remained young, dynamic, and aggressively pro-active in its endeavors even after 25 years. Because this is well beyond the usual age, where most institutes/institutions in India experience the inertia and arthritic pains that comes with middle age. In contrast, DBT continues to lead from the front, goading the scientific community to aim for even higher pinnacles. It is befitting, therefore, to conclude by raising a toast to DBT on its silver jubilee, and wishing it many more decades of youth. Because only then will we also be assured of the overall health and vitality of biological research in India!



Patron: M. K. Bhan, Secretary Department of Biotechnology Government of India

Editor in Chief: S. Natesh Senior Advisor & Scientist ‘H’ Department of Biotechnology

Editorial Advisory Mohd. AslamCommittee: Alka Sharma Anamika Gambhir M. S. Shashi Kumar Niloo Srivastava Sanjay Kalia Vaishali Panjabi

Editor : Manoj Dabas Editorial Assistance : Sonali Jha Chatterjee Neha DharmashaktuDTP Assistance : Pramod Kumar Jha

Designed, Produced and Circulated by:Communication & Outreach Division Aravali Foundation for Education Aravali House, 431/D-22, Chattarpur HillsNew Delhi - 110074, India

Disclaimer : Views expressed in invited articles are those of the authors and not necessarily subscribed to, or endorsed by DBT or any other organisation associated with the publication of Biotech News.

Department of BiotechnologyMinister of Science & TechnologyGovernment of India

Printed and published by Md. Aslam (Scientist F & Director) on behalf of Department of Biotechnology, Government of India from Block-ll, CGOComplex, Lodhi Road, New Delhi-110 003. Printed at Montu Press, A-43/1, Narayana Industrial Area Phase-I, New Delhi-110 028, www.archanapress.com


The Department of Biotechnology (DBT) was established in February

1986 and it has completed 25 years in February 2012. During these past 25 years, it has touched many lives, roughened many feathers and flattened the skyline of biological, chemical, physical and engineering sciences, which was so compartmentalized that interactions even between subjects of botony and zoology were impossible to think about.

Dr. S Ramachandran recognized that a demand driven livestock revolution is taking place in most developing countries, and this trend is likely to continue. With growth rates of 4.5 % per annum over the next twenty years in the livestock sector, current annual growth rate in milk, poultry and meat sector need not only to be improved but sustained. Historically, growth has come

primarily from the expansion of the livestock numbers rather than an increase in productivity. If this trend continued. there would be a tremendous pressure on the available feed resources and thus, this had to change. This was a major challenge facing the livestock sector. Biotechnology has tremendous potential for increasing food production through improving effectiveness of livestock and generating improved food processing industries, leading to nutritional security. Animal productivity has therefore to increase due to efficient and effective use of biotechnologies, as in developed countries. If animal production has to be self sustaining in India, we have no choice, but to effectively use these new technologies.

In 1986, the DBT set up a committee to look into the needs for biotechnology research in the animal sector. The DBT requested

me to draw out a blue print for this area. The committee made several recommendations. One of the first recommendations accepted by the DBT was the recognition that genetic improvement in livestock species was not possible through traditional genetics and therefore new biotechnologies could be used to obtain this goal, and in order to do so one has to bypass the reproduction barrier. It was decided to obtain this goal by use of Embryo Transfer Technologies (ETT). A project in mission mode was established in collaboration with Indian Council of Agriculture Research (ICAR) and National Dairy Development Board (NDDB) in a multi-centric, multi-institutional mode. In the first phase, embryo transfer technologies were to be standardized on Indian livestock, followed by development of herds of superior cows (high milk producing cows of cattle and buffaloes) and

P.N. Bhat

So far, So good

P. N. Bhat is Chairman at World Buffalo Trust and Centre for Integrated Animal Husbandry & Dairy Development, Flat No.205, F-64, C/9, Sector 40, Noida-201301, Gautam Budh Nagar District, Uttar Pradesh. Email: [email protected]




then to develop several MOET based sire selection programme to develop a bull repository, for use in the National Programme of Artificial Breeding. This was to be followed in 2nd phase by transgenesis and animal cloning on the commercial scale. First part of this programme was completed by 1992.

The salient achievements of this mission mode, multicentric project were:

i. Embryo transfer technologies:

The technique for collection, processing and freezing of embryos and semen and the necessary trained personnel to do so, have been produced and are available. We have however failed to get the private sector involved in this initiative to develop livestock stations

attached with semen and embryo processing laboratories, so that India could become a global player in the sale of semen and embryos of Indian breeds of cattle and buffaloes, in the world market. India has now 20 million crossbred cows, 1% of which produce more than 5000 L of milk in 305 days. The semen and embryos from these could bring in at least Rs.500 crores annually, from sale of semen and embryos from export alone, if we can succeed in bringing private sector investments into this area.

ii. New Institutions : We have by now established 50 institutions in the country (ICAR Institute, Universities) which are able to conduct research in E.T. Technologies and produce a

large number of competent personal who can successfully perform this option.

iii. Transgenesis : Transgenesis is a powerful technique for studying fundamental problems of mammalian gene expression and development, for establishing animal model systems for human diseases and for using the mammary gland to produce pharmaceutically important proteins in milk. The expression of foreign proteins in milk is a system which would allow the recovery of products in a non invasive way (i.e. through milk), without causing any adverse effects on the animal’s physiology. The research on limited scale, on this subject, was initiated at several institutes like Indian Veterinary Research




Institute (IVRI), National Dairy Research Institute (NDRI) and several universities. Considerable research results are now available to bring this technology to the next level of commercialization.

In the developed countries, several recombinant proteins have been produced in large amounts, in the mammary gland of transgenic sheep, goat, pig and cattle purified from milk and characterized biologically. Thousands of animals, which express the desired protein, are now available (Niemann and Kues 2000). Several products such as human antithrombin III (AT III), alpha-1 antitripsin, tissue plasmogen activator (tPA), alpha glucosidase, factor VIII, IX and lactoferrin are currently available or in advanced clinical trials stage. It is hoped that this chain is continued when the new Animal Biotechnology Institute is fully operational. We need to focus on this area.

I have firm faith that knowledge developed, and new capabilities in transgenic livestock and animal cloning, to improve the production status of farmers animals and society’s understanding of these, will provide the basis for innovation for end users. This could be reflected in a greater opportunity to enhance our international competitiveness through new, value added products and alternatively, more efficient processes to alleviate poverty.

The most important initiative was in respect of diagnostics and vaccines. With the production of cheaper diagnostics, vaccines, drugs and reagents, biotechnology has opened new vistas in animal health care. Significant work has been done

over the past two decades, its commercialization, however, has been limited. This needs to be expanded through an institutional mechanism following - a model perfected in other fields of private public partnership which can fill the industrial gap.

In the area of vaccines and diagnostics, significant development was to introduce molecular biology and DNA mapping in diseases of Animal importance. The first disease was Sheep and Goat pox who’s DNA profiling was completed at IVRI by 1988, by the group headed by Dr. Pran P. Bhat. New Recombinant Vaccine development included a Rabbies vaccine at National Institute of Immunology (NII) by Pran Talwar’s group and Anthrax vaccine at JNU developed by Prof. Bhatnagar’s group. This is a landmark development. The antigenic DNA fragment of anthrax vaccine has been purified for human use and is undergoing phase II trials. It should be cleared for human use soon. This vaccine has been commercialized by Panacea Biotech Limited, New Delhi.

In the area of Animal Biotechnology, we recognized that the paucity of trained personals to take forward the research portfolio and to produce young trained biotechnologists, our focus was to establish a P.G. Scheme on Biotechnology leading to Masters Degree Course in Veterinary/Biotechnology at IVRI in the year 1987. This was followed as a regular scheme of DBT on Post Graduate Education in Biotechnology across the country. Today, all the universities both Veterinary, Agriculture and general are offering Masters Programmes in Biotechnology. I consider this

as a great revolution in putting modern biology as the Central Pivot cutting across the discipline specific barriers.

In the area of joint collaboration of centres of excellences and bilateral programmes in the department, the largest single arrangement of collaboration was between India and the then USSR. This Protocol was signed by Shri Rajiv Gandhi and President Gorbachou in 1989. This long term integrated programme on Science and Technology had Biotechnology and Immunology as one of the thrust areas. I was asked to be the Area Coordinator from the Indian side and the Dr. A.P. Tretjakov from the Soviet side. The governance model was through a joint council mechanism with Prof. C.N.R. Rao as the Indian Co-Chairman and the President of Soviet Academy of Sciences as another Co-Chairman. All branches of Science and Technology were involved. We had identified 11 major areas of collaboration at 5 Indian institutions and it was under this programme that we created the project facility on oral poliomyelitis manufacturing at Bulandshahar, which is a landmark project of DBT.

In view of shortage of green fodder and concentrates, all we have to feed livestock is around 500 million metric tons of crop residues annually. The feed biotechnology could develop feed grade protein and energy by converting 500 million tonnes crop residues produced annually, into celluloses and hemicelluloses through the use of rDNA technology. Research in the area have yielded good results so far. Delhi University (DU), IIT Delhi and Ayurvet as industry partner, have identified




the lignin digesting genes. About a dozen genes have been identified which generate enzymes that digest lignin ring in the plant cell wall thus releasing celluloses and hemicelluloses. We have also looked at the solid state fermentation process which could be used for this conversion. Some peripheral work has been done in trying to develop constructs with yeast/ bacteria as the base, so that several genes can be put into one clone. What is required , is to develop a system in which recombinant microbes containing several genes in the chain, can be used in a systematic process such that crop residues can be converted into animal feeds via break-down of lignin in plant cell wall. This can only be done through an institutional structure of a centre / institute where all the four groups comprising of microbiologists, molecular biologists, fermentation experts/ engineers and animal nutrition scientists work under one roof with an industry’s backing, so that, as technology improves the industrial evaluation is simultaneously.

One of the suggestions to quickly improve the livestock, was to initiate a major programme of animal cloning. To this effect, we persuaded Mrs. Manju Sharma, who had joined as Secretary, DBT to formulate a multi-centric programme to be coordinated by a high focus institute which would link the various findings together with the purpose of fully cloning of indigenous livestock species, which could give dividends both in bypassing traditional genetics for improvement as well as disease control. I made a presentation to the department who agreed with the proposal, but it could not find a

place in the proposal of 10th Plan of the Department.

