Professional Documents
Culture Documents
.P.
D, MALGAVKAR
Bombay
Calcutta
e)
ISBN 81-204-0287.1
Published by Mohan Primlani for O$ford A IBH Publishing Co. Pvt. Ltd.,66 Janpath, New Delhi 110 001 and Drinted at
Radiant Printers,
li{ ew
Delhi I lO M8
l':r8-7
Foreword
Biotechnology
policy.makers,
is, however, still so much a part oi laboratory research that its terminologies, 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 the field of agriculture, health, chemicals and energy, he has brought home the ethical issues and engineering challenges involved in its developmetrt and comrnercialization. He has suggested entry avenues
It
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 placing before the policy and acadenric cotnmunity fresh opportunities for development and growth as also new and emerging technology packages that will make this possible. In line with this, we hope that this publication will help in introducing the concerned development agencies to the breath-taking possibilities of biotechnology and to the pragmatic approach in converting it to succbssful business
enterprises"
New Delhi
January 1988
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 injecting public funds to usher in biotechnology in their countries. Just as computers elevated International Business Machines (IBM) to corporate 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) Longterm investment value, (5) Financial soundness, (6) ^{bility to
attract, 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 multinationals like Hoechst, Ciba-Geigy have enteted into this field. With the 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
Prefoce
to it:
I am grateful to Dr. N.K. Notani, d, Biology and Agriculture Division. Bhabha Atomic Research Centre, Bombay, for having gone through the draft very care Thc buggestions and corrections made by him Xrave greatly d in ensuring technological relevance in the overall framework of the book. Thc ooinions
expressed, however, are entirely that Dr. Pai Panpndiker, as usual,
the author.
strong support
to
my
years, went through a succession publication of the book and has con ing a glossary of terms and the inde
useful to researchers going in for in biotechnology, colnpanis and
technological forays by ensuring li financial and administrative $upport. It is gratifying to get such support to high tech areas from the prime Policy Research of India. Shri B.G. Shirgurkar, who has helping me for the last feW
It
ialisation of their findings tions entering into bioin 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 of California 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 into the 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 containing genetic 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.
Poss ibi
Ii
The molecule has four buildins rmain difference in the nucleotides are
bases
C: The
: Adenine Guanine
sequence
T
C
bases,
Thymine
Cytosine
of these
The bacterium Escherichia coli million base pairs and about 4,000
human cell may have between 10,000
paired, contains the genetic and functioning of cells. a genome with about four
It is estimated that a
100,000 genes.
In
is
use
of
such as yeast and bacteria to produce carry out a broad range of tasks, E cultures for over 6,000 years to make
ialcohol by fermenting vegetable mat bacteria have been put to increasing rnent and for the manufacture of advances in the early 1970s permi cells and micro-organisnrs in a manufacture substances that they enhancing their ability to perform im Genetic engineering can be used to modify the hereditary code of unique abilities. Biotechnology requi engineers since it utilizes a collection tecliniques. The output of this and animal health-c&re oroducts. chemicals, and even foods and is the use of biological systems to
decades
otic drugs. But the scientific the scientists to manipulate manner causing them to not normally .produge and
bioloeical tasks.
as the laboratory technologl
it
new or
the involvement of chemical industrially-based production includes manv human chemicals, speciality The common denominator
these products. This is which can be defined as ln a nutntlve
product.
new biotochnology has gonc
iu their own
equipment and has scientists, who alnost They have already office with nearly 1,000 years. These seientists have
Introduction
tumed recombinant DNA technology from a scientific feat of the highest order into what is now almost a routine laboratory procedure. with highly specialized enzymes, researchers can snip individual genes out of the mass of DNA that controls the heredity of living organisms. The genes containing the code that direct biological processes can then be implanted in other organisms such as bacteria. By growing these bacteria in vats, scientists can now obtain large amounts of hormones and enzymes that exist in minute quantities 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 the ease of access to and manipulation of its vital functions like
biosynthesis, etc.
Out of more than 100,000 species of nricrobes on earth only a few hundred are likely to be useful. They include yeast, moulds, bacteria and actinomycetes (rvhich make antibiotics). They can produce some 200 commercially useful materials, only a few of which the industry makes biologically today. The technology is moving at an astonishing pace, what with vast capital 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 of small biotechnology companies has sprung up around many university campuses in the United States. The small companies are often associated with university scientists who are attempting to turn their research findings into commercial products. Moreover, the British and French Governments have launched biotechnological companies with injection of public funds. France has made biotechnology a national priority whilst Japan leads the world in enzyme and
fermcntation technology. Several drug and chemical companies have research efforts under way that rival those of the largest biotech start-ups. For instance, Du Pont Company is exploring a broad range of projects from pharmaceuticals and improved varieties to pesticides and chemical feedstocks. Monsanto Company has completed a huge research Laboratory in Chesterfield that will house one thousand scientists. Paralleling the growing role of large companies is the declining role of venture capital in biotechnology. Shares of the biotech companies began to fall sharply in the summer. of 1983 and in 1984
160 conrpanies spent more than research. U.S. comoanies have at ments that give thb Japanese mark On the other hand, Scheringtechnology from $untory. Other Japan for the expertise to grow said to excel. Even though the world's leading biotechnology capital to form new companies has biotechnology indiustry. But now, trying to close the gap. The Frenc its own silicon valley by helping maior academic centres. No more than a handful of are exoected to succeed in
:200 million
I
in gene splicing 5 technology transfer agreerights in return for royalties. has licensed gamma interferon
.S. companies are tapping into ia in which the Jaoanese are universities emnlov some of
the lack of venture the develooment of local he European govemments are Govemmeirt is trying to create up hightech companies near
start-up companies, however, the necessary marketing expergrow into major companies. It tise and manufacturing capability is believed that a6 rnany as irds of the b.iotechnology companies will merge or be acquired one of the drus or chemical ventures the small comoanies to tetain a manufacturers. Joint greater share of theil revenues does licensine. Others are seeking niches that lnay be too [or big firms. Also helping to make it easier for the larger tb move into the stattj ups' turf is the gnowing of biotech trained scientists. As a result, it is gettimg easier for com ies not involved in biotechnology to recruit the scientists. Most the giant pharmaceutical firrns consider that it is fiskv not to be the biotech business.2
By 1984 about two-and-half bi
in the U.S.A. in setting up more to pioneering new products from panies have failedo whilst most stage. The products of gene-spli
olace en masse. Diabetics are now insulin produced tty modifying br than with animal insulin. The F of the U.S.A. is on the verge of growth hormone to counteract a to become drvarfs. Gamma type more promising than alpha-type in of cancer, are on the way to the
tins themselves with human ia in fermentation vats rather & Drug Administration (FDA)
ing the marketing
of
human
that causes some children interleron and interleukin (II), for treating ieveral kinds
et. New-born
Introduction
vaccinated against a fatal disease called scours, and green-houses are being filled with new varieties of corn and tomatoes that are hardier and more nutritious because they have been genetically modified. The Office of Technology Assessment (OTA) predicts that sometirne before the turn of the century annual sales of chemicals and drugs that are produced by gene splicing could top g 15 billion.:
1975,
1) Genetic EngineeringlRecombinant DNA is the technique of introducing hybrid DNA containing genes of interest into organisms (Escherichia coli, Bacillus subtilis or yeast) in order to make the organisms produce enzymes' amino acids, hormones and proteins. (Stanley Cohen and Herbert Boyer of Stanford University developed this technique, and applied for sealing the patent in 1974. lt 1976, Boyer formed Genentech, one of the successful biotechnology firms). 2) Bioprocessing involves the conversion of a raw material
substrate
enzymes.
The antibiotics, enzymes, amino acids and other speciality chemicals can be produced on an industrial scale with the introduction of recombinant DNA. Continuous sensor devices and the interfacing of process control with computer is being attempted to ensure automation and continuous processing. 3) Hybridoma Technology: Antibodies are proteins produced in
in response to foreign proteins or substances. Conventional antisera consists of a number of antibodies. Hybridoma technology allows the production of highly specific antibodies from
vertebrates
Incidentally, MAB technique was developed by Ceaser Milstein and George Kohler of Cambridge University in 1975. Their request to the British Govemment to patent the process evoked no response. In the process Britain lost the opportunity to take advantage of this important innovation.
MABs being very specific are utilised in diagnostic system; tn viyo diagnostic imaging for detection of tumour cells; therapeutics including immunization and immunotoxins, targetable drugs for tumour cells; tissue typing, purification and separation of biological
molecules, etc.
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 of ternperature 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$lting and chemical synthesis of DNA,' 5) Bioinformatics covers fields suph as the use of computers in protein engineering, software for DNA sequence alalysis, automated DNA synthesizers, automated proce$s control, etc.' HISTORIC^L MILESIONES IN THE
DEVSLOPS4ENT OF BIOTECHNOLOGY
Dotc
tation.
1857
I
Event
by fermen-
A.D.
Pasteui proves fermentation caused by micro-o rganisnrs' Frederick Miescher discofvered DN,\. Citric aoid produced by ifrdustrial fermentation' Penicillin mass-Produced. Francis Crick and Jamps Watson elucidated double helical structure of DN^A']. Hybridoma Technology for producing Monoclonal .dntibodies develoPed. Monoclonal Antibodies (MAB) discovered ,by Ceaser Wilstein and George Kohler, Cambridge, England (not
Patented).
