I

Biotechnology-Business Possibilitiesand Prospects

.P. D, MALGAVKAR

Under the auspices of the Centre for Policy Research

Bombay Calcutta

e) 1988 Cenlre for Policy Research

ISBN 81-204-0287.1

Published by Mohan Primlani forPvt. Ltd.,66 Janpath, New DelhiRadiant Printers, li{ ew Delhi I lO

New Delhi

O$ford A IBH Publishing Co.110 001 and Drinted at

M8l':r8-7

Foreword

Biotechnology is receiving wide attention from policy.makers,researchers, business houses, financial institutions and entrepreneurs.

It is, however, still so much a part oi laboratory research that itsterminologies, techniques, processes and developments are still an

enigma. And taming this technology as a business enterprise is

proving complex and difficult.In the present publication Prof P.D. Malgavkar has attempted to

explain the intricacies of this technology so that these could be

understood by a layman. Whilst indicating its possibilities in thefield of agriculture, health, chemicals and energy, he has broughthome the ethical issues and engineering challenges involved in itsdevelopmetrt and comrnercialization. He has suggested entry avenues

in biotechnology business for both the existing business houses and

new research entrepreneurs and has spelt out specific financial and

marketing strategies suitable at different stages of the business

ven t ure.

We at the Centre for Policy Research are interested in placingbefore the policy and acadenric cotnmunity fresh opportunities fordevelopment and growth as also new and emerging technologypackages that will make this possible. In line with this, we hope

that this publication will help in introducing the concerned develop-

ment agencies to the breath-taking possibilities of biotechnologyand to the pragmatic approach in converting it to succbssful business

enterprises"

Centre for Policy ResearchNew DelhiJanuary 1988

V.A. Per PANANDTKFR

Director

Preface

Biotechnology, a discipline that has blossomed only after scientists

developed gene splicing technology in the seventies, is moving at a

breath-taking pace, what with vast capital investment and concerted

involvement of biotechnologists, leading universities and innovative

firms. Some of the world's largest corporations are investing heavily

in the field and a rash of small biotechnology companies has sprung

up around many university campuses eager to cash upon the

technology fallout. Governments of developed countries are inject-

ing public funds to usher in biotechnology in their countries. Just

as computers elevated International Business Machines (IBM) tocorporate stardom in the 1950s, the biotechnology revolution has

enthroned Merck, the king of the medical molecule makers, at the

summit of Fortune's 1986 list of America's most admired companies

based on eight key attributes, namely, (l) Quality of management'

(2) Quality of products or services, (3) Innovativeness, (4) Long-

term investment value, (5) Financial soundness, (6) ^{bility toattract, develop and keep talented people, (7) Community and

environmental responsibility, (8) Use of corporate assets.

Government of India have set up National Biotechnology Board

which has chosen genetic engineering photo-synthesis, tissue-culture,

enzyme engineering, alcohol fermentation, and immuno-technology

as areas of immediate interest to it. A number of private firms such

as Hindustan Lever Ltd., Vulcan Laval, Ranabuxy, and multi-

nationals like Hoechst, Ciba-Geigy have enteted into this field. Withthe glittering prospects, concerns unconnected with this relative field

are diversifying in genetic engineering (Orkays collaborating with

Cetus Corporation of USA).It is in this context, therefore, that we thought it necessary to

briog together in a layman's language the advances that have taken

!vl

place in biotechnology till date andragriculture, health-care, chemicals

'such as engineering challenges,,advance, and financing and m.organizations entering into this field.

I am grateful to Dr. N.K. Notani,Division. Bhabha Atomic Researchgone through the draft very caretions made by him Xrave greatlyrelevance in the overall frameworkexpressed, however, are entirely that

Dr. Pai Panpndiker, as usual,technological forays by ensuring li$upport. It is gratifying to get suchareas from the prime Policy Research

Shri B.G. Shirgurkar, who hasyears, went through a successionpublication of the book and has coning a glossary of terms and the indeuseful to researchers going in forin biotechnology, colnpani€s andtechnology field and to thebiotechnology industry within the co

Prefoce

impact this will have onenergy; stress the constraintsissues, and the barriers to it:strategy for technologists and

d, Biology and AgricultureCentre, Bombay, for having

Thc buggestions and correc-d in ensuring technologicalof the book. Thc ooinionsthe author.

strong support to myfinancial and administrative

support to high techof India.

helping me for the last feWdrafts before finalising the

extensively in prepar-It is hooed the book will be

ialisation of their findingstions entering into bio-

in accelerating the pace of

P.D. Mel,cevr,c,r

CHAPTER I

Introduction

The era of biotechnology stems front the work of Francis Crick and

James Watson who, in I 953, untangled the linal clues of the double

helical structure o1' Deoxyribonucleic Acid (DNA), the immensely

complex chemical that contains an organism's genetic programme'

DNA, a polymeric macro-molecule, was discovered in I 869 by the

Swiss scientist, Frederibk Miescher' By 1966 the complete genetic

code was established and genes were synthesised chemically. Only in

1973, scientists at Stanford University and the University ofCalifornia developed the gene splicing technology for manipulating

this genetic material which the two universities patented. They

inserted foreign DNA fragments into plasmid Drr-A to create

chimeric plasmids. It was found that these could be introduced intothe bacterium Escherichia colir wherein they would start rnaking

multiple copies of themselves.

*

The basic unit of all living things is a cell. Within each cell'

cncoded in DNA molecules, is an information bank containinggenetic information characteristic of the cell aLrd of the organism'

The totality of the information bank is called its Genonte.

There are two major classes of organisms :

l) Eukaryote : for plants and animals whose DNA is sequestered

in a nucleus within the cell.2) Prokaryote: have a nuclear body but unbonded by a nuclear

membrane.The DNA structure is like a twisted step-ladder with thousands of

millions of rungs.

2

inlormation for the teproduction,

rnent and for the manufacture of

cells and micro-organisnrs in a

manufacture substances that they

Genetic engineering can be

tecliniques. The output of thisand animal health-c&re oroducts.chemicals, and even foods andis the use of biological systems tousually accomplished through ferr

in equipping the laboiatories withdttracted a breed of young entre4lways own stock iu their ownswamped the U.S. Pbtent and T4pplications in biotecXrnology in

Poss ibi I i ties and Prospect s

The molecule has four buildins called nucleotides. Thermain difference in the nucleotides are bases which are:

ThymineCytosine

The sequence of these bases, paired, contains the geneticand functioning of cells.

The bacterium Escherichia coli a genome with about four

A : Adenine TC : Guanine C

million base pairs and about 4,000human cell may have between 10,000

. It is estimated that a100,000 genes.

In broad terms, biotechnology issuch as yeast and bacteria to produce

use of cells and organismsa variety of products and to

carry out a broad range of tasks, E have been using yeastcultures for over 6,000 years to make bread and to produceialcohol by fermenting vegetable matbacteria have been put to increasing

. In the past few decadesuse such as for sewage treat-otic drugs. But the scientific

advances in the early 1970s permi the scientists to manipulatemanner causing them to

not normally .produge andenhancing their ability to perform im bioloeical tasks.

used to modify the hereditary code ofas the laboratory technologlliving cell giving it new orthe involvement of chemical

industrially-based productionunique abilities. Biotechnology requiengineers since it utilizes a collection

includes manv humanchemicals, speciality

The common denominatorthese products. This is

which can be defined as

the process of growigrg a culture of ln a nutntlvemedium to produce a useful and desi product.

The huge investmemt, till date, in new biotochnology has goncequipment and has

scientists, who alnostThey have already

office with nearly 1,000years. These seientists have

Introduction 3

tumed recombinant DNA technology from a scientific feat of thehighest order into what is now almost a routine laboratoryprocedure. with highly specialized enzymes, researchers can snipindividual genes out of the mass of DNA that controls the heredityof living organisms. The genes containing the code that directbiological processes can then be implanted in other organisms such

as bacteria. By growing these bacteria in vats, scientists can nowobtain large amounts of hormones and enzymes that exist in minutequantities in the human body.t

Escherichia coli or E. coli, a work horse of molecular biology,is the bacterium extensively used in genetic engineering (GE)research because of the ease with which it can be cross-bred and theease of access to and manipulation of its vital functions likebiosynthesis, etc.

Out of more than 100,000 species of nricrobes on earth only a fewhundred are likely to be useful. They include yeast, moulds,bacteria and actinomycetes (rvhich make antibiotics). They canproduce some 200 commercially useful materials, only a few ofwhich the industry makes biologically today.

The technology is moving at an astonishing pace, what with vastcapital investment and conce ed involvement of biotechnologists,leading universities and innovative firms. Some of the world's'largest corporations are investing heavily in the field and a rash ofsmall biotechnology companies has sprung up around many univer-sity campuses in the United States. The small companies are oftenassociated with university scientists who are attempting to turn theirresearch findings into commercial products. Moreover, the Britishand French Governments have launched biotechnological companieswith injection of public funds. France has made biotechnology a

national priority whilst Japan leads the world in enzyme andfermcntation technology.

Several drug and chemical companies have research efforts underway that rival those of the largest biotech start-ups. For instance,Du Pont Company is exploring a broad range of projects frompharmaceuticals and improved varieties to pesticides and chemicalfeedstocks. Monsanto Company has completed a huge researchLaboratory in Chesterfield that will house one thousand scientists.

Paralleling the growing role of large companies is the decliningrole of venture capital in biotechnology. Shares of the biotechcompanies began to fall sharply in the summer. of 1983 and in 1984

they were selling far below their ye:

160 conrpanies spent more thanresearch. U.S. comoanies have atments that give thb Japanese markOn the other hand, Schering-technology from $untory. OtherJapan for the expertise to growsaid to excel. Even thoughthe world's leading biotechnologycapital to form new companies hasbiotechnology indiustry. But now,trying to close the gap. The Frencits own silicon valley by helpingmaior academic centres.

No more than a handful ofare exoected to succeed intise and manufacturing capabilityis believed that a6 rnany as

panies will merge or be acquiredmanufacturers. Joint venturesgreater share of theil revenuesseeking niches that lnay be toomake it easier for the largerups' turf is the gnowinga result, it is gettimg easier for comlogy to recruit the scientists. Mostconsider that it is fiskv not to be

By 1984 about two-and-half biin the U.S.A. in setting up moreto pioneering new products frompanies have failedo whilst moststage. The products of gene-spli

olace en masse. Diabetics are nowinsulin produced tty modifying br

than with animal insulin. The Fof the U.S.A. is on the verge ofgrowth hormone to counteract ato become drvarfs. Gamma typemore promising than alpha-type inof cancer, are on the way to the et. New-born calves are being

Biotechnology- Possibilities and Prospects

y highs. In Japan, an estimated:200 million in gene splicing

I 5 technology transfer agree-rights in return for royalties.

has licensed gamma interferon.S. companies are tapping into

ia in which the Jaoanese areuniversities emnlov some of

the lack of venturethe develooment of local

he European govemments are

Govemmeirt is trying to createup hightech companies

start-up companies, however,the necessary marketing exper-grow into major companies. Itirds of the b.iotechnology com-

one of the drus or chemicalthe small comoanies to tetain a

does licensine. Others are

[or big firms. Also helping totb move into the stattj

of biotech trained scientists. Asies not involved in biotechno-the giant pharmaceutical firrns

the biotech business.2

dollars may have been investedhundred cornoanies dedicatedtechnology. Only three com-ies have passed the founding

.are beginning to hit the markettins themselves with human

ia in fermentation vats rather& Drug Administration (FDA)

ing the marketing of humanthat causes some children

interleron and interleukin (II),for treating ieveral kinds

near

Introduction

vaccinated against a fatal disease called scours, and green-houses arebeing filled with new varieties of corn and tomatoes that are hardierand more nutritious because they have been genetically modified.The Office of Technology Assessment (OTA) predicts that sometirnebefore the turn of the century annual sales of chemicals and drugsthat are produced by gene splicing could top g 15 billion.:

The following techniques developed between 1970 and 1975,ushered in the explosive era of biotechnology:

1) Genetic EngineeringlRecombinant DNA is the technique ofintroducing hybrid DNA containing genes of interest into organisms(Escherichia coli, Bacillus subtilis or yeast) in order to make theorganisms produce enzymes' amino acids, hormones and proteins.

(Stanley Cohen and Herbert Boyer of Stanford Universitydeveloped this technique, and applied for sealing the patent in 1974.lt 1976, Boyer formed Genentech, one of the successful biotech-nology firms).

2) Bioprocessing involves the conversion of a raw materialsubstrate into a product using microbial fermentation or enzymes.The antibiotics, enzymes, amino acids and other speciality chemi-cals can be produced on an industrial scale with the introduction ofrecombinant DNA. Continuous sensor devices and the interfacingof process control with computer is being attempted to ensureautomation and continuous processing.

3) Hybridoma Technology: Antibodies are proteins produced invertebrates in response to foreign proteins or substances. Conven-tional antisera consists of a number of antibodies. Hybridomatechnology allows the production of highly specific antibodies fromsingle clones of cells, termed monoclonal antibodies (MAB).- Incidentally, MAB technique was developed by Ceaser Milsteinand George Kohler of Cambridge University in 1975. Their requestto the British Govemment to patent the process evoked no response.In the process Britain lost the opportunity to take advantage of thisimportant innovation.

MABs being very specific are utilised in diagnostic system; tn viyo

diagnostic imaging for detection of tumour cells; therapeutics includ-ing immunization and immunotoxins, targetable drugs for tumourcells; tissue typing, purification and separation of biologicalmolecules, etc.

6 Biotechnology- Buslness Possibilities and Prospects

4) Prctein Engineering involves the modification of protein

structure to improve the functions of proteins or to desigp entirely

new proteins. It could modify enzymbs to improve their tolerance ofternperature or alter pH optimum oi other characteristics and even

produce therapeutic proteins' Pro$ress in protein engineering is

dependent on developments in other areas such as X-ray diffraction

methods, computer molecular mod$lting and chemical synthesis ofDNA,'

5) Bioinformatics covers fields suph as the use of computers inprotein engineering, software for DNA sequence alalysis, automated

DNA synthesizers, automated proce$s control, etc.'

HISTORIC^L MILESIONES IN THEDEVSLOPS4ENT OF BIOTECHNOLOGY

Dotc Event

6,000 B.C. ,Alcoholic beverages, bre{d and cheese made by fermen-

tation.1857 A.D. Pasteui proves fermentation caused by micro-o rganisnrs'

I 869 Frederick Miescher discofvered DN,\.1923 Citric aoid produced by ifrdustrial fermentation'

1944 Penicillin mass-Produced.1953 Francis Crick and Jamps Watson elucidated double

helical structure of DN^A'].

1970 Hybridoma Technology for producing Monoclonal

.dntibodies develoPed.

19'r,5 Monoclonal Antibodies (MAB) discovered ,by Ceaser

Wilstein and George Kohler, Cambridge, England (not

Patented).lg82 Human insulin, first com$ercial DNA product appeared.

REFERENCES

1. Malgnvkar, P.D. Technologies for E[onomic DeveloP4]ent, New Delhi,

Oxford & LB.H. Puhlishing Co. Pvt. LtF', 1987.

2. "Biotech Comes of Age" article in Busihess Week, Jan. 23' 1984.

3- Daly Peter, The Blotqchnology Basinesf-A Strategic Awll'sis' New Jersey,

Rorvman & Allanhold, 1985.

SUGGESTED READING

sasson, Albert, Biotechmlogy, Oxtorf a IBH Publishing co. Pvt. Ltd.,New Delhi.

CHAPTER 2

Agriculture

For developing countries, it is in agriculture and health care thatbiotechnology will have a pronounced irnpact. In recent years,

scientists have developed techniques that can greatly speed up theprocess of breeding new varieties and permit more precise selectionof promising strains. The basis of this new technique is a method ofgtowing many copies of entire plants from single cells or even fromprotoplasts of plant cells, whose walls have been chemicallyremoved. t

Known as tissue culture, the new technology permits multiplecopies or clones of a particularly productive plant to be grownwithout waiting for the plant to produce flower sexually. Firstdeveloped on a commercial scale for orchids, tissue culture has been.perfected for a variety of plants ranging from redwood trees topotatoes.

*Although the earth's surface is made up of more than 100

elements, only l6 elements in the fonn of gases or dissolved salts are

essential for plant growth, namely, carbon, hydrogen, oxygen,phosphorus, potassium, nitrogen, sulphur, calcium, iron, magnesium,molybdenum, boron, copper, manganese, zinc, and chlorine, Thisknowledge of mineral requiremants formed the basis of all plantnutritional research, including that of hydroponics in 1940s fdr thcU.S. troops stationed on the soil-less atolls of the South Pacific.Hydroponics and aeroponics a.re, however, expensive ways to growplants aod arc economically feasible under limited circumstances.

' The succeeding portion is derived from "The development of planl bio-technofogy", John e, Torrey, American Scientit, July/August, 1985,

:g Biotechnology- Bus Possibil it ies and P ros p ect s

i Most plant production for man's fit continues to use the soil as

the source and subgtrate of Plantor chemical fertilizels.

wth, supplemented bY organic

As early as 1930s, plant parts h as excised root tiPS were

cultured separately. These tips would grow in nutrient solutions in

the normal form if specific vitami including the B vitamins,

thiamin, nicotinic acid and pyridoxi were added in tiny amounts

of 0.1 to 0.5 parts per million' Th vitarnins were essential forroots in culture. The 1930s

also saw the beginning of an in sifying pursuit of previouslY

organic substances believed tohypothesized but ndt then identifiedserye as plant hormones i.e., substanc that act at very low concen-

. trations to control cell and tissue leading to normal growth

and develooment. Indole-3-acetic aci (IAA), one of the hormones

. controlling cell enlatgerrent in the s ts of plants, was identified in

.1937. Since then, the whole grouP of organic compounds with

similar biological activity known as has been identified.

A second class ol plant es called cytokinins includes

derivatiyes of a univprsally occurring ic compound, the purine

base adenine in DNrd.--iil; il; oi prun, hormones and studied since the

. | 950s incllde the gitrberellins (GAS),etc.

bscisic acid (ABA), ethylene,

If the tiny apex of a shoot is t and placed in a sterile

qrineral-sugar mediurn in the light, it rill grorv provided it is not too

' 2 mm in length and posses-

gate and develoP leaves, oftensmall. Shoot tips moasuring about Ising two or three primordia will el

forming a root and going on to v into a whole Plant. Thts

by Morel in 1975 has been

elongation and development of

" me stem .culturgl' 4 lechnique pioneI used . commercially to rid plants .oamounts of plant hormones are adde

but multiple shoots are formed. l

viral diseases. When trace

to such a medium., not one

such shoot is capable of

. growing into a whole plant or clone, making it possible torost identical plants in a year'increase a single plant to a million. a

Merislem .culture is effective in con ing diseases because viruses

.well established elsewhere in the infe(shgot apex. If the ppex is excised i

plant do not grow into thegrown in culture, virus-free

plants can be produoed and the croP This method is also used

tg ir,nprove plants that are usua

cuttings., guch as ghrys4nthemumpropagated by rooted stem

caroation, and to increase

Agriculture 9

productivity in crops such as white potatoes. A great increase iayields results from using virus-free stocks of seed potatoes. Afterthree to four harvests, tbe seed potatoes are liable to re-infection inthe field. This requires a repetition of meristem culture to produce

new virus-free stock,Researchers have been able to excise and culture shoot apexes

only 100 gm in length, that is the ultimate apical dome of the shootapex. Such tiny apexes usually require some supplementary hormonessuch as gibberellic acid and potassium, in addition to the nutrientsneeded by excised root tips. If appropriate trace amounts of an

auxin and a cytokinin (usually determined empirically throughexperimentation) are added to such a medium for culturing shootapexes, instead of a single elongated shoot, several new buds orshoot apexes come up around the base of the new apex. In place ofone shoot, within a few weeks, four to five or, over longer periods,dozens of tiny shoots come up. These tiny plants can either be

subdivided and transferred to a fresh batch of medium where theprocess can be repeated or transplanted to a different mediumwhere each bud can be made to grow into a whole plant.