It was only when Dr M.K. Bhan joined the DBT as Secretary that we were able to persuade him of the need for an institute on Animal Biotechnology. In the 11th Plan proposals, among the establishment of new institutes for the DBT, the Planning Commission, agreed to this new institute. Credit must also be given to Dr. E.A. Sidique to get this institute recommended by the PM’s Advisory Committee on Science & Technology. It goes to the credit of Dr. Bhan that he relentlessly followed it up with theFinance Ministry and other sister department, that enabled us to get it moving. E.A. Sadiq and I were then asked to prepare the detailed Project Report of the institute for which 250 acres of land were offered by Dr. Hasnain, VC, Central University at Hyderabad.

A Search Committee has been appointed to select a Director for this new institute, for which currently an OSD has been appointed. We will have a Centre of Excellence on Animal Biotechnology of global standing. Dr. Natesh and Dr. G. John were responsible in piloting this Institute in the DBT and suggesting the Administrative Structure. The new model suggested by Dr. Natesh with an Industrial Hub being an integral part of commercialization of technologies, is totally new innovation in technology development in which the industrial partners would be the stakeholders right from the beginning.

the Major eMPhaSiS iS going to Be on:

(i) vision: To demonstrate excellence in identifying,

developing and commercializing biotechnology research to produce globally competitive livestock and pharmaceuticals for animal and human health care.

(ii) focus: Development of technologies arising from the field of numerical and operational genetics, immunogenetics, farm animal genomics and medical biotechnology and to achieve successful commercial outcomes yielding significant increases in value of the underlying technologies.

(iii) Commercialization Strategy: To identify technologies and manage the development of research programmes which demonstrate initial proof of safety and efficacy, in order to attain commercial success though the licensing of products for global development and marketing to companies.

There were several new initiatives which were taken up in a mission mode, the most important among them was the leather technology mission for sustainable development led by Dr. Ramaswamy who was then Director of Central Leather Research Institute (CLRI). Considerable progress was made but due to lack of industrial partner, the initiative could not be sustained.

A buffalo genomic initiative was taken up at the Institute of Human Genetics, Bangalore in 2003. This was further expanded in 2007 in collaboration with ICAR and CCMB. Landmark developments were made in development of concepts and infrastructure for taking up this progrmame on an all India basis.




The word ‘Seribiotechnology’ was coined in 1986-87, in an International Conference

on ‘silkworm molecular biology and genetics’ held in Crete Island (Greece) at my suggestion. At this juncture in discussions with Central Silk Board (CSB) authorities, it was decided that biotechnology which is coming up as new science, should be included in CSB research agenda. Consequent to this, a Seribiotech Research Lab was developed with support of the World Bank project initiated in 1989. I now recall that prior to this, I came in touch with Department of Biotechnology of Govt. of India for formulating the research programmes of the department and held discussion with Dr. S. Natesh of DBT as well as the senior biotechnologists from across the globe (USA, Japan, U. K. etc) in a meeting organized by CSB held in 1988. Interestingly,

R. K. Datta

Exploring horizons

R. K. Datta is Former Director at Central Sericultural Research and Training Institute (CSRTI) and Central Silk Board (CSB), Mysore. Email: [email protected]




the Seribiotechnology lab was first initiated at CSRTI, Mysore campus, sometime in 1989 and later transferred to Bangalore as an independent research lab of CSB in 1992.

Sericulture in India is an important cottage industry based on agro-forestry earning foreign exchange worth about Rs.3500 crore per annum. Presently, sericulture is practiced at over 60,000 villages, providing employment to around 6 million people who hail from the weaker sections of the society and are in rural and tribal areas. Silk production has reached over 20,000 MT and India is the second largest silk producer (20% of world production) after China (70%). Even so, our present production falls very much short of the domestic demand. Nearly 85% of our silk is mulberry silk produced by the silkworm, Bombyx moriL. India has the unique distinction of producing all the four varieties of silk - mulberry, eri, tasar and muga. The silk industry has a lot of social, cultural and traditional linkages in the country. Sericulture has two co-ordinate components the silkworm and host plant, the leaves of which constitute the silkworm feed; both silkworm and host plants play cardinal roles in production of raw silk. Despite continuous increase in silk production in the country, the quality and the productivity are still not up to the mark, as compared to China.

Realizing the above, the Department of Biotechnology (DBT) in association with Central Silk Board (CSB) organized many brainstorming sessions and identified thrust areas in

sericulture (both mulberry and non-mulberry) in which biotechnology can play a vital role in increasing productivity, enhancing silk quality and improvement of host plants. I was very happy with the DBT when I met Dr. S. Ramachandran, the then Secretary of the DBT, who really supported the need for developing trained scientists to carry biotechnological research in the field of sericulture as a new science research branch. Thus, the scientists from CSRTI, Mysore could be trained in NII for developing monoclonal antibodies and diagnostic tests for different silk pathogens like Pebrine and Nuclear Polyhedrosis.

In the past 25 years, Biotechnology played an important role in the economic development of the country in all the sectors like medical, human health, animal health, pharmaceutical/new drugs, agriculture and environment etc. We are grateful to DBT as it identified Seribiotechnology as an area of high priority during the 8th five year plan, in order to generate trained/skilled human resource in this critical area of biotechnology. Growth in biotechnology has accelerated particularly during the last decade, due to path breaking advancements in biology and new technologies that produce large high quality data.

Accordingly, a focused programme for seribiotechnology was initiated with the advice of DBT, New Delhi. So far, over 60 R&D projects have been supported by DBT involving various leading institutions such as IISc, Bangalore; NII, New Delhi, NBPGR, New Delhi; NCL, Pune; CDFD, Hyderabad; CCMB, Hyderabad;

IIT, New Delhi; IIT, Kharagpur; MKU, Madurai and University of Delhi, Delhi along with various Labs/Institutions of Central Silk Board. Out of these 60 projects, 15 projects were jointly funded with Central Silk Board.

Now, I will be failing in my duties, if I don’t affirm the impact of these projects sponsored by the DBT. However, the full impact of the seribiotechnology research support provided by DBT would lead to another article, which I propose to write at a later date. Hence, here, I just mention briefly, the overall impact. The DBT has created separate a Task Force committee to look into seribiochnology projects proposed from different institutions. The reasons being many, Universities started researches on Seribiotechnology i.e. research endeavour has become broad based of late, increasing the areas of research interest in this field. The biggest achievement of DBT is the new biotechnology knowledge which has been acquired in the field of sericulture and many epoch making works which have now become possible. The new institution of DBT like CDFD is already marching ahead with organized researches on silkworm and mulberry molecular biology and genetics. The isolated repertoire of wild silk moths of North-East and elsewhere has been brought under molecular biology studies like gene mapping and genomics now, and much new information has come out in the process. I whole heartedly welcome DBT’s effort for the promotion of seribiotechnology.



The Department of Biotechnology (DBT) was initially set up as an

independent Board in 1982 and subsequently established as a full fledged Department under Ministry of Science & Technology in 1986. The extensive sweep of the footprint of the Department of biotechnology – to borrow a phrase commonly used in respect of satellite coverage – covering, as it does, a large spectrum of diverse disciplines, provides a fertile field of research unique among the Ministries and Departments of Government of India Mandated to facilitate basic and applied research in various branches of science. The unfolding possibilities of inter-institutional and trans-discipline research in Biotechnology offers, the diehard research scientists, exciting prospects both of daunting challenges and rewarding achievements.

During the period from the 8th Five year Plan to 11th Five year Plan, funding to the Science & Technology Sector as a whole increased eight fold whereas the funding of the Life Science Sector rose Sixteen fold. While the Department of Biotechnology has been the prime mover in terms of policy and fiscal support to the Biotechnology Sector, Department of Science & Technology, Indian Council for Medical research, Indian Council for Agricultural Research and Indian Council for Scientific and Industrial Research have all contributed significantly, through extra-mural funding, towards the growth of the Indian Biotechnology Sector. The cumulative outcome of these efforts is the general strengthening of the ambience of education and research in the country. An important component of this process has been the nurturing and sustaining

of world-class R&D institutions that are internationally competitive in the field of biotechnology. DBT proactively created a large pool of trained human resource (at M.Sc/M.Tech., doctoral and post doctoral levels) by providing funding support for R&D efforts in agriculture, forestry, human health, animal productivity, environmental safety, bio-energy, forensic science and industrial production. Consequently, a firm foundation for growth of life sciences has been created in public-funded institutions and it is now possible-and indeed necessary – to build a strong edifice of innovation and enterprise.

Recognizing the vast potential and possibilities of high growth of the Indian Biotechnology Sector, DBT has prepared a road map for the coming year with the drawing up of the National Biotechnology Development Strategy (NBDS).


K. P. Pandian

A challenging journey

K. P. Pandian served DBT as Joint Secretary/Financial Advisor from February 2005 to January 2010 . Email: [email protected]


The recommendations of the NBDS include creation of new inter-disciplinary human resource and research infrastructure that can support product development; improve biotechnology skills; establish an ecosystem of discovery and innovation and create an intellectual property regime that promotes innovation. Besides, the NBDS envisages public-funded institutions being partners in directly promoting the indigenous biotechnology industry for economic growth and social benefit. Thus, the NBDS while envisaging the continuation of the push for generating quality human resource and sustained acceleration of research efforts in biotechnology sector proposes additional focus being given to innovation and entrepreneurship. The proposal to promote innovation is based on encouraging early translational research in the public sector institutions and universities and product development through market oriented innovation system. In regard to entrepreneurship, the two important approaches are based on the public-funded institutions led public-private partnership to follow up leads from discovery and early translation programmes in the public-funded institutions and secondly, through industry led research for product development facilitated by novel funding schemes like Small Business Innovation Research Initiative (SBIRI) and Biotechnology Industry Partnership Programme (BIPP). Through these programmes, the industry is co-investing with DBT in challenging innovation programmes.