Oxford & LB.H. Puhlishing Co. Pvt. LtF', 1987. "Biotech Comes of Age" article in Busihess Week, Jan. 23' 1984.
for
SUGGESTED READING
sasson, Albert, Biotechmlogy,
Oxtorf
a IBH
Publishing
New Delhi.
CHAPTER 2
Agriculture
biotechnology will have a pronounced irnpact. In recent years, scientists have developed techniques that can greatly speed up the process of breeding new varieties and permit more precise selection of promising strains. The basis of this new technique is a method of gtowing many copies of entire plants from single cells or even from
it
protoplasts
removed.
t
Known as tissue culture, the new technology permits multiple or clones of a particularly productive plant to be grown without waiting for the plant to produce flower sexually. First developed on a commercial scale for orchids, tissue culture has been. perfected for a variety of plants ranging from redwood trees to
copies
*Although the earth's surface is made up of more than 100 l6 elements in the fonn of gases or dissolved salts are essential for plant growth, namely, carbon, hydrogen, oxygen,
elements, only
potatoes.
knowledge of mineral requiremants formed the basis of all plant nutritional research, including that of hydroponics in 1940s fdr thc U.S. troops stationed on the soil-less atolls of the South Pacific. Hydroponics and aeroponics a.re, however, expensive ways to grow plants aod arc economically feasible under limited circumstances.
phosphorus, potassium, nitrogen, sulphur, calcium, iron, magnesium, molybdenum, boron, copper, manganese, zinc, and chlorine, This
'
The succeeding portion is derived from "The development of planl biotechnofogy", John
e, Torrey,
:g
i
Biotechnology- Bus
Possibil it ies and P ros p ect s use the soil as wth, supplemented bY organic
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 vitarnins were essential for of 0.1 to 0.5 parts per million' Th roots in culture. The 1930s elongation and development of also saw the beginning of an in sifying pursuit of previouslY hypothesized but ndt then identified organic substances believed to that act at very low concenserye as plant hormones i.e., substanc
leading to normal growth trations to control cell and tissue aci (IAA), one of the hormones and develooment. Indole-3-acetic s ts of plants, was identified in . controlling cell enlatgerrent in the .1937. Since then, the whole grouP of organic compounds with has been identified. similar biological activity known as es called cytokinins includes A second class ol plant ic compound, the purine derivatiyes of a univprsally occurring base adenine in DNrd. and studied since the oi prun, hormones (GAS), bscisic acid (ABA), ethylene, . | 950s incllde the gitrberellins
.
Most plant production for man's the source and subgtrate of Plant or chemical fertilizels. As early as 1930s, plant parts
fit continues to
--iil; il;
etc.
and placed in a sterile If the tiny apex of a shoot is t qrineral-sugar mediurn in the light, it rill grorv provided it is not too small. Shoot tips moasuring about I ' 2 mm in length and possessing two or three primordia will el gate and develoP leaves, often v into a whole Plant. Thts forming a root and going on to " me stem .culturgl' 4 lechnique pione by Morel in 1975 has been viral diseases. When trace I used . commercially to rid plants .o amounts of plant hormones are adde to such a medium., not one
such shoot is capable of but multiple shoots are formed. l growing into a whole plant or clone, making it possible to . increase a single plant to a million. a rost identical plants in a year' Merislem .culture is effective in con .well established elsewhere in the infe( shgot apex. If the ppex is excised i plants can be produoed and the croP ing diseases because viruses plant do not grow into the grown in culture, virus-free
This method is also used
tg
ir,nprove plants
that are
usua
cuttings., guch
as ghrys4nthemum
Agriculture
productivity in crops such as white potatoes. A great increase ia yields results from using virus-free stocks of seed potatoes. After three to four harvests, tbe seed potatoes are liable to re-infection in the 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 shoot apex. Such tiny apexes usually require some supplementary hormones such as gibberellic acid and potassium, in addition to the nutrients
appropriate trace amounts of an determined empirically through experimentation) are added to such a medium for culturing shoot apexes, instead of a single elongated shoot, several new buds or shoot apexes come up around the base of the new apex. In place of one 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 the process can be repeated or transplanted to a different medium where 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 and stem pieces. From the stem tissues there developed unorganized
needed excised root tips.
by
auxin and
a cytokinin (usually
If
"callus tissue", reminiscent of the tissues formed around wounds on the stems of trees. Cultured under sterile conditions on appropriate hormone mixtures, these tissues could potentially be grown indefinitely. Such callus culture is possible with tissues from any plant part or plant group. The proliferative capacity, rate of development and cellular characteristics expressed may vary, but the general requirements for the development of plant callus are well defined. By using the technique of culturing single cells and then inducing mor-
by the manipulation of hormones, it became possible to demonstrate conclusively that living plant cells of diverse types from diferent 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". Callus tissues produced on a solid medium can be transferred to a liquid medium and grown with constarit stirring. Under favourable hormonal 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.
phogenesis
10
Biotechnology--
Posslbil it ies
an
d Pros p ect s
Such single cells cad grow into to form organs and a whole plant.
for culture
a root tip was the final technical modem era of plant biotechnology. that dissolved the dell walls so that membrane-bound living matter within the cells was released and fl a suspension of spherical, wallless cells or protoplasts. Given change 'in medium and sonre time, each of these irrotoplasts 1i a new surrounding wall and began to divide creating a new colonv. ProtoDlasts could bc produced in this way from tissues of stem, leaf, or other plant parts. An astounding observation made in 1971 that under' appropriate nutrient conditions oDtimum ooncentration of hormones, cells that had been from protoplast and stimulated to divide could di directlv into embrvo like structures capable of developing whole plants by thousands or tens of thousands. In recent years bryogenesis from protoplasts, cell suspension, or cultured callus been achieved in a rvide variety of tissues in flowering plants, The discovery that hydrolytic such as cellulases and pectinases could be used to dissolve walls in a living plant organ prepared the way fof current ex ts in which the living wall-less cells or protoplasts of different plan are fused to create new olant hybrids or are used for the introd of new genetic matedal. In the relatively short period the time protoplasts are produced by enzyme treatment and time they form new cell walls-a matter of hours or per a couple of days-the naked cytoplasmic membranes of p can be made to fuse either by the addition of appropriate agents as polyethylene gtycol, or by the use of electric shock. Fusion of plasts brings together the entire living contents of two cells d more if care is not taken to prevent it. With careful attention t conditions, the fused protoplasts form a new cell wall and eir nuclei enter into mitosis
together and .dividee forming two sing twice the chrofirosome number , each with a nucleus
posses-
a living grorving organ such as which set the stage for the e did this by using enzymes
the protoplasts from which they are derived. This cell fusion is most suceessful when the two cells share a single parental source. The further apart the protoplasts are genetically, the greatef difficulty--not of cell fusion, which usually ogcutg-but,of the of the fused product.
Agriculture
11
The transformation by a bacterium is the porfect mechanism for introducing DNA into a plant cell, and serves as a model for much of 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 to propagate. 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 or embryos, are placed in cold-storage at 4-9"C, or frozen in liquid nitrogen 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. This storage, 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 Centres (MIRCEN) have come into being, the main centres being Brazil, Kenya, Senegal and the United States. By a choice of appropriate nredium, researchers can select cells tolerant of special conditions,' such as the presence of high concentrations of salt or specific herbicidal substances. Most cells will die, but cells with nalural resistance will grow, allowing workers to single out the exceptional cells which will develop into plants better adapted to a given field situation. Such selections have been made not only for tolerance of saline soils and herbicides, but for a number of other traits such as resistance to drugs or the ability to grow in the absence of certain metabolites. Although these methods have proved to be effective in field trials;. so far none of these mutations-
12 Microbiological Resource
12
Biotechnology
Poss
,.
I
success.
to
harness
the
special,
sometimes unique, biosynthetic cap .lations. This approach involves cul conditions that allow the cells to fi economic value-such compounds pigments, and the like which have
growing
as drugs, oils,
of selected plant cell popucallus tissues in bulk under a secondary product that has
the best examples of the potential of the success of the Japanese in ind . common gromwell (Lithospermum) ishikonin, a naphthaquinone used n
been
to
from 12 to 15 per cent of the dry t of the cultured tissue. Other products actively sought the alkaloids vinblastine and vincristine which are formed from the tured cells of the periwinkle (Catharanthus) and are used in therapy. Another area of itlterest and ent is sornatic hybridizationthe production of new plant types by ging together two dissimilar ' genomes, .esulting irt crosses beyond normal limits possible with sexual methods. In spite of the suc of cell fusion across generic ,lines, few such crosses have gone to form tissues capable of regenerating whole plants. Thus f, , interspecific somatic hybrid plants have been obtained from genera: Nicotiana, Datura, Solanum, Petunia, and Daucus. the basis of oresent knowledge it seems doubtful whether rem somatic hybrids can produce
regular, functional, competitive and
plants.
for the future is the use of as receptors for selected c information which can be cells or in organised plants
effiort among a number
e use
in pultured
of the Ti-plasmid from A. tumefacians. Plants studied as hosts are relatively few, 'including tobacco, petunia, carrot, potato and flax. Work with these rnodel systems has now dem that it is possible to 'modify the Ti-plasmid by gene on to allow efficient T-DNA . transfer without ttmour forn Thus, specially engineered the non-oncogenic Ti-plasmid of host plant cells, which can 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' First is 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 of
plants. Problems such as the lack of an easy method of producing genetic markers for cell selection, the difrculty of generating and maintain-
isolation of particularly interesting genes, the analysis of their control, and the improvement of the techniques of plant tissue culture to make it feasible to study more agronomically important
species.t
embryogenesis 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
engineers will have to cooperate plant breeders as selective breeding remains the key closely with the 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. Similarly, 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.