At about the same time Roger Gautheret, a French scientist,began experimenting with the culture of excised mature root andstem pieces. From the stem tissues there developed unorganized"callus tissue", reminiscent of the tissues formed around wounds onthe stems of trees. Cultured under sterile conditions on appropriatehormone mixtures, these tissues could potentially be grownindefinitely. Such callus culture is possible with tissues from anyplant part or plant group. The proliferative capacity, rate of develop-ment and cellular characteristics expressed may vary, but the general

requirements for the development of plant callus are well defined. Byusing the technique of culturing single cells and then inducing mor-phogenesis by the manipulation of hormones, it became possible todemonstrate conclusively that living plant cells of diverse types fromdiferent tissues have the genetic capacity to form all the parts of a

whole plant through successive cell divisions and cell enlargements,a capacity that came to be known as "cellular totipotency". Callustissues produced on a solid medium can be transferred to a liquidmedium and grown with constarit stirring. Under favourablehormonal conditions, the cells separate and divide repeatedly,forming a cell suspension that can then be passed through a fine'nylon filter to produce a dense suspension of single living plant cells.

10 Biotechnology-- Posslbil it ies an d Pros p ect s

Such single cells cad grow into which can then be inducedto form organs and a whole plant.

The success of Cocking in obtai single protoplasts for culturea living grorving organ such asby separating cells from each other

a root tip was the final technicalmodem era of plant biotechnology.

which set the stage for thee did this by using enzymes

that dissolved the dell walls so that membrane-bound living matterwithin the cells was released and fl a suspension of spherical,wallless cells or protoplasts. Given change 'in medium and sonre

a new surrounding wall andcolonv. ProtoDlasts could bc

time, each of these irrotoplasts 1i

began to divide creating a newproduced in this way from tissues ofparts. An astounding observationappropriate nutrient conditionshormones, cells that had beenstimulated to divide could distructures capable of developingtens of thousands. In recent yearscell suspension, or cultured callusvariety of tissues in flowering plants,

The discovery that hydrolyticpectinases could be used to dissolve

they are derived. This cell fusion iscells share a single parental source.

stem, leaf, or other plantmade in 1971 that under'oDtimum ooncentration of

from protoplast and

directlv into embrvo likewhole plants by thousands or

bryogenesis from protoplasts,been achieved in a rvide

such as cellulases and

most suceessful when the twoThe further apart the proto-difficulty--not of cell fusion,

walls in a living plant organprepared the way fof current ex ts in which the living wall-less

are fused to create new olantcells or protoplasts of different planhybrids or are used for the introd

In the relatively short periodof new genetic matedal.

produced by enzyme treatment andthe time protoplasts are

time they form new cellwalls-a matter of hours or per a couple of days-the naked

can be made to fuse either bycytoplasmic membranes of pthe addition of appropriate agents as polyethylene gtycol, or bythe use of electric shock. Fusion of plasts brings together theentire living contents of two cells d more if care is not taken toprevent it. With careful attention t conditions, the fused proto-plasts form a new cell wall andtogether and .dividee forming two

eir nuclei enter into mitosis

sing twice the chrofirosome number, each with a nucleus posses-

the protoplasts from which

plasts are genetically, the greatefwhich usually ogcutg-but,of the of the fused product.

Agriculture 11

The transformation by a bacterium is the porfect mechanism forintroducing DNA into a plant cell, and serves as a model for muchof the research directed towards genetic engineering of plant cells.

The methods of meristem culture are already in use today by

hundreds of growers for the production of a large number of plants

of relatively high commercial value which are otherwise difficult topropagate. Orchids, omamental plants such as begonia, Boston

fern, day lilies and others lend themselves to the technique and when

grown to maturity, bring a price justilying the somewhat gteater

expense of using in-vitro culture' For crops such as potato, where

virus-free stock makes a dramatio difference in productivity, meristem

culture has proved a remarkable tool.In another application, the methods of plant tissue culture have

been adapted to make the long-term storage of plant parts economic

and effective. Plant structures, usually cultured shoot apexes orembryos, are placed in cold-storage at 4-9"C, or frozen in liquidnitrogen at -196'C after treatment with a protective substance'

They are held at these temperatures for months, even years, and

then thawed and returned to sub-culture and propagation. Thisstorage, which replaces expensive propagation in the field, is

economic with regard to cost of space and maitenance, allows rapid

recovery for further propagation and retains the plant material in a

genetically s{able state free of pests, pathogens and viruses. Such

aseptic materials can be shipped around the world without the need

for quarantine or disinfection.Conversion of cultured plant tissues to cell suspensions makes it

possible to plate out millions of plant cells, each theoretically capable

of forming a whole plant. Already 12 Microbiological Resource

Centres (MIRCEN) have come into being, the main centres being

Brazil, Kenya, Senegal and the United States. By a choice of appro-priate nredium, researchers can select cells tolerant of special

conditions,' such as the presence of high concentrations of salt orspecific herbicidal substances. Most cells will die, but cells withnalural resistance will grow, allowing workers to single out theexceptional cells which will develop into plants better adapted to agiven field situation. Such selections have been made not only fortolerance of saline soils and herbicides, but for a number of othertraits such as resistance to drugs or the ability to grow in theabsence of certain metabolites. Although these methods haveproved to be effective in field trials;. so far none of these mutations-

i selected has led to slgnificant success.,. Plant tissue cultune has also been used to harness the special,I sometimes unique, biosynthetic cap.lations. This approach involves cul

of selected plant cell popu-callus tissues in bulk under

conditions that allow the cells to fi a secondary product that hasas drugs, oils, fragrances,economic value-such compounds

pigments, and the like which have usually collected from plantsgrowing in the wild, often in ex out of-the-wav olaces. One ofthe best examples of the potential of kind of synthesis has been

the cultures of the roots ofthe success of the Japanese in ind. common gromwell (Lithospermum)ishikonin, a naphthaquinone used n

to form a natural product,in quantities ranging

from 12 to 15 per cent of the dry t of the cultured tissue.Other products actively sought the alkaloids vinblastine andvincristine which are formed from the tured cells of the periwinkle(Catharanthus) and are used in

Another area of itlterest andtherapy.ent is sornatic hybridization-

the production of new plant types by ging together two dissimilar' genomes, .esulting irt crosses beyondsexual methods. In spite of the suc

normal limits possible withof cell fusion across generic

,lines, few such crosses have gone to form tissues capable of, interspecific somatic hybrid

genera: Nicotiana, Datura,the basis of oresent know-

regenerating whole plants. Thus f,

ledge it seems doubtful whether remregular, functional, competitive and

somatic hybrids can produce

12

plants have been obtained fromSolanum, Petunia, and Daucus.

One of the most attractive prcultured plant tissues, cells or picloned DNA conveying specific

'modify the Ti-plasmid by gene. transfer without ttmour forn

Biotechnology - Poss ibilit ies and P r os p ec t s

for the future is the use ofas receptors for selected

iexpressed either in pultured tissuesc information which can be

cells or in organised plants'derived from the culitured cells. The. effiort among a numberof laboratories has been in developing e use of the Ti-plasmid fromA. tumefacians. Plants studied as hosts are relatively few,

'including tobacco, petunia, carrot, potato and flax. Work withthese rnodel systems has now dem that it is possible to

plants.

on to allow efficient T-DNAThus, specially engineered

the non-oncogenic Ti-plasmidof host plant cells, whichcan be regenerated from

Agriculture 13

these selected transformed cells, using the techniques of cell and

tissue culture.Unsolved problems still remain in research on plant tissue culture,

limiting its usefulness as a tool for agricultural improvement' Firstis the general problem of getting plant tissues to respond in the way

the model system behaves' Although it is easy to organise plants

from single cells or callus tissues of tobacco and carrot, it is much -

more difficult in the case of soybean, corn and important cereal

grains, and more difrcult still, if not impossible, with many other

plants. Sirr,ilarly, although the use of protoplasts to regenerate whole

plants by embryogenesis or organ initiation works well for tobacco,

petunia, carrot, rapeseed, asparagus' and Datura, effective

ptocedures have not as yet been established for most species ofplants.

Problems such as the lack of an easy method of producing genetic

markers for cell selection, the difrculty of generating and maintain-

ing haploid tissues readily, and the uncertainty of routinely initiatingembryogenesis from cells have to be sorted out.

. The successful use of DNA transfer vectors for plants depends on

advances in several major areas of'plant research, namely the

isolation of particularly interesting genes, the analysis of theircontrol, and the improvement of the techniques of plant tissue

culture to make it feasible to study more agronomically importantspecies.t

Even with crop plants, genetic engineers will have to cooperate

closely with the plant breeders as selective breeding remains the key

technology. The International Plant Research Institute (IPRI) hopes

to improve the plant's genetics, perhaps, by improving the protein

content or by genetically eliminating the toxic substances the plant

produces and which must be retnoved by special processing. A wild

melon collected in India was the source of resistance to powdery

mildew and prevented the destruction of California melons. Simi-

larly, a seemingly useless wheat strain from Turkey rffas the source

of genetic resistance to stripe rust when it became a probleru in the

Pacific North-West. Genetic engineering is not yet ready to match

the natural wealth of genetic diversity and thus to meet challenges.

Plant geneticists ultimately hope to equip crops that depend on

heavy fertilization with the nitrogen producing ability that occurs

naturaUy in peas and beans, and let plants do their own fertilization' '

They hope to perfect the protein composition of key food crops'

Biotechnology-

:They expect to bregd resistance to:sume 25 to 35 per cent of crops,.resistant to saliniiy, pests, weeds,, Chemical companie$ arechemicals will come fromwith cell culture has been tonew characteristics intact.

There are schemes to alter thegenetically engineered bacteria. Aforeign biopesticide gene and a leafice nucleation mighi provide frost-Ithe experiment of roleasing theseOrder).

The exciting pro$pect for develengineering of plants to raise yieldsto drought, cold, pests or other envicould be higher if the scientiststhe inborn ability of legume crops totheir own sustenance. Professorknow about plants hAs historicallylnicro-organisms, like bacteria and vipriorities is the needl for strong suof plant physiology and plant genetics

Experts say that the world foodthrough the developrnent of more dilocal conditions of soil wealth and wacould be achieved throushboost given by high yielding varietiesthat there are no better yielding varifories. Moreover, tho scientists holdways to increase the yields of raibreakthrough has, thoreflore, to comeI Biotechnology can increase theplant sources to l0 kg per hectareprotein. Moreover, technology ofproteins indicates that a few thousand llOapacity each could sbtisfy the world.l Biological pesticides are nottarget will be specifio pests.and theylhsect world.

Possibilities and Prcspects

and diseases which con-d they expect to make crops

t and extreme temDeratures.that the next generation ofengineered plants. The trick

cells into whole plants with

vironment of plants withsoil bacterium containing a

lacking the gene fort crops. (In the U.S.A.was stayed by a Court

g countries is the geneticto make croos less vulnerable

tal hazards. The rewardsin implanting into cereals

w nitrogen from the air forThomas savs that what webehind our knowledge ofand animals.s One of the

to increase basic knowledee

requires raising -yields

strains suited to specificsupply. This diversificationof plant genes. Despite therice and wheat, the fact is

es in the offine in the labora-t no prospects of finding

bd crops significantly. Them biotechnology.of protein from leguminous

0.6 to 1.5 kg of animalof single cell (microbial)

tanks of 200 cu. m.of protein.

and will not pollute. Theirwill not harm the beneficial

Agriculturc 15

The major pathways to productivity improvement in agriculture

will have to be: increased yields and greatel intelsity of cropping,

says M. S. Swaminathan.4 Though multiple cropping is possible in

the tropics the rnajor constraint is the availability of water' More-

over, t greater nutrient supply will be needed by the crops' In

South and South-East Asia, about 86.5 million hectares of land

could be made more productive if problems of salinity, alkalinity

and other adverse soil conditions are rectified. Agricultural techno-

logy development is faced with the challenge of improvement in the

productivity of major farming systems per unit of land, water' time

and energy without detriment to the long-term production potential

of the soil.World demand for grain is growing not just from more mouths to

feed, but from a very rapidly rising demand for more animal feed'

F-urther down the line is a new source of demand should enough

grain be converted into fuel.FAO has projected the needs for an additional production- of

300 million tons of paddy between 1974-76 and the end of 'thecentury. On an average it takes about 10 years from the tirne a

closs is made to the time it makes a widespread impact' Swami-

nathan states that experimental yields indicate that further increases

in rice yields by 2.2 tons per hectare for the wet season and 3'5 tons

per heciare foithe dry season would be realistic targets' For genetic

engineering to be useful for improvements of plants, such as rice,

further advances in tissue and cell culture techniques are indispens-

able " The incorporation of nitrogen-fixing genes into rice by genetic

engineering is the most ambitious project at the International Rice

Research Institute (IRRI). The scientists fear that at least 17 genes

are involved in the nitrogen fixation system and they stilt do not

know if manipulation of such a large number of genes will be

possible, continues Swaminathan. (There are also some theoretical

constraints. )Scientists are hoping to use gene-splicing techniques to equip crop

plants with the ability to nanufacture their own nitrogen fertilizers

instead of relying on the application of energy-intensive synthetic

fertilizers. One line of research seeks to isolate genes responsible for

fixing nitrogen in the root bacteria of leguminous plants and then

transplant these genes into the cells of other plants' There are many

scieniific problems in that even if such trasfer could be accomplished

the result may not be too useful' Crop plants genetically engineered

16 Biotechnology- Possibilities and Prospect s

fixing ability of existingbacteria, a develodment that s lead to increased yields from

, leguminous plants, says Norman.ltransfer the nitrogen-fixing genes

tually, it may be possible to

legumes to other strains of known to exist in the roots ofcereal crops-in thoory an easierthe cells of the plant itself. If

than translerring them into, such development may

make nitrogen available to the plant ithout the plant itself havingto use its own energy in the synthesi

Though the bigggst gains in Amer farm production came frornoil-based mechanical technology by the usage of tractors,combines and other farming , fertilizers, pesticides, electri-

to fix nitrogen may have to, energy into the ta$k that there. desired fruit or grains. Potent

directed towards improving the

city, etc., in the l|hird Worldgains in farm prodtrction have

mechanical technology does notcapital for labour. [n fact, it isSecondly, it involves villagers and

Posslble applicatibn of biotechnology

so muclr of their metabolicbe little left over to make themore pnomising is research

bacteria associated with

g about 1967-68 the biggestfrom biological technology

advances in output per unit of land. Biotechnology, unliked the same substitution oflabour intensive, not less.

ts, says Micheal Edessess.s

TABLE I

research to dce improvement

Research technique End resultTissue arul cell culture

Induction and selection of usefulmutants at the ce ulaf level

Embr2o cultureAnther and pollen cultureProtoplast fusioo

t tolerancetoxicity tolerance

lysine and high proteinphotorespiration

resistanceoxygen tolerance

- and interspecific hybridizarionbreediDg time

and intergeneric

rlce lmprovementlla improvement

Genetic engineeting of nitrogen fixing genes

Source: Table 3, Biotdchnology and Third World Agriculturc,, M.S. Swaminafhan-Science 8, 3 December 1982.

Agriculture 17

Biotechnology works best where there is year round warmth' sun

and controlled water, i.e. irrigation' The United States has about 39

million acres of irrigated land, China has 116 million irrigated acres,

India irrigates about 135 million acres and is trying to add another

six to seven million acres every year, and has the potential to irrigate

275 million acres. Moreover, the most authoritative current projec-

tions on climate change suggest that rising COz in the atmosphere

might benefit rather than harm the Third World agriculture' India,

China and Northern Africa are forecast to grow just slightly warmer

but with greater reliable rainfall.The consultative group of the World Bank presented a heavily

documented case in 1980 that the spread of biotechnology increases

rural employment, and that land size lirlitations need not prevent

adoption of the most sophisticated new crops. Once the land hold-

ings are of equitable size, women are given fairly equal rights towork and education, land is farmed by the family which owns it'and attention is given to better seeds, good water management,

multiple cropping, hydro-electric power, the agricultural productivity

would jump up. The role of biotechnology in improving the health,

weight and yield from aninrals is elaborated in the chapter on

"Health-Care".

FOODS AND BEVERAGES

Alcoholic beverages, sweetners and single cell proteins are the

three major products important to biotechnology. High-fructose

corn syrup (HFCS) is one of the success stories of biotechnology' In

this process corn starch is converted by the glucose isomerase to

fructose-rich syrup that is 1.3 times as sweet as sugar' Another

successful story is that of aspartame. This sweetner is two hundred

times as sweet as sugar. Aspartame was introduced commercially

in 1983 and within a year came to dominate the artificial sweetner

market.

Sugar consists of carbon, oxygen and hydrogen but the composi-

tion thereof differs for sucrose, glucose and fructose. This change

in the composition can be brought about by bacteria and the

enzymes produced by them' Starch is first converted into glucose

I8 Biotechnology*

by using anraylage enzyme.fructoSe either by lusing IsomeraseI 960, Weste rn courtries and JaoanIsomerase. enzyme. iThis process is'done under ambient temperatureWhen about 45 oet cent ofprocess of transforrnation stops; butlronr, the enzyme reaction restartsglucose into fructose. The enzymemonth.

Fructose is in liquid form and issweets, cold-drinks, ice-creams, jams aby persons rvanting to reduce their

In I 978, 1.2 million tonnes of frThe production thoreof in 1985Already about 30 per cent of theand Japan is met by fuuctose. Inproducing fructose by getting enzymethe one in Ahmedabad has a

,day and will be selling its product urSweet; the other is a joint sector pro

ln India, tapioca, because of itsused for ptoducing starch. Effortstechnology to convert tapioca starcmaterial easily available in thefructose.6

REFEREN

Cotin Norman. "The in.rpact of biotechnSevier,.Autumn 1982.

2. Torrey,'John C. "Ttre devcrcpmc.nrScient ist, July/Augusr 1985.Mukerjee, Dilip. "Biotechnology, ATitnes ol lzdra, 15 Feb. 1983.Swaminathan, M.S. "Biotechnologyculture", Sclencc, Vol.2l8, December 3,Critchlield, Richard. "Scicltce and theForeign Afuirs, Fall 1982."qrvecter sugar from Corn" , Daily Sukal

,i.

J.

5.

6.

Possibilit ies and Prospects

, glucose is transformed intoor bacteria. By about

launched upon the search ofirly complicated and has to be70-90'C and 7-9 pH acidity.is converted into fructose theif fructose is separated there-imately converting 95 per cent

needs to be renewed every

used for nredicinal syrup, forjellies. Fructose is preferred

was produced from corn.t up to 4.3 million tonnes.

ent of sugar in AmericaIndia, two companies will beand technology from outside;

of one tonne of fructose perthe trade-name of Maizo-in Tamil Nadu.availabilitv and low cost. is

have to be made to developinto fructose so that the raw

could be converted into

: The ouflook", The Anrcricqn

plant biotechnolo95". Atttcricutr

out, Expert report to OECI)"

and Third World Agri-

lager: The last sleeper wakes"

16.3:1986.

CHAPTER 3

Health Care

The technique known as recombinant-DNA, or gene splicing'

enables the scientists to transfer the genes from one organism to

another. This, an inrmensely useful research, should permit research-

ers to produce large quantities of genes and study them in new

environments.t It gives the scientists the power to breach genetic

barriers between species and to give living things new propertles

that they would not naturally acquire. This has pertnitted human

genes that govern the production of compounds such as insulin'

interferon and growth hormone, to be incorporated into bacteria

which could then be induced to manufacture the compound'

Researchers are working on the production of vaccines against

malaria and hepatitis. A vaccine produced by gene splicing has been

made against hoof"and-mouth disease, one of the most destructive

of cattle diseases, whose trials began in 1982. Scientists at the City

of Hope National Medical Centre have isolated a gene that produces

a specific antibody that attacks colon cancer cells.