The eight already existing Institutions under the DBT umbrella have been active partners in the implementation of the National

Biotechnology Development Strategy. These eight Institutions, covering different aspects of modern biotechnology are National Institute of Immunology, New Delhi, National Brain Research Institute, Manesar, National Centre for DNA Fingerprinting, Hyderabad, National Institute of Plant Genome Research, New Delhi, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Institute of Life Science, Bhubaneswar and Institute of Bio-resource and Sustainable Development, Imphal. Each one of these institutions is unique in the country, and has made tremendous impact in its mandated sphere of activities and contributed to the growth of Biotechnology Sector in terms of high quality research, generation of world-class scientific human resource, valuable intellectual property as well as industry collaborations. Recently, towards implementation of the National Biotechnology Development Strategy, these Institutions have taken up newer programmes that include: synthetic biology, animal science research, cell and tissue culture collection, human health biology, gut microbiomics, clinical immunology, cancer genomics, functional genomics and such other frontline research activities in biotechnology. Entrepreneurial opportunities to young investigators, the network research activities and out-reach initiatives are other expansions in their endeavors to facilitate relevant research involving other Institutions/Universities and Industry, thus enhancing their scope and competence. The steadily growing diversification of activities and achievements of these Institutions testify, not only to their increasing global competence in

fundamental research in all aspects of modern biology, but also to their commitment to follow premising innovation leads as they occur in the course basic research.

In addition to the eight existing institutions of DBT, approval of the Cabinet has been obtained and action of various advanced degrees has been taken to establish six new institutions under the DBT fold. These six new institutions are Translational Health science and Technology Institute, UNESCO Centre for Biotechnology Training and Education, National Agri-Food Biotechnology Institute, Institute of stem Cell Research and Regenerative Medicine, Institute of Animal Biotechnology and National Institute of Biomedical Genomics.

The strong network of public funded institutions – existing and upcoming – constitutes the executing arm for achieving the objectives of the programmes of the Department of Biotechnology, included in the Eleventh Five year Plan (2007-12). These



programmes include development of improved crops, development of functional foods, nutraceuticals and nutrition rich foods for combating malnutrition, R&D on bio-drugs, vaccines, biological reagents an adjuvant, diagnostics, implants, bio-medical devices; clinical research; stem cell research and research in regenerative medicine. Nano-biotechnology applications for drug delivery, biosensors, microbial prospecting for discovery of novel compounds, biomedical genetics, bio-energy and bio-fuels, bio-remediation, DNA fingerprinting, etc. are other important thrust areas covered by the approved programmes of research under the Eleventh five year Plan.

In order to focus on and strengthen the translational and innovation activities, it has been proposed to remodel the scope of activities of the DBT institutions to allow them to partner universities, other academic institutions and private enterprise and also to allow them to provide extra-mural

funding for research activities in their mandated areas of research activities. The paradigm shift in the nature of research funded by Department of Biotechnology is the result of a not too unreasonable or unrealistic ambition of DBT to strive towards global recognition and leadership in the field. Accelerated development of a world-class bio infrastructure and conscious efforts to build a critical mass of committed manpower in build to make India a redoubtable force in the field of biotechnology in the not too distant future. While these inexorable forces of development are at play, I would like to add a note of caution – as I had once made bold to whisper into the non-committal ears of Dr. MK Bhan, Secretary, DBT before he launched into a typically brilliant convocation address at the 64th convocation of the medical graduates of Christian Medical College, Vellore extolling the virtues of innovation and enterprise to an appreciative audience – that the social relevance of research should not get swamped and lost sight of in an enthusiastic scramble for commercial success. In any field, for that matter, remarkable economic success alone cannot be viewed as an index of great achievement if the benefits of such success do not percolate down to all segments particularly the weaker segments - of Society. Affordable health care, increased agricultural productivity, development of cheaper bio-fuels, arresting environmental degradation through biotech intervention, etc. provide ample scope for tangible social impact. The Department also need to tread the path of PPP cautiously ensuring that partnership principles are equitable. While, the private partner will, presumably,

push for profit of the private entity, the public partner should keep in mind, at all times, the principles of propriety of public-funded programmes for the greater public good. The Biotechnology Industrial Training Programme is a case in case in point. It would be interesting to know how many of the trainees whose stipend in paid by BDT, through BCIL, are actually employed by the Industry, is the programme unwittingly turning out to be a regular supply line of work force for the biotech companies, at Government expense? Is the programme adding to the number of well-qualified and trained unemployed young men and young women, year after year? The Department has a responsibility as the funding agency to seriously address these issues.

The youthful exuberance of the Department of Biotechnology, which just turns 25 years old, needs to be harnessed in a manner that combines parameters of economic development with an appropriate prognosis for all-round social benefit. I am confident that the Department is well and truly poised to be the catalyst for ushering in remarkable achievements in biotech research, translation and product development by the closing years of the 12th Five year Plan, if not earlier. A large measure of credit for this success story rightfully belongs to the scientists and researchers, both past and present, both in the Department and its autonomous institutions, who have worked with tireless devotion and far-sighted vision. May their increase to position India as an acknowledged global leader and a champion model in the exciting frontiers of Biotechnology.

MeMory lane


PROFILE

INDIAN AGRICULTURAL RESEARCH INSTITUTE

The Indian Agricultural Research Institute (IARI) is country’s premier national institute for agricultural research, education and extension. It has served the cause of science and society with distinction through first rate research, generation of appropriate technologies and development of quality human resource. In fact, the Green Revolution that has sustained the agricultural economy of the country for nearly five decades was born in the fields of IARI and its graduates constitute the core of the human resource deployed in India’s agricultural research and education.

Originally established at Pusa (Bihar) in 1905, the Indian Agricultural Research

Institute (IARI) started functioning from New Delhi since 1936, when it was shifted to its present site after a major earthquake damaged the Institute’s building at Pusa. Ever since its inception, the Institute has generated technologies and processes of relevance to improve production & productivity in Indian agriculture. In keeping with the national mandate and to make the country self-sufficient in agriculture, these technologies and processes were passed on to the farmers for effective adoption. The benefits that accrued to the nation are estimated to the tune of several trillions worth of rupees, besides the pride brought to the nation through self sufficiency

in food. Achieving nutritional security, efficiency in natural resource management, enhancing profitability from agriculture, technology commercialization and international trade are currently the key areas of concern in Indian agriculture, which have been integrated in the institute’s programmes.

Flagship of India’s agriculture research and education, the institute over the past more than 100 years had responded most dynamically to the needs, challenges and opportunities of Indian agriculture and adjusted its mandate, plans and programmes accordingly. During the fifties, the advancement of scientific disciplines constituted the core programme and provided the base for its expansion in the

1960’s and 1970’s in all its three interactive areas namely, research, education and extension, which played a key role in transforming Indian agriculture. Besides basic research, applied and commodity research gained great importance resulting in the development of several popular high yielding varieties of almost all major crops their production and associated management technologies, which brought about an unprecedented increase in the national food and agricultural production. The perspective plan sets IARI’s path of scientific research, technology development and extension and human resource development leading to the realization of new paradigms for achieving the congruence among enhanced


productivity, sustainability, ecological and environmental security and socio-economic equity.

Having been granted by the University Grant Commission (UGC) the status of “Deemed to be University” in 1958, IARI is also the leading Post Graduate School in agricultural sciences in the country. The forward looking academic environment at the Institute attracts the most talented students available for agricultural sciences in the country.

The Board of Management headed by the Director as its chairman, is served by four councils namely, Research Advisory Committee, Academic Council, Extension Council and Executive Council, which provide the overall management directions. The institute has a strength of more than 400 scientists, who are

supported by about 600 technical, 400 administrative and over 1000 supporting staff. The organizational set up of the Institute is presented below.

The • vision of the Institute is science led sustainable agriculture for attaining food, nutrition and livelihood security.

The • mission of the Institute is excellence in science, technological innovation and human resource development for enhancing agricultural productivity.

To accomplish its mission, •the Institute is focusing on the following strategic areas:

Enhancing the productivity and •quality of field and horticultural crops for food and nutritional security

Strengthening the basic •

and strategic research for development of cutting edge technologies for meeting the future challenges

Enhancing crop production •through conservation and management of natural resources

Enhancing the resilience of crop •production systems to climate change

Post-harvest management •and value addition to crop commodities for enhancing profitability

Bio-security and plant health •management

Development of globally •competitive human resources and capacity building of stakeholders

Enhancing the institutional •reach through effective linkages



& technology dissemination for higher profitability and improved livelihood

The Institute is moving upstream with an increased thrust on strategic and basic research for enriching the stream of scientific knowledge, technology generation of cutting edge technology and product development, which would also enhance the nation’s competitiveness in this age of scientific revolution. IARI has strengthened its research in the areas of molecular biology and biotechnology, agrochemicals and nanoformulations, precision and conservation agriculture, remote sensing and simulation modelling for adaptation to climate change, waste water & soil remediations and biofuels. In crop improvement strategies include exploitation of heterosis and development of hybrids, MAB and genetic engineering, new plant types combining better photosynthetic efficiency, high biomass production with high harvest index, identification of genes for resistance/tolerance to biotic and abiotic stresses, allele mining and creation of pre-breeding stocks combining multiple resistances and other desirable attributes.

Basic and strategic researches have also been strengthened in the areas of efficient resource management, GIS, remote sensing, and crop modelling to generate new concepts, tools and methodologies based on systems approach. Agronomic research addressing to the needs and opportunities of small farmers are being undertaken through the development of new cropping systems and crop diversification modules consistent with sustainable use of land, water and other natural and purchased production

resources. Basic research in nutrient management, soil-plant-water relations and kinetics leading to the development of integrated plant-soil-water-nutrient management systems are given high priority. The Institute provides leadership in the emerging areas of environmental sciences, impact, mitigation and adaptation to climate change, impact of CO

2 enrichment on crop

productivity, methane emission from rice fields and approaches for minimizing emission of greenhouse gases. The institute also has a leading programme on policy research on evaluation of agro-biodiversity, farmers and plant breeders’ rights, intellectual property rights and bio-safety issues. Programme, mission, and centres of excellence modes are being adopted to ensure inter-disciplinary as well as inter-institutional, excellence and efficiency in research.

The various programmes and projects of the institute are primarily funded by the Indian Council of Agricultural Research (Department of Agricultural Research and Education, Min. of Agric., GOI) and supplemented through external funding by other Governmental / International / Inter-Governmental agencies and also through the consultancy and contract research project services.

infra-StruCtural faCilitieS

To impart the diverse research need, the institute has developed the following infrastructural facilities at its headquarter and its regional stations:

i) farms

Located in an area of 500 ha, IARI has a cultivable farm area of 280 ha. Nearly 85 per cent of the total area is irrigated and the rest is available for rainfed / dry land research of different

crops. In addition, the Regional Stations of IARI, located across the country, have an area of 218 hectares of experimental farms.

ii) laboratories

Apart from the divisional laboratory facilities, catering to the needs of the respective disciplines, the Institute takes pride in having developed sophisticated specialized laboratories to undertake research in different areas of agricultural sciences.

nuClear reSearCh laBoratory

The Nuclear Research Laboratory was established as a national facility in 1969 for peaceful application of nuclear research in agriculture. Since then it has surged ahead in the pursuit of science through in inter disciplinary and inter/intra institutional collaborative research to address the challenges in natural resource management through application of nuclear approaches and allied instrumentation techniques. This laboratory is equipped with sophisticated equipment like Electron Microscope, NMR, X-ray Diffraction, HPLC, etc.