Even
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 and diseases which con:sume 25 to 35 per cent of crops, d they expect to make crops .resistant to saliniiy, pests, weeds, t and extreme temDeratures. Chemical companie$ are that the next generation of chemicals will come from engineered plants. The trick with cell culture has been to cells into whole plants with new characteristics intact. There are schemes to alter the vironment of plants with genetically engineered bacteria. A soil bacterium containing a foreign biopesticide gene and a leaf lacking the gene for ice nucleation mighi provide frostt crops. (In the U.S.A. Ithe experiment of roleasing these was stayed by a Court
,
Order). engineering
or other envi the scientists the inborn ability of legume crops to their own sustenance. Professor know about plants hAs historically lnicro-organisms, like bacteria and vi priorities is the needl for strong su of plant physiology and plant genetics Experts say that the world food through the developrnent of more di local conditions of soil wealth and wa could be achieved throush boost given by high yielding varieties that there are no better yielding vari fories. Moreover, tho scientists hold ways to increase the yields of rai breakthrough has, thoreflore, to come I Biotechnology can increase the plant sources to l0 kg per hectare protein. Moreover, technology of proteins indicates that a few thousand ll Oapacity each could sbtisfy the world .l Biological pesticides are not target will be specifio pests.and they lhsect world.
if
countries
is the
in implanting into
cereals
Thomas savs that what we behind our knowledge of and animals.s One of the
of plant
es
of protein from leguminous 0.6 to 1.5 kg of animal of single cell (microbial) tanks of 200 cu. m. of protein. and will not pollute. Their will 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' Moreover, 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 technology 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 'the century. On an average it takes about 10 years from the tirne a closs is made to the time it makes a widespread impact' Swaminathan 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 indispensable " 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-
,
.
,
so muclr of their metabolic be little left over to make the more pnomising is research fixing ability of existing lead to increased yields from
transfer the nitrogen-fixing genes legumes to other strains of cereal crops-in thoory an easier
city, etc., in the l|hird World gains in farm prodtrction have advances in output per unit of mechanical technology does not capital for labour. [n fact, it is
Secondly,
, such development may make nitrogen available to the plant ithout the plant itself having to use its own energy in the synthesi Though the bigggst gains in Amer farm production came frorn oil-based mechanical technology by the usage of tractors, combines and other farming , fertilizers, pesticides, electrig about 1967-68 the biggest from biological technology
it may be possible to bacteria associated with known to exist in the roots of than translerring them into
tually,
it
land. Biotechnology, unlike d the same substitution of labour intensive, not less.
ts, says Micheal Edessess.s
I
End result
oxygen tolerance Embr2o culture Anther and pollen culture - and interspecific hybridizarion
breediDg time
Protoplast fusioo
Source:
Agriculture
17
275 million acres. Moreover, the most authoritative current projections 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 holdings are of equitable size, women are given fairly equal rights to work 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
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
corn syrup (HFCS) is one of the success stories of biotechnology' In this process corn starch is converted by the glucose isomerase to
Alcoholic beverages, sweetners and single cell proteins are the three major products important to biotechnology. High-fructose
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 composition thereof differs for sucrose, glucose and fructose. This change in the composition can be brought about by bacteria and the enzymes produced
glucose
I8
Biotechnology*
Possibilit
ies
and Prospects
960,
Weste
'done under ambient temperature 70-90'C and 7-9 pH acidity. When about 45 oet cent of is converted into fructose the process of transforrnation stops; but if fructose is separated there-
lronr, the enzyme reaction restarts glucose into fructose. The enzyme month.
Fructose is in liquid form and
sweets, cold-drinks, ice-creams, jams a by persons rvanting to reduce their
is used
In I 978, 1.2 million tonnes of fr was produced from corn. The production thoreof in 1985 t up to 4.3 million tonnes. Already about 30 per cent of the ent of sugar in America and Japan is met by fuuctose. In India, two companies will be producing fructose by getting enzyme and technology from outside; the one in Ahmedabad has a of one tonne of fructose per ,day and will be selling its product ur the trade-name of MaizoSweet; the other is a joint sector pro in Tamil Nadu. ln India, tapioca, because of its availabilitv and low cost. is used for ptoducing starch. Efforts have to be made to develop technology to convert tapioca starc into fructose so that the raw material easily available in the could be converted into
fructose.6
REFEREN
,i. Cotin Norman. "The in.rpact
of biotechn
Sevier,.Autumn 1982.
2. Torrey,'John C. "Ttre
J.
plant biotechnolo95".
Atttcricutr
5. 6.
culture", Sclencc, Vol.2l8, December 3, Critchlield, Richard. "Scicltce and the Foreign Afuirs, Fall 1982. "qrvecter sugar from Corn" , Daily Sukal
CHAPTER
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 researchers 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
20
Blotechnology-
Poss
rr
can turn them out names-Interleukin-2. tissue III are beginning to move These chemicals helo , dissolve the blood clots in
of a
hemophiliac,
Diagnostic Tests
broad variety
of
faster,
reaching the market for ordinarilv to diagnose diseases such as prostate cancer. Less costly, effective and safer vaccines are now being developed for diseases as heDatitis B. A vaccine against herpes infections is also bein tested.3 These easy-to-use diagnostic will take the delays out of detecting infectious diseases such pneumonia, inherited diseases such as sickle-cell anemia and vari cancers. The new tests can
' days
g of suspect microbes.
, in hours
as opposed to
Doctors will be able to prescribe the right antibiotic or other drug in time to save lives. This can also revolutionise the treatment of such recalcitrant and killers as rheumatoid arthritis, heart disease, and cancer. F. Drake, a biotechnology : analyst in New Yonk, predicts that new diagnostic tests based on biotechnology will add more than million in sales to the $4
by 1987.4 Drake believes that the strongest contributors in this period will be tests using monoglonal antibodies, laboratory produced clones of man's natural soldiFrs against diseases. A few monoclonal antibodies have alreadv been by the Food and Drug Administration (FDA) for sale in di ic kits. Deoxyribonucleic acid (DNA) probes, a new and more versatile product of biotechnology, unlike antibodies, work by hybridizing to some specific sequence of DNA. DNA p are designed to attach to
the invader's core. In designing DNA probe as a advantage of the propensity for two . to anneal. When heated or chemica be separated into tlvo strands, and
.
If
Heal
th Care
2l
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 multiply rapidly. Once made, the DNA probes are used as a kind of fishhook 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 or urine. 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 of disposal problerns, the short life of isotopes and the need for costly and complex instruments. Today, fluorescent tags that glow under microscopes and enzyme tags that cause colour changes are beginning 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,
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. In prenatal diagnosis, DNA probes promise to make much earlier and speedier determination of whether a foetus is affiicted with sickle-cell anaemia, for instance. Currently, only a few laboratories can conduct 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 the mechanism of sonre of the major auto-immune diseases such as rheumatoid arthritis or multiple sclerosis, is not only a fantastic market but also a conceptual, intellectual, and social development of major proportions". For instance, nearly half the 66,000 patients on kidney machine need frequent blood transfusions with the accompanying 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-
to
l3
volunteers in the U.S" in 1986. These new vaccines are expected to be safer, more effective and cheaper. There is a probability that researchers will develop successful control measures lor tropical diseases and population control
Hormones
Hormones are another area where significant advances have been made. Hormones are chemical messengers or metabolic regulators produced by the organs of the' endocrine system' Llntil
recently, only simple hormones lvere produced by chemical synthesis.
More complex hormones such as insulin required extraction from pancreases of dead animals. Hormones extracted from other species 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 in desi;ed quantities, such as human insulin, human growth hormone
the
(HGH) and tissue plasminogen activator (TPA). Tissue plasminogen activator is a hormone that selectively dissolves blood clots that cause 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' Genetically engineered HGH is now in clinical trials and should be on the market in the near future.
Cancer
to take advantage of the body's own to control all cancers. They have found that they. can either bolster the immune system by activating natural ki'ller cells, or use copies of other substances the system produees to
lliotechnologists hope
immune system
.
'
poietin (EPO), the principal red' blood cells, would build up eliminate the need for transfusions.. because there has never been be made in large qmantities using
techniques.
blood. Administering erythroinvolved in the production of patients' red blood cells and cannot be given to patients of it. Now the hormone can ventional genetic engineering
used as ."masic bullets" to that kill cancer cells but . antibodies tipped with tiny prepared by Hybritech in cancer oatients. Monoclonal to kill leucaemia cells in
Monoclonal antibodies will soon carry drugs, toxins or radioactive i leave healtby cells alone. M amounts of cancehkilling radioi San Diego are being tested on antibodies have also been used with the bone marrow of young children. For some purposes such as hormones, drugs and other . nronoclonal antibodies can act as
of
levels
of
protein
missions antibodies are inadequate because some pathogens can \vithdraw their antigens, alter them, shed tbem entirely, all to fool
the antibodies' surveillance systenl.
known as antigenic
drift. It
in
Vaccines cannot cure disease it is present. Traditional , vaccines are preparations of disease ' g vituses that have been killed and work because they i the viral oroteins that stimulate the prodtrction of antib, When this material is injected into the human body, the immune system develops antibodies that will attack and deacti the specific virus causing
d
isease.