Microbes can be used to detect the most minute presence of toxic

chemicals in drugs, food, blood, etc. Pollution control, neutralization

and prevention at source are all possible with biotechnology'

Anand M. Chakraborty has developed a bacterium that can eat

toxic chemicals which may enable biologists in the future to develop

antidotes instead of banning chemicals. In a unique judgement, the

U.S. Supreme Court not only granted the process claims relating to

the mode of carrying such bacteria to water borne oil spills, but

even the patent rights to the bacteria themselves in 1980''

Instead of testing one chemical after another ryhich would make a

useful drug, scientists are identifyiog the substances that lofm the

body's natural delbnces so that rrcommercially. Products with mysterplasminogen activator, and factor

20 Blotechnology- Poss ibilities and Pros oects

can turn them outnames-Interleukin-2. tissue

III are beginning to moveThese chemicals helo

, dissolve the blood clots in

through FDA's clinical testingregulate the body's irnmunea heart-attack victim, and clotrespectively.s

the blood of a hemophiliac,

Diagnostic TestsA broad variety of faster, accurate diagnostic tests is

reaching the market for ordinarilv to diagnose diseases suchas prostate cancer. Less costly, effective and safer vaccines arenow being developed for diseases as heDatitis B. A vaccineagainst herpes infections is also bein tested.3

will take the delays out ofpneumonia, inherited diseases

These easy-to-use diagnosticdetecting infectious diseases suchsuch as sickle-cell anemia and vari cancers. The new tests canperform with startling speed and , in hours as opposed to

g of suspect microbes.right antibiotic or other drug

in time to save lives. This can also revolutionise theand killers as rheumatoidtreatment of such recalcitrant

arthritis, heart disease, and cancer. F. Drake, a biotechnology: analyst in New Yonk, predicts that new diagnostic tests based on

biotechnology will add more thanbillion a year world.wide diagno$tics

million in sales to the $4by 1987.4

' days consumed in conventionalDoctors will be able to prescribe the

Drake believes that the strongestbe tests using monoglonal antibodies,man's natural soldiFrs againstantibodies have alreadv been

contributors in this period willlaboratory produced clones of

diseases. A few monoclonal

Administration (FDA) for sale in diby the Food and Drugic kits. Deoxyribonucleic

acid (DNA) probes, a new and more versatile productof biotechnology, unlike antibodies,specific sequence of DNA. DNA p

work by hybridizing to someare designed to attach to

the invader's core.In designing DNA probe as a tool, scientists took

advantage of the propensity for two. to anneal. When heated or chemica

plementary strands of DNAtreated the double helix can

be separated into tlvo strands, and proper condition, strands. with bases that match can be If the tesearchers know the

2lHeal th Care

makeup of the target organism's DNA they can manufacture strands

of it, either by isolating a strand from the diseased organism or by

making DNA from scratch with off-the-shelf chernicals' The

machines can make lots of copies but more often the strands are

reproduced by being inserted into harmless bacteria, which multiplyrapidly. Once made, the DNA probes are used as a kind of fish-

hook to isolate a strand of helix from the target. All this happens

outside the body as both monoclonal antibodies and DNA probes

do their probing in samples of tissue or body fluids such as blood orurine. In both cases, clinicians get answers by observing whether the

probes find the target.Until the last few years scientists tagged practically all monoclonal

antibodies and all DNA probes with radioactive isotopes to find out

whether the detectors had bound to a target. Lately, however, the

trend has been away from using radioactive isotopes because ofdisposal problerns, the short life of isotopes and the need for costly

and complex instruments. Today, fluorescent tags that glow undermicroscopes and enzyme tags that cause colour changes are begin-

ning to replace isotopes. The plan is to make the test kits so simple

that they can be used in a doctor's omce or even the patient's

home.Since the new diagnostics are not used in the body, the FDA can

approve them more quickly than new drugs, and the approvals can

be had in as little as 90 days, rarely more than a year.

DNA probes will truly shine in diagnosing genetic diseases. Inprenatal diagnosis, DNA probes promise to make much earlier and

speedier determination of whether a foetus is affiicted with sickle-cellanaemia, for instance. Currently, only a few laboratories can con-

duct the-test and they take weeks to get the results, making decision

about abortions more difficult. By the end of the year, Cetus hopes

to bring out a test for sickle-cell anaemia that can be completed in a

day or two.Says Ronald E. Capte, Chairman of Cetus, "The opportunity to

diagnose early, and more important, to figure something about themechanism of sonre of the major auto-immune diseases such as

rheumatoid arthritis or multiple sclerosis, is not only a fantasticmarket but also a conceptual, intellectual, and social development ofmajor proportions". For instance, nearly half the 66,000 patients on

kidney machine need frequent blood transfusions with the accom-panying risks of contracting hepatitis B and auto immune deficiency

Health Care 23

technique to prevent the spread of disease. Also they do not require

testing for residual activityllife of virus present therein. Currently'such vaccines against parasitic infection (hepatitis, herpes, malaria,

leprosy, polio, cholera, rabies and fertility), are being developed by

a nttmber of different companies in the field. A laboratory prepara-

tion of the first anti-malaria vaccine was

volunteers in the U.S" in 1986.

administered to l3

These new vaccines are expected to be safer, more effective and

cheaper. There is a probability that researchers will develop success-

ful control measures lor tropical diseases and population control

and a new generation of diagnostic tools for bacterial and viral

diseases such as leprosy, tuberculosis and diarrhoeal infebtion'

HormonesHormones are another area where significant advances have

been made. Hormones are chemical messengers or metabolic

regulators produced by the organs of the' endocrine system' Llntilrecently, only simple hormones lvere produced by chemical synthesis.

More complex hormones such as insulin required extraction fromthe pancreases of dead animals. Hormones extracted from otherspecies are not identical to human hormones and some people suffer

allergic responses to them. Genetic engineering has pennitted the

manufacture of hormones previously impossible to obtain indesi;ed quantities, such as human insulin, human growth hormone(HGH) and tissue plasminogen activator (TPA). Tissue plasminogen

activator is a hormone that selectively dissolves blood clots thatcause heart-attacks and strokes. This is also in clinical trials.ln the past the only source of HGI{ has been through tissue

extraction from the pituitary gland of human cadavers' Geneticallyengineered HGH is now in clinical trials and should be on the

market in the near future.

Cancerlliotechnologists hope to take advantage of the body's own

immune system to control all cancers. They have found that they.

can either bolster the immune system by activating natural ki'llercells, or use copies of other substances the system produees todirectly destroy tumour. cells. : :

The immune system is highly complex. One section is calledhumeral antibody system in which blood cells known as "B Lympho-

ss Possibilities and Prcspects

. syndrome (AIDS) through the blood. Administering erythro-involved in the production ofpoietin (EPO), the principal

red' blood cells, would build up patients' red blood cells andeliminate the need for transfusions.. cannot be given to patients

' because there has never beenbe made in large qmantities usingtechniques.

Monoclonal antibodies will soon used as ."masic bullets" tocarry drugs, toxins or radioactive i that kill cancer cells butleave healtby cells alone. M . antibodies tipped with tinyamounts of cancehkilling radioi prepared by Hybritech inSan Diego are being tested on cancer oatients. Monoclonal

of it. Now the hormone canventional genetic engineering

antibodies have also been used withthe bone marrow of young children.

For some purposes such as of levels of proteinhormones, drugs and other that contain no DNA. onlv

. nronoclonal antibodies can act as But for other sleuthinsmissions antibodies are inadequate\vithdraw their antigens, alter them,

because some pathogens canshed tbem entirely, all to fool

the antibodies' surveillance systenl. echnically this phenomenon isknown as antigenic drift. It in influenza viruses andsalmonella, the organism that causesother pathogens.

Vaccines

ria, cancer cells and nrany

Vaccines cannot cure disease it is present. Traditional, vaccines are preparations of disease ' g vituses that have beenkilled and work because they i the viral oroteins that

When this material isimmune system develops anti-

bodies that will attack and deacti the specific virus causingd isease.

Successful cloning of genes for a, makes it possible tO synthesize viral

variety of antigenic proteinsfor use in the prepara-

tion of vaccines. Viruses are co of a number of differentproteins that are antigenic--thatantibodies.

is they stimulate to produce

Vaccines p{oduced by genetic en are simply preparationsof synthesised viral proteins that the immune system in anidentical,-melq9r,, and as. such do require elaborate isolation

24 Blotechnology- iness Possibilties and Prospects

cytes" manufacturg protein called antibodies. Sometimesor they alert other components

job. The second section oft or "TJymphocyte"

stimulate the prodtrction of antib,injected into the human body, the

cellular immunity system whichkiller and suppresspr cells. Theconsists of macrophages whichscavengers. Besides; they can alsointeract with intruders to make

types of,IL-l, alpha and beta, en

that makes orotectiVe substancesTumour necrosis factor in test.

explodes cancer cells and leavesit works against a whole range ofnf new lymphokines, colony stimfor some months. Researchers can

to kill leucaemia cells in

many forms including helper,section of the immune systemp dispose the debris, likecancer cells outright and theyrecognisable to killer T-cells as

production of IL-2. Twoproduction of lymphocyte

as antibodies.and animal experiments

cells untouched. Like lL-2,Tests on the third family

factor, are going on in Japanpin-point the very molecules

binant DNA.

targets. The immune system, thus, aof weapons.

cancer cells witb an array

After the age of 40 the i system begins to fail and thecancer cells, then b0ve ways of ing these multiple defences.The substances that have excited t scientists belong to the familyknown as lymphokines. Lym are produced in minuteamounts by white blood cells in to an gxternal challenge,such as the appearance of canceralpha and gama, are classed as

. Two types of interferon,kines because thev are

produced by white;blood cells. Il. released into the blood stream. sti

, another lymphokine, when

that make-up components of the i system. Genetic engineer-ing makes it possible to extractand mass-produce them by using

The patient is glven massive

components, synthesize them

. Bethesada, USA, first withdrawswhite blood cells and mixes th

of lnterleukin-2, (IL-2), animmune system activator, togethercancer-killing cells, Rosenberg of

ith a oatient's own activatedNational Caocer Institute,

t I0 per cent of patient'swith IL-2 which he iniects

together with large doses of IL-2 into the Datient. The IL-2, multiplies the killer cells in the patithe tumour. IL-2 is effective ag

' tumours-in the lurlgs, colon, and e

's body, which start attackinga broad range of solid

vhere.

ve obtained remission in half' - Rosenberg's first istudy seems to

Health Care

of 30 critically ill patients. Two were totally free of cancer ninemonths after the initial monthJong treatment; in the other 13patients tumours shrank by more than half and stayed that way atleast a month after the treatment.

Tumours recurred in people when IL-2 treatment was stopped. Inall cases the cancer disappeared again with further doses. It is notyet clear whether cancer patients will need lifetime doses of IL-2, as

diabetics do of insulin, and whether the treatment will work foranyone suffering from cancer. Scientists note that as much as fve toten years of observing patients will be needed to determine whetherlL-2 can cure cancer, patients permanently.

Besides IL-2, other potent new weapons called tumour necrosisfactor and colony stimulating factor, as well as about a dozen otherbiological substances show prolrise in combating tut]lours.

Genentech seems to be the first. to come out with tumour necroslsfactor as it feels that this and gamma interferon can be developedfaster than IL-2. Cetus and Immunex have gone in for IL-2 besidestumour necrosis factor. The company will also try out immuno-toxine, which are genetically engineered antibodies linked to potenttoxins designed to seek out and kill cancer cells more specificallythan conventional chemotherapy can. Immunex with its staff of 125works on lymphokines. It has a powerful partner in Hoffmann-LaRoche, which manufactures IL-2. An Immunex variant of colony-stimulating factor will be tested soon on cancer patients in Europe.Many other companies in the U.S., Japan and Europe are workingon lymphokines and other cancer drugs, says Gene Bylinsky.6

ANIMAL HEALTH CARE

Genetically engineered vaccines for rabies, hoof and mouthdiseases and several viral poultry diseases are being developed.Bovine growth hormone can raise milk production by an average ofl0 per cent. Avian growth hormone promotes rapid maturity inchickens and porcine growth hormone reduces litter mortality rates.

Application of biotechnology in pharmaceuticals is gradually beingcovered by patents and proprietary rights. But generic substitutes

25

26 Biotechnology- P ossibilit ies and P ros pect s

can be manufacture{. The areas ofbiotechnology are:

1) Drucs

benefiting from

Prodoction of any proteins fl in the bodv such as Aloha-interferon, Gamma-interferon, in-2, Human Growth Hor-

' mone, Tissue plasrninogen activator for breakdown of blood clots).DNA technology.etc., is possible with the recombi

2) LyrrlpsoruursSubstances produced bv (white. blood cells) for treat-

ment of cancer and viral infections.

LytrlprloroxtNTo attack cancer cells.

Tuvoun Nrcnosls F,ccronFor tumoul repregsion; besides intebferon and interleukin-2

3) Dnuc TrncerrNcCan be reproduced with genetic erigineering. Cytotoxic drugs can

be directed against specific antigen] on cancer with the use ofmonoclonal antibodies.

4) VACCINES

Instead of producing vaccines frbm blood infected with virus,. production of the relevant antigen through DNA fermentation ormammalian cell culture.

5) CorvenrloNAL DRUc PRoDUcrtoNAll existing microbial processes c{n be improved upon through

biotechnology, e.g. antibiotics, hormQnes, etc.

6) New Drecrosrrc TecnNor-ocrrsForty-one diagnostic kits were afiproved for use in USA by

summer of 1983. Assays and tests can be used in surgeries by generalpractitioners and even in homes.

Health Care

REFERENCES

l. Colin, Norman, "The impact of biotechnology: The outlook", The AmericanRevrew. Autumn. 1982.

2. Kass, Leon R. "The impact of biotechnology: The right to patent", TheAmerican Reurew, Autumn 1982.

3. "Biolech comes ofage", Business Lleek, January 23, 1984.

4. ByUnsky, Gene "Biotech breakthrough in detecting disease", Forrune, July9, 1984.

5. "Rapid strides in bio-tech", Economic Tlrzc.s, November 18, 1985.6. Bylinsky, Gene "Science scores a cancer breakthrough", Fortune, Novembet

25, 1985.

SUGGESTED READING

Daly, Peter. The Biotechnology Business-A Strategic Analysis, New Jersey,Rowman & Allanheld, 1985,

27

CHAPTER 4

Speciality chemicalsExisting speciality chemicals made using fermentation technolbgy

can benefit a great deal fromBiotechnology introduces:1) Genetic engineering to fermen production, and2) Application of protein and

fication of existing chemicals orengineering to the modi-

(Of course, much morefor the second category.)

research mav be necessarv

Some of the developments in this

1) EnzymesAre protein molecules which chemical reactions in cells

for detergents, sweeteners, cheese- ing and medical products.Enzymes allow biocherrical reactions proceed towards equilibriumat a faster rate and at lower tem

a) Enzymes can be made more efrb) Where enzymes are extracted

the genes coding for these enzym

of new chemicals.

t, andplants or anirllal tissue,

may be cloned into micro-organisms. CHYMOSIN (RENNIN) currently obtained from calfstomachs for making cheese is now

2) Amino acidsAre used in food and animal fi to enhance flavour and

nutritional supplements or for pAjinomoto (Glutamic Acid)

applications-used in

Chemicals 29

3) Microbial polysaccharidesXanthan gum, for gelling in food and to enhance oil recovery.

This technology is dominated by Japan, U.S.A. and European

countries, but niches are available.Many of the older chemically produced herbicides, pesticides and

fungicides will eventually be withdrawn from the market and will be

replaced by genetically engineered products as they do not have

adverse effects on environment such as was witnessed in Bhopal.

Commodity chemicalsExisting production of chemicals is based on petroleum feedstocks.

High cost of plant and distribution network are formidable barriers

for new entrants. Of course, industrial applications have not to go

through the long duration of checks to which drugs are subject.

CHAPTER 5

Ener

By allowing energy intensive reactions to takerelatively low temperatures andindustrial energy use significantly.

biotechnology

By helping the farmers tochemicals for fertiliLers andtially benefit agriculture.

less dependent on oil derivedbiotechnology can substan-

It can aid secondary and tertiary recovery of some 200 billionbarrels of dornestic oil worth trillion by, for example, supply-ing xanthum gum to help push oil of the wells.

Biotechnology may also have anproduction of fuels from renewable

role to play in the

tion process at the rnoment is i as the fermentation process

reaches a level at which itceases when the conoentration ofbecomes toxic to the yeast. One y around this would be to

place atcan cut

develop yeast strains that arewould be to develop strains that

The ethanol fermenta-

tolerant to ethanol. Anotherexist at high temperatures so

that the ethanol could be distilled the fermentation vat as soonas it is produced. Methane from plants which are nowsubject to temperature of 30-35"C, ratio of 30 : I and pH of 7could be made to operateof variables.

the year at an increased range

CHAPTER 6

Engineering Challenges

The making of natural products with genetically engineered

organisms, poses new questions for engineers and offers them new

opportunities. Doing a fermentation with organisms crippled by

heavy genetic manipulation creates difficulties not seen in traditionalfermentation. Moreover, genetically engineered micro-organisms thatoverproduce proteins create difficulties in terms of subsequent

separation. Ralph W. F. Hardy, Director of Life Sciences in the

Central Research and Development Department of E.I. du Pont de

Nemours and Comparry, feels that this requires a new breed ofprofessional biochemical engineer: a petson trained both in fermenta-

tion technology and bacterial genetics, which is very difrcult.Genetic engineering is evolutionary rather than revoiutionary lt

draws on techniques and analyses that have been developed in otber

disciplines such as chemical engineering, microbial genetics and

protein chemistry. Shift from batch fermentation to continuous-

culture fermentation is the likely shape of the future in this fie1d.

Continuous reactors are associated with a greatly increased produc-

tivity. Batch processing was the best hedge available against

contamination by mutant organisms. During the two-to-seven day

batch fermentation, no mutation of consequence could occur.

Advances in the continuous fermentation and genetically engineered

organisms show that the growth associated materials are made

throughout the growth cycle, and that continuous culture is ideal forharvesting these products. Engineers are seeking to combine these

two advances in new fermentation plants' Absolute sterility may be

the most important challenge of continuous-culture fermentation.

Says Guidoboni, "We do not allow anything like screwed connec-

JZ Biotechnology*- Poss ib il it ies and P rospec t s

tions for continuous operations. thread on a screwed fittingflanged fittings. We had tois a perfect bug tfap. We do not

thoroughly re-design the whole system. Traditionallyacceptable valves, duch as ball are totally unacceptable". Byclosing the ball valve you have a pocket of liquor or broth.The best approach to a sterile is a diaphragm valve suitably

stem is itself sterile as thercPipe work is another

In addition to designing new fi reactors for recombi-mlcro-organlsms, engmeefs are to develoo new wavs topurify the end-products from these fermentations and they need tolearn how to scale up recovery of new products most of whichare proteins or peptides. En hope for irnproved large-scalepurifi cation with high-pressure chromatography to get conti-nuous culture throu,gh ultra

The Caltech engineers started the information in the literatureabout the genetic elements that i the reproduction of

and repressors of DNAplasmids, the variorus initiators,synthesis and developed models of biochemical reactionwith gratifying results. The Eli Company was the first U.S.ficm to market human insulin by genetically engineeredbacteria which had to take afermentation process,l

of precautions in the

India's first sophisticated cell and separator system called

modified. If a diaphragm valveone with a rising stem, then thewhich one has to be sure thatare spores that can survive inimportant area.

'Flow Cytometer' is being installedMolecular Biology, Ilyderabad.

Flow cytometry combines thebiochemical analysis in a singleanalysis and sorting of individualseveral parameters gn the same cetl

A typical flow pytometer haschamber and a photo-assembly.

t be used, you have to havehas to be steamlocked for

the Centre for Cellular and

of microscopy andprecision technique for rapid

cells. The ability to quantifyunique to flow cytometry.

as light source, a sampledetectors and processors

convert light signals into electrical and digital signals. Acomputer system analyses and the digitized data. The high

JJEngincering C hallenge s

potential of the cytorneter for biotechnology could also help in

research in tropical medicines.

Dr. Nagesh S. Mhatre, President of the Becton Dickinson

lmmunocytometry Systems, Mountain View, California, which sup-

plied the equipment to the Hyderabad Centre, says that the analyser

irelps undeistand clearly the various aspects of the immune status of

a patient. One of the emerging applications of flow cytometry is in

graft transplantation, where the rejection rate of donor organs has

proved a hurdle. The equipment can be used for monitoring the-efectiveness

of "suppressor" cells, reducing the rate of rejection of a

donated kidney or heart.He is also interested in monoclonal antibodies which are specific

antibodies to a given diseased cell. His company has bought new

and useful. antibodies developed by scientists all over the world and

has mass produced thsm for supplying to research laboratories':

REFER ENCES

l. Check, William. "The engineering challenges biotechnology is posing"'

Mosaic, Yol. 15, No' 4, 1984.

2. "Flow cytometer to be s€t up Hyderabad", Times of -Indra, November 25'

1985.

CHAPTER ?

Other

The reportr to the Organization fl Economic Co-operation andof scientists drawn fromDevelopment (OECD) by a

universities and industries states that biotechnology has applicationin medicine, conversion of agri wastes into energy throughbiological processes, control of on and improvements in

and even in recovery ofsewage disposal through benignmetals from inaccessible ore bodies biological leaching.