B. water technology Centre

The Institute was the first to establish a Water Technology Centre in 1970 for conducting research on all aspects dealing with water science & technology in relation to agriculture. The laboratory is equipped to design appropriate structures for farm irrigation, water conveyance and control, develop suitable techniques for use of saline water for irrigation, computer-based procedure for calculation of water balance in crop root zone, conduct studies on water harvesting, irrigation management and agricultural land drainage and



Dr. Hari Shankar Gupta, Director, IARI, New Delhi, received his Ph.D. from IIT, Kharagpur in 1981 and did his Post doctoral research at University of Nottingham, UK and Washington State University, Pullman, USA. Dr. Gupta served the ICAR in various capacities since 1978, including the positions of Joint Director, ICAR Research Complex for NEH Region, Barapani and Director, VPKS, Almora before taking over as Director, IARI in 2009. An accomplished plant breeder, he has released 36 varieties of field crops for the Himalayan states. His contribution in molecular plant breeding led to the development of country’s first short duration quality protein maize

containing 30% higher lysine and 40% more tryptophan than the normal maize. He has led/leading several research program touching a application of molecular technology. Dr. Gupta is recipient of several individual honors and team awards and is a Fellow of National Academy of Agricultural Science.

Biotech news (BTn): What are the three most important research findings at iAri during the last five years?

Deployment of Marker Assisted Selection for Incorporating Resistance against major diseases

rice : improved pusa Basmati-1 : IARI in collaboration with NRCPB developed Pusa 1460, the improved Pusa Basmati-1, through marker assisted backcross breeding, incorporating Xa 13 and Xa 21 genes for resistance against bacterial leaf blight. Further, following a similar approach, Pi54, the gene for blast resistance and qSHB, QTL for sheath blight were also introgressed in Pusa 1460. Similarly, the genes for resistance were also incorporated in the parental lines of PRH-10, the first aromatic rice hybrid.

Wheat : The leaf rust is one of the most important diseases in wheat, which affects its productivity significantly in the main wheat growing regions of NWPZ and NEPZ. In order to build an effective system of resistance, genes for rust resistance were identified from alien sources (Aegilops speltoides, A. umbellulatum, Agropyron elongatum), tagged and incorporated in different wheat backgrounds. The molecular breeding programme of

IARI for wheat has the distinction of leading the team, which has not only mapped and tagged markers for most number of genes such as, Lr9, Lr19, Lr24, Lr25, Lr28, Lr32 and Lr48, but also made concerted efforts in pyramiding Lr 24, Lr 28 and Lr 9 in two most popular wheat varieties HD 2329 and PBW 343. These genes and their markers have been validated in the Australian, European and Indian wheat breeding programmes for rust resistance.

Viral diagnostics, genomics and Transgenics: Maximum number of viral diseases on field and horticultural crops are caused by aphid transmitted Potyviruses and whitefly transmitted Begomoviruses. Besides, thrips transmitted Tospo- and Ilar-viruses are now emerging as serious pathogens. These viruses have wide host range and in recent years they have spread to new hosts. To manage the major plant pathogenic viruses, immuno- and nucleo- based diagnosic reagents and protocols have been developed to facilitate detection in seeds and tissue culture raised vegetative propagules.

This has led to the identification of etiological agents of new diseases like sunflower necrosis, tomato bud blight, cotton leaf curl and potato

apical leaf curl.

Genome of these viruses have been sequenced and characterized, thus providing better understanding of diversity of viruses and identification of new genes which have been employed in developing virus resistant transgenic plants (VRTPs).

BTn : Which are the five best publications during the last three years?

Agarwal, P; Arora, R; Ray, S; Singh, AK; Singh, VP; Takatsuji, H; Kapoor, S; Tyagi, AK. Genome-wide identification of C2H2 zinc-finger gene family in rice and their phylogeny and expression analysis. Plant Molecular Biology, 65 (4): 467-485.

Gopalakrishnan, S; Sharma, RK; Ra-jkumar, KA; Joseph, M; Singh, VP; Singh, AK; Bhat, KV; Singh, NK; Mohapatra, TM. Integrating marker assisted background analysis with foreground selection for identifica-tion of superior bacterial blight re-sistant recombinants in Basmati rice. Plant Breeding, 127 (2): 131-139.

Amarawathi, y; Singh, R; Singh, AK; Singh, VP; Mohapatra, T; Sharma, TR; Singh, NK. Mapping of quantitative trait loci for basmati quality traits in rice (Oryza sativa L.). Molecular Breeding, 21 (1): 49-65.



to analyze physiological basis of drought resistance in crops.

agroMet adviSory ServiCeS

The Institute established a Weather based agro-advisory service for issuing timely and need-based crop management practices to the farmers of Delhi and NCR. Weather information along with crop wise weather-based agro-advisories is passed to the progressive farmers on real time basis through print, electronic media and speed-post. Bi-weekly agromet advisories bulletins were prepared in Hindi as well as in English and published in the newspapers (Dainik Jagran and Haribhoomi) and uploaded at IARI website (http://www.iari.res.in) and being sent through e-mail

to IMD for their website for district agro-advisory and also for preparing national agro-advisory bulletin.

d. national research Centre on Plant Biotechnology (A sister institute located in the IARI premises)

The National Research Centre on Plant Biotechnology (NRCPB) was established in 1985 to provide leadership in plant biotechnology research in the country. It has highly sophisticated equipments used for plant biotechnology research. NRCPB has advanced laboratories for work on molecular biology, recombinant DNA, cloning and sequencing of genes, genome analyses, tissue culture, plant transformation and somatic hybridization.

IARI in collaboration with NRCPB is involved in the Indian initiative for the rice, tomato and pigeon pea genome sequencing (IIRGS) under International genome sequencing project (IRGSP) as well as in the development of transgenic plant varieties.

e. national Phytotron facility

IARI established the National Phytotron Facility (NPF) in 1997 with the assistance of the Department of Science and Technology, Indian Council of Agricultural Research, FAO and United Nations Development Programme. NPF provides a battery of plant growth chambers with environmental controls which are proving extremely useful in


Mangrauthia, SK; Singh, P; Praveen, S. Genomics of Helper Component Proteinase Reveals Effective Strategy for Papaya Ringspot Virus Resis-tance. Molecular Biotechnology, 44 (1): 22-29.

Basavaraj, S.H., Singh, V.K., Singh, Atul, Singh, Ashutosh Singh, Anita Singh, Sheel yadav, Ranjith K Ellur, Devinder Singh, Gopala Krishnan, S., Nagarajan, M., Mohapatra, T., Prabhu, K.V. and Singh, A.K. 2010. Marker-assisted improvement of bacterial blight resistance in parental lines of Pusa RH10, a superfine grain aromatic rice hybrid. Molecular Breeding, DOI 10.1007/S11032-010-9407-3.

G. K. Chikkappa, N. K. Tyagi, K. Venkatesh, M. Ashish, K. V. Prabhu, T. Mohapatra and A. K. Singh. 2011. Analysis of transgene(s) (psy+crtI) inheritance and its stability over generations in the genetic background of indica rice cultivar Swarna. J. Plant Biochem. Biotechnolgy. DOI

10.1007/s13562-010-0021-6.

BTn : how is iAri promoting innovation?

The Institute has an Institute Technology Management Unit (ITMU), which is also supported by a Business Promotion & Development Unit (BPDU) to interface with the industry partners and end-users. It also promotes entrepreneurship through the technologies developed by the institute providing technical support and mentoring the business incubatees. The technological interventions/innovations developed by IARI are being commercialized through non-exclusive licensing director or via NRDC.

BTn : Which technologies have been transferred to industry/user agencies recently?

RNAi gene construct against ToLCV virus (M/s Bejo Sheetal Seeds Pvt. Ltd.)

Transgenic Tomato Technology

(M/s. Syntenta India Ltd.)

Event for TOSPO resistance in To-mato (M/s Advanta India Ltd.)

Plant Virus detection kit, (M/s Chro-mus Biotech)

Truncated rep gene construct devel-oped using conserved viral sequence in the replicase gene of tomato leaf curl virus for plant transformation (M/s. Beejo Sheetal Seeds Pvt.Ltd. )

BTn : What measures is iAri taking to attract first-rate human resources?

IARI attracts the best scientific manpower by providing a scientifically enabling environment, state of the art research facilities and ample opportunity to interact with the international scientific experts through visits, collaborations, exchange, training etc. The academically vibrant environment also provides additional attraction of Post-Graduate teaching and research guidance to its faculty.



developing our understanding of complicated interactions of physiochemical environments and living systems, specially the plants and their pathogens. This is a unique national facility to study the life responses of plants and pests for biotic as well as abiotic stresses under controlled conditions and the possible impact of climate change and greenhouse gases. The facility is also serving the purpose of transgenic research in plants by numerous users from across the country.

f. advanced Centre for Plant virology

Advanced Centre for Plant Virology (ACPV) is identified as the lead centre for plant virology not only in the country, but also in the South Asian Region. It plays an important role in identification of viruses, supplying diagnostic reagents and

providing training. ACPV is well equipped with facilities to work on electron-microscopy, purification, production of polyclonal and monoclonal antibodies, cloning of viral genomes, use of radioactive and non-radioactive probes, electrophoresis, sequencing, use of PCR in disease diagnosis, tissue culture and plant transformations.

g. Pesticide referral laboratory

Pesticide Referral Laboratory (PRL) is set up with the financial assistance of the World Bank under Team of Excellence (National Agricultural Technology Projects) programme. PRL conforms to Good Laboratory Practices (GAP) and is equipped with state-of the-art equipments such as GCMS, GC, HPLC, and UV-VIS spectrophotometer. PRL is accredited to National Accreditation Board for testing in Calibration Laboratories (NABL) as per the

ISO/IEC/17025.