, makes
of antigenic for use in the tion of of a number of proteins that are antigenic--that is they stimulate to
Successful cloning genes
it
of
for
variety
proteins prepara-
different
produce
antibodies. Vaccines p{oduced by genetic en of synthesised viral proteins that identical,-melq9r,, and as. such do
24
Blotechnology-
called antibodies. Sometimes or they alert other components job. The second section of t or "TJymphocyte" cellular immunity system which many forms including helper, killer and suppresspr cells. The section of the immune system consists of macrophages which p dispose the debris, like scavengers. Besides; they can also cancer cells outright and they interact with intruders to make recognisable to killer T-cells as targets. The immune system, thus, a cancer cells witb an array
of weapons.
system begins
cancer cells, then b0ve ways of The substances that have excited t
to fail and the ing these multiple defences. scientists belong to the family are produced in minute to an gxternal challenge, . Two types of interferon, kines because thev are , another lymphokine, when production of IL-2. Two production of lymphocyte
as antibodies.
in
test.
explodes cancer cells and leaves it works against a whole range of nf new lymphokines, colony stim
and animal experiments cells untouched. Like lL-2, Tests on the third family factor, are going on in Japan
pin-point the very molecules system. Genetic engineercomponents, synthesize them binant DNA.
The patient is glven massive immune system activator, together cancer-killing cells, Rosenberg of . Bethesada, USA, first withdraws white blood cells and mixes th together with large doses of IL-2 , multiplies the killer cells in the pati the tumour. IL-2 is effective ag ' tumours-in the lurlgs, colon, and e ' - Rosenberg's first istudy seems to
t I0 per
a broad range of
vhere.
solid
Health Care
25
patients. Two were totally free of cancer nine months after the initial monthJong treatment; in the other 13 patients tumours shrank by more than half and stayed that way at least a month after the treatment.
Tumours recurred in people when IL-2 treatment was stopped. In all cases the cancer disappeared again with further doses. It is not yet clear whether cancer patients will need lifetime doses of IL-2, as
of 30 critically ill
diabetics
do of
anyone suffering from cancer. Scientists note that as much as fve to ten years of observing patients will be needed to determine whether lL-2 can cure cancer, patients permanently. Besides IL-2, other potent new weapons called tumour necrosis factor and colony stimulating factor, as well as about a dozen other biological substances show prolrise in combating tut]lours. Genentech seems to be the first. to come out with tumour necrosls factor as it feels that this and gamma interferon can be developed faster than IL-2. Cetus and Immunex have gone in for IL-2 besides tumour necrosis factor. The company will also try out immunotoxine, which are genetically engineered antibodies linked to potent toxins designed to seek out and kill cancer cells more specifically
than conventional chemotherapy can. Immunex with its staff of 125 It has a powerful partner in Hoffmann-La Roche, which manufactures IL-2. An Immunex variant of colonystimulating factor will be tested soon on cancer patients in Europe. Many other companies in the U.S., Japan and Europe are working on lymphokines and other cancer drugs, says Gene Bylinsky.6
works on lymphokines.
Genetically engineered vaccines for rabies, hoof and mouth and several viral poultry diseases are being developed. Bovine growth hormone can raise milk production by an average of l0 per cent. Avian growth hormone promotes rapid maturity in chickens and porcine growth hormone reduces litter mortality rates.
diseases
Application of biotechnology in pharmaceuticals is gradually being covered by patents and proprietary rights. But generic substitutes
26
Biotechnology-
P ossibilit ies
and
P ros pect s
of
benefiting from
biotechnology are:
in-2, Human Growth Hor' mone, Tissue plasrninogen activator for breakdown of blood clots). etc., is possible with the recombi DNA technology.
fl
2) Lyrrlpsoruurs
Substances produced bv
for treat-
3) Dnuc TrncerrNc
Can be reproduced with genetic erigineering. Cytotoxic drugs can
4)
VACCINES
Instead of producing vaccines frbm blood infected with virus, . production of the relevant antigen through DNA fermentation or
mammalian cell culture.
5) CorvenrloNAL DRUc PRoDUcrtoN All existing microbial processes c{n be improved upon through
biotechnology, e.g. antibiotics, hormQnes, etc.
6) New Drecrosrrc TecnNor-ocrrs Forty-one diagnostic kits were afiproved for use in USA by summer of 1983. Assays and tests can be used in surgeries by general
practitioners and even in homes.
Health Care
REFERENCES
27
l.
2.
Colin, Norman, "The impact of biotechnology: The outlook", The American Revrew. Autumn. 1982. Kass, Leon R. "The impact of biotechnology: The right to patent", The American Reurew, Autumn 1982.
Forrune, July
3. "Biolech comes ofage", Business Lleek, January 23, 1984. 4. ByUnsky, Gene "Biotech breakthrough in detecting disease",
9, 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,
CHAPTER 4
Speciality chemicals Existing speciality chemicals made using fermentation technolbgy can benefit a great deal from Biotechnology introduces: 1) Genetic engineering to fermen production, and 2) Application of protein and engineering to the modification of existing chemicals or of new chemicals. (Of course, much more research mav be necessarv for the second category.) Some of the developments in this 1) Enzymes
Are protein molecules which for detergents, sweeteners, cheeseEnzymes allow biocherrical reactions
t, and b) Where enzymes are extracted plants or anirllal tissue, the genes coding for these enzym may be cloned into microorganisms. CHYMOSIN (RENNIN) currently obtained from calf stomachs for making cheese is now
at a faster rate and at lower tem a) Enzymes can be made more efr
2) Amino acids Are used in food and animal nutritional supplements or for p
Ajinomoto (Glutamic Acid)
fi
to
Chemicals
29
3) Microbial polysaccharides Xanthan 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 chemicals
Existing 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
Ener
By allowing energy
intensive
biotechnology can substantially benefit agriculture. It can aid secondary and tertiary recovery of some 200 billion barrels of dornestic oil worth trillion by, for example, supplying xanthum gum to help push oil of the wells. Biotechnology may also have an role to play in the production of fuels from renewable The ethanol fermentation process at the rnoment is i as the fermentation process ceases when the conoentration of reaches a level at which it becomes toxic to the yeast. One y around this would be to develop yeast strains that are tolerant to ethanol. Another would be to develop strains that exist at high temperatures so that the ethanol could be distilled the fermentation vat as soon as it is produced. Methane from plants which are now subject to temperature of 30-35"C, ratio of 30 : I and pH of 7 could be made to operate the year at an increased range of variables.
relatively low temperatures and industrial energy use significantly. By helping the farmers to chemicals for fertiliLers and
CHAPTER 6
Engineering Challenges
natural products with genetically engineered for engineers and offers them new Doing a fermentation with organisms crippled by opportunities. The making
of
overproduce 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 of
professional biochemical engineer: a petson trained both in fermentation technology and bacterial genetics, which is very difrcult. Genetic engineering is evolutionary rather than revoiutionary draws on techniques and analyses that have been developed in otber
heavy genetic manipulation creates difficulties not seen in traditional fermentation. Moreover, genetically engineered micro-organisms that
lt
disciplines such as chemical engineering, microbial genetics and protein chemistry. Shift from batch fermentation to continuousculture fermentation is the likely shape of the future in this fie1d. Continuous reactors are associated with a greatly increased productivity. Batch processing was the best hedge available against contamination by mutant organisms. During the two-to-seven day
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 for harvesting 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,
of
screwed connec-
JZ
Biotechnology*-
Poss ib il it
ies and
P rospec t s
tions for continuous operations. is a perfect bug tfap. We do not thoroughly re-design the whole
acceptable valves, duch as ball closing the ball valve you have a The best approach to a sterile
If a diaphragm valve with a rising stem, then the which one has to be sure that are spores that can survive in
modified.
one
thread on a screwed fitting flanged fittings. We had to system. Traditionally are totally unacceptable". By pocket of liquor or broth. is a diaphragm valve suitably t be used, you have to have has to be steamlocked for stem is itself sterile as therc Pipe work is another
reactors
for recombi-
mlcro-organlsms, engmeefs are to develoo new wavs to purify the end-products from these fermentations and they need to learn how to scale up recovery of new products most of which are proteins or peptides. En hope for irnproved large-scale purifi cation with high-pressure chromatography to get continuous culture throu,gh ultra The Caltech engineers started the information in the literature about the genetic elements that i the reproduction of plasmids, the variorus initiators, and repressors of DNA synthesis and developed models of biochemical reaction with gratifying results. The Eli Company was the first U.S. ficm to market human insulin by genetically engineered
to
take
of
precautions
in
the
India's first sophisticated cell 'Flow Cytometer' is being installed Molecular Biology, Ilyderabad. Flow cytometry combines the
biochemical analysis
of
microscopy and
chamber and a photo-assembly. convert light signals into electrical computer system analyses and
precision technique for rapid analysis and sorting of individual cells. The ability to quantify several parameters gn the same cetl unique to flow cytometry. A typical flow pytometer has as light source, a sample
single
in a
detectors and processors and digital signals. A the digitized data. The high
Engincering
C hallenge s
JJ
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 supplied 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.