Removal of pesticides from water, nitrogen fixation for fertilizerusing immobilized living cells andby splitting water molecules in aoossibilities.

ion of hydrogen for fuel-synthetic reaction are good

The Office of Technology (OTA, U.S.A.) opines thatbiotechnology will cut across the en spectrum of chemical groups.

satisfies 90 Der cent of its rawModem chemical industry whichmaterial needs with oil has valuable in microbes that cantransform wood, organic wastes,needs.

sweetened with the products of bioeven high volume chemical feeds

other biomass to meet certain

rlogy. Experts believe thatsuch as ethylene, which is

Today, nearly $ 50 billion worth products are sold annually bythe chemical industry most of which derived lrom oil. But manyimportant chemicals could be nrade, , more cheaply, with thewater-based chemistry of living For example, indigo-dyeis being made experimentally by.diferent organisms lnto bacteria.

ing several genes from two-free soft drinks are beine

hsed to make plastic, could betechnology.

commercially with bio-

Other Areas 35

Leslie Glick, President of Genex, has pinpointed a range oforganic chemicals worth more than $ 12 thousand nrillion in sales'

*hi"h h. believes are likely to be produced in the near future by

genetically engineered organisms. One of the approaches is toproduce industrial chemicals in much the same way that reseatchers

are producing interferon and insulin. Another approach is to use

enzymes (bioiogical catalysts that govem chemical reaction in cells)

to catalyse chemical processes. Many chemical processes now

depend upon metallic catalysts which operate at high temperatures

uod ptettua"s, whereas, enzymes, in contrast, usually work at low

temperatures and pressures.

Mining engineers anticipate using microbes to recover valuable

metals from poor ores. Already bacteria of Thiobacillus are used

commercially to win copper and uranium frorn low-grade ores'

Quick response required for next generation computers requires

Josepbson Junction or gallium arsenide. ln place of the silicon

wafer, an ultra thin piece of glass with layers of proteins invisible to

the naked eye could be a good replacement for these as bio-chips'

Each protein molecule has atoms of hydrogen, oxygen and nitrogen

in a farticular configuration' The hydrogen atom, in an ordered

..rponi. to electric current' changes position in relation to other

atoms' in the process behaving like a molecular switch, either bring-

ing on or cutting off the flow of electricity.The utility of microbes lies only partly in the kind of products

they can make. Equally valuable is the fact that they can use a

variety of materials and perform chemical reactions at low temper-

atures and pressures. Economic environment and technical factors

will increase the industry's interest in biomass as an alternative

source of raw naterial. Biology will thereby take on the dual role ofproviding both raw materials and a process for production of ethyl

alcohol or ethanol. Organic wastes such as corn-stalks could be used

if the more complicated biochemistry involved were developed' As

the research advances, we may foresee not only alcohol production

but direct fermentation of wood to such other basic organic chemical

materials as acetic or lactic acids' Oil products such as lubricants

can be upgraded by biological processing of heavy oil and residuals'

Many of the early developments in biotechnology were simply

experiments undertaken by university scientists with no thought ofthe commercial potential. Currently, splicing of genes has become a

routine task performed by technicians. Even the painstaking process

JO Biotechnology- Possibilities and Prospects

of copying the genes so that they be spliced into bacteria is nowdone by automaled "gene machiway from maturity. At the start 1

:'. But biotechnology is a longtrick was to move genes, now it

is to alter them or to build new from scratch. Scientists believef new l'bio-materials". Alreadvthat they can create a vast array

some groups are exploring a new ipline called "protein engineer-ing" which promises to alloworganisms to produce materials

td use living

medical researchers are rnakinggenes and the substances thatbody.

Protein engineering is barely offscientists believe that enornrously

never existed in nature andtic progress in learning how

ploduce function in the human

he starting blocks, but alreadyfibres or plastics could be

manufactured by nlaking specific ifications in genes to improvethe products they can nake. Si , wool might be so changedto make it non-combustible. Thein protein engineerrng. In Britainis building fast.

Group seems to be leadinginterest in protein engineering

In medicine, several genes as oncogenes th4t cause thehave been identified and identi-uncontrolled growth of cancer

fying the gene that causes Huntin 's disease is imminent. Bvisolating these disease-causing researchers hope to find out

stop them. That is where thehow they work and then find a waynext breakthrough will come.

These leaps in understanding are lpading scientists closer to usingsuch techniques od humans, both tp diagnose new diseases and totry to cure them by correcting genetlc defects.

Professor Anand Chakrabarty fr{m Illinois University, U.S.A.,felt that the beneflts of research in biotechnology had already beenfelt in the introduction of vaccinei for vjral diseases, hepatitis,herpes, malaria, blood-clotting factdrs to cure haemophilia, and thepurest form of insulin (humulin) fdr treating diabetes. Althoughinterferon (proteins extracted from human cells) 'heid out promise,it had not made a great impact becairse of its limited ayailability forclinical trials.

Human growth hormones have be{n used to treat wounds quiclly,repair fractured bones faster and dure dwarfism in some cases.Genetic engineering could bring ilp exciting new discoveries likeplants which produce artificial sJveeteners, plants resistant todroughts, fruits or vegetables with increased protein content, and

Othet Areas 37

milch cattle which could yield more milk. Scientists are also work-ing on how to make plants fix their own nitrogen so that dependence

on nitrogeneous fertilizers could be reduced. This is, however, very

complex as genetic engineers have to deal with too many genes forintroduction and expression in plants.s

Chakrabarty feels that biotechnology would make its full impactonly after 10 or 15 years as a scientific assessnrent of introducinggenetically engineered organisms into the environment has yet to be

made. Currently, there is a national debate in the U.S. on theintroduction of such organisms before assessing their environmentalimpact. Unfortunately, there is no readily available technology todetermine this. The basic problem is that environmentalists feel it is

dangerous to introduce such organisms because they associate micro-organisms with diseases. We hope that fears of unknorvn side-effectswill prove baseless.

Much is still left to be uncovered. For example, researchers arenow beginning to understand the complex process by which theplants convert solar energy in the form of sunlight to tissue and thereis as yet only a hazy knowledge of what causes genes to switch onand of as they direct a cell's protein nraking machinery. There maybe environmental hazards associated rvith genetically engineeredbacteria and other organisms.

DELPHIC PREDICTION OF BIOLOGICAL BREAKTHROUGHS4

New nitrogen fixing plantsSingle cell edible proteinPlant resistant to predators (insects, pests)

Bacteria for use in waste treatmentand pollution control

Petrochemica I substit u tes

Gene therapy fcrr diseases such as

sickle cell anaemia-HPRTGenetic screening to isolate genes

responsible for birth defectsMapping of human genetic codeBetter knowledge of senescence

Understanding of immunological process

50 per centprobability

r 9851982r990

19841988

1993

1985

1984

1990

1984

90 per centprobabilitl,

t9951987

2000

1990

1995

2010

1990

1985

20001991

38 Blotechnology- Bu\iness Possibilities dnd Prcspects

REFERE}|{CES

1. Mukerjee, Dilip. l'Biotechnology, A way out, Expert Croup Report toOECD", Times of r'rdra, February 15, f983.

2. Business India, Match 16, 1983.

3. "Fear ofefects slows down biotech leap", Tinte.s of India, August 26, 1985.4. Clark. Robin. Scielce onct Technology ilr IVorkl Developtaeirr, Oxford, 1985.

succEsTED +EADTNC

Sasson, Albert. Biotechnolog ies, Oxforfl & IBH Publishing Co. Pvl. Ltd.,New Delhi.

CHAPTER 8

Ethical Issues

The shining success of this basic research fie1d has led to issues

involving safety, effect on environment, ethical choices, social and

economic impact, pattern of government support, the role ofuniversities, and the value system of the scientific community, says

Plof. Charles Weiner of M.LT.IThough at one time, biologists were worried that they might

create novel microbes that are dangerous to life and that mightescape lrom laboratories, even -6. coli with the ability to makehuman growth hormone is believed to pose no threat, for it wouldnot be likely to survive outside the controlled environment of labora-tory glassware or industrial vats. This led biologists to seek a

relaxation of the guidelines which many of them considered needlessly

restrictive and alarmist. Only two dangerous types of experimentswould continue to be banned, namely, those using genes able tosynthesize extremely toxic poisons and those which would transferdrug resistance if these were deemed detrimental to public health.

Testing adults for susceptibility to genetic diseases is another area

that may meet with opposition. For instance, one of every 20

Caucasians is a carrier of defective cystic fibrosis gene, a severe

dysfunction of the respiratory system. It is often fat4l, in youngchildren. Will people carrying such genes want to know it, and howrvill it affect their decisions to have children? Would a young personwant to know that he or she has muscle-debilitating Huntington'schorea which kills many victims by the age of 40? Less controversialwould be probes to screen people carrying a gene known to cause

heart trouble.A number of universities have been signing new kinds of agree-

40 Bioteclmology-

ments with genetic engineering and

which give a single corporationlaboratory or institute usually in thepublication reviews of discoverieslong term.r The critics argue thatmise academic ideals. HarvardMonsanto for cancer research in 197

Company and Hoechst for biin combustion studies and withbiology; Washington UniversityMallinckrodt in immunology. Inblished its own genetic engineeringfaculty opposition vetoed the pro'The special arrangements of pri

exchange for re$earch funds fromscientists . concealing their findingsProprietory restraints on the freebegun to crop up at biomedical

Corporations are more conscious

often unable to rhanage itapparent than in geneticceutical and agri-business look for

Many scientists ptefer industrialcorporations frequently offer theirtaDe than most researchers havegrants. The most serious question ofsities have privileges based onsalaries belorv what they could earn

the ability to study those questi

superiors, think fundamental. Theirindirect tax support as well as

many regulations affecting privatehow universitiest can establish . new

and government in the field oftheir integrity and credibility is .a

Llniversities and companies pointreturn of about $ 4.7 billion fromout of the new. discoveries on twhose manufacture will have been

technology.

Possibilities and Prospects

her high+echnology companiesaccess to a single

form of patent rights or pre-

return for funding it over a

agreements could compro-the first agreement with

. and with Du Pont Chemical

; MIT has joined with Exxonin Whitehead in molecular

St. Louis has joined with1980, Harvard nearly esta-

rporation, but. the public and

agreement.rity access to discoveries tn

industrial houses has led tothe hope of gaining patents.

ge of data have alreadY

meetings.the need for research but are

Nowhere is this moreto which chemical, pharma-products and techniques.

today precisely because

with less control and red

under government

all may be symbolic. Univer-unciation. Professors accept

corporate .life, in return forwhich they, and not their

receive direct and

of and exernption fromln the circumstances

lationships with corporationsengineering while preserving

issue.

that there will be a richpaid and the profits emergingwide bulk sales of products

bv recombinant DNA

Ethical Issues 41

Genetic engineering promises such vast medical and economicbenefits that working with the industrial sector to deliver them isfulfilling rather than compromising the universities' mission.

In 1982, between 40 and 50 professors were involved in consultingor profit-sharing arrangements with bio-engineering firms. Thisraises ethical problems as it conflicts with the scientific mandate forfree publication and discussion of research. Patent licensing involvesuniversities lar more than professors. The faculties have special tieswith donor corporations like that of consultants. The marketableproducts ofthe laboratories are offered to the sponsoring corpora-tions as patents. Co-sponsored research and longer term commitmentsin return for a more exclusive pay-off bring bigger sums. If thesponsoring company does strike it rich, competitors will take boththg company and the university to the court charging misuse ofuniversity's tax exemption. Collaborative research gives corporationsan even larger role in selecting research goals ihan in conventionalarrangements. Cdtics sugggst that areas like environmental eflects onhealth, which may reveal industrial pollutants as causes of cancerand other diseases may be neglected if research funding shifts froma government to a corporate base. A similar conflict may exist inagricultural research between the development of productive hybridsand the study and preservation of genetic variety in plants.

l.

REFERENCES

The Five Year Outlook on Science and Technology-|98|, Source materialsvols. I and 2, National Science Foundation, U.S. Government PrintingOffice, Washington. D.C. 2040I.Tenner, Edward. "The Impact of Biotechnology: Research Industry andUniversity", The American Rerrew, Autumn, 1982.

CHAPTER 9

Barriers to Technolpgical Advances

Biotechnology developments started a$ late as 1973. This technology,though young, is destined to change {griculture, healthcare, pharma-ceuticals, chemicals,. energy, etc. Ma4y expect that its impact will be

as profound as that of electronics, if hot more. Realising its impor'tance, many countties including Japan, Frane, United Kingdonr,Federal Republic of Germany and U.t.A. are taking special measures

to foster this technology.We will first examine the difficulties new entrants may face in

biotechnology business.

Entry barriers to new biotechnology fftms (NBFs)

l) Process technologies patentedSome of the process are patented, whilst many

because of their commercialprocesses are shrouded in secrecy,possibilities, e.g. Tissue Plasrninogen Patent by Genetech.Similarly, contract research by may be secret, or firstoption reserved thus precludingrecombinant DNA.r

of substances made by

2) Cost of researclr and devblopmentLarge scale recovery, puri and oualitv control

necessarily lead to specialised the Drocurementwould be very costly.

Cost is related in turn to the level. undertake clinical tests for a period

measures

of which

regulation. It is necessary to7/10 vears for in-vrvo human

drugs which raises the cost of to about $ 70 million'

Barriers to Technological Advances 43

Similarly, food and feed ingredients are highly regulated.Besides regulation, R & D costs augment with technical difficulty,

research facility requirement, size of research team required, andthe cost of pilot plant, e.g., sterile fermentation is necessary forpharmaceutical and for in-vivo diagnostics.

3) Hish investmenlSingle cell protein or commodity chemicals production require

massive investment and high quality and reliability in the plant andequipment. For instance, Microorganisms, plasmids, vectors andequipments for large scale cell culture, purification technology, andautomatic control systems, require high investment.

4 (a) Uncertainty of resultsBecause of the uncertainty of results, the cost of venture capital is

lairly high. Moreover, established companies are reluctant to investin unproven technologies. Because of this, established pharmaceuticalfirms shied away from biotechnology till 1980. Similarly, I.B.M.stayed away from personal computers till Apple succeeded.

4 (b) Process uncertaintyThe process of fermentation or cell culture is central to many

businesses. But each recombinant DNA product requires a specificprocess at the molecular level, which may be proprietory.

Besides, recombinant DNA technology uses a variety of hosts suchas bacteria, yeast, streptomycetes or manrmalian cells. And theremay be marked differences in costs depending on the alternativetechnologies. For example:

Mammalisn cellsE. coliB. subtillis

(Unglycosylatedi Glycosylated/without sugar with sugar groupgroup)

Recovery efficiencyAnnual production

Extracellular

8o9i'25,000 lbs.

Intracelfular

s0%10,000 lbs.

S 767 per lb.

Unit cost(Raw material, labour) $ t24 per lb.

44 Biotechnology-

4 (c) variety ofuncertaintY

For instance,tried, viz.,

technologies-

for cancer a

Alpha interferonGamma interferonBeta interferonInterleukin-2B cell grorvth

factorsB cell diferentiation

factors

A large number of diagnostic

RadioimmunoassayEnzyme-linked

immunoassayChemiluminescenceDNA ProbeNew enzymeJinked immunoassay

5) Learning and exPerience periodBio-engineering expertise can take

6) Access to distribution channels

NBFs do not have distributionthey afford to go in for exclusive

requires sizeable sales force. The wa

a) License the technology tolicensed Eli-Lilly for insulin;

b) Enter into marketinge. g. Biogen/Schering-Plough

c) Matketing the drugs to a

instance, Genentech markets humanin speciality chemicals, a small

large share of domestic market-contacted.

7 ) Management unaertainq)With rapid technological chapge

Possibilit ies and Pr os p ec t s

second generation Products'

of technologies are being

hage activating factorr necrosis factor

xlnstoxins

on of oncogene research

are also in the run:

vclonal/Monoclonal

Monoclonal

years to acquire.

of their own, nor can

tion or marketing whichout of this is to:

firms, e.g. Genentech has

and in-house manufacturing,for alpha-interferon;

group of specialists. Forhormones to hospitals;

of companies may hold a

y for enzyme-who can be

extreme uncertainty, a high

,Barriers io Technologtcall Advances 45

degree of flexibility is needed in resource allocation and acquisition

ofiechnology. (There should always be contingency tilternative plan')

Continuous and high research and development commitment is amust for success in biotechnology.

8) Global competitionFactors favour globalization because ofa) High capital intensity of R & D and manufacturing;Lr) Accelerating rate of technological change & ditrusion;

c) Emergence of global consumers as a result of mass media and

travel;d) Imposition of neo-protectionist measures.

This necessitates global perspective covering information sources'

technology breakthroughs, marketing network, and manufacturing

capacity. [A Japanese company noted that establishing a subsidiary

in U.S. would cost $ 80 million and decided instead to form joint

venture with an American company (1982 study)].

9) Knowledsi intensity of biotechnology involves intimate relation'ship between basic science and economic activity

Special relationship between science and technology in biotechno:

logy implies:a) High capability. and involvement of basic research;

b) Research and development claiming high percentage of sales

revenue;

c) Rapid generation of new proprietory knowledge acts as an

entry barrier;d) Global emergence and competition of industry'Basic research in biotechnology has moved into the commercial

arena and the firms are engaged in grabbing.the best scientific talent

they can get.

Porter" lists the following barriers to entry:I ) Economies of scale

2) Product differentiation3) Capital requirements4) Switching cost- from existing technology to tbe new technology

5) Access to distribution channel6) Cost advantages to established firms independent of scale:

Proprietary product technology

I

Biot echnolog y - Bus lyress Pos s i I

rle acoess to raw mateflplrle locationent sdbsidiesor expenence curve

Lent policv

so impediments to get {ut of an ir

d ass@ts

ts of exit-labour lay {ff, spares ,

inter-te'lafionshin

46 Biotechrtology-Buslyress Possibilities and Prospects

Favourable access to raw materialFavourable locationGovernment subsidiesLearning or experience curve

7) Government policy

There are also impediments to get {ut ofan industry such as:

Exit barriersI ) Specialized assets2) Fixed costs of exit-labour lay {ff, spares write off3) Strategic inter-relationship4) Emotional barriers

2.

J.

ResearchpersonnelPatents

4. Funding

5. Licensing

(Bell Lab)Business LabScientistsPatented-(But easy to copy)(Collective R&D dom-ing up since 1980 forpre-competitive bro-jects)

Because of defence andspace programmPs-large Govt. Fundin!

Bocause of fear of enti-trust suit, Bell Labs boldthe process for $ 2510@advance royaltyBell Labs alone sirentl: 57 million till 1964.Now largely t'unded both

Professors

No patent

As basic researgh maygive rise to com-mercial product nocollective researchNo direct Govt. fundsin USA. Japan andEurope-Large Govt.supportOpen field

6. Budgets Massive R&D budgets

Barriers to Technological Advances

7. Lead time Medium to long

8. Focus Both ooen and directed

47

Long for in-vivo Pro'ductsMedium for in-vitroproducts and Diag-nosticsDirected

New firrns founded ii Biotechnology in USA

lg77 3

tg78 4

tg7g 6

t980 26

1981 43

rg82 22

1983 3

r07

Many of the founders or co'founders were academic scientists'

Typically, such firms are research intensive.

No. of Ph.Ds in some NBFs-1982-83

Company

AMGENCalifornia

BiotechnologyCHIRONCollaborative

ResearchGENEXIntegrated

Genetics

Total no. ofemployees

100

44o/

t25219

125

Ph.Ds

45

21

44

25)+

25

1.

2.

REFERENCES

Daly Peter. The Biolechnological Business-A Stategic Analysis, New Jersey,

Rowman & Allanheld. 1985.

Porter, Michael E. Competitive Slrategy, McMillan, 1980.

I

CHAPTER 10

Financing and Mdrketing Strategy

Though early work in innovationsout with small finance, the middleof large resource, For instance,million till 1931. But scaling upproduction facility required i 26

new products can be carriedlater stages require deploymentresearch was funded with $ I

technology and setting up theion between 1934 and 39 of

which $ 5 million rvas for R&D andBecause of huge costs and risks,

2l million for the plant.prefer to go in for small

advances just to keep ahead of comAt the same time, social accrue from basic product

engine, etc.--whilst.firms aredevelopments -nylon, T.Y., V.C.R.,more interested in small

FinancingNBFs have to go slow in raising {he funds. Initially; they go to

venture capital market for funds. Tftrey may also enter into R&Dlimited partnership," or enter intq joint venture agreement for

t R & D Limited Partnership, where mohey is earmarked for speciflc R & Dprojects gets write off against taxable incbme and gets R & D tax credits. Ifsuccessful, they get favourable tax treattnent in U.S.A. (with profirs taxed atcapital gains rate-2o per cent-rather thdn at income-tax rate*s0 per cent).R & D L.P. is aiso used to fund clinical trials.During 1981-84 Biotechnology R & D L.f. raised:

1981 $ 55 million1982 $ 105.5 million1983 $ 170 mi ion1984

(Part of theyear) t 90.7 million

Financing and Marketing Stategl' 49

limited functions. After establishing their credentials' they can enter

into licensing agreements for product manufacture and marketing'

They start earning substantial funds by undertaking contract

research.