h. Microbial and insect Conservation facilities

IARI recognises the importance of conserving the diversity of biological forms and their importance in maintaining the ecological balance. Hence, it established Herbarium Cryptogamae Indae Orientalis in 1905. Since then the Institute has also developed a National Culture Collection of fungi, which has more than 30,000 live cultures, a National Insect Collection, which has 0.5 million insect collections, a National Nematodes Collection of India and a National Facility on Blue Green Algae.

i. quality Seed facility

With a Japanese Grant Aid Project IARI established state-of the-art facilities for seed research, processing and storage,

Pusa 1608 : Pusa 1460+blast (pi54) + SB (qSHB)


with necessary infrastructure development and sophisticated equipment at its Regional Station, Karnal and New Delhi. The facilities are utilized for advanced seed research as well as capacity building.

j. Centre of Protected Cultivation technology

Centre of Protected Cultivation Technology (CPCT), covering an area of about 10 ha, is equipped with semi climate controlled green houses, zero energy naturally ventilated green houses, insect proof net houses, shade net houses and other temporary structures, different types of temperature, humidity and fertigation controlled glass and plastic houses to meet the research and technology development needs of protected agriculture, specially for horticulture, vegetable seed production and modern nursery

raising. CPCT is not only a national facility for human resource development but also provides research support.

k. unit of Simulation and information

The Unit of Simulation and Informatics was established with the objectives to generate, collate information and data to construct and validate reliable computer simulation models on crop growth, input management, pest dynamics and yield prediction; provide internet connectivity, maintain dynamic web site, farmers’ advisory service, tele-conferencing and e-mail services to IARI; and to create database on pedigree management of wheat, rice, chickpea and mungbean; develop appropriate statistical packages for enabling field data analysis, matrix comparison and variability analysis as applicable

to Marker Assisted Selection and Molecular Biology.

l. other laboratories

The Institute has also developed specialized laboratories and field-based facilities on various aspects of crop improvement, plant protection, basic science and natural resource management in the Divisions of Microbiology, Environmental Sciences, Entomology, Nematology, Biochemistry, Plant Physiology, Pathology and Post-Harvest Technology.

l. ztM and BPd unit

A Zonal Technology Management and Business Planning and Development Unit has been established recently at the institute to serve as knowledge pool and support the intellectual property protection and technology dissemination and transfer activities. One of the activities of the unit is to foster institute –industry partnerships and promote its technologies for mutual benefit.

iii) Auditoria, Conference Halls, Training facilities, Guest houses/Scientist Homes,

hostel and residential complex

IARI is a vast campus comprising a large number laboratories across the 20 Divisions, 4 multi-disciplinary centres, 6 student hostels, 4 guest houses, administrative block, library, conference halls and auditoria for meeting the research and academic needs of the Institute. In addition, there are about 1800 staff quarters providing accommodation in the campus to different categories.

iv) Sophisticated instruments/ equipments

The Institute is well equipped with sophisticated instrumentation facilities such


Page 84-86


as Gas Liquid Chromatograph, GCMS, LCMS, HPLCs , Infra-red Thermometer, Leaf Canopy Analyser, Rhizoctron, Pressure Plate and Membrane Apparatus, Atomic X-Ray Film Developer, NMR, Hand Held Spectro-radiometer, Atomic Absorption Spectrophotometer, UV-VIS Spectrophotometer, Gel Documentation Units, Environmental Shaker, CO

2

Incubator, Biofermentator, High Performance Ion Chromatograph DX, Leaf Chamber Fluorometer, Scanning Electron Microscopes, TEM, Gamma Irradiation Chamber, , Auto Analyser (Micro-processor controlled), Petro logical microscope, Portable in-situ Water Quality Multiparameter Monitoring System, Plant Canopy Analyser/Imager, Spectro-radiometer, DNA Micro-Array Facilities, PCR and Real Time PCR, Root Scanner, Laboratory Flour Mill, Alveoconsistograph and many more.

v) library facilities

One of the largest inventories on agricultural sciences in the South Asia, IARI library today houses over 6.5 lacs highly specialized publications on agriculture, and related sciences consisting of books, monographs, reference materials, journals advances and annual reviews, abstracting and indexing journals, translated periodicals, statistical and data publications, bulletins, reports, pamphlets, reprints, newsclippings, posts graduate thesis of IARI and ICAR research theses. It has the status of National Agricultural Library of India, and is regarded as one of the 10 best agro-biological libraries of the world. Presently the library has on its role 2500 users consisting of Scientists, PG Students, and Technical staff. The library also serves 2000 outside

research scholars in their literature search through reference and reprographic services. As the nodal centre of the consortium for e-Resources in Agriculture (CeRA), it provides access to information, especially to journals online to the National Agricultural Research System.

A compulsory course on Agriculture Information System is offered to the students of the Post Graduate School by the IARI Library. It also imparts training to the Library Professionals of 120 ICAR Institute / SAUs.The library has created the database for the bound journals post 1975, generated the bar codes for online issues/reprints and created database for more than 1.25 lacs reference records of BIA. The library has a full fledged CD-ROM Work Station.

vi) regional research Stations

In order to meet its national mandate and to complement and strengthen its research and extension activities, IARI has set up eight Regional Research Stations located at Pusa (Bihar); Karnal (Haryana), Indore (M.P), Shimla (H.P.), Pune (M.S.), Wellington (T.N.) and Kalimpong (W.B.) In addition, two off-season nurseries at Aduthurai (T.N.) and Dharwad (Karnataka) are also used for advancing breeding generations in rice and pulses, respectively, and to strengthen shuttle breeding programmes of the Institute.

Major ContriButionS of iari in agriCultural BioteChnology reSearCh

The institute is actively involved •in biotechnological researches across the disciplines in close collaboration with its sister organization “National Research Centre for Plant Biotechnology” and has made the following

achievements:

IARI in collaboration with •NRCPB developed Pusa 1460, the improved Pusa Basmati-1, through marker assisted backcross breeding, incorporating Xa 13 and Xa 21 genes for resistance against bacterial leaf blight. Further, following a similar approach, Pi54, the gene for blast resistance and qSHB, QTL for sheath blight were also introgressed in Pusa 1460. Similarly, the genes for resistance were also incorporated in the parental lines of PRH-10, the first aromatic rice hybrid.

Wheat leaf rust resistance genes •mapped and tagged: A unique distinction has been achieved by IARI with the tagging and mapping of six leaf rust resistance genes (Lr genes) such as Lr9, Lr19, Lr24, Lr25, Lr28, Lr32 and Lr48 (Figure 1).

Five genes namely, SusHSP 23.3 •gene, HSP 90 gene, HSP 70 gene, TasHSP 17 gene, (isolated from C 306), and SOD gene (isolated from HDR 77 cultivar of Triticum aestivum L.) were identified for biotic/ abiotic stresses. Partial cDNAs of SOS pathway genes (SOS1, SOS2 and SOS3) involved in salt tolerance were cloned from salt tolerant wheat genotype, Kharchia 65.

For effective resistance against •stem rust Sr25, Sr26, Sr27, Sr36+pm6, Sr39, Sr40, Sr41, and Sr44 genes were incorporated either singly or in combination with Sr24 or Sr2 in the background of elite Indian bread wheat cultivars, which was also confirmed through molecular markers to combat the threat from the new stem rust pathotype Ug99 virulent on Sr31 and stripe rust genes (Yr10, Yr15, Yr16).

To avoid the use of grow-out test •



(GOT) for testing the genetic purity of hybrid seed (which requires one full season), a strategy based on the Rf-gene linked marker RM258 was developed for testing the genetic purity of the seed of aromatic rice hybrid Pusa RH10.

Biotechnological researches led •to the development of transgenic materials of various crops. At present transgenics of potato, cucumber and tomato for viral resistance and rice, brinjal transgenic for insect resistance are in different stages of development.

Abiotic stress regulated genes, •namely ABA receptor, SnRK2 kinase and MyB transcription factor were cloned from drought tolerant rice cultivar Nagina 22.

Gene constructs have been •developed for conferring resistance against tomato leaf curl (ToLCNDV-rep.), tomato mosaic (CMV-CP), soybean yMV (MyMIV-rep.) and bud necrosis in groundnut (GBNV-NP).

PCR-based detection kits have •been developed for citrus viruses and greening bacterium and the causal bacterium of pomegranate bacterial blight.

Transfer of viral resistance •into vegetables through genetic engineering: Virus resistant transgenic tomato varieties for leaf curl, bud blight and root knot nematode; papaya against ring spot and leaf curl; potato against PVy, and sunflower and groundnut against Tobacco streak virus (TSV), have been developed.

Full length sequences of phytase •and myo-inositol phosphate synthase (MIPS) genes involved in phytic acid metabolism were isolated and characterized by computational and expression

analysis for use in genetic engineering strategies to reduce phytate levels in soybean seeds.

Mapping downy mildew •resistance in maize : QTLs conferring resistance to sorghum downy mildew (SDM) and Rajasthan downy mildew (RDM), were mapped which resulted in the identification of three QTLs (one each on chromosomes 2, 3 and 6) for SDM resistance and two QTLs (one each on chromosomes 3 and 6) for RDM resistance. The significance of the major QTL on chromosome 6 (bin 6.05) that confers resistance to diverse DMs in tropical Asia, including SDM and RDM in India, was also verified.

Molecular typing of nationally •important pathogens and biocontrol agents has been done and PCR diagnostic kits developed for Fusarium oxysporum (FOC, Race 4) causing wilt of chickpea and Bipolaris sorokiniana causing spot blotch of wheat.

ELISA and PCR based •diagnostics are available for most viruses affecting crops. Among these, PCR based diagnostic kit developed for simultaneous detection of RNA and DNA viral pathogens affecting citrus can be exploited for indexing planting materials. The etiology of foorkey disease of large cardamom was unfolded and the virus was identified as Large Cardamom bushy dwarf virus (LCBDV).

For the first time, full genome •sequencing of important plant viruses like, Indian citrus ring spot virus (ICRSV) and Citrus yellow mosaic virus (CMBV), Banana streak virus (BSV) and Papaya ring spot virus (PRSV) was completed and annotated. Besides, small (S)

and medium (M) RNA segment of Groundnut bud necrosis virus (GBNV-mungbean isolate) and M-RNA segment of Watermelon bud necrosis virus (WBNV) were sequenced.

The major genes involved in •lipid biosynthesis pathway were isolated from Brassica juncea and subjected to in silico characterization. For soy oil quality improvement the microsomal omega-6-desaturase gene (fad 2-1) has been isolated from the developing seeds of soybean and characterized.

