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,