2.
CHAPTER
Other
in medicine, conversion of agri wastes into energy through biological processes, control of on and improvements in sewage disposal through benign and even in recovery of metals from inaccessible ore bodies biological leaching. Removal of pesticides from water, nitrogen fixation for fertilizer using immobilized living cells and ion of hydrogen for fuel by splitting water molecules in a -synthetic reaction are good
oossibilities.
The reportr to the Organization fl Economic Co-operation and Development (OECD) by a of scientists drawn from universities and industries states that biotechnology has application
The Office of Technology biotechnology will cut across the en Modem chemical industry which material needs with oil has valuable
Today, nearly $ 50 billion worth the chemical industry most of which important chemicals could be nrade, water-based chemistry of living is being made experimentally by .diferent organisms lnto bacteria. sweetened with the products of bio even high volume chemical feeds
hsed
to
be
-free soft drinks are beine rlogy. Experts believe that such as ethylene, which is commercially with bio-
technology.
Other
Areas
35
Glick, President of Genex, has pinpointed a range of organic 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 to produce industrial chemicals in much the same way that reseatchers are producing interferon and insulin. Another approach is to use
Leslie
enzymes (bioiogical catalysts that govem chemical reaction in cells)
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
to
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 bringing 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 temperatures 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 of providing 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 of the commercial potential. Currently, splicing of genes has become a
routine task performed by technicians. Even the painstaking process
JO
Biotechnology-
of copying the genes so that they be spliced into bacteria is now :'. But biotechnology is a long done by automaled "gene machi way from maturity. At the start trick was to move genes, now it is to alter them or to build new from scratch. Scientists believe that they can create a vast array f new l'bio-materials". Alreadv
1
ing" which
td
never existed
purest form of insulin (humulin) fdr treating diabetes. Although interferon (proteins extracted from human cells) 'heid out promise, it had not made a great impact becairse of its limited ayailability for
clinical 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 like
body. Protein engineering is barely off he starting blocks, but already scientists believe that enornrously fibres or plastics could be manufactured by nlaking specific ifications in genes to improve the products they can nake. Si , wool might be so changed to make it non-combustible. The Group seems to be leading in protein engineerrng. In Britain interest in protein engineering is building fast. In medicine, several genes as oncogenes th4t cause the uncontrolled growth of cancer have been identified and identifying the gene that causes Huntin 's disease is imminent. Bv isolating these disease-causing researchers hope to find out how they work and then find a way stop them. That is where the next breakthrough will come. These leaps in understanding are lpading scientists closer to using such techniques od humans, both tp diagnose new diseases and to try 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 been felt in the introduction of vaccinei for vjral diseases, hepatitis, herpes, malaria, blood-clotting factdrs to cure haemophilia, and the
plants which produce artificial sJveeteners, plants resistant to droughts, fruits or vegetables with increased protein content, and
Othet
Areas
37
milch cattle which could yield more milk. Scientists are also working 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 for introduction and expression in plants.s Chakrabarty feels that biotechnology would make its full impact only after 10 or 15 years as a scientific assessnrent of introducing genetically engineered organisms into the environment has yet to be made. Currently, there is a national debate in the U.S. on the introduction of such organisms before assessing their environmental impact. Unfortunately, there is no readily available technology to determine this. The basic problem is that environmentalists feel it is dangerous to introduce such organisms because they associate microorganisms with diseases. We hope that fears of unknorvn side-effects
will prove baseless. Much is still left to be uncovered. For example, researchers are now beginning to understand the complex process by which the plants convert solar energy in the form of sunlight to tissue and there is as yet only a hazy knowledge of what causes genes to switch on and of as they direct a cell's protein nraking machinery. There may be environmental hazards associated rvith genetically engineered
bacteria and other organisms. DELPHIC PREDICTION OF BIOLOGICAL BREAKTHROUGHS4
50 per cent probability
90 per cent
probabilitl,
t995
1987
New nitrogen fixing plants Single cell edible protein Plant resistant to predators (insects, pests) Bacteria for use in waste treatment and pollution control
Petrochemica I substit u tes Gene therapy fcrr diseases such as
985 1982
r
r990 1984
1988 1993 1985 1984
2000
1990 1995
2010
1990 1985
1990
1984
2000
1991
38
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
1. Mukerjee, Dilip. l'Biotechnology, A way out, Expert Croup Report to OECD", Times of r'rdra, February 15, f983.
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 of universities, and the value system of the scientific community, says
Plof. Charles Weiner of M.LT.I Though at one time, biologists were worried that they might create novel microbes that are dangerous to life and that might escape lrom laboratories, even -6. coli with the ability to make human growth hormone is believed to pose no threat, for it would not be likely to survive outside the controlled environment of laboratory 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 experiments would continue to be banned, namely, those using genes able to synthesize extremely toxic poisons and those which would transfer drug 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 young children. Will people carrying such genes want to know it, and how rvill it affect their decisions to have children? Would a young person want to know that he or she has muscle-debilitating Huntington's chorea which kills many victims by the age of 40? Less controversial would 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 her high+echnology companies which give a single corporation access to a single laboratory or institute usually in the form of patent rights or prepublication reviews of discoveries return for funding it over a long term.r The critics argue that agreements could compromise academic ideals. Harvard the first agreement with Monsanto for cancer research in 197 . and with Du Pont Chemical Company and Hoechst for bi ; MIT has joined with Exxon in combustion studies and with in Whitehead in molecular biology; Washington University St. Louis has joined with Mallinckrodt in immunology. In 1980, Harvard nearly established its own genetic engineering rporation, but. the public and
faculty opposition vetoed the pro agreement. 'The special arrangements of pri rity access to discoveries tn exchange for re$earch funds from industrial houses has led to the hope of gaining patents. scientists concealing their findings ge of data have alreadY Proprietory restraints on the free meetings. begun to crop up at biomedical the need for research but are Corporations are more conscious Nowhere is this more often unable to rhanage it to which chemical, pharmaapparent than in genetic products and techniques. ceutical and agri-business look for today precisely because Many scientists ptefer industrial with less control and red corporations frequently offer their under government taDe than most researchers have grants. The most serious question of all may be symbolic. Univerunciation. Professors accept sities have privileges based on corporate .life, in return for salaries belorv what they could earn which they, and not their the ability to study those questi receive direct and superiors, think fundamental. Their of and exernption from indirect tax support as well as ln the circumstances many regulations affecting private how universitiest can establish . new lationships with corporations engineering while preserving and government in the field of issue. their integrity and credibility is .a that there will be a rich Llniversities and companies point paid and the profits emerging return of about $ 4.7 billion from wide bulk sales of products out of the new. discoveries on t bv recombinant DNA whose manufacture will have been
.
technology.
Ethical
Issues
41
Genetic engineering promises such vast medical and economic benefits that working with the industrial sector to deliver them is fulfilling rather than compromising the universities' mission. In 1982, between 40 and 50 professors were involved in consulting or profit-sharing arrangements with bio-engineering firms. This raises ethical problems as it conflicts with the scientific mandate for free publication and discussion of research. Patent licensing involves universities lar more than professors. The faculties have special ties with donor corporations like that of consultants. The marketable products ofthe laboratories are offered to the sponsoring corporations as patents. Co-sponsored research and longer term commitments in return for a more exclusive pay-off bring bigger sums. If the sponsoring company does strike it rich, competitors will take both
l.
The
vols.
Five Year Outlook on Science and Technology-|98|, Source materials I and 2, National Science Foundation, U.S. Government Printing
Tenner, Edward. "The Impact of Biotechnology: Research Industry and University", The American Rerrew, Autumn, 1982.
CHAPTER
Biotechnology developments started a$ late as 1973. This technology, though young, is destined to change {griculture, healthcare, pharmaceuticals, 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.
l)
Some
may be secret,
or
first
of
substances made by
the Drocurement
regulation.
of
which
Cost is related in turn to the level clinical tests for a period drugs which raises the cost of
It
is necessary to
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, and
the cost
of pilot
3) Hish investmenl Single cell protein or commodity chemicals production require massive investment and high quality and reliability in the plant and equipment. For instance, Microorganisms, plasmids, vectors and equipments for large scale cell culture, purification technology, and automatic control systems, require high investment.
4 (a) Uncertainty of results
Because of the uncertainty of results, the cost of venture capital is lairly high. Moreover, established companies are reluctant to invest in unproven technologies. Because of this, established pharmaceutical
businesses. But each recombinant DNA product requires a specific process at the molecular level, which may be proprietory. Besides, recombinant DNA technology uses a variety of hosts such
as bacteria, yeast, streptomycetes or manrmalian cells. And there may be marked differences in costs depending on the alternative
technologies. For example:
E. coli B. subtillis
(Unglycosylatedi
without
group)
sugar
Extracellular
Recovery efficiency Annual production
8o9i' 25,000 lbs.
s0%
10,000 lbs.
S
Unit cost
(Raw material,
labour)
44
Biotechnology-
for
cancer a
of
r necrosis factor
xlns
vclonal/Monoclonal Monoclonal
to acquire.