Antiviral proteins (AVPs) have •been isolated, purified and characterized from four non host plant sources (Chenopodium album, Celosia cristata, Amaranthus tricolor, Bougainvillea x buttiana) and found to impart resistance (localized, systemic) when applied prior to virus challenge. Genes encoding the AVPs/RIPs have also been isolated and characterized for developing transgenic crop plants.

Analyses of morphological, •genetic and functional diversity of cyanobacteria in diverse rice based ecologies of India, led to the development of a comprehensive database on novel genes/metabolites, molecular /biochemical markers and core collection of strains with agriculturally useful traits.

Novel metabolites /enzymes •from cyanobacteria generated first time reports on chitosanase and endoglucanase activity, their gene(s) and regulation in nitrogen-fixing cyanobacterial strains.

A large number of DNA •sequences, novel genes/alleles have been deposited in the NCBI database.



Courses and meetings around “The biology of disease paradigm using leukemia as

a focus” : Sudhir Krishna (NCBS, TIFR) Cecil Ross (SJMC) and Seema Nanda (TIFR) have initiated a series of courses and meetings in the last few years:

l The fundamental aim is to familiarize scientists in the early phase of their careers to the fundamental of human biology and disease by including teachers as medical faculty with specialization in pathology, hematology etc.

l Teaching in the dual setting of both research institutes and hospitals also provides a wider framework to define biomedical challenges

REPORT

Dr. Sudhir Krishna

over the last few years, there has been an impetus to expand the interactions between scientists engaged in basic biological research and physicians operating in an academic setting. Towards this end, faculty at NCBS and St. John’s Medical College have come together to develop a joint programme which spans research, teaching and infrastructure development.

New Initiatives

Unravelling the biology of disease

Sudhir Krishna MBBS, Ph.D is a Professor at the National Centre for Biological Sciences, TIFR, Bangalore. E-mail : [email protected]


We chose hematology as hematological research inclusive of discoveries on Leukemias have served as path breaking templates in biology and medicine. Examples include the identification of the Philadelphia chromosome and consequent development of targeted tyrosine kinase inhibitors, bone marrow stem cell transplants and the emergence of the leukemic stem cell paradigm.n 2009 Jan-March: Leukemia as

a disease paradigm for research students: 16 contact sessions: 60 % basic science, 30 % medical faculty, 10 % maths modelling.

n 2010 Aug: Meeting on hematological malignancies: Around 100-150 mix of around 1:1 physicians and scientists: 15 and 7 basic science and clinical talks respectively, location: NCBS, JNCSR and St. Johns Medical College (Supported by ICTS).

n 2011 Oct-Nov: Biology of disease with Leukemia as focus: 20 students (inclusive of post-doctoral fellows, medical post-graduates and young research investigators,: 2 weeks, first week single module and then all combined: combination of hematopathology, clinical case presentations, bio-informatics, proteomics and flow cytometry. This culminated in an international hematology meeting (Supported by InStem) to coincide with the EHA initiative in Bangalore.

develoPMent of the reSearCh PrograMMe and infraStruCture:

The initial focus of the research activities is built aroundl Exploring the basic biology of

cancer stem like cells in human cervical cancers and Chronic Myeloid Leukemia (CML). The initial programme has centred around an analysis of novel RNA expression in CML. The hematology programme is also

supported by already ongoing effort on exploring drug targets in multiple myeloma cells.

l Integrating bio-informatics into experimental research in a hospital setting to lay the foundation for a bio-informatics in disease programe

l Facilitating a ear/tracheal stem cell programme in collaboration with ENT surgeons. The initial attempts are using bone marrow mesenchymal cells under the broader bandwith of the focus on hematological activity. These cells can be used for a potential transplant programme, development of novel drugs, toxicity testing etc.

infrastructure development and working principles of the collaborative researchl The infrastructural component

of the programme is designed to establish all the facilities in close collaboration with the various hospital and college medical departments such as cytogenetics, pathology, hematology and medicine, central laboratories and clinical pathology etc.

l The initial infrastructure has included setting up tissue culture laboratories and FISH and is rapidly being expanded to include molecular biology and flow cytometry facilities. The next phase would involve expanding the animal facility, high through put and genomic capacity.

l The research programme is closely linked with the expansion of diagnostic services that include molecular biology, flow cytometry etc. This is being undertaken by familiarizing the medical faculty through the research programme and specific workshops, courses and possible exchange visits.

l We visualize the emergence of a “clinical centre of excellence in flow cytometry and microscopy” analogous to the NCBS imaging facility. The future growth of

both facilities will be achieved in a complementary and synergistic manner with exchange of personel, joint research, courses and technology development.

l The core programme has been developed by faculty of NCBS and St. John’s Medical College. We visualize close interactions with hospitals such Kidwai Memorial Insttute of Oncology, CMC Vellore and research centres such as IISc, InStem etc. In addition, new initiative such as CCAMP will offer opportunities for co-development of programmes and facilities.

Core teaM

The team includes physicians, surgeons and basic research scientists. The initial grant was submitted by Sudhir Krishna (NCBS), Cecil Ross (SJMC), Seema Nanda (TIFR) and Elizabeth Vallikad (SJMC). The resubmission was joined by Ravi Nayar (SJMC), R. Sowdhamini (NCBS), Amit Mandal (SJMC), H. Krishnamurthy (NCBS), Karuna Ramesh (SJMC) and Das Palokedi (InStem). Dr. Sweta Srivastav, a research scientist already has joined in a senior capacity in the programme.

SuMMary:

We hope that the NCBS-St. John’s initiative will serve tol nucleate both basic and

translational research initially in cancer biology followed by other areas of bio-medical research

l expand the efforts to provide training in translational efforts in neurobiology, human genetics, bio-informatics and modelling, regenerative medicine etc

l Offer a platform to develop new inter-disciplinary curriculae

l Create an incubator and micro-environment for novel efforts that might span vaccine design, infectious diseases etc.

New Initiatives

Unravelling the Biology of Disease


Cancer screening is the detection of cancer in a population before

appearance of symptoms. It is only feasible if the cancer type is a definite public health hazard; there should also be screen detectable early lesion which can be effectively treated with low cost. This may involve single or many tests, like blood or urine & other tests, or medical imaging. The test has to be simple, safe, precise and validated with high sensitivity and specificity. India still lives in its villages, so any such screening to be successful has to be so in rural areas where people suffer due to inaccessibility, illiteracy, ignorance, poverty and many taboos. Un-fortunately, in view of competing

priorities and economic conditions, the introduction of screening of cancer in India represents a greater challenge than it has been in more developed countries.

In India cancer screening will necessarily mean screening of cervical, breast, and oral cancer. As per WHO statistics, a staggering three and a half lakh people, mostly

women, get these diseases every year among about 12 lakh total cancer cases. Other cancers worth mentioning in matter of screening are colorectal, prostate and lung.

First cancer screening reported from India is by a group of doctors from Maulana Azad College of Delhi in 1967, about two decades after the same was first

REPORT

Chinmoy K Bose MD, Ph.D is a Consultant (Gynaecological Oncology Section) at Netaji Subhash Chandra Bose Cancer Research Institute, 16A, Park Lane, Park Street, Kolkata 700 016. E-mail : [email protected]

Chinmoy K Bose

India still lives in its villages. For cancer screening to be called successful it has to succeed in rural areas where people often suffer due to inaccessibility, illiteracy, ignorance, poverty and many taboos.

Cancer screening in rural areas

Nipping it in the bud

R SankaranarayananHans Hinselmann


reported in world literature. In 1940, the incidence of invasive cervical cancer in the United States was 32.6 per 100000 women, which is similar to that currently seen in many developing countries including India. But, by 1984 it came down to 8.3 per 100 000 due cytology screening USA whereas the incidence has fallen only to 27 per 100 000 by 2008 in India, which is seemingly due some socioeconomic change rather than due to screening. Though early diagnosis of breast cancer started in thirties, screening was reported in late sixties as also the screening of oral cancer.

Biotechnology always remained in the core of progress. In the 1950s Greek doctor Papanicolaou developed (Pap) smear―a simple test of staining technique in which a sample of cervical cells recovered from cervix by Ayre’s spatula (Ernest J.Ayre) or “cytobrush” is examined under a microscope to detect cellular abnormalities.

The National Cancer Control Programme (NCCP) of India was initiated in the year 1975. However, the current allocation is not expected to provide an adequate

cover. The ICMR has initiated some projects which only fall short of huge requirement.

Commendable work is done by one Indian, Dr R Sankaranarayanan in WHO. He found that organized cervical cytology screening programs are not feasible and has shown limited success in many developing countries due to cost and want of man power. He established visual inspection of the cervix after application of 3-4% acetic acid (VIA) which along with colposcope (by a Nazi physician, Hans Hinselmann) as triage is replacing cytology. However, even introduction of this method hasn’t brought about any change, especially in mortality in developing countries.

Integration of screening activities, with primary health services which seems to have the potential to replicate most of these service delivery conditions in routine programs, has remained an unmet need. Hence, there has only been less than 1% coverage in cervical cancer screening mainly by camp approach with no sign of any practical coverage in sight in

presently allocated funds.

There are other inherent problems also in screening process-es. Data from two recent large trials do not suggest a beneficial effect of screening by breast self-examination (BSE) whereas there is evidence for harming. There were no randomised trials of clinical breast examination thus, BSE cannot be recommended. There is no well concerted effort in case of oral cancer also.

However, the role of early detection and screening in such cancer cannot be overemphasized. Though DBT has validated many such screening procedures in field studies in rural areas, they have insisted on finding new, simple and perceptible technology.

While there are about 90 on-going investigator driven projects adopting various intervention strategies, the focus continues to be towards early diagnostic and prognostic markers. Emphasis is on molecular diagnostics like DNA methylation profile, gene expression signatures & proteomic profiling of breast cancer, low-cost genetic vaccines, markers for cervical and oral cancers and stem cell biology. There has been a major development in human Papilloma Virus diagnosis using “Papilloma chip” to give maximum protection against oncogenic strains. Technology transfer of rHPV-16 L1 for VLP preparation and purification to produce cheaper vaccine is in progress.

Attempts to make rural cancer screening realistic is very much in the agenda of DBT by not only finding out ways to extract maximum from existing technologies but also to cause a paradigm shift in technology itself making this huge onus simpler, safer and cost-effective.