It is only after entrenching themselves successfully in the techno-

logy, and establishing their reputation, that they can market the

products/processes developed by them on their own (excepting where

ihe number of clients is small and can be approached directly)'

NBFs which have targeted less expensive areas such as food,

speciality chemicals and agriculture may enjoy more success in

bicoming independent manufacturers; e.g., Genex with speciality

chemicals is the most successful. (Many of the smaller health care

oriented NBFs are likely to be acquired')

Established finns adopt some of the methods listed below to get

into biotechnology business:

I ) In-house investment in R&D and plant;

2) Licensing and marketing arrangements with NBFs;

3) Investment and linkagcs with univcrsities;

4) Acquisition of NBFs or equity participation in NBFs;

5) Joint ventures or limited R&D partnership with NBFs;

6) Consortium members.

Established firms can afford to go in for high cost innovation and

can support high development cost, when they are convinced that

the ultimate risks are low. (I.C.I. invested Sl50 million in single cell

protein (trade rlame " Pruteen") but is unable to compete with

soybean on price).Froduct and market strategy followed by innovative firms may be

classified .as follows:

Broad Broad MarketEarly Product

MarketFocusNarrow

Product TimingEarly Late

Narrow MarketEarly Product

Broad MarketLate Product

Narrow MarketLate Product

Focussing oo a specifrc narrow rnarket early products niche to

obtain overall product differentiation or cost leadership is a stlategy

adopted by NBFi whose resources are severely limited'

'J-

)(, Biotechnology - Possib:ilitiei and : Pros nec t s

NBFs generally go in for low high uncertaintiesprovided it is relatitely easy to ini

Genentech

Genex

RisksEstablished corporations can beat

and marketing advantage or byproducts or by developing andMAB dlagnosi ics.

Rrtk,r.' Intefse competition--lt

chemicals-Low unit cost andessential.

-- has gone in for volume, high value therapeuticproducts.

- his gone in for

R&D

uld beefforts for late productsof supplying MABs to

h as in Ln yjyo drugs. The costdiagnostic kits is about i4

million and takes over years in the USA. Developingfinal diagnostic kits may five to ten times more,

Elements of success

For bulk products such as

's because of their resources

ccll protein or commodityto cheap raw material are

D is a must.For pharmaceuticals-Innovative

Marketing strategyFor NBF: Is detern-rined by its proprietary technology and

perceived opportunity;It could offer specializpd research services such as-technoNogy expertise in protein engineering, geneticscreening, diagnostics, {isease susceptibility based onmolecular data, specialiy'ed software for biotechnology,etc.

Because of the high costs and long gestation period involved, firstin R&D and then in testing before the products are introduced inthe market, the NBFs generally start by undertaking contract R&D:Gaining reputation, they enter into c{llaboration with big companiesto market their products; where marlets are specialised and small,they enter into direct marketing. timultaneously, they enter intomanufacturing phase. Only when thfy are well settled and havesurpluses, they develop a nrarketing nftwork of their own.

Financing and Marketing Stategy f, |

Marketing strategy

Established firnsGo in for technology acquisition through licensing and investtnent

in R&D.May select specific biotechnology portfolioMay opt for innovation witbin existing market (Humulin) or diver-

sificationThey must opt for continuous R&D for process innovation (e'g'

Encapsulation for fermentors ).They should constantlY undertake

weaknesses, opportunities and threats).

Market share

Economic sizeGenerally, doubling rnanufacturing capacity of process plants

reduces unit cost of production in real terrns by 20 to 30 per cent'

Experience: Leariing Curve: Familiarity with the process and

practice leads to enhanced productivity. The Japanese have taken

the economics of the learning curve for granted atid adjust their

prices accordingly.

II

I Problems ariseI

)

Market penetrationIt takes about ten/twelve years to achieve 50 per cent market

penetration. Another ten years have to be devoted to increase the

penetration to about 90 per cent of its potential'

Technological strategy for established firmsl) Pioneering technological leadership: The advantage of being

the first producer together with the reputation earned, because ofthe pioneering effort, go a long way.

2) Late entry leafurship: By leap-frogging to second generation

technology based on technological advances and irreversibility ofinvestments, customer response, externalities' etc.

SWOT analYsis (Strengths,

lf costs do not reduce with experience

and expansion, orlf manufacturing does not increase as

fast as that of comDetitors

s2

CHAPTER iI

Policy

Biotechnology is still in the embryo stage though scientists predict

that it will have as wide an impact as electronics, if not more' As it

rnay have impact on food, agriculture, forests, pollution control'

health-care, medicine and drugs, chemicals, mining and even on

computers it may well be said to be an infrastructural technology with

its pioducts and processes helping a large number of industries and

services. For its fruition, it would require high involvement of sQien-

tists, technologists, engineers, industrialists and marketeers' 'It is

breaking into areas which pose challenges to the existing concepts

and values.Leading industrial countries such as U.q.A.' France, Germany,

Japan, England have already taken the lead of almost a decade in

the development of this technology. Japan with its pre-eminence in

enzymes and ferrnentation is now leading the yay in pharr4aceuticals

development and may assuu.e leadership in biotechnology just as itassumed technology leadership in textiles, steel, shipping, auto-

mobiles, electronics, computers and telecommunications in thc past'

The glittering prospect of biotechnology bas been attracting th€

attention of the leading industrialists and pharmaceutical houses who

have been vying with one another to take advantage of the

biotechnology developed by' the scientists whether in universities orelsewhere. On the other hand, prospects of making fortunes is

beckoning scientists and academicians to channelize their energies in

biotechnology and to reap the benefits emanating therefrom., Anumber of professors in America have already tied themselves withspecific biotechnology industries and important universities likeHarvard and ldlT are.bejng funded by industrial houses for the

Biotechnology- Possibilities and Prosoects

biotechnolosv researches in their laboratories. Even inencashing of an idea'is lookedscientists from universities toand the possibility ol the

the United States of Americaupon with favour, the large exodusthe lure of biotechnologyuniversities and scientists mainly ed by public funding, whichare tax exempt, side-stepping which may be of use to the

to the individuals or organisa-society but which may not paytions engaged in it, are causing This has raised ethicalissues about which continued debate is going on.

The multi-national and private firms have been increasinglydeciding research priorities through their control over the nascent

biogenetic firms and by research to universities. By patenting

the findings, they are turningexploited by firms in developed

controlled water supply (irrigationbiotechnology. We have also seen 1

into a secret trove to be

in the last decade. ln

is ideally suited to devclopt a number of Igdians such as

biotechnology development as in Indfa we have as yet not developed

instltutional ethos of converting scierltific ideas and technologies intosuccessful industrial oroducts. The restraints, controls, and thepetmissions required in advance er a negative climate, ftustrateScientists and foice them to leave the countrv and eircash their ideas

through Boards did notBoard did not enable the

electronics industry in the country tospurts inrelectionics and computer

advantage of the enormous

fact, we seem to be lagging behind losing ground in the techno-

logy development taking place in industry.The Gtrvernment of India has up a National Biotechnology

Board which has chosen geneticcultuie, enzyme engineering, a

g, photo-synthesis, tissue-' fernientation, and immuno-

technology ds areas' of imrnediate interest to it. India with its

year-around wainr climate, long of sun and high level of

Har Govind Khorana and,Anarid' have been pioneers

Folicy 55

in biotechnology, but unfortunately not on Indian soil.

To enter this field at this stage and to attract leading scientists'

technologists, and industrialists interested in this field to the country,policy-makers in India rvill have to create a conducive environmentand, develop infrastructural facilities and go well out of their way by

ushering an all-out promotioi policy. Inoentives such as freedom ofpricing for specific number of years for the products that would be

. developed from this technology as also modification of the "Patentlaw", so that industrialists and researchers can look forward toreaping the benefits from the technology for a longer period; infra-structural facilities including well equipped laboratories nlanned by

competent technologists with close inter-relationship with the indus-. tries will have to be set up, and easy availability of instruments'

. equipmeqts, radio-isotopes, fluorescent and enzyme tags and

biochemicals will have to be ensured.. ..

One of the cost escalation factors in U.S.A. is the 7/10 years loogperiod of clinical tests before in-vrivo drugs are cleared by F.D.A. tobe offered to the public. This raises the pre launch cost of an in-vivodrug to over $ 70 million. It rvould be worthwhile consideringwhether the clinical test period could be shortened, as this wouldinduce drug manufacturers to undertake research and clinical tests inthe country. Of course, these measures should be in addition tothose suggested elsewhere for encouraging'technological developmentin general.

Biotechnology Board will have 1o be organized so that it does notbecolne an instrument for control and restiictions, but an agency forpromotion, assistance and development of genetic engineering and

biotechnoloev.UNIDO sponsored Intemational Centre for Genetic Engineering

and Biotechnology has 36 participating nations. They are nowengaged in tbe modalities for the search and selection of theDirector. The Centre would have two components: One, the JNUCampus at New Delhi;-.and the other in Trieste, Jtaly. The major

. facilities proposed for the Centre are : A fermentation pilot plantand a computer centre. The Indian component of the Centre willwork on problems related to the areas of agriculture and human andanimal lrealth. The Italian Centre would concentrate on industrial

r,,. , applications. [t seems that hydro-carbon microbiology would get, . priority. in the work piogramme. The Centre wor.rld have affiliated

centres in different countries. The policy-maksl's jn the country will

56 Blotechnology-- Possibilities and Prospects

have to ensure that the Centre acts as a catalvst forgenerating biotechnology in and specialised institutionsand develoo "Industrial Park" in ximity of the InternationalCentre.

The setting up of the Institute and developing an

Industrial Park in the vicinity of the Centre, the inter-

way, especially as its climate and number of iriigation facilitiesare well suited to the development o this technology. India can lookforward to a high impact of this on agriculture, health,energy, pollution control, mining, icals, chemicals, etc.,which would lead to an growth in the industrialstructure, a strong position in the i market and a fresh

orientation in nursing the and industrialists tbr highinvolvement and cornmitment.

SPINKS Reoort forms the basis fi encouraging biotechnology in"Mobilization" programme:Trade and Industry (MlTt).

the United Kingdom. France haswhilst the Ministry of IJapan has evolved in cooperationyear programme.

COMPARATIVE TAX TREATMENT

fourteen companies, a ten

IN SOI\IE

mingling of technologists,India an opportunity of a

Country CapitalonR&D

and industrialists, may give

in biotechnology in a big

F INNOVATION .{CTlVn'lES

Venture capital investment. in New Firms

(3)

Research and develop-ment lirnited partner-ships, Pooling ofinvestment funds ininvestment companies.(Profits taxed at Capitalgains rate, 20 per cent)

(2)(l)

UnitedStates

As for otherassets

Policy 57

(r) (2)

Japan 100% depreciation No special provisionsallowance for memberfirms of Research Asso-ciation

Federal Depreciated as for No special provisionsRepublic of other assets

Germany

United 100\ tax allowance for No special provisionsKingdom research assets. Allow-

ance for both capitaland current expenditure

France 50'l of cost depreciable Businesses which pur-in first year with chase shares in Qualifiedbalance depreciable Research Companiesover useful life and shares in Innova-

tion Finance companiesmay deduct 50o/n of thecost of shares in theyear of acquisition

Source: O.T.A. Report, 1984.

In India, Government can increase national competitive abilityb.y:

l) Identifying basic and applied research priorities, setting targetsand generating adequate funds to support these activities;

2) Developing infrastructure;3) Initiating programmes for joint university/industry research;4) Establishing centres of excellence (in university or outside);5) Sponsoring industrial research consortia;6) Identifying critical manpower shortages and taking remedial

action:7) Relaxing regulatory laws; (In U.S.A. it takes a minimum of

seven years of clinical tests to get approval for the introduction ofdrugs and may cost about $ 70 million. In Switzerland the trialperiod is much shorter);

8) Modifying Patent Act; and

(3)

Blotechnology*

9) Ensuring financial supportcapital, encouragement of industrialof scale and concenfration of tal€nt.

l. Malgavkar, P .D. Technologies forPublishing Co. Pvt. Ltd., New Delhi,

Possibilities and Prospec ts

equity participation, ventureto maxmlze economres

Development, Oxford & tBH

CHAPTER 12

Conclusion

The assessment of the business possibilities from biotechnology leadsto the following conclusions:

l) The technology has yet to reach a plateau as innovations inproducts and processes are coming up at a fast rate;

2) Even in the advanced countries the possibilities of this techno-logy for business opportunities came to be realized onlv after 1975:

3) As research is an integral part of the final product andprocesses, the business has to be built around ph.D. and researchscholars;

4) As commercialization of the technology is dependent uponresearch inputs, the percentage of sales a'llocated to research isunusually high and ranges from 30 to 90 per cent;

5) Though more than 100 companies are now engaged in the ,

biotechnology business in the U.S.A. very few of them are as yetpaying dividends;

6) Despite the long time required for commercializing a product,of the many companies that have come about only three have goneout of business, which shows that the prospect of the industry isbright.

A few companies that went public found their shares rising sharplyin the market initially, though the value of the shares later camedown because ofthe long delays anticipated in introducing pharrna-ceutical products to the market because of the time span required tosatisfacrorily complete the clinical tests for iz-vjyo druss.

7) Whilst a number of processes and invention-s have beenpatented there are quite a number of processes and techniques whichare open including that of MAB.

60

8) Intensive research for thcthe production visualised has toindustry.

9) At the same time there is an' and unprecedentdd possibilities.

agriculture, pharnhaceuticals' speci

established houses, thereforc, are

logy by funding research in unito bio-technologists, by enteringof the research, by enteringinvesting in the new biotechnology

l0) The minimum that the bia) Biotechnologists at the cuttib) About Rs. 5 crores of e

diagnostics and diagnostic tests

establishment costs:

c) Period of three/four years

testing the product even for11) The costs go on mounting fi

wherein the equipment requirelmonoclonal antibbdies would clai

pesticides,As biotechnology promises to:sticides. weedicides and cherr

fertilizers and chbmicals not fromand bacteria, as it promises toadverse climatic conditions such

produce them in millions to meet

developed diagnostic tests whichoractitioner or at home and are m

mises break-through inAIDS, as it has a potential forsuch as malaria, leprosy, diarrhto reduction in ddmand for energY

development, the hopes placedeven than on electroltics. Myears old even in thenumber of Indians involved at

every effort should be made tobusiness flall-out within the coun on a priority basis.

Biotechnology- Possibilities and Prospects

technologies appropriate toundertaken before launching an

because of the startlingthis technology whether inchemicals, energy' etc. ManY

active support to biotechno-

, by giving research contracts

contracts for commercialisationR&D Lirnited PartnershiP, bY

etc.,ology complex requires is:

edge;even for launching in

crores for theanother Rs. 5

br de-bugging the Process and

medicines and drugs.in-vivo dtugs and for chemicals

as also the enzymes and

considerable investment.the ecolosical hazards of

as it is expected to Producethe crude-oil base but from genes

uce crops and plants resistant toarid zones, saline soils, and

the emerging demand, as it has

be used even bY the general

accurate and speedy, as it Pro-diseeses such as cancer, herPes,

g various tropical diseases

hepatitis, etc., as it would lead

which is a constraining lactor fortechnology are very high, higheras the technologY is hardlY 10

sphere and has alreadY a large

froirtier level of the technologY,

this technology and to get its

ANNEXURE I

Areas Likely to be Beneficial toAgriculture

Ganguli of Hindustan kver, listed biotechnology areas likely to be

highly beneficial to Indian agriculture as follows:

For crops and plants

l) H]'brid seeds

As the advantage ofthe hybrids are restricted to the first genera-

tion, the farmer has to buy hybrid seeds anew every season. As aresult, hybrid seeds production has grown into a big industry. TheIndian Council of Agricultural Research developed 20 high yieldingvarieties of national importance and about 80 of specific suitabilityfor variable agroclimatic conditions in the country.

The traditional method of producing plant hybrids could bereplaced by tissue culture technology through clonal propagation andclonal technology. The technique is to take a piece of growing tissueof a plant, disinfect it and culture it in a suitable medium so thatthe mass of cells begin to reorganize into whole plants.

The outstanding advantage of tissue culture is the propagation oftrue progenies, ensuring uniform growth and productivity behaviourfor each species in a given agro-climatic environment throughsuccessive generations.

Tissue cultlrre research could provide major breakthroughs inplantation crops, coconutr polm, sugarcane, cashew, banana, oilseeds, forest trees, spices and essential oil-bearing plants.

Through cloning process rose plants have been reproduced in

62

these facts,novel organic compounds in

Blo:techntlogy - Poss'ibi lit ies and P ros o ec t s

millions and are'ofered at $ 3 for rplete plant (in retail), a priccsinsle cut flower. Commercialcomparable to the rate charged for

opportunities for this omamentalthe U.S.A.

have already been seized in

2). Genetic engineetingThe role of symbiotic bacteria in improving the

fertility of pulses and certain o is widely undentood. Attemptsmust now be made to genetically bacteria to enhancetheir nitrogen fixing ability several-ti as also of the crop and soil-

productivity. This is a highlyrequiring control on quality

specific species of bacteria forsophisticated, science-based

and application. However, once a snecies is modified itspropagation is within the of those equipped to undertakoindustrial fermentation. Research work and field tests showedencouraging results for pulses and

The other possibilities pursued laboratories involve nitrogenfixation to partially substituteis still a distant dream.

ing plant productivity. Ninety-fivecomes not from the soil but fromThe major criterion for deterrnining

in cereals and millets. This

is better. Scientists have

3) P hotosynt hes is inry r orter s

Photosynthesis implovers are a of new naturally occurringchemicals which are ushering in novel techniques for advanc-

cent of the weight of plantscarbon and water.

the yield of crops is phre dry weight of the plant and

which is the maior determinantof plant productivity. India is asunlight hours per year and any in

tly blessed with about 3,000which improves photosynthetic

efficiencv will have a maior rm Scientists have discovered aeven in one part per millionmixture of organic compounds whi

doses increases photosynthesis inupon the species.

by 100 per cent depending

The roots of this discovery lie in seemingly unconnected observa-tions such as the gr,ass grows better hen cattle qraze on it because

of the effect of cattle saliva on grass

to rose bushes produce better, largeron wheat fields, the productivity of

; spent tea leaves appliedroses; and when alfalfa is grown

found the commod presence of

Annexure I 63

4) Growth promoters and regulatorsThe principal aim of the agro-chemical industry has been to

provide chemicals that control competition to the crop, i.e. theweeds, insects, fungus and nematodes that reduce the yield or quality

or interfere with harvesting. This is the fastest growing segment ofagri-inputs in the Western World. Among the largest uses are

defoliating cotton in the U.S., a compound for enhancing wheat

output in Europe; for rubber in Malaysia; and ripeners on sugarcane

throughout the tropics. Most of these compounds mimic the naturalsubstances preseut in the plants, such as hormones and toxins.

5) Bio-insect icidesWhile the use of chemical agents for insect vector control has

glown by leaps and bounds, because of concern about over usage,

and other ecological controversies, a new series of bio-insecticides is

gaining rapid prominence. These are products of biological, as

opposed to chemical, origin and hence considered more eco-

compatible. The scientific developments in this field are fairiyrecent, complex and closely guarded. The major advantage of bio-

, insecticides is their high species-specific activity, target accuracy andabsence of adverse effects. Bio-insecticides are ol bacterial, fungalor viral origin. The major problem with them is that the micro-organisms from which they are derived are normally sp<,rulative, i.e.

they can remain in the atmosphere or earth for long periods.

6) Pheromones

The discovery of pheromones is opening up another new area ofbio-chemical vector control. Pheromones are insect sex hormonesand many of them can be synthesized in the laboratory. In actualfield conditions in U.S.A., pheromones are used as artificial traps toattract aod destroy insects of the same species but of the oppositesex, progressively eliminating harmful insects. The technique is likelyto become an ecologically acceptable tool in selective pest control as

weil as for several common domestic species such as mosquitoes,domestic flies and cockroaches.