6) Access to distribution channels of their own, nor can NBFs do not have distribution tion or marketing which go in for exclusive they afford to requires sizeable sales force. The wa out of this is to: firms, e.g. Genentech has a) License the technology to licensed Eli-Lilly for insulin; and in-house manufacturing, b) Enter into marketing for alpha-interferon; e. g. Biogen/Schering-Plough group of specialists. For to a c) Matketing the drugs
instance, Genentech markets human in speciality chemicals, a small
large share
contacted.
7
of
domestic market-
Management unaertainq)
,Barriers io Technologtcall
degree
Advances
45
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 a must for success in biotechnology.
8) Global competition of a) 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
Factors favour globalization because 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)].
involves intimate relation' science and economic activity ship between basic Special relationship between science and technology in biotechno:
a) High capability. and involvement of basic research; b) Research and development claiming high percentage of
revenue;
sales
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.
Economies of scale
2) Product differentiation 3) Capital requirements 4) Switching cost- from existing technology 5) Access to distribution channel
46
7)
Government sdbsidies ent subsidies Learning or expenence curve experience Government policv Lent policy
Exit barriers
I ) Specialized ass@ts d assets 2) Fixed costs of exit-labour lay {ff, ts 3) Strategic inter-relationship inter-te'lafionshin 4) Emotional barriers
off
(Bell Lab)
2. Research Business Lab Professors
personnel J. Patents
Scientists
No patent
R&D
dom-
jects)
4. Funding
5. Licensing
of
enti-
6. Budgets
47
7.
Lead
time
Medium to long
8.
Focus
Directed
ii
Biotechnology
in
USA
3
4 6
26
43
22
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
Total no.
of
Ph.Ds
45 21
AMGEN
California Biotechnology
employees 100
44
CHIRON
Collaborative
Research
o/ t25
219 125
REFERENCES
44
25
GENEX
Integrated
Genetics
)+
25
Daly Peter. The Biolechnological Business-A Stategic Analysis, New Jersey, Rowman & Allanheld. 1985. 2. Porter, Michael E. Competitive Slrategy, McMillan, 1980.
1.
CHAPTER
10
production facility required i 26 which $ 5 million rvas for R&D and Because of huge costs and risks,
advances just
Though early work in innovations out with small finance, the middle of large resource, For instance, million till 1931. But scaling up
ion between 1934 and 39 of 2l million for the plant. prefer to go in for small
accrue from basic product engine, etc.--whilst.firms are
At the
NBFs have to go slow in raising {he funds. Initially; they go to venture capital market for funds. Tftrey may also enter into R&D limited partnership," or enter intq joint venture agreement for
t R & D Limited
Partnership, where mohey is earmarked for speciflc R & D projects gets write off against taxable incbme and gets R & D tax credits. If successful, they get favourable tax treattnent in U.S.A. (with profirs taxed at capital 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:
$ 55
million
(Part of the
year)
90.7
million
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.
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
is only after entrenching themselves successfully in the technology, and establishing their reputation, that they can market the
It
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).
be
Late
Broad Market Late Product
Broad
Market
Focus
Narrow
Narrow Market
Late 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
provided
Genentech Genex
--
products.
Risks
of their resources
uld
be
of
supplying MABs to million and takes over final diagnostic kits may
Elements
Ln yjyo drugs. The cost diagnostic kits is about i4 years in the USA. Developing five to ten times more,
h as in
of
success
to
D is a must.
detern-rined by its proprietary technology and perceived opportunity; could offer specializpd research services such astechnoNogy expertise in protein engineering, genetic screening, diagnostics, {isease susceptibility based on molecular data, specialiy'ed software for biotechnology,
Is It
etc. Because of the high costs and long gestation period involved, first in R&D and then in testing before the products are introduced in the market, the NBFs generally start by undertaking contract R&D: Gaining reputation, they enter into c{llaboration with big companies to market their products; where marlets are specialised and small, they enter into direct marketing. timultaneously, they enter into manufacturing phase. Only when thfy are well settled and have surpluses, they develop a nrarketing nftwork of their own.
Stategy
f,
Marketing strategy
Established
firns
in R&D.
May select specific biotechnology portfolio May opt for innovation witbin existing market (Humulin) or diver-
sification They must opt for continuous R&D for process innovation (e'g' Encapsulation for fermentors ). They should constantlY undertake SWOT analYsis (Strengths, weaknesses, opportunities and threats).
Market share
Economic size
Generally, 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.
lf
I
I
lf
as
I
I
Problems arise
Market penetration It 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 firms
Pioneering technological leadership: The advantage of being the first producer together with the reputation earned, because of
l)
the pioneering effort, go a long way. 2) Late entry leafurship: By leap-frogging to second generation technology based on technological advances and irreversibility of investments, customer response, externalities' etc.
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 sQientists, 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 it assumed technology leadership in textiles, steel, shipping, automobiles, 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
to
take advantage
of
the
biotechnology developed by' the scientists whether in universities or elsewhere. On the other hand, prospects of making fortunes is
beckoning scientists and academicians to channelize their energies in
biotechnology and
specific biotechnology industries and important universities like Harvard and ldlT are.bejng funded by industrial houses for the
Biotechnologybiotechnolosv researches
encashing of an idea'is looked scientists from universities to the the lure of biotechnology and the possibility public funding, which universities and scientists mainly ed by are tax exempt, side-stepping which may be of use to the society but which may not pay to the individuals or organisations engaged in it, are causing This has raised ethical issues about which continued debate is going on. The multi-national and private firms have been increasingly deciding research priorities through their control over the nascent biogenetic firms and by research to universities. By patenting into a secret trove to be the findings, they are turning exploited by firms in developed
the United States of America upon with favour, the large exodus
ol
biotechnology development as in Indfa we have as yet not developed instltutional ethos of converting scierltific ideas and technologies into successful industrial oroducts. The restraints, controls, and the petmissions required in advance er a negative climate, ftustrate Scientists and foice them to leave the countrv and eircash their ideas
up a National Biotechnology g, photo-synthesis, tissue' fernientation, and immunotechnology ds areas' of imrnediate interest to it. India with its year-around wainr climate, long of sun and high level of controlled water supply (irrigation is ideally suited to devclop biotechnology. We have also seen 1 t a number of Igdians such as
Har Govind Khorana and,Anarid'
have been pioneers
spurts inrelectionics and computer fact, we seem to be lagging behind logy development taking place in The Gtrvernment of India has Board which has chosen genetic cultuie, enzyme engineering, a
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 environment and, develop infrastructural facilities and go well out of their way by ushering an all-out promotioi policy. Inoentives such as freedom of pricing for specific number of years for the products that would be developed from this technology as also modification of the "Patent law", so that industrialists and researchers can look forward to reaping the benefits from the technology for a longer period; infrastructural facilities including well equipped laboratories nlanned by
. tries
. equipmeqts, radio-isotopes,
fluorescent and enzyme tags and biochemicals will have to be .. One of the cost escalation factors in U.S.A. is the 7/10 years loog period of clinical tests before in-vrivo drugs are cleared by F.D.A. to be offered to the public. This raises the pre launch cost of an in-vivo drug to over $ 70 million. It rvould be worthwhile considering
competent technologists with close inter-relationship with the induswill have to be set up, and easy availability of instruments'
ensured..
to undertake research and clinical tests in the country. Of course, these measures should be in addition to
induce drug manufacturers those suggested elsewhere for encouraging'technological development
in general. Biotechnology Board will have 1o be organized so that it does not becolne an instrument for control and restiictions, but an agency for promotion, assistance and development of genetic engineering and
biotechnoloev.
UNIDO sponsored Intemational Centre for Genetic Engineering and Biotechnology has 36 participating nations. They are now engaged in tbe modalities for the search and selection of the Director. The Centre would have two components: One, the JNU Campus at New Delhi;-.and the other in Trieste, Jtaly. The major facilities proposed for the Centre are : A fermentation pilot plant and a computer centre. The Indian component of the Centre will
r,,.
, .
work on problems related to the areas of agriculture and human and animal lrealth. The Italian Centre would concentrate on industrial 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--
have to ensure that the generating biotechnology in and develoo "Industrial Park" in
Centre.
Centre, the interand industrialists, may give in biotechnology in a big number of iriigation facilities are well suited to the development o this technology. India can look on agriculture, health, forward to a high impact of this icals, chemicals, etc., energy, pollution control, mining, growth in the industrial which would lead to an market and a fresh structure, a strong position in the i and industrialists tbr high orientation in nursing the involvement and cornmitment.
SPINKS Reoort forms the basis fi the United Kingdom. France has whilst the Ministry of I Japan has evolved in cooperation
year programme.
COMPARATIVE TAX TREATMENT
ten
F INNOVATION .{CTlVn'lES
IN SOI\IE
Country Capital
Venture capital investment
.
onR&D
in New Firms
(3)
(l)
United
States
(2)
As for other
assets
ships, Pooling
Policy
57
(r)
Japan 100%
allowance
(2)
(3)
Federal Republic of
Germany
Depreciated
other assets
as for
No special provisions
100\ tax allowance for research assets. Allowance for both capital
and current expenditure
No special provisions
Businesses
which purCompanies
life
and shares in Innovation Finance companies may deduct 50o/n of the cost of shares in the
In India, Government
b.y:
l) Identifying basic and applied research priorities, setting targets and 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 of drugs and may cost about $ 70 million. In Switzerland the trial period is much shorter);
8) Modifying Patent Act; and
Blotechnology*
9) Ensuring financial support capital, encouragement of industrial of scale and concenfration of talnt.
to maxmlze economres
l. Malgavkar, P .D.