Cancer screening in rural areas

Nipping it in the bud

A cancer screen camp in progress


As part of the Silver Jubilee celebrations of the DBT Centre for DNA

Fingerprinting and Diagnostics (CDFD) Hyderabad, organized a series of distinguished lectures in the month of February 2012. The theme of these lectures was selected keeping the target audience in mind, and were given wide publicity. The response was overwhelming. Apart from the CDFD scholars and scientists, a large number of college students, faculty from several institutions and invitees from the press/media attended the lectures, all of which were followed by an

extensive question-answer session.

In his lecture, Prof. Martin Killias, Director, Institute of Criminology at the University of Zurich, Switzerland, highlighted several significant issues related to the need of conducting scientific studies on crime for an efficient criminal justice delivery system and the importance of data sharing at a global level.

Prof. Junjie Chen, from University of Texas, MD Anderson Cancer Centre, USA spoke about the components involved in DNA damage pathways and how research

in this area has helped in better understanding of the mechanisms underlying genomic instability, tumorigenesis and aging process.

Prof. Toru Shimada of the University of Tokyo, Japan threw light on the genetic and genomic studies on the food habits of the silkworms. He enlightened the audience on the genetics of mechanisms that are involved in male sex pheromone preference diversification.

Ankkur goel Ph.D.

Staff Scientist, [email protected]

UPDATE

Silver Jubilee of DBT

Prof. Martin Killias delivering his lecture ‘Experimental research in criminology and criminal research’

Prof. Junjie Chen being felicitated after his lecture “DNA damage signalling and DNA repair”

leCture SerieS at Cdfd, hyderaBad


The National Institute of Plant Genome Research, New Delhi, an autonomous

institution of the DBT, celebrated the Silver Jubilee of DBT’s establishment by organizing debate and poster competitions on February 17 & 21, 2012 at New Delhi. The debate competition was held on February 17, 2012 where the topic was “To benefit from technology, knowledge is the necessity”. The debate competition evoked a good response and highlighted current and future concerns in science, particularly regarding the ways and means of application of science & technology.

Students at B.Sc. level from various colleges of the University of Delhi were invited who exchanged their views in ‘favour’ and ‘against’ the topic. Twenty four students from eleven colleges participated in the competition. Out of those, five best speakers were selected for awards.

On February 21, 2012, the function started with a keynote address by Prof. Akhilesh K. Tyagi, Director, NIPGR, who shared his experiences with DBT and appreciated DBT’s contributions towards the growth of biological sciences in India. Prof. M.K. Bhan, Secretary, DBT and Chairman of NIPGR Governing Body in

his address shared the significant contributions and efforts made by DBT which have been considered significant in the service of the nation. He elaborated on new opportunities available for discovery, innovation and translation, and reiterated DBT’s commitment towards agriculture, animal productivity, human health, environmental security and industrial growth. The function included an exhibit of achievements and future plans of DBT.

Five best speakers from debate competition on February 17th made their presentations. A poster competition was also

organized where in nineteen posters were presented by NIPGR researchers/students on two themes, namely “Bioeconomy” and “Biopiracy”. This poster session was followed by lectures of three eminent scientists covering a broad range of scientific and social themes.

The first lecture was delivered by Dr. Amit Ghosh, Emeritus Scientist, National Institute of Cholera & Enteric Diseases, Kolkata on “Creativity: Enhancing it”. Connecting several forms of reference from art and science for creativity, he quoted


deBate and PoSter CoMPetition PreCede leCtureS at niPgr, delhi

UPDATE


Einstein who said “imagination is more important than knowledge”. The second lecture was delivered by noted social worker and Padma Shri, Dr. Anil P. Joshi of Himalayan Environmental Studies & Conservation Organization, Uttarakhand. Speaking on the topic “Common mistakes”, Dr. Joshi laid emphasis on environmental sustainability and called for the use of Gross Environmental Productivity (GEP) in place of Gross Domestic Productivity (GDP) to reflect true “growth” of the nation. The third lecture was delivered by Professor Usha Vijayraghavan, Indian Institute of Science, Bangalore who spoke on the topic “Building a flower : Learning the ABCs of flowering regulators in model plants”. The lecture illustrated the intricacies involved in flower development beyond ABC model and its utility, not only to produce beautiful flowers but also more seed of food crops. All the lectures

were thoroughly enjoyed and appreciated by the audience as it was a good opportunity for an exposure to scientific temper and social relevance.

At the end of the day, Institutional Committees, constituted to judge and recommend the “best speakers” (in order

of merit) from the debate competition and “best posters” (one on each theme) from the poster competition, selected the winners. They were conferred with the Winner’s Certificates and token cash prizes, and all the participants of debate competition were given the Certificate of Participation by Dr. (Mrs.) Manju Sharma, former Secretary, DBT, who also expressed her views on the spectacular growth of DBT since its inception and admired the progress of NIPGR as well.

On the whole, the two one-day events were highly successful as young as well as

experienced minds shared the joy of science. In retrospect, it was a great event, full of knowledge and entertainment, truly befitting the celebrations of the Silver Jubilee of the establishment of DBT.

Akhilesh TyagiDirector, NIPGR

[email protected]


Functions to celebrate the silver jubilee of the Department of Biotechnology

were held at the National Institute of Immunology during the month of February. A public lecture was organized for school children for increasing awareness and interest in science at the grassroots level. The lecture was delivered by Dr S. V. Eswaran, Head, Chemistry Department and Dean, (Academics), St. Stephen’s College, New Delhi on an interesting topic of “Scientific Wanderings" on February 23, 2012. Students from Kendriya Vidyalayas of Delhi were invited to attend the lecture. Laboratory visits for the students were also organized to sensitize them to laboratory life in biological sciences.

Poster competition was held on February 28, 2012, the National Science Day to continue the celebrations. Ph.D. students

from the National Institute of Immunology were invited to showcase their work in the form of posters so that all students and faculty can discuss about the merits of the projects being pursued by the students. A total of 27 students presented their research work during the competition. Posters were evaluated by external judges who were scientists of repute from neighboring institutions. This event was celebrated with much enthusiasm by the students and the faculty. Five students were selected for the presentation of their work and given cash prizes.

Chandrima shahaDirector, NII

[email protected]


PuBliC leCture and PoSter CoMPetition at nii, new delhi

Dr. S. V. Eswaran, St. Stephen’s College addressing student’s queries

Poster Competition at NII on February 28, 2012

UPDATE


The department organized a road show on small business innovation research

initiative (SBIRI) in Kochi on 17th February, 2012 to reach out to bio-entrepreneurs in the peninsular zone of the country. The programme was coordinated by BCIl, SBIRI Management Agency.

event highlightS

The first session of the event was scheduled to create awareness among the Indian biotech industries on the availability of governmental funding support, effective grant writing, R & D recognitions, patenting innovations, infrastructure support available in their vicinity in terms of incubators and biotech parks and the prospects of

instrumentation industry in India. Eminent speakers in the respective locations delivered talk addressing these concerns. In the second session, there were interactions with the SBIRI applicants. The beneficiaries elaborated on the support they had received and suggested few improvements in the process. The unsuccessful applicants received clarifications on their non-recommendations from the SBIRI team. There were also queries on the process of protecting innovations, advantages of R& D recognitions and academic collaborations. Some of the successful applicants also displayed their product/process developed through SBIRI support through posters/exhibits at these venues.

PartiCiPation

The industry participation in the show was overwhelming. Apart from industry a large proportion of academicians, public-sector research scientists, research scholars and students of life sciences disciplines attended the event enthusiastically.

outCoMe

Earlier in the year similar shows were organized in Kolkata and Mumbai. The SBIRI call for proposal that followed each road-show witnessed a number of applications from companies located in the respective locations. This merits the need for organization of these events. The department is planning to organize more of these in other locations in this year.

UPDATE

SIBRI Road Show at Kochi

suchita ninawe [email protected] Kalaivani ganesan | M.s. shashi Kumar

[email protected] [email protected]


understanding of microbial processes at molecular level and controlled field trials are required to determine the cost-benefits and efficacy of these products under culture system.

future StrategieS:

Ample scope for application of biotechnology lies in environmental management of fast growing aquaculture sector. It can contribute to better fish health management through the development of accurate and sensitive disease diagnostic tools and vaccines. Genomic tools connected with genetic improvement of aquatic organisms can provide valuable

help in developing fast-growing and healthy strains of cultured species tolerant to various biotic and abiotic stresses, thus strengthening the adaptive capacity and resilience of the sector against the ever-threatening issue of climate change. Bioprospecting of genes from extremophilic aquatic organisms inhabiting in severe environmental conditions such as high pressure, temperature and salinity can lead to development of unexploited products useful for the mankind. Basic studies such as understanding the molecular mechanisms underlying sex change in species such as groupers would also help in increasing the fish

production of the country. In addition to addressing the issues of high-value commercial aquaculture species, low-cost biotechnological tools also have to be developed for newer varieties of aquaculture species to meet the ever growing demands of food production. Dedicated attempts have to be made at SAARC level in gathering and sharing of information on aquatic biotechnology, strengthening capabilities, policy development and long-term planning of strategies for a guaranteed approach to address the food security concerns of the entire region.

Electric Supply Corporation, which pioneered and co-ordinated this programme, has documented it in a publication: `Offering...a blessing in true sense’.

uP-gradation of laBoratory aniMal faCilitieS

Animal experimentation is vital to bio-medical research. Most animal facilities in India used to be sub-standard and apart from the quality of research done using such animals, these facilities were questioned from animal welfare point of view. In early 80s, DBT

initiated a programme of upgrading animal facilities in three institutions – Laboratory Animal Information Service Centre at National Institute of Nutrition (NIN), Hyderabad, Central Drug Research Institute (CDRI) Lucknow and Primate Facility at the Indian Institute of Science, Bangalore, besides setting its own institute the National Institute of Immunology. For the first time access to Specific Pathogen Free (SPF) animals, immunologically compromised mice etc and use of good quality animal feed became available in

India, putting the country on the world map. Training programmes for technicians working in animal facilities were also initiated.

The need of the hour is to identify national needs, and address them both in terms of right application of science and technology and building human resource. DBT’s strength lies in its vision to adopt such a holistic approach. The author’s association with DBT’s societal programmes, and up-gradation of the animal facility at NIN has been a learning and rewarding experience.