7) Oilseeds, plantations and non-conventional oilsCoconut productivity in India is the lowest in the world. Oil palm

is virtually non-existent in the country. The neighbouring countrieswith similar agro-climatic conditions for instance, coconut in the

64 Pos sibi I it ies and ProsDec ts

Philippines, and oil palm inresults. Plantation is a macro-

have achieved soectacularactivity and must be

recognized as such in our

For animals

l) Embryo transfet,Embryo transfer is a new by which embryos from a

donor female are transferred to females who serve as sur-rosate mothers frrr the remainder of pregnancy. This technique is

improvement, planned mating,being utilised for such goals as

twinning, disease control and of reproductive function. The

advantage to the buyer is that he not have to go through a

long regimen of bteeding to the desired traits. More impor-of the existing animals astantly, the farmer does not have to

they can be used as recipients ofcedure for embryo transfer is very

ior embryos since the pro-like artificial insemination.

xygen at the prevailing higherresulted in unsuccessful com-

2) Milk prodrrctionOur knowledge of buffalo is inadequate and this has

to enhance milk productivity.been a limiting factor in our attemScientists have devoloped a by which dietary proteins are

protected in their passage through rurnen so as to mak€ feeds

thus formulated or fnodified more in enhancing milk output.The same group of scientists wbile working with biogas, observed

that methanogenesis is inhibited byremoves more than 50 per cent offood, the inclusioo of branched

acids. Since methanogenesis

carbon supplied in terms ofin fattv acids in the diet of

cattle led to incrdase in milkequivalent calorie levels.

bv 15-20 Der cent at

3) Fish farmingThe inability of tropical waters

mainly due to pauclty of dissolvedsupport large shoals of fish

temperatures in tropical waters,mercial deep-sea trawler fishing in coastal waters. The averaseyield of prawns if appropriately is 300-400 kilograms perhectare per annum compared to I 12 tonnes (Intensive) or 5-6

perr annum in Thailand, theHawaii. The high outputs in

tonnes (semi-intengive) perPhillippines, Taiwatr, Hongkong

Annexure 1 o)

these countries are the result of sustained research into and scientific

breeding of prawns in captivity. Scientists have been working on

ffio sp;cies of prawn, P. rnnodon and P. indicus, in the breeding

stations set up in Tamil Nadu in 1981 ' When properly developed it

would be poisible to extend scientiflc fish farming to other popular

sweet watir and brackish water species. Deep-sea trawling will

continue to be marginal and unremunerative.(The subject of animal bealth care-drugs, vaccines, etc , has not

been covered by Ganguli.)

ANNEXURE IJ

Some Pace

British CompttnyFoundedFunding

Achievements1982

1983

Compet itor

Celltech Drocess.

Products and P

ln 1980.€12 million.

It has enteredfor diagnostic

and one Iproduce 5

annually.

method forin air-upliftvolume than in

mpanies, Theirrformances

ational Enterprise Board took

joint venture with Bootsbased on MAB: Has first

of Medicaloption on

The company lras two 100 litre

44 per cent of ity, balance by four privateindustries, of ich I I per cent was sold toBiotechnology Investment Trust set up by N&M

Commercial of high purity interferons.MAB for typing.Alpha interfi

litre fermenter,of monoclonal

fermentersand can

antibodies

of USA using encapsulationhybridomas in suspension

with lower bioreactor

Annexure IICETUS

FoundedDiverse interests

Financing

CANTOCORFoandedFocus

Technically alrcad

ELI.LILYFoundedSales

R & D budgetAchievements

Has funded

Being small, it accesses outside business functions for marketingand for research. It markets products that can be introduced early

to the market, viz., diagnostics. It offers non-exclusive licences tomarketing partners to cover the world market. It supplies key-

components of a new health care system at high royalty (20 per

cent).

67

In 1971.

Such as high purity fructose, plaut genetics,

hormones, diagnostics, antibodies, cancertherapeutics, monoclonals, Interleukin-2Immuootoxin.Contract R & D, Licensing, Joint venture andmarketing arrangements, Venture capital,R & D Limited Partnership.

ln 19'/9.

Cancer diagnosis and therapeutics.In cancer resea rch,MAB based: Diagnostic test for hepatitis

'B', Gastro intestinal andovarian cancer test. (lntro-duced in Europe and for exPeri-

mental use in USA.)External academic research rvith option forlicensing and 4.8 per cent royalties on

product sales.

In 1982$ 2.7 billion$ 294 millionFirst biotechnology involverlent in recom-binant DNA technology to produce humaninsulin. Till recently, only porcine insulin was

available. With licence from Genetech whichcloned the genes coding Eli-Lilly introduced

68

Conxpetitors

GENENTECHFoundecl

Funding

EyolLttion

Pharmaceuticalareas

Personnel

FinancialstrategyFinancialproblerns

Strategy

Biatechnology- Pos s ibilit ies and Pr o.sp ec t s

"Humulin"later in USA

British market in 1983 and

NOVO of k, who have developed aprocess to precursor of insulin "Pro-insulin". NOadvanced

O leap-frogged to a morecost effective recombinant

& D contracts,share offering

process. ln 19 , Eli-Lilly opened BiomedicalResearch as transition from chemicalto biotec

In 1976.

Through capital, RR&D Partnerships,to the public.Contract R &Licensing own to other companies,Inhouse g and marketing.Immunology, , Cardiovascularagents, Virology.

Consists of sciences and manufactur-ing personnel, research and regulatoryaffairs staf, an marketing personnel.To operate at breakeven point.

Cost ofperiods

clinical trials for long

yield returnsraising funds which will

many years. (Raised $ 120million three R & D Limited Part-nerships. Mr 990).

more will be resuired till

It has focused human/animal health care.It has all functions of an integratedpharmaceuticalIt markets own

business.products to hospital special-

ists in fourendocrinology,

iority areas: Immunology,

Oncology,Cardiovascular agents, and

69

It meets its operating expenses from contract

R & D and royalties. Seventy-six per cent ofits earnings is lrom this source.

Its clinical trials are financed through R & DLimited Partnerships.Its non-drug tesearch spin-off has enabled itto start joint ventures as follows:

With Hewlett Packard for developing

instrumentation in biotechnology;With Corning Glass Works for industrial

enzymes;

With Travenol Laboratories for diag-

nostic Products.(lt has purchased 230 acres of land and built

74,000 sq. ft of manufacturing plant in 1983)'

lg77 - SOMATOSTATtrN' a brain hor-

tnone.

1978 - Clones human insulin.1979 - Human growth hormone.I980 - LEUKOCYTE interferon.

1981 - Bovine growth hormone.

Its achievements Cloning and expression of LYMPHOTOXIN

in molecular GENE.hiology Ctoning of gene for tumout necrosis factor'

Cloning and expression of human oncogene'

Partial characterization of human tissue

Plasminogen activator for dissolving blood

clots

Genentech reported the deciphering of the gene for factor-Vlll; a

blood clotting substance needed in large quantities by hernophiliacs

to stop bleeding. Factor'VIII is so scarce, even in the blood of the

healthy people that it must be painstakingly concentrated from the

blood oi many donors, increasing the danger of contamination by

transfusions. It has already developed human insulin and is concen-

tral ing on growlh horntones.

Ln 1977.

Speciality chemicals and enzymes (for.quicker

Annexure II

Strategy

GENEXFoundecl

Focus

Its scientifcachievements

Biotechnology-. Possibilities and Prosoects70

Achievements1982

r983

1984

entry into kets).

Cloned gene

making).PhenylalnineSearle.

lor rennot (used in cheeseaspartic acid (an amino acid).an amino acid) supplied to

product for dissolving

grammes of proprietary

pilot plant, and Start up

D with number of U.S. andies to produce interleukin-2.

& D contract lor protein

new processes for vitamins,costs '$ 2000/3000 per lb).

Lo,rses in earlieryears due to

Sales-$ 20.6Enzymatichair in drainsAcceleratedR&D,Process scale

Constructionexpenses.

It lws entered into Contract R &Japanese

Consultancy $ 1 6.5 millionengineering

(currently, B-lIt is preparing for its own technolo obsolescence by going in

for second generation products (pro

GREEN CROSS

engineering).

Green Cross, desp'ite being one of a pan's lead ing biotechnologycompanies is behind the West in engineering. It has been

been in cultures of cells, amaking interferon for I years, but thisinethod that has several dra It has, therefore, given anArner.ican company a contractengineering technique.

the necessary genetic

Most firms have concentrated on interferon asainstcancer, but its application will be the to commercialise as theright kind of interfeton has to be and developed and largedoses of interferon wi be needed whi raises the question of inter-feron's safety. So Green Cross has to concentrate on rises ofinterferon where snrall doses can betaken into the body. It hopes to sell i

iven externally rather thaneron to treat eye diseases

like viral conjunctivitig and keratitis.development of interforon to treat skin

It is also well advanced or.infections,

Annexure II 7l

Green Cross has taken a conceptual idea to develop into a

commercial project, the idea being "artificial blood". Dr. Naitofirst came across the idea in 1960 when he was reading a reportabout some research at Harvard. Though Green Cross formed a

consortium, all other companies pulled out of it long ago' However,Green Cross is now ready,to market artificial blood, governnrent

approval permitting the project. The product is a chemical that can

temporarily fulfil blood's function of carrying oxygen. A patientwith sudden loss of blood can be treated right arvay without waitingto sort out his blood tvoe.

/8i".-MOIWTNTO

EnteredBiotechnologySales

Achieyements

Polic y

THENATIYE PLANTS INCORPORATED, SALT LAKE CITY,U.S.A.

The company has a staff of about 125 research scientists and hadsales of $20 million in 1980. lt markets commercially seed potatoes(mini tubers) and rose plants. As rose plants are developed throughtissue culture technology they do not have to be grafted on to otherroot-stock. The plants begin to bloom in two months. Potted andpackaged they are sold at $ 3.99 each (retail), roughly the price ofa single cut rose, whilst the buyer gets a complete plant.

SUNTORYSuntory, a whisky company is making efforts to diversify into

biotechnology. Japanese excel at fermentation, the basic process

technology in scaling up biotechnology. Continuous fermentation as

opposed to "stop and start batch fermentation" is the key develop-

In 1983.

$6.3 billion.It has entered into agreements with universi-ties which can publish the results and patent'but Monsanto has right to prior review and

licence option. Has developed mammaliancell culture technology and plant biotechno-logy and licensed it exclusively.It wants to move away from petrochernicalsand concentrate on higher value specialityproducts.

I -- I

ment. They have hired a universlceutical subsidiary; He has engaged

scientists.

DNA PLANT TEOHNOLOGYThe Cotporation has developed

of solids to water for Campbellr 985.)

ENZO BIOCI{EMEnzo Biochem expect to receive

probe kits to detect herpes I & IIDNA probes for hepatitis-B.ailments) and chlamydia.

GENETIC SYSTEMS, SEATTLEInfectious diseases are

victory was scored by monoclonaldetecting chlamydia, a veneral1983. Dificult to diagnose, the diwith antibodies. The chlamydiaGenetic Svstems ofl Seattle.

INTEGRATED GS,NETICS.lntesrated Cenetics of Framin

that will not require FDA a

contamination in food ratherroutinely check their products forToday's slow culturing tests whichas a week .tvhile results are awaited,Intesrated Genetics found that itstrains of salmonella with a- single

which the company hopes toin onlv about a dav. Anothertest usins monoclor.ral antibodies.

MOLECULAR GENETICSMolscular Genetics is a leading

ing on animal health care productsapproves faster thah it does dru$s fl

72 Biotechnology-* Possibilities and Prospects

professor to run a pharma-number of expatriate Japanese

RPORATTON, NEW JERSEYtomatoes with high. proportion

Company. (Fortune, 2 Sept.

irus (which causes respiratory

popular targets. Here, the firstwhen a kit for rapidlY

was approved by FD.{ inonce spotted is easy to cure

kit was developed by

GHAMhas developed a DNA probe

because it is used to spotin humans. Food companics

a common bacterium.food to be stored as long

lfood companies a bundle.detect 350 of the most common

of DNA probe. The probethis year will do its work

y is developing a competitive

in biotechnology concentrat-which the government typically

humans.

Annexure II

BIOGENBiogen is concentrating on low-volume, high-profit pharmaceutical

products such as gamma-type interferon, factor-Vlll, a clotting

agent for hemophiliacs.

GENAXGenax is concentrating on speciality chemicals market. Its major

product is low-calorie sweetener. By early 1985 it planned toproduce calf renin for making cheese, tryptophan for supplementing

animal feeds and vitamin B-12.

ONCOGENOncogen, a cancer-diagnostic company reports that they have

already used monoclonal antibodies to detect tumours in laboratorytissue culture containing only one million cells, as against today'smostly observational techniques for diagnosing cancer where the

victims are already having tumours the size of pea containing at least

one billion cells before the growth is spotted.

CETUSCetus is engaged in the development of probes for bacterial

intestinal diseases such as scours that affict new born animals,sexually transmitted diseases, blood-borne or lymph-borne cancer orother illnesses (,Abbott has financed Amgen to come up with DNAprobes for infectious diseases and cancer).

73

Blatechnology-.

l\taiorR&DLimited

Agrigenetics

Ca!ifornia Biotechnology

Genetic Systems

Hybritech

Molecular Genetics

Neogen

Genentech

Cetus

Alza

Genentech

Serono Labs

Xoma

Biogen

Senentech

Soatce : Biotechnology, V.i. 2, No. 8,

Possibil i t ies and Prospec t s

In Biotechnology

Year

55.0

.5

1981

| 982

1982

I982

1982

1982

1982

l98l

1983

1983

1983

1933

1984

1984

3.4

11 .1

1.0

F5.0

i75.0

t6.0

p4.0

P9.o

[6.0

60.0

Annexur e II -

Comparative Financial

75

Dsta on Selected Public New Biotechnology Firms

le83 ($ 000)

Company Revenue Expenses Net Income Total Assets

Amgen'

Biogen

BiotechnicalInternational

CaliforniaBiotech "

CambridgeBioscience

Centocor'

Genex

Hybritech

Integrated

Genetics

Molecular

Genetics

( 3,479)

( l l ,664)

( 2,2s'

( 20t

( 986)

( 836)

( 5,37e)

( 474)

( 2,1',71,)

1 as2)

4,347

18.437

698

5,266

535

7 ,407

11,091

15,965

3,046

6,915

7 ,826

29,453

2'952

4,986

1,521

8,243

16,470

t6,439

5,217

6,463

55,438

I1l,428

171185

s lt{24.ffi4

52,107

48,066

)'t 7<<

' Nine months" 30th November 1983

,Sorrc? : Biotechnology News, Vol.4, No, 14, lst June 19g4.

Comparative Financial Data for

ACTUAL DATA

Company/Qtr. Ending

2W.( 7

264.( |Hazleton Labs 3/31/85 1,596.( 7

Hybridoma Sciences 3/31/85 82.( 7

Hybritech 3/3U85Imre 3/31/85Immunex 3/31/85Immunogenetics 3/31i85Integrated Genetics 3/3 l/85Interferon Sciences 3/31/85Microbiological Sci. 3/31i 8tMolecular Genetics 3i3 l/85

600.( 7

15. (

s5.( 7

Monoclonal Antibodies, 3/31/85 l0O.(

Otisville Biotech 3l3l /85Ribi Immunochem 3i3ll85Summa Medical 3/31/85

Taeo 4/30/85Univ. Genetics 4/30/85

Ventrex 3i81l85

Revenues Expenses

Inter- Earned Total R&D Totalest Income Reve- ExPen. ExPen-

Income nues ses

(Thousands of $)

5,260 5 '202

396 590 986 2.445

74 836 961 958 | '4203 5,488 5,433 82 5'404

578 1,762 2,340 1,336 2,820| 525 I,918

91 98 352

82 161 350

l9s 69 362 570 2'9984 454 458 77 1,056

& 325

154 4,335 4,674 316 5'73e

Empyees

(date)

150.( 7

r"{

380.

86.( 3

2s0.( 773.( 3

Adv. Genetic Sci. 3/31/85Alfacell 4/30/85Amsen 3/31/85Applied Biosystems 3/29185

Bio-Response 3/31/85Biogen 3/31/85Biotechnica 3/31i85Biotechnology Genl. 3/31/85

Cal Biotech 2/28/85Cambridge Bio Sci. 3/31/85

Centocor 3/31/85Cetus 3/31/85Collaborative 3/2/85Cyrox 2128185

Damon Biolech 2/28/85ens Bio Logicals 3i31l85Endotronics 3/31/85Enzo Biochem 4/30/85Gama Biologicals 3/31/85Genentech 3/31/85Genetic Diag. 3/31/85

Genetic Systems 3i 3l185

Genex 3/31/85

7s.(88.(30. (

140.(610. (

135.(

15. (

120.(4.(

80.(

60.(173.(

674.(.t

13.(

87.( r

260.(.

130.(

360. (128. (

13.(240.(

)\ (

r 8.(1

37.( 757.( I

I7

83 23 106 1,651 2.120

1 122 123 266 600

613 ?,737 3,350 5,068

954 g,sls 10,469 1,365 8,510

428 558 1'565

1,834 3,030 4,864 7,893 9,840

l'225 I '983286 1'l5e

1,695 1,987 2,096

131 638

4,480 3,985

2,'t76 9,852 12,628 --'t2,411492 1,708 2,215 f ,2'7s

636 71O 12 530

568 108 151 3 '6'72

187 217 283

50 1,029 1,13?. 485 \'495

34s 1,508 1,857 560 l'3964,180 4'095

1,t53 19,011 20,164 15'116 19,449

22 226 248 200 349

711 2"367 8.503 1,076 4,838

s2 4,'l6s 4,861 2,185 1'313

-- 18,108 -- 17'618

1,714 l;867 1'981

-- 11,584 12,195 -- I I '82950 9 59 335 ',1rz

) 264 347 611 1,553 1,887

7

1

7

7

7'l

7,|

Public Biotechnology ComPanles

ANNU ALIZ ED DA TA

Net Profit Assels(Loss) Total

AssetsCurrent

TotalRevs./Emp.

yr.

Total Profit Current Total Revenue

Expen./ (Loss) Asset/ Assetl /AssetEmp. /Emp. EmP' EtrP.yr. yr. loyee loyee

(Thousands of $) (Thousands of $ Peremployee per year)

(Thousand of S

per employee)

(2,014)(417)

(1.718)1,939

0 ,007)(4,976)

(7s8)(873)(109)(507)495

2t1(1,060)

180(2,921)

(6)

(363)

461

85

715(101)

3,665(2,452)

490(114)

366(653)

(r,2't6)id

0,45e)(45e)

55(480)(393)(2s4)(18e)

(2,636)(5e8)

Q61)(1,06')

18.7 5 5.9

258.7

8,386 2,802569 136*:: "!:

l0t,353 72,O13

13,475 7,264

20,351 15,522

2,845 1,813

2'1,344 11 ,282144,9s3 93,45225,441 19,0251,427 576

8,381 8,0254,713 2,676

23,608 20,80326,582 14,339

a1a 1'r) l?{ <R4

1,197 1,584

44,683 36,79141,317 8,93479,135 28j765,720 4,205

61,889 33,729

3,694 3,083

16.096 10,950

16,2784,6689,282

26.3232,387

395

3,783

6,7892,7342,691

13,539

2.8

72.4 109.6 (9.3) | 28.o

16'7.5 136.s 7.8

30.6 85.8 (13.8)

51.2 103.6 (13.1) l8e.:57.0 92.2 (8.8) 84,-5

15.3 6l.8 (11.6)

90.3 95.3 (1.2) t'76.4

17.5 85.1 (16.9) 60.4

128.0 113.9 3.5 123.4

82.8 81.4 0.3 t53.2

65.6 97.0 (7.8) 140.9

189.3 141.3 12.0 38.4

25.0 122,4 Q4.3)276.6 282.7 (1.5) 2,006.2

56.6 74.7 (4.5) 33.+

123.8 93.1 7.7 346.7

96.7 94.7 0.5 82.9

I 19.7 115.4 | .l 201 .2

76 .3 lO7 .4 (7 . 8) 12t .8

170.1 96.8 18.3 184.0

73.6 110.8 (9.3) 33.8

4s.4 44.2 0.3 17.9

91.2 96.6 (1.4) 51.3

81.3 78.9 0.6 s6.?

ts.1 189.9 (43.s) 205.s

28 .t 86 . 8 (r4 .7) 125 .e

80.9 80.0 0.2

30.3 7s.2 (rr.2\ r2s.269.9 103.3 (8.3) 84.9

6t.0 ffi.4 0.1 25.8

73.1 88.1 (3.8) 205.761.0 76.7 (3.9) 23.e

15.7 s6.3 (10.2) 15.8

35.8 77.8 (10.5) 210.2

39.1 324.1 ('71.2' | 83.5

32.1 74.1 (10.5) 39.2

19.7 100.0 (20.1) 207.0

77.9 95.7 14.4) 56.4

56.5 (13.4) 0.05

0.870.28

20,511

9,02s24,8753t,5973,979I,5045,513

lo,7692,6275,624

u,zl2

266.7 0.19156.1 0.36

231.3 0.3994.8 0.18

195.3 0.66237.6 0.35

188.5 0.3595.1 1.99

2,095.3 0.1358.9 0.96

393.s 0.31

153.'t 0.63

330.5 0.36138.2 0.55223 .4 0.76156.5 0.4749.6 0.9269.8 1.31

103.2 0.19246.3 0.06I 85.0 0.15

157.8 0.19164. t 0.43

69.1 0.88246.9 0.3039.8 1.53

60.2 0.26306.3 0.12291 . t O.l4

. 46.1 0.70432.6 0.05100.9 0.77

ANNEXURE III

development of technologies ofcountries.