Technologies
for
Development, Oxford
&
tBH
CHAPTER
12
Conclusion
The assessment of the business possibilities from biotechnology leads to the following conclusions: l) The technology has yet to reach a plateau as innovations in products and processes are coming up at a fast rate; 2) Even in the advanced countries the possibilities of this technology for business opportunities came to be realized onlv after 1975: 3) As research is an integral part of the final product and processes, the business has to be built around ph.D. and research
scholars;
4) As commercialization of the technology is dependent upon research inputs, the percentage of sales a'llocated to research is unusually 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 yet paying dividends; 6) Despite the long time required for commercializing a product, of the many companies that have come about only three have gone out of business, which shows that the prospect of the industry is bright. A few companies that went public found their shares rising sharply in the market initially, though the value of the shares later came down because ofthe long delays anticipated in introducing pharrnaceutical products to the market because of the time span required to satisfacrorily complete the clinical tests for iz-vjyo druss. 7) Whilst a number of processes and invention-s have been patented there are quite a number of processes and techniques which are open including that of MAB.
,
60
Biotechnology-
'
of the startling
this
technology whether in
to bio-technologists, by entering
chemicals, energy' etc. ManY active support to biotechnoby giving research contracts , contracts for commercialisation
R&D Lirnited PartnershiP, bY research, by entering etc., investing in the new biotechnology ology complex requires is: l0) The minimum that the bi a) Biotechnologists at the cutti edge; even for launching in b) About Rs. 5 crores of e another Rs. 5 crores for the diagnostics and diagnostic tests
of the
establishment costs:
three/four years br de-bugging the Process and medicines and drugs. testing the product even for 11) The costs go on mounting fi in-vivo dtugs and for chemicals as also the enzymes and wherein the equipment requirel monoclonal antibbdies would clai considerable investment. the ecolosical hazards of As biotechnology promises to as it is expected to Produce pesticides, weedicides and cherr :sticides. fertilizers and chbmicals not from the crude-oil base but from genes uce crops and plants resistant to and bacteria, as it promises to arid zones, saline soils, and adverse climatic conditions such produce them in millions to meet the emerging demand, as it has be used even bY the general developed diagnostic tests which accurate and speedy, as it Prooractitioner or at home and are m diseeses such as cancer, herPes, mises break-through in g various tropical diseases as it has a potential for AIDS, hepatitis, etc., as it would lead leprosy, diarrh such as malaria, to reduction in ddmand for energY which is a constraining lactor for technology are very high, higher development, the hopes placed as the technologY is hardlY 10 even than on electroltics. M sphere and has alreadY a large years old even in the froirtier level of the technologY, number of Indians involved at this technology and to get its every effort should be made to on a priority basis. the coun business flall-out within
c) Period
of
ANNEXURE I
Agriculture
of Hindustan kver, listed biotechnology areas likely to be highly beneficial to Indian agriculture as follows:
Ganguli For crops and plants
l)
H]'brid
seeds
As the advantage ofthe hybrids are restricted to the first generation, the farmer has to buy hybrid seeds anew every season. As a result, hybrid seeds production has grown into a big industry. The Indian Council of Agricultural Research developed 20 high yielding varieties of national importance and about 80 of specific suitability for variable agroclimatic conditions in the country.
be
of a plant, disinfect it and culture it in a suitable medium so that the mass of cells begin to reorganize into whole plants. The outstanding advantage of tissue culture is the propagation of true progenies, ensuring uniform growth and productivity behaviour for each species in a given agro-climatic environment through
successive generations.
replaced by tissue culture technology through clonal propagation and clonal technology. The technique is to take a piece of growing tissue
Tissue cultlrre research could provide major breakthroughs in plantation crops, coconutr polm, sugarcane, cashew, banana, oil seeds, forest trees, spices and essential oil-bearing plants. Through cloning process rose plants have been reproduced in
62
Blo:techntlogy
millions and are'ofered at $ 3 for comparable to the rate charged for opportunities for this omamental the U.S.A.
(in retail), a pricc sinsle cut flower. Commercial have already been seized in
rplete plant
2). Genetic engineeting The role of symbiotic bacteria in improving the fertility of pulses and certain o is widely undentood. Attempts must now be made to genetically bacteria to enhance their nitrogen fixing ability several-ti as also of the crop and soilproductivity. This is a highly specific species of bacteria for
sophisticated, science-based
industrial fermentation. Research work and field tests showed encouraging results for pulses and The other possibilities pursued laboratories involve nitrogen
fixation to partially substitute is still a distant dream.
in
3)
P hotosynt hes
is inry r orter s
novel techniques
ing plant productivity. Ninety-five carbon and water. comes not from the soil but from The major criterion for deterrnining re dry weight of the plant and which is the maior determinant the yield of crops is ph tly blessed with about 3,000 of plant productivity. India is a
sunlight hours per year and any in
efficiencv will have a maior rm mixture of organic compounds whi doses increases photosynthesis in
upon the species.
which improves photosynthetic Scientists have discovered a even in one part per million by 100 per cent depending
tions such as the gr,ass grows better hen cattle qraze on it because of the effect of cattle saliva on grass ; spent tea leaves applied to rose bushes produce better, larger roses; and when alfalfa is grown on wheat fields, the productivity of is better. Scientists have found the commod presence of novel organic compounds in
these facts,
Annexure
63
4) Growth promoters and regulators The principal aim of the agro-chemical industry has been to provide chemicals that control competition to the crop, i.e. the
weeds, insects, fungus and nematodes that reduce the yield or quality
or interfere with harvesting. This is the fastest growing segment of agri-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 natural substances preseut in the plants, such as hormones and toxins.
5) Bio-insect icides While 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 ecocompatible. The scientific developments in this field are fairiy recent, complex and closely guarded. The major advantage of bioinsecticides is their high species-specific activity, target accuracy and , absence of adverse effects. Bio-insecticides are ol bacterial, fungal or viral origin. The major problem with them is that the microorganisms 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 of bio-chemical vector control. Pheromones are insect sex hormones and many of them can be synthesized in the laboratory. In actual field conditions in U.S.A., pheromones are used as artificial traps to attract aod destroy insects of the same species but of the opposite
sex, progressively eliminating harmful insects. The technique is likely to become an ecologically acceptable tool in selective pest control as weil as for several common domestic species such as mosquitoes,
7)
Oilseeds, plantations and non-conventional oils Coconut productivity in India is the lowest in the world. Oil palm is virtually non-existent in the country. The neighbouring countries with similar agro-climatic conditions for instance, coconut in the
64
and ProsDec ts
be
For animals
l)
Embryo transfet,
advantage to the buyer is that he long regimen of bteeding to tantly, the farmer does not have to they can be used as recipients of cedure for embryo transfer is very
2) Milk
prodrrction
to enhance milk productivity. by which dietary proteins are Scientists have devoloped a 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 acids. Since methanogenesis that methanogenesis is inhibited by removes more than 50 per cent of carbon supplied in terms of food, the inclusioo of branched in fattv acids in the diet of cattle led to incrdase in milk bv 15-20 Der cent at
equivalent calorie levels.
is
inadequate
and this
has
3) Fish farming The inability of tropical waters mainly due to pauclty of dissolved temperatures in tropical waters,
mercial deep-sea trawler fishing in yield of prawns if appropriately hectare per annum compared to tonnes (semi-intengive) per Phillippines, Taiwatr, Hongkong
support large shoals of fish xygen at the prevailing higher resulted in unsuccessful comcoastal waters. The averase is 300-400 kilograms per
I 12 tonnes (Intensive) or
perr annum
5-6
in
Annexure
o)
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
these countries are the result been covered by Ganguli.)
ANNEXURE
IJ
Some Pace
British Compttny
Founded Funding
ln
1980.
12 million. ational Enterprise Board took 44 per cent of ity, balance by four private
industries,
of
ich
&M
Achievements
1982
1983
Commercial
It
has entered
for diagnostic
option
on
of
Medical
and one
produce
annually.
Compet 5
of
litre
fermenter,
and
can
monoclonal antibodies
itor
method for
in air-uplift
volume than in
Annexure
II
In
1971.
67
CETUS
Founded Diverse interests Such as high
purity fructose, plaut genetics, hormones, diagnostics, antibodies, cancer therapeutics, monoclonals, Interleukin-2
Financing
Immuootoxin. Contract R & D, Licensing, Joint venture and marketing arrangements, Venture capital, R & D Limited Partnership.
CANTOCOR
Foanded
Focus
ln
19'/9.
Technically alrcad
'B',
for
hepatitis
Being small,
it
for
marketing
to
components
cent).
marketing partners to cover the world market. It supplies keyof a new health care system at high royalty (20 per
markets products that can be introduced early the market, viz., diagnostics. It offers non-exclusive licences to
It
ELI.LILY
Founded
Sales
In
R & D budget
Achievements
First biotechnology involverlent in recombinant DNA technology to produce human insulin. Till recently, only porcine insulin was
available. With licence from Genetech which cloned the genes coding Eli-Lilly introduced
68
Biatechnology-
and Pr o.sp
ec t
"Humulin"
later in USA
Conxpetitors
k, who
precursor
have developed a
of insulin "Pro-
leap-frogged
to a
more
to biotec
GENENTECH
Foundecl
In
1976.