Biotechnology

Food Security and SocietyContd. from page 121


Requiring a multipronged approachContd. from page 131


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NEWS NEWS NEWS NEWSProgramme for northern eastern (ne) region The Department has initiated strengthening of R&D activities in the area of Biotechnology in the Northern Eastern (NE) region through twining programme in collaboration with other national institutes from any part of the country. A total of 230 twinning R&D proposals were received from

different parts of the NE region. These proposals were reviewed by an Expert Committee in its meeting held on 6 - 7 September, 2011. The Committee recommended 60 proposals for financial support and also suggested specific modifications in some of the proposals.

Expert Committee meetings to consider the Overseas Associateship for the scientists working in NE region and

establishment of Biotech Hubs in NE region institutions were held on 12th - 13th September, 2011. A total 34 Scientists have been recommended for Overseas Associateship and establishment of 53 Institutional Biotech Hubs for the institutions of NE region have been recommended for financial support.

Madhan [email protected]

joining hands with university of edinburghA Letter of Intent (LOI) was signed between the University of Edinburgh (UOE), United Kingdom and the Department of Biotechnology, Ministry of Science and Technology, Govt. of India on 20th January, 2012. Through this LOI, both sides agreed to cooperate towards education, training and research

in the field of medical sciences and will promote collaboration in research, innovation, higher education, training and capacity building. This collaboration will include academic interactions at the graduate, doctoral, post-doctoral level and would include exchange programmes, training courses and joint workshops on mutually agreed terms. The parties would also mutually explore the possibilities for

developing a M.D., Ph.D. program. Letter of Intent will be followed by a detailed document with outlines for five year collaborative programs for:•Ph.D.exchange•Post-doctoralfellowships•Jointresearchprojects•Anyotherareaof mutual

interest.shailja gupta

[email protected]

BiPP technical Screening Committee Meeting DBT has been supporting Biotechnology Industry Partnership Programme (BIPP) to promote and support innovation and discovery in the biotech industry. The meeting of the Technical Screening Committee of BIPP was held on 18-19th January, 2012 to short list sixty new proposals received under special and general calls of the BIPP scheme for presentation before the committee in its next meeting. The committee considered and discussed the site visit reports; clarifications received from the companies; expert recommendations and revised proposals of various sectors. The committee also reviewed the

progress of ongoing and projects which had completed their first phase and being considered for next phase. Some of the major achievements of the projects are as:

•PhaseIIIclinicaltrialsof Japanese Encephalitis vaccine has been successfully completed and the company has got the market license for India in the age group of >1 yr to 3year and >18 years to <49 years.

•PhaseIstudiesof amolecule TRC150094, a novel Diiodothyronine (T2) analogue, for the treatment of cardiovascular (CV) risk factors have been successfully completed.

•Inordertodevelopanaffordable Asia specific 15 valent Pneumococcal Polysaccharide - CRM 197 Protein Conjugate Vaccine, studies on one India specific serotype have been successfully completed.

•Toxicityandsafetystudiesof a new molecule, Galnobax for treating diabetes for dermal application as well as chronic application have been successfully concluded in rodents and non-rodents.

DBT is taking necessary follow up on the recommendations.

renu [email protected]


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NEWS NEWS NEWS NEWSfirst embryo transfer Mith-un Calf (Bharat) Born at nrC on Mithun (iCar), nagalandWorld’s first ever mithun calf through embryo transfer technology was born at the National Research Centre on Mithun (NRC-M), Indian Council of Agricultural Research, Jharnapani, Nagaland on March 27, 2012. Mithun (Bos frontalis), a rare bovine of South-east Asia is mainly confined to four different states viz., Arunachal Pradesh, Nagaland, Manipur and Mizoram of North-eastern Hill region of India. Presently, free range system of mithun rearing at its natural habitat (forest) results in considerable inbreeding within mithun and crossbreeding with the local cattle thereby resulting in loss of quality mithun germplasm. To address the issues of inbreeding and crossbreeding, the scientists of Animal Physiology section of NRC-M have successfully applied the Artificial Insemination (AI) technique both at farm and field (Khonoma village of Nagaland) and produced AI-borne calves. Embryo transfer technology (ETT) is one of the best approaches for faster multiplication of quality germplasm, the scientists have been working to standardize the

techniques for mithun since last five years. The programme was initiated by Dr. Kishore Kumar Baruah, Principal Scientist and Dr. Mohan Mondal, Senior Scientist under the dynamic leadership of Dr. Chandan Rajkhowa, Director, NRC-M. Other members of the team member were Dr. B. C. Sarmah, Dr. B. C. Deka and Dr. D. J. Dutta from College of Veterinary Sciences, Assam Agricultural University, Dr.

P. Chakravorty from NRC on yak and Dr. Bhaskar Bora, Research Associate of NRC-M. The team is hopeful to get three more ETT calves soon. One of the calves born, is through transfer of cryopreserved mithun embryo. This programme was a part of a DBT funded project.

A. K. [email protected]

Prospecting for biomolecules from microbesChemical characterization of selected hits for bio-actives has been carried out under the project “Screening for Bio-molecules from microbial diversity collected from different ecological niches”. More than 2,00,000 bacteria have been collected from different

niches and approximately 14,500 three star hits have been obtained across four therapeutic areas viz. anti-cancer, anti-infective, anti-diabetes and anti-inflammation. Based on the hits obtained, the Phase II activity i.e. chemical characterization of selected hits of bioactives was undertaken. Chemical characterization of

150 extracts has been completed and 150 more extracts have been prepared for analysis. The bacteria have been deposited at International Depository Authority, NCCS, Pune for future use.

Manoj [email protected]

Calf born with help of ETT with its mother


india’s first ovum pick up – ivf cattle calf ‘holi’ born at ndriScientists of National Dairy Research Institute, Karnal have produced a cattle calf using Ovum-Pick-Up and IVF technology. In OPU technology, oocytes were collected from the ovaries of a live Sahiwal cow using ultrasound-guided needle. The oocytes were matured, fertilized and kept in incubator for 7 days until development to a transferrable stage of embryo called ‘blastocyst’. The transfer of a blastocyst stage embryo to a surrogate mother led to the birth of a female calf with a normal birth weight of 23 kg, on Wednesday, 7th March, 2012. The female calf is named ‘Holi’

The team that made this development possible comprised of Dr. M.S. Chauhan, Dr. R.S. Manik, Dr. S. K. Singla, Dr. P. Palta, Dr. M.K. Singh and Dr. Shiv

Prasad. Congratulating the team members, Director NDRI, Dr. A.K. Srivastava said that India has a large population of infertile, aged/tired and problematic, yet valuable dairy cattle. This technology could be very useful for obtaining calves from such animals. It could also be applied to those animals which

do not respond to the conventional embryo transfer program. He further informed that ‘Holi’ is first Cattle Calf produced by OPU-IVF technology in India.

(This work was supported by DBT.)


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OPU-IVF, Calf ‘Holi’ with the team of scientists

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NEWS NEWS NEWS NEWSBrainstorming workshop on Poultry Biotechnology A brainstorming workshop on “Identifying Biotechnological Research Priorities in Poultry” was organized jointly by DBT and Central Avian Research Institute (CARI), Izatnagar on 2nd September, 2011 at CARI, Izatnagar. The basic objective of the workshop was to generate ideas for a viable R&D programme in

this priority area and to identify novel themes for research aimed at resolving major problems that restrict poultry productivity. Based on the presentations and discussions, it was decided that future research in this area should focus on:

a) Molecular diagnostics and multivalent vaccines for poultry

b) Genomic selection or GWMAS

c) Metagenomics in chicken and other diversified species

d) Development of transgenic

chicken for pharmaceuticals

e) De-novo genome sequencing and development of molecular tools for differentiating diversified specifies

f) Development of MHC specific antisera.

g) Molecular breeding for resistance to specific diseases.

An action plan is now being now put in place to operationalise these recommendations.


dBt-iit Partnership ProgrammeDBT is engaged in building a PAN IIT programme to promote biological and interdisciplinary Science and to push the frontiers of Biology in Engineering Schools to next higher level. In this connection, the first meeting of DBT-IIT Partnership Program for IIT Kanpur

was held on September 2, 2011 at IIT, Kanpur. Similar consultations have already taken place with other older IITs. The areas identified include Cell & Tissue Engineering Program; creation of Animal House facility; creation of Interdisciplinary Graduate School for MS and PhD in Biopharmaceutical Sciences,

Bio-innovation Program in Health Science Technology & Translation. This should create desired expansion in biotechnology by linking existing institutes and link engineering, medicine and biology.

sandhya [email protected]


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215BIOTECH NEWSJULY - DECEMBER, 2011 215BIOTECH NEWSAUGUST - DECEMBER, 2011

to the readerS

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Cover Story

104Spider Silk

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featureS

112 Silk fibre based Biomaterials

Lifesaving constructs Dr Sourabh Ghosh

115Indian S&T

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118Herbal drugs

Potent promise Dr Pradip Bhatnagar | Ms. Suman Gupta

120Biotechnology

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Window of opportunityGerlind Wallon

124Agri-biotech in 2025

Need to match policy with science Usha Barwale Zehr

126Fisheries Biotech in 2025

Need for a technological push Prof. I. S. Bright Singh

129Fisheries biotech in 2025

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132Bacterial diseases in fishes

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135Molecular Breeding for Crop Improvement

Harnessing the genes Pushpendra Gupta

138Mechanical Heart Valves

Anticipating the glitchesA. Subrahmanyam

140Biological control of crop pests

Going full circleRaj K Bhatnagar | K. Sowjanya Sree | Bindiya Sachdev

143Vaccines against diarrheal diseases

Where do we stand?G. Balakrish Nair

145Biotechnology and Art

Creative Connections Chandrima Shaha

148Human Resource Development in Science

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152DBT and Human Resource Development

A view from the standsBharat B Chattoo

155Virology Research in India and the Role of DBT

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horSe’S Mouth

159 Francis Collins

Medicine gets personal

MeMory lane

164 DBT, the triplet code of Indian bilogistsProf. K.P. Gopinathan

168 New pride to Indian science Navin Khanna

170 Nurturing agri-biotechnologyE.A. Siddiq

176 Setting the paceAsis Datta

178 Enhancing YieldsJ. L. Karihaloo

180 Leading from the frontKanury V.S. Rao

183 So far, So goodP.N. Bhat

187 Exploring horizonsR. K. Datta

189 A challenging journeyK. P. Pandian

Profile

192 Indian Agricultural Research Institute

rePortS

201New Initiatives

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203Cancer screening in rural areas

Nipping it in the budChinmoy K Bose

205 Silver Jubilee of DBT

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211 newS deSk

C O N T E N T SRe. 1/-

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