Agencies Engaged Biotechnologyin In

National Biotechnology Soard (NBftB) constituted in 1980 hasidentified the following priority areas] for research:

Hormones, Antibodies, Antibiotic$, Enzymes and Genetherapy.It hopes to isolate a vaccine againsf leprosy and parasitic infectionwithin a decade.

UNIDO sponsored International Qentre for Genetic Engineeringand Biotechnology would becorne a legal entity when at least 24countries ratify the legal formalities. The Centre would have twocomponents: one, the JNU Campus, New Delhi, and the other inTrieste, Italy. The major facilities for the Centre are: afermentation plant and a Computer tre. Tbe Indian comoonentof the Centre will work .on related to the areas of agri-culture and human and animal The Italian Centre would

The Centre would haveconcentrate on industrial .

affiliated centres in different countriThe International Biotechnology at Nerv Delhi is moving

are to create a centre ofahead fairly rapidly. The basicexcellence where scientists will be in research, training and

relevance to developing

Other agencies engaged inl) At the Council of Scientific and dustrial Research Centre for

Biochemicals a support facility been created to ensure thatrestriction enzymes and other important materials are

Annexure III 79

readily available. They have already started manufacture of a few

enzymes.

2) The Indian Agricultural Research Institute is studying charac-

terization of translation and transcription process in Escherichia coliduring cell division and gene expression in plant tissues.

According to Dr. R.M. Acharya, Deputy Director-General' ICAR,the country has 2l agricultural universities lraving faculties ofveterinary and animal science and with departments of animalgenetics and breeding.

ICAR has set up several institutions for preserving animal genetic

resources, including the National Bureau of Animal Genetic Re-

sources at Izzat Nagar, Arunachal Pradesh, the National Institutefor Goats at Mathura, and the Breeding Centre for Camels atBikaner, Rajasthan.

3) The Indian Institute of Science, Bangalore, is working on gene

expression in rinderpest virus, histogene, rice embryos structure, and

regulation of nitrogen fixation.4) The Indian Institute of Technology, Delhi, is concentrating on

conversion of cellulose to alcohol and other aspects of fermentation.5) Madurai Kamaraj University is working on molecular cloning

and sequencing of genes, coding for restriction and anti-restrictionproteins in Escherichia coli and shigella dysentries as well as cloningof biocide gene.

6) National Chemical Laboratory, Pune, is working on immobilisedenzymes and microbial whole cells (ethanol fermentation), develop-

ment of enzyme teagents and other biochemicals for genetic

engineering and biotechnology for cellulose utilization; plant tissue

culture including work on virus-free sugarcane; hybrid Napier grass;

studies on plant tissue culture for forestry (eucalyptus' bamboo and

salvadora); study on somatic hybridization.It has received Rs. 1.3 crores grant from NABARD to develop

forestry pla4ts through tissue culture and to train propagation

thereof through selected State forestry departrnents. After successfully

cloning the trees, the first training programme was held in 1986'

NCL has achieved micro-propagation of elite forest trees like teak

and eucalyptus and has developed choice varieties of fruit trees likepomegranate, and plantation crops like sugarcane' cardamom,

turmeric and ginger.

7) The National Institute of Immunology is engaged in the cons-

truction of mycrobacteriumJeprees' DNA library' human chgrionic

80 Biotechnology- Possibilities and Prospects

gonadotorpin (HCG) and human tal lactogen. They havetried anti-fertilitv vaccines on and trials on human beinqsare expected to start in coming few onths.

8) Osmania University and Cen

Biology, Hyderabad, as well as Boseworking on the application ofstudies of biological nitrogen fixation

9) The School of En Sciences, Jawaharlal Nehrunitrogen fixing genes into theUnivemity is studying the transfer

chromosomes of cereal bearinstechnology.

ts throush recombinant DNA

l0) Tata Institute of Fundamental h and Bhabha AtomicResearch Centre are carrying on work of cloning of genes ofagrobacterium and drosophila. Bhab Centre has introduced gene

cloning streptomycete, a technique genetic engineering. Formerly,

for Cellular and Moleculartitute of Nuclear Phvsics areengineering techniques and

used to take as much as tenselecting strains of high qualityto fifteen vears.

ll) Scientists at the Central Research Institute, Lucknowto identify protective

development. They also

n of cellulose.institute began functioning

at Aligarh Muslim University in 1 6. Set up at a cost of Rs. 50

lakhs, the institute will train students and researchers in the use ofcompulers in genetic engineeriug.

have applied recombinant DNAantigens of cholera bacteria forhave cloned genes involved in biod

The first post-graduate biotechn

Five centres of biotechnology haNehru University, Benaras Hindu

batch has just graduated orit irbiotechnology.

Some private firms such as HiHoechst and Tata Oil Mills are

a joint sector project in Tamil NaduAhmedabad factory has a capacity

e been started atUniversity, M S

987 with Master's

Poona University and Maduraipower in biotechnology for institu and industries.

JawaharlalUniversity,train man-The firstdegree in

research. Besides, two companies, in Ahmedabad and the other

Lever Limited, Ranabuxy,engaged in biotechnology

ill be producing fructose. Thef one tonne per day and will

sell fructose under the trade name " sweet".Hindustan Lever Ltd., has considerable success in oils

and fats which are the maior raw terials of their business. Theyhave investigated the feasibility of modified bacteria to

Annexure III 8l

produce edlble quality oil and glycerine for industrial use' Such a

proposition is of great interest to a perennially oil-short country

like India.Although the developments are at an early stage' the results are

encouraging. Scientists in the laboratories have manipulated genes

of two edible varieties of yeast to produce a hybrid cell capable of

not only producing and accumulating high amounts of fats of the

order oi 50 per cent of the biomass, but also capable of utilising

sugar at high rates and producing fat within three/four days' This

hai been accomplished by protoplast fusion and gene technology'

Having succeeded in growing this newly engineered species of yeast

in piloi fermenters and successfully extracting good quality oil from

the biomass, the scientists estimate that they could one day produce

good quality edible fats from nrolasses at a cost of Rs' 9,000-

Rs. 10,000 per tonne.

G loss ry

Asscrsrc Acm (ABA): A plant rne produced by fruits andand dormancy and retardsleaves that pl.omotes

vegetxtive growth; formerly kno as abscisin.AcrrNoMycETEs : Any mernber of the cterial farnilv ACTINOMY-

animal pathogen. UsuallyCETACEAE; includes hurnanregarded as lilamentous

AoeNrNn : Alkaloid obtained fromAtos : Acquired imrlrune deficiency

or by synthesis.

Alrrloros : An organic nitr compound having abitter taste as nicotine,insoluble in water arld physi

or quinine. Typicallyr'fiwa

ine

AlrrNo Acn : Anv of the organic corir-rpounds that contain one ortnore basic amino groups and one or more acidic carboxylgroups that are polymerized to form peptides and proteins.Only 20 amino acids serve as building blocks for proteins.They are component molecules o[ proteins.

Artrrony : A particular form of gldbulin present in the serum ofan animal and developed in respbnse to invasion by an antigen(protein foreign to the host whicfr stimulates the production of

- antibodies). It confers immunity against subsequent infectionby the same antigen.

ANTrBIorrc : A chemical substance, produced by rnicro-organismsand synthetically that has the cApacity in dilute solutions toinhibit the growth of and even to destroy bacteria and othermicro-organisms, e.g. penicillin pr streptomycin. Used in thetreatment of infoctious' diseases.

ANrtcnu : A protein or other molecu]e which when injected into ahuman or anirnal body will g$nerate the production of anantibody.

Glossar y 8 3

ANTtsBnl : Any immune serum that contains antibodies active

chiefly in destroying a specific infecting virus or bacterium.Aspentel,rn : A sweetener composed by two amino acids, phenyla-

lanine and aspartic acid.Assa,v : A technique that measures a biological response.

AuxtNs : An organic compound which promotes plant growth alongthe longitudinal axis when applied to shoots free from indigen-ous growth-promoting substances.

Azotte,: A five membered heterocyclic compound that containstwo or more cyclic atoms.

Blcrerul : Extremely small, relatively simple micro-organism tradi-tionally classified with fungi.

BIo-E\-GTNEERTNc : The application of engineering knowledge to the

fields of medicine and biology to assist defective body functions,e.g. hearing aids, limbs for thalidomide victims.

BlorNFoRMATrcs: Covers fields such as the use of computers inprotein engineering, software for DNA sequence analysis,

automated DNA synthesizers, automated process control, etc.

BropRocESsrNG: lnvolves conversion of a raw material substrate

into a product using microbial fermentation or enzymes.

BrosyNTsEsrs : The method of synthesis of complex molecules withinthe living organism.

BrorEcuNolocv : The application of engineering and technologicalprinciples to the life sciences.

Clr.lus (Tlsue) : A hard tissue that forms over a damaged plantsurface.

CeTAlvst : Substance that alters the velocity of a chemical reactionand may be recovered essentially unaltered in form and amountat the end of the reaction.

CslL: The microscopic functional or structur!1l unit of all livingorganisms consisting of a nucleus, cytoplasm and a limitingmembrane.

Cer"l CurrunE : The in-vitro growth of cells usually isolated froma mixture of organisms. These cells are usually of one type.

Crnurasp : The enzyme that digests cellulose to sugars.

Cnrt-ul-oss: A polymer of six carbon sugats found in all plantmatter; the most abundant biological compound on earth.

Cmrvrnu: An organism or a pa made up of tissues ol cells

exhibiting the admixture of cell populations frorn more thanone zygote (an organism produced by the union of two mature

B4 Biotechnology - Possibilities and Prospec ts

germ cells).Cstonopnvll : The green pigment occurs in plants and func-

g and utilising the radianttions in photosynthesis byenergy of the sun.

Csyuoslr (Rrnnr,.-) .: An enzyme li in the gastric juice of thefourth stomach of calf; used(albuminous content of milk) in

or coagulating milk caseinheesemaking.

CloNr : A group of genetiqally i tical cells or organlsmsproduction asdescended from a common , by asexual

by cuttings, graftings, etc., inColr-oroel SYsruu : An intimate mi of two substances. one of

which called the dispersed pdistributed in a finely divided

(or colloid) is uniformlv

ance called the dispersion medite through thc second subst-or dispersed phase may be aas colloidal dispersion orgas, liquid or solid. Also kno

colloidal susDension.

CttroMosoNrs : Any of the complex,animal and plant nuclei duringlinearly arranged genetic units.

the chromosome threads so tha

DroxynrsoNuclErc ActD (DNA) :

constituent of the chromosomesviruses), The DNA molecule

threadlike structures seen inkaryokinesis, which carry the

are constant in number

uplication and separation ofeach of the two dauehter

identical to that of

tosis.

for any species. In the h cell there are 22 Dairs ofchromosomes and 2 sex . (Karyokinesis-Nucleardivision characteristic of exact

nuclei carries a chromosomethe parent nucleus).

Curruns : Experimenthl growth micro-organisms such as

bacteria, fungi in a nutrientCvsrrc Frsnogs : A congenital c disease of the mucous gland

which affects the pancreas anddisorders.

digestive and pulmonary

CyrourNEs : Division of cytoplasmof a cell occurring at the end of

Cvroprlsu: The "liquid" portion o

plasm excluding nucleus)

a cell outside and surroundinsthe nucleus.

CyrostNn: A white, crystalline,rnetabolism.

idine. used in the studv of

nucleic acid that is thef all organisms (except some

ists of two polynucleotide

main

chains in the form of double containing phosphate and

Glossary 85

the sugar deoxyribose and linked by hydrogen bonds between

the complementary bases adenine and thymine or cytoslne ano

guanine. DNA is self replicating, plays a central role in protein

Jynthesis and is responsible for the transmission of hereditary

characteristics from parents to offspring'

Dlncsosrlcs (IN Vrrno) : Diagnostic kits and systems ftrr use on

tissue or fluid samples in the laboratory' Included here are tests

which have been available for some time and also new tests

incorporating monoclonal antibodies

Ducr'rosrtcs (IN Vrvo) : Diagnostic technology for use within the

body such as monoclonal antibody-based visualisation of cancer

' 'cells.

EMBRYocENEsIs : The formation and development of an embryo'

Exzvun : A protein which acts as a catalyst in biological reactions'

EnvnrnopotsirN (EPO) : A hormone thought to be produced by

the kidneys, that regulates formation of red blood cells' Itmay have therapeutic uses in treating anemia in patients with

chronic kidneY disease.

EscnERIcHlA Corr (E.Coll) : A species of bacterium which lives in

the intestinal tiact of a man and other'vertebrates' It is widely

used as a bost for recombinant DNA work'

ETHANoL: Ethyl alcohol, a colourlcss liquid miscible with water

and most organic solvents. Also known as alcohol'

EtsvI-ENE : A cilcurless flammable gas, boiling at 102'7'C used as

an agricultural chemical, in medicine, and for manufacture of

organic chenricals and polyethylene; also known as ethene'

Errreniore: Organisrn for plants and animals whose DNA is

sequestered in a nucleus in the cell'

Fecron VIII : Antihemophilic factor' A soluble protein clotting

factor in mammalian blood.

FrnunNtlrIol'- : An enzymatic transformation of organic substrates'

especially carbohydrates, generally accompanied. by the evolu'

tion of gas; a physiological counterpart of oxidation' permitting

certain lrganisms to live and grow in the absence of air' Used

in variouslndustrial processes for manufacture of products such

as alcohols, acids and cheese'

Fnucross : White crystalline water soluble sugar occurring in

honey and many fruits. Also called fruit sugar'

GrntNc : To form become a gel (gelatine), jelly-like'

Ger,ltut'.1 AnsrNtos : A crystalline material, melting point 1238'C;

6()

frequently alloys of this maphosphide.

Crrr: The unit of hereditycon trols the development ofof replication and mutation,chromosome and transmittedreproduction.

GpNr SpucrNc : (see GeneticGrxrrlc ; Of or relating to genetics,CeNrrc Coor : The order in which

are arranged in the moleculeamount of protein synthesised

. arranged in groups of three i' actjng as a unit which specifies z

,GENErlc ENcrNrenrwc (Also knownconstruction and maniDulationgenes coding for desired proteint

GrNovs : The complernent cf haploisingle gamete or nucleus.

Gtnsunnl-r-lxs : Any member of lrpounds which have a gibbaneof biological activity but are no

GnowrH HonN,roNs : A shortregulation of grorvth. Secretigrowth promoting properties, e.plants called auxins.

GunNrNe : A colourless solid used chHeploto (Trssurs) : Having half the

chromosomes as in maturc sermHnltcal : Spiral in shape or form li'HruoplrrLrL: A rafe, hereditary

' tendency toward bleeding andof Factor VIII.

Hpparrrs B : Inflammation of theHr:nsrcroE : An agent (e.g. a

plant growth; $pecifically, ainjurious to crop plants.

Hrnpns : An acute inflamrnation ofcharacterized by theinflammatory base.

Bioteclmology - Bus Possibilities and Prospect s

are formed with gallium

in the chromosonre thatry character. It is capable

a fixed position on aparent to offspring during

grnes.e nitrogenous bases of DNAich determines the type andthe cell. The four bases area specific order, each group

particular amino acid.as Recombinant DNA) : ThoI hybrid DNA to introduceinto specific organisms.chromosomes contained in a

ily of naturally derived com-sleton and a broad spectrum

as plant growth regulators.of protein invotved in the

of endocrine glandd havingpituitary growth hormone, in

fly in biochemical research.ploid or full cornplement of

marked by a

to deficiency

used to destroy or inhibitve weed-killer thar is not

skin or mucous membranes,

screw thread.ood disorder

due

of groups of vesiclcs on an

Glossary 81

HonuoNp : An internally secreted compound formed in endocrineorgans whictr afects the functions of specifically receptiveorgans or tissues when carried to them by the body fluids.

HuNulrctoN's Cnonrl : Disorder of the central nervous systen'characterized by uncontrollable, irregular brief jerkey move-

, ments, intellectual deterioration and psychosis.

HvenIo : The otrspring of genetically dissimilar parents.HYBRTDoMA TBcHNoLocy: The use of hybridomas (product of

fusion between myeloma cell, which divides continuously inculture and is immortal, and lymphoeyte -antibody producingcell); the resulting cell grows in culture and produces mono-clonal antibodies.

Hvpnopor.llcs : A method of cultivating plants by growing them ingravel, etc. 'through which water containing dissolved inorganicnutrient salts is pumped

INsur-tN: A hormone, produced by the islets of cells of thepancreas, that regulates the metabolism of glucose and othercarbohydrates.

INTERFERoN : A protein used by intact animal cells when infectedwith viruses acts to inhibit viral reproduction and to induceresistance in host cells.

INrsnI-EurtN (II): A type of immunomodulator which is beingtested for anti-cancer efects. It stimulates T cell srowthin-vivo.

IN-VIrRo: Literally, in glass; pertaining to a biological reactiontaking place in an artiflcial apparatus. In-vitro diagnosticproducts are products used to diagnose disease outside of thebody after a sample has been taken from the body.

IN-VNo : Literally, in life. Pertaining to a biological reactiontaking place in a living cell or organism. In-vivo products areproducts used within the body.

ISoMERASE: An enzyme that catalyses isomerization reactions (aprocess whereby a compound is changed into isomer; forexample, conversion of butane into isobutane).

Isoiopr : Any of two or more forms of a chemical eleme nt havingthe same number of protons in the nucleus but having diferentnumbers of neutrons.

JosEpHsoN JuucrroN : If two superconductors were weakly coupled,one could have current through such a junction without drop involtage.

88 Biotechnology- Bfsiness Possibilities und Prospects

LElcstnc : The removal. of a solirble compound such as an ore

from a solid mixture by washifrg or percolating'

LrcuMs (Legumirtous) : Any of a large family of flowering plants

having pods that split open w$en dry' comprising beans, peas,' clover, etc.

LyMpHocyrEs : Specialised white !!ood cells involved in the immune

response; B lymphocytes prodfrce antibodies,

LyMpHoKINEs : Pfoteins that media,te interaction among lymphocytes

and are vital to proper immurie function.LvsrNn: An essential, basic amilpo acid, (obtained from ntany

proteins by hydrolysis).Mrsrsrnu : Plant tissue for growth, whose cells divide

and differentiate to form tissues and organs of the plant.

Ivteristems occur within the

stems and roots.

and leaves and at the tiPs of

MEIABoLISM: The phYsical and processess by whichinto complex eiements,chemical components are

complex substances are brmed into simpler ones, and

energy is rnade available for by an organism.

Mpunoltru : A Product of inte iarv metabolism.

MtcRoBE : A mlcro-organlsm, y a bacterium of a Patho-

genic nature (disease bacterium). It can be seen

with the aid of a microscoPe.

MrcRo-oRGANISM :

or protozoan.MITosts : The process bY which cell divides to produce trvo iden-

tical cells that differ from the cell only in size.

MolEcurln ElclNEentlc: The of solid state techniques to

build, in extremelY small

orovide the functionalthe compcnents necessary to

of overall equipments

which when handled in mo

bulkier.

conventional ways are. vastly

MoLEcuLBs : A grouP of atoms ld together bY chemical forces:

the atoms in the molecules v be identical. or different.

MoNocLoNAL ANTIBoDIES (MAB) A highly spccific type of antibody produced bY a single of cells which can recognize

A microscopic plant or animal as a bacterium

I structure. MAbs are useful inonly one antigenic site/chemt

easily produced in large

specificity.

a varietY of industrial and ical capacities since they areand have a remarkable

Gtossary

Mur.lTIoN : A sudden appearance in the offspring of an organismof a characteristic not present in its parents.

MvBroul : Antibody producing tumour cells usually in the marrowof several bones.

NnrurnoqutNoNn : Greenish yellow powder soluble in organicsolvents used as an antimycotic agent in synthesis.

NITRocEN FIXATToN : The conversion of atmospheric nitrogen gas

to a chemically combined form, ammonia which is essential togrowth. Only a limited number of micro-organisms can fixnitrogen.

NucLErc Actps : Macromolecules composed of sequences of nucleo-tide bases. There are two kinds of nucleic acids; DNA, whichcontains sugar deoxyribose, and RNA which contains the sugarribose. Nucleic acids play a central role in protein synthesisand in the transmission of hereditary characteristics, since theyembody the genetic code.

NucLEorIDEs: An ester (compound formed by elimination ofwater and the bonding of an alcohol and an organic acid) of anucleoside and phosphoric acid; the structural unit of a nucleicacid.

ONcocBNE : A gene that causes cancer in an animat. Two or moretypes of oncogenes may need to co-operate to turn a cellcancerous,

OnclNrc (ColrpouNps) : Of or relating to animal or plant consti-tuents or products having a carbon base.

Otclxrsu : An individual constituted to carry out all life functions.PnntxprocnNnsts : A special type of reproduction in which an egg

develops without entrance of a sperm; common among rotifers,thrips, ants, bees and wasps.

Perrnt: A limiting property right granted to inventors by agovernment allowing the inveltor of a new invention the rightto exclude all others from making, using or selling the inventionunless specifically approved by the inventor, for a specifredtime period in return for full disclosure by the inventor aboutthe invention.

Persocnr : A parasite producing damage in its host. Any diseaseproducing micro-organism or substance.

PEcrrN : A purified carbohydrate obtained from the inner portionof the rind of citrus fruits, or from apple pomace.

hcrrNAsE : An enzyme that catalyzes the transformation of pectin

89

PH:

90 Biotechnology -into sugars and galacluron ic

Pos sibilit ies and P r ospect s

'PBprDss : Substances resultins from : breakdown of proteins/acids.A compound of two or more

A term used to describe the ion activity of a system,

A sotution of pH 0 to 7 is aci pH of 7 is neutral and pHover 7 to 14 is alkaline.

PggxvrllNnsn : An essential aminoby hydrolysis of proteinsbody.

PnrnouoNrs : d hormonal sccreted by certain animalssuch as insects and stimulating a

invididual of the same species.

havioural resDonse from an

PnmonssprRlrroN : Reaction in that competes with thefixing COr, RUBPCASEphotosynthetic process. Instead

' (ribulosebiphosphatecarbc' can utilise oxygen, which

out by plants where carbon

dioxide from the atmosphere is

of sunlight; the transformationinto sugars in the presence

solar energy into biological

results in a net loss of fixed CO'.PnotosvNrnssls : The reaction

energy.Pusurc : Combining form.Plesuro : An extrachromosomal

various strains ol E.coli andPLASMTNocEN Acrrv.rron : The

plasmin (a proteolytic enzymeblood or lymph). A factor whi

, which breaks down blood clots.Por,yunn : Substance made of eiant

of simple molecules, such as

Pot-vslccnlntoes : A group of

obtained in the levo formto tyros;ne in the normal

etii element found amongbacteria.precursor, br zymogen, ofplasma- the fluid portion ofcauses activation of plasmin

es formed bv the unionene (the unit of polythene).plex cartrohydrates such as

regarded as derived lrom x

rts

of

starch, cellulose, etc. They maymolecules of water.

Powornv Mtr-nnw : A funsus cterized bv oroduction ofabundant powdery conidia on host, a member of the familyErysiphaceae or the genus ofby po*dery mildew fungus.

A plant disease caused

'Glossary 9.1

high molecular weight that occur in alt living cells and that arerequired for all life processes in animals and plants.

PnornN ENclNrrnrNc : The study of the relationship of proteinstructure and function with a view to designing proteins withspecifi c characteristics.

Pnotopt,rst: The living portion of a cell considered as a unit;includes the cytoplasm; the nucleus, and the plasma membrane.Cocking succeeded in obtaining protoplast by using enzymesthat dissolved the cell walls so that membrane bound livingrnatter within the cells was released and formed., a suspensionof spherical, wall-less cells.

Pnotoplest FusroN : The joining of two cells in ttre laboratory toachieve desired results; such as increased visibility or antibiotic-producing cells.

PuntNr : A heterocyclic compound containing fused pyrimidine andimidazole rings; adenine and guanine are the purirte componentsof nucleic acids and co.enzylnes.

RlotoncrtvE IsoropB : An isotope rvhich exhibits radio activity.Reco {urNlNr DN.A : (See Genetic Engineering).SllnaoNrr-u: A genus of parhogenic bacteria in the family of

Enterobacteriaceae. Associated with food poisoning in man.ScLERosls : Hardening of a tissue, especially by proliferation of

fibrous connective tissue.SruroNtN : Greenish yellow powder soluble in organic solvents,

slightly soluble in water. Used as an antimycotic agent insynthesis.

Slltcou : A non-metallic eiement occt rring in a combined state inminerals and rocks and constituting rnore than one-fourth ofthe earth's crust.

Sorrw.ltr : The totality of programmes usable on a particular kindof computer together with doculnents associated with acomputer or a programme, such as manuals, diagrams andoperating instructions.

Sorrr,trtc : Of the body as distinguished from the mind.Sotrt.qtosr,qtrN: A brain hormone.Spncrelry CHErvlrcAL : Low-volume, high value chemicals such a^s

enzymes.Srnetrs : A group of organisms of the sarne species having distinc-

tive characteristics but not usually considered a separate breedor variety.

92 Biolechnology-Bussifuess Possibilities and Prospects

SussrnATB : A substance acted uponj e'g. by an enzyme.

Susprusor.t: The state in which th$ particles of a substance are

mixed with a fluid but are undissolved. Substance in such astate.

SvNonorrar: A concurrence of sev{ral symptoms or signs in a

disease which are characteristic bf it.THERAPEUTTCS: Phdrmaceutical products used in the treatment of

discases.

Tnrog.qcrlr-uu : A genus of grani-negative bacteria used forrecovering metals from low gradb ores, (copper and uranium).

Tuvuus : A gland near the base of tfre neck in human beings.

Tr-Plesrr,uo : Plasmid from agrobactbrium tumefaciens, used as a

plant vector.Ttssun : An aggregation of cells morf or less similar morphologically

and functionally. (Morphology: A branch of biology thatdeals with strubture and form $f an organism at any stage ofits life history.

Trssur Cur,runn : Growth of tissue in artificial media.Ttsus PlmurxocEN AcrrvAron (TPA) : A substance which causes

activation of plasmin which is involved in the breakdown ofblood clots, that cause heart a and strokes.

produced protein whichof tumour cells. lt has about

30 per cent homology of amino trlcid sequence with lymphotoxin.UnorrNlss : A thrombolvtrc involved in breakdown of

blood clots. It occurs in humanV.tcctxn : A preparation of any or virus for intro-

duction into the body in order stimulate the production ofantibodies to the mi introduced, in order toconfer immunity against any

type of micro-organisn.infection by the same

VEcroRs : DNA molecule used to i foreign DNA into host

Tulroun Necno$s FlcroR : Aexhibits in vitro and in vivo

cells. Vectors include plasmids'A vector must be capable ofmust have cloning sites for the

and other forms of DNA.ting autonomously and

ion of foreign DNA.VBNrurn Ceptrel : Money that is in companies with which

a high level of risk is associated

VTNBLAsTINE : An alkaloid from the periwinkle plantsalt as antineoplaslic drug.(vinca rosga) and used as

periwinkle plant and used

Glossary

as antineoplastic drug.Vnus : Submicroscopic infectious agent, smaller than bacteria,

capable of passing through filters that will retain bacteria andmultiplying only within a living susceptible host cell. Viruses

differ from all other living entities by possessing only one kindof nucleic acid, either DNA or RNA. RNA-containing viruses

differ from all other living entities in that their RNA serves as

genetic material because it not only stores genetic informationbut is multiplied by identical reduplication similar to DNA.

VrteurN : (Vita: Life) An organic compound present in variable

minute quantities in natural foodstuffs and essential for the

normal processes of growth and maintenance of the body'Vitamins do not furnish energy but are essential for energy

transformation and regulation of metabolism'X.LNrsuu Guu : A high molecular weight, water soluble natural

gum; produced by pure culture fermentation of glucose withXanthomonas campestris.

ZvlroonN : The inactive precursor of an enzyme. A non-catalyticsubstance formed by plants and animals as a stage in tbe

development of an enzyme. Also called pro-enzyme.

93

Index

Abbott 73

Abscisic Acid (ABA) 8

Acharya, R.M. (Dr.) 79

Actinomycetes 3

Adenine 2, 8Ahmedabad l8AIDS 22, 60Ajinomoto 28America 18, 53American 16, 45,7OAmgen 47, 73,75,76Amino acid 28, 70Antibiotic 2, 3, 5,20,26Antibody 5, 20, ZZ,23,24, 32, 66Antigen 22

Antisera 5Aspartame l7Assay 26A. tum<faciens 12

Auxins 8, 9Lzolla 16

Bacteria 2, 3,4, 11,14, 16, 11, 19, 21,35, 43, 60, 62, 80

BARC 80Becton, Dickinson, Immunocyto-

metry systems, Mountain View 33BeU Lab 46Biochip 35

Bio-engineering 4t,44Biogen (Coy)..44, 73,74,75, '76

Biomaterials 36

Biopesticides 14

Bioproc€ssing 5Biosynthesis 3, 12

Biotechnology Investment Trust 66Boots (Coy) 66Bose Institute of Nuclear Phlsics 80Boyer, Herbert 5Brazil I 1

Breeding Centre for Camels, Bikanel79

Britain 36

British 3, 5, 66, 68

Bylinsky, Gen€ 25

California 13, 33, 47Callus (tissue) 9, 10, \2, 13

Caltech 32

Campbell Soup Coy. 72

Capte, Ronald E. 21

Caucasian 4O

Cell culture 14, 15, 16

Celltech 66

Cellulase l0Cellulose 79Centocor 67,75,76Central Drug Research Institute,

Lucknow, 80Centre for Cellular and Molecular

Biolosy 32, 33, 80

Cetus (Coy) 21 ,25, 67, 73. 74, 76Chakraborty, Anand IU. 19, 36,37,

54Chesterfield 3

Chemotherapy 25China l7Chiron 47Chromosome 10, 80Chymosin (Renin) 28, 73

'96

, City of HoP€: Centre 19

Clone 5,7 ,20,79Cohen, Stanley 5

Research 78

Crick, Francis ICulture 2, 8, 9, 10, 16, 61

Cystic fibrosis 39

cytokinin 8, 9

Cytoplasm l0Cytosine 2

Damon Biotech 66

Denmark 68

7Z

DNA Probes 20, 21, 44Drake, Peter F. 20Du Pont 3

Embryogenesis 13

England 53

Erno Biochem 72,76

Established firms 51

Ethanol 30, 35, 79

Ethylene 8

Eukaryote IF!',ope 25, 46,67European 29EuroDean Govemment0 4

Colony stimulatin g factar 25

Corning Glass Works 69

Council of Scientifi.c and Industrial

Deoxyribonucleic Acid (DNA) 1, 3' 5'

6,8, 11, 12, 13,20,21,24,32Diagnostics 20, 21, 4'1,50,66,67DNA Plant Technolosy Corporation

Du Pont Chemical Cornpany zl0

Du Pont de Nemours ComPanY 3l

Edessess, Michael 16

Egyptians 2. Electronics Board 54

' Blements 7Eli Lily Company 32, M, 67 ,68

Enzyme 5, 10, 17, 18,21,28,35,44,53,54,69, 79

Erythropoietin (EPO) 22Escherichia <oli (E. coli) 1,2' 3, 5, 39,

43,79

Posslbilities and PrcsPect s

40

or VIII20, 69, 7J

.A.O. 15

Republic of Germ any 42, 57

2, 3, 4, 6, 30,3t,32,43,<1 <,r << 71 70

Batch fermentation 3lContinuous culture fermentation 31,

1.,

low Cytometer 32, 3jood & Drug Administration (FDA)4,20,21,55,72rance 42,53, 57

17, 18, 67, 80

61,65R-oger 9

arsenide 35

2,14, 15, 16, 19,22,28, 15,36'31,54,60,69,80

25, 44, 67, 68, 69,74splicing 4, 5, 19

Code 37

Defects 36

Diseases 21, 39

Diversity 13

Engineering 1, 2, 3, 5, 13, 14, 15, 16,

22,23, 24, 26, 28, 31,36, N, 41,

54, 55,62,70, 79, 80

Information IProgramme IScreening 37, 50

variety 4lengineered

antibodies 25

bacteria 32,37micro-organisms 3lorganisms 31, 35, 37

products 29vaccines 25

Systems, Seattle 72, 76

36,47,49,69,751,2)J

Index

Gestation period 50

Gibberellins 8Glick, Lesli 35

Cllobal competition 45

Glucose 17, l8Glucose isomerase 17

Government of India, 54

Oraf t transplantation 33

Green Cross 70, 71

Growth hormon€ 25, 26

Guanine 2Guidoboni 31

Haploid l3Hardy, Ralf W.F. 3lHawaii 64

Helical IHemophilia 20, 36, 69, 73

Hepatitis B 20, Zl, 36, 60, 67 , 12

H€rbicide I l, 29flerpes 20, 23, 36, 60

Ilewlett Packard 69

Hindustan Lever 61, 80

Hoechst 40, 80Hoffmann-La-Roche 25

Hongkong 64Ilormones 4, 5, 8, 9, 22, 23, 25, 26,

39, 44, 63, 67, 69

Humulin 36, 68

Huntington's disease/chorea 36. 39

Hybrid 5, 10, 12, 41, 61, 8lIlybridization 12, 16, ZO, 79

Hybridoma 5, 6, 66

Hybritech 22Ilyderabad 32, 33

Hydrolytic enzyme 10

Hydroponics 7

I.8.M.43t.Q.r. 49Immunex 25, 76

India 18, 54,55,78Indian 54, 55,78,79Indian Council of Agricultural Re-

search 61, 79

Indian Institut€ of Technology, Delhito

91

Industrial park 56

Insulin 4, 6, 19,23,25, 35, 36' 44' 67'

69

Integrated Genetics, Framingham 72

Interferon 4, 19, U,25,26,35' 36' ++'

66,69,74,13Interleukin II 4, 20, 24, ?5, 26' 61

International Centre for Cenetic

Engineering and BiotechnologY 55

56,78International Plant R€search Institute

13

hternational Rice Res€arch Institut€t5

In-vitro 47, 60

Ln vivo 5, 42, 43,41,55, 59' 60

lsomerase 17, 18

Isotope 2lItaly 55, 78

Italian 55, 78

Japan 3, 4, 18,25,29, 42' 46' 53' 56'

51 ,70Japanese 4, 12,45, 51,7O' 7lJ.N.U. 55, ?8, 80

Josephson Junction 35

Kenya i.tKhorana, Har Govind 54

Kohler, George 5

Leaching 34

Leguminous l4Lynphocyta 23,24Lymphokirte 24 , 25 , 26

Lysine 16

Maizo sweet 18, 80

Malaysia 63, 64

Mallinckrodt 40Meristem 8, 9, 11

Methanogenesis 64

Mhatre, Nagesh S. (Dr') 33

Microbe 3, 19,34,35,39Microbiological Resource Centre

(MIRCEN) 11

Micro-organisms 2, 6, 3t,37, 43, 63

Eiotechnology -Miescher, Fredrick lMilstcin, Ceaser 5M.I.T. 40, 53M,I.T.I.56Mitosis l0Molecular biology 40

€ngineering 28Molecule 5, 35Monoclonal antibodies (MAB) 5, 6,

20, 2t, 22,26, 33, 50, 59, 66, 72, 73Monsanto 3, 40, 71Morel 8Mutation I l, 3t

NABARD 79Naito (Dr.) 7lNational Biotechnology Board 54, 55,

78

National Bureau of Animal GeneticResources 79

National Cancer Resoarch Institut€(usA) 24

National Chemical Laboratory 79National Enterprise Board (UK) 66National Institute for Goats 79National Institute of Irnmunology 79Native Plants Inc. (USA) 7lN.B.F. (New Biot€chnology firm) 42,

44, 48, 49, 50New l]elhi 55, 78New Jersey 72New York 20Nitrogen-fiixing genes 15, l6N. & M. Rothschild 66Norman 16Northern Africa t7

o.E.c.D. 34'Office of Technology Assessment

(usA) 5, 34, 57Oncogen (co) 73,Oncogen€ 12, 35Organism 1,2,3, 5, 3L

Pacific North-West 13?atett 25 , 40 , 4l , 42, 46, 55 , 57Pathogen ll, 22

98 Possibili ties and Prospects

H 18, 30

t, 43

on 16

34, 54, 62

activator 26, 69arides 29

mildew 13

15, 36, 43

engineering 6, 28, 35, 407, 10,12, t3

oactive Isotopes 2l , 22, 55

13, 1.1, 16, 11, ?2,24,28,

80

&D Limited partnetship 48, 60, 67,68, 69

DNA 5, 19, 26, 42, 43

osenberg 24oya,lty 61 , 69

'r, 1')

t Lake city 71

an Diego 224, 44

of Environmenlal Sciences 80

21

l1ilicon 35

rz,79tostanin 69East Asia 15

Pacific 7chemicals 2, 5,28, 44, 49,

69,1356

Louis ,lO

1, 16, 30te 5,74,7l

Inde x

Suspension 9, 11, 66Swaminathan, M.S. 15, 16

Switzerland 57

Taiwan 64Tamil Nadu 18, 65

Tapioca 18

Tata Oil Mills 80

Tax 40Tax allowance 57

Tax at capital gains rate 56

Tax exemplion 56

TechnologyAgricultural l4Breakthrough 45Clonal 61

Commercialisation 59

D€velopment 54

Diagnostic 26DNA 40, 67

Enzyme & fermentation 3

Fermentation 28, 3lGama interferon 4Gene 8lGene splicing 1, 14, 19

High ,10

Hybridoma 5, 6

Immuno 54ImmunoassaY 44Infrastructural 53

Laboratory 2

Mechanical 16

New 52Process 7lProprietary product 45

Protein engineering 70Recombinant DNA 3, 26, 40, 43, 67

Second generation 5lTissue culture 61, 7lUnproven 43Varieties (for cancer cur€) 44Xanthan gum 29

Therapeutics 5, 6, 67

Thiobacillum 35Third World 16, 17

Thomas, Daniel (Prof.) l4Thymine 2, 8

oo

T.I.F.R.80Ti-plasmid l2Tissue culture 7, ll, 12, 13, 15, 16,

54, 73Tissue plasminogen activator (TPA)

20, 23

Travenol Laboralories 69

Trieste 55, 78

Turkey I 3

Tumour necrosis faclor 24,25' 26' 69

u.K, 42,56, 57

UNIDO 55, 78

United States (US/USA) 3' 4,7' ll.14, 17, 23, 25, 26,29, 32, 37' 42' 45'

46, 48, 50, 53, 54, 55, 56, 57' 59' 62,

63,66,67, 68,70,7lUniversity

Aligarh Muslim 80

Benares llindu 80

California ICambridge 5

European 4Harvard 40, 53, 7lIllinois 36

Jawahar Lal Nehru 55, 78, 80

Madurai Kamraj 79, 80

M.S. 80Osmania 80

Stanford I, 5

Washington ,10

U.S. Patent & Trademark Office

U.S. Supreme Court 19

Vaccine 19, 22, 23, 25, 26, 36

Vectors 13,43, 63

Venlure capital 3, 67, 68Vinblastine l2Vincristine l2Virus 9, 1l, 14,22,23Vitamin 8

Watson, James 1

Weiner, Charles (Prof ) rtWhitehead, Edwin 40World Bank 17

Xanthan gum 29,