Funding
Through
R&D
EyolLttion
Pharmaceutical
areas
Immunology,
agents,
Personnel
Cost of
periods
yield returns
million
nerships.
r
clinical trials for long raising funds which will many years. (Raised $ 120 three R & D Limited Partmore will be resuired till
human/animal health care. all functions of an integrated
Strategy
It
has
pharmaceutical business.
Annexure
II
It
69
Strategy
meets its operating expenses from contract R & D and royalties. Seventy-six per cent of
its earnings is lrom this source. Its clinical trials are financed through R & D Limited Partnerships. Its non-drug tesearch spin-off has enabled it to start joint ventures as follows: With Hewlett Packard for developing instrumentation in biotechnology; With Corning Glass Works for industrial
enzymes;
diag-
has purchased 230 acres of land and built 74,000 sq. ft of manufacturing plant in 1983)'
(lt
Its scientifc
achievements
lg77
1978 1979
SOMATOSTATtrN'
tnone.
brain
hor-
Its
in molecular hiology
achievements
- Human growth hormone. - LEUKOCYTE interferon. I980 - Bovine growth hormone. 1981 Cloning and expression of LYMPHOTOXIN
GENE.
Ctoning of gene for tumout necrosis factor' Cloning and expression of human oncogene' Plasminogen activator
clots
for
dissolving blood
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 concentral ing on growlh horntones.
GENEX
Foundecl Focus
Ln 1977.
Speciality chemicals and enzymes (for.quicker
70
Achievements
Cloned
gene
lor
rennot (used
in
cheese
making).
Phenylalnine
Searle.
Sales-$ 20.6
Enzymatic
product
for
dissolving
hair in drains
Lo,rses in earlier years due to
Accelerated
grammes
R&D,
Process scale
of
proprietary
Construction
expenses.
up
It
lws entered
into
Contract R &
Japanese
D with
number
of U.S.
and
Consultancy
$ 6.5 million
1
protein
engineering
(currently, B-l It is preparing for its own technolo for second generation products (pro GREEN CROSS Green Cross, desp'ite being one of companies is behind the West in making interferon for I years, but this inethod that has several dra Arner.ican company a contract
engineering technique.
new processes for vitamins, costs '$ 2000/3000 per lb). obsolescence by going in engineering).
pan's lead ing biotechnology engineering. It has been been in cultures of cells, a It has, therefore, given an
the
necessary genetic
interferon asainst
to commercialise as the and developed and large raises the question of inter-
like viral conjunctivitig and keratitis. development of interforon to treat skin infections,
to concentrate on rises of iven externally rather than eron to treat eye diseases It is also well advanced or.
Annexure
II
7l
a conceptual idea to develop into a project, the idea being "artificial blood". Dr. Naito commercial first came across the idea in 1960 when he was reading a report about 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 patient with sudden loss of blood can be treated right arvay without waiting to sort out his blood tvoe.
Green Cross has taken
MOIWTNTO
Entered
Biotechnology
Sales Achieyements
/8i".-
In
1983.
$6.3 billion.
has entered into agreements with universities which can publish the results and patent' but Monsanto has right to prior review and licence option. Has developed mammalian cell culture technology and plant biotechnology and licensed it exclusively. It wants to move away from petrochernicals and concentrate on higher value speciality products.
It
Polic y
The company has a staff of about 125 research scientists and had of $20 million in 1980. lt markets commercially seed potatoes (mini tubers) and rose plants. As rose plants are developed through tissue culture technology they do not have to be grafted on to other root-stock. The plants begin to bloom in two months. Potted and packaged they are sold at $ 3.99 each (retail), roughly the price of a single cut rose, whilst the buyer gets a complete plant. SUNTORY Suntory, 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-
-I
72
Biotechnology-*
RPORATTON, NEW JERSEY DNA PLANT TEOHNOLOGY The Cotporation has developed tomatoes with high. proportion Company. (Fortune, 2 Sept. of solids to water for Campbell
r
985.)
ENZO BIOCI{EM
Enzo Biochem expect to receive
I & II
irus (which causes respiratory
hepatitis-B.
was approved by
kit
GHAM
INTEGRATED GS,NETICS. lntesrated Cenetics of Framin that will not require FDA a contamination in food rather routinely check their products for Today's slow culturing tests which as a week .tvhile results are awaited, Intesrated Genetics found that it strains of salmonella with a- single which the company hopes to in onlv about a dav. Another
test usins monoclor.ral antibodies.
in
because it is used to spot humans. Food companics a common bacterium. food to be stored as long lfood companies a bundle.
has developed a
DNA probe
detect 350 of the most common of DNA probe. The probe this year will do its work
y is developing a competitive
MOLECULAR GENETICS
Molscular Genetics is a leading
in biotechnology
concentrat-
ing on animal health care products which the government typically approves faster thah it does dru$s fl humans.
Annexure
II
73
BIOGEN
Biogen is concentrating on low-volume, high-profit pharmaceutical products such as gamma-type interferon, factor-Vlll, a clotting agent
for
hemophiliacs.
GENAX
Its major early 1985 it planned to product is low-calorie sweetener. By produce calf renin for making cheese, tryptophan for supplementing
Genax is concentrating on speciality chemicals market.
ONCOGEN
Oncogen, a cancer-diagnostic company reports that they have already used monoclonal antibodies to detect tumours in laboratory tissue culture containing only one million cells, as against today's mostly observational techniques for diagnosing cancer where the victims are already having tumours the size of pea containing at least one billion cells before the growth is spotted. CETUS Cetus
is engaged in the development of probes for bacterial intestinal diseases such as scours that affict new born animals, sexually transmitted diseases, blood-borne or lymph-borne cancer or other illnesses (,Abbott has financed Amgen to come up with DNA probes for infectious diseases and cancer).
Blatechnology-. l\taiorR&DLimited
Possibil
it
In
Biotechnology
Year Agrigenetics
55.0 .5 3.4
1981
| 982
Ca!ifornia Biotechnology
Genetic Systems
1982
I982
1982 1982 1982
1.0
F5.0
i75.0
l98l
1983 1983 1983 1933
Alza
Genentech Serono Labs
t6.0
p4.0
P9.o
Xoma
Biogen
[6.0
60.0
1984
1984
Senentech
Soatce
Annexur e
II
75
Comparative Financial Dsta on Selected Public New Biotechnology Firms le83 ($ 000) Company
Revenue 4,347
18.437
Expenses
7
Net
Income
3,479)
l l ,664)
Total Assets
55,438
Amgen'
Biogen
,826
(
(
29,453
I1l,428
Biotechnical
International California
Biotech
698
2'952
4,986 1,521
8,243
( 2,2s'
"
5,266
535
7
(
( (
(
20t
986) 836) 5,37e)
171185
Cambridge Bioscience
Centocor' Genex
lt{
,407
24.ffi4
52,107
11,091 15,965
16,470
Hybritech
Integrated
Genetics
t6,439
(
(
474)
48,066
3,046
5,217
2,1',71,)
)'t
7<<
Molecular
Genetics 6,915 6,463
as2)
' "
Nine months
30th November 1983
,Sorrc?
ACTUAL
Revenues
DATA
Expenses
Company/Qtr. Ending
Emp
yees
(date)
150.( 7
r"{
2s0.( 7 73.( 3
380.
83 23 106 1,651 2.120 1 122 123 266 600 5,068 613 ?,737 3,350 954 g,sls 10,469 1,365 8,510 1'565 428 558
9,840
86.( 3
7s.( 88.(
30.
( 7
140.( 7
610. ( 1
Collaborative 3/2/85
Cyrox 2128185 Damon Biolech 2/28/85
ens
4.( 'l
,|
Endotronics 3/31/85 Enzo Biochem 4/30/85 Gama Biologicals 3/31/85 Genentech 3/31/85 Genetic Diag. 3/31/85 Genetic Systems 3i 3l185 Genex 3/31/85 Hazleton Labs 3/31/85
80.( 7
60.(
173.( 674.(.t 13.(
I l'225 '983 1'l5e 286 2,096 1,695 1,987 638 131 3,985 4,480 2,'t76 9,852 12,628 --'t2,411 f ,2'7s 492 1,708 2,215 636 71O 12 530 568 108 151 '6'72 283 217 187 50 1,029 1,13?. 485 \'495 34s 1,508 1,857 560 l'396 4'095 4,180 20,164 15'116 19,449 1,t53 19,011 22 226 248 200 349
3
2W.( 7 264.( |
1,596.( 7 82.( 7 600.( 7
15.
3/31/85
(
r
87.( 260.(.
130.(
s5.( 7 Interferon Sciences 3/31/85 360. ( Microbiological Sci. 3/31i 8t 128. ( Molecular Genetics 3i3 l/85 Monoclonal Antibodies, 3/31/85 l0O.( )\ ( Otisville Biotech 3l3l /85 r 8.(1 3i3ll85 Ribi Immunochem 37.( 7 Summa Medical 3/31/85 57.( I Taeo 4/30/85
II '829 --50 11,584 12,195 -9 59 335 ',1rz ) 264 347 611 1,553 51,887 5,260 '202 2.445 396 590 986 74 836 961 958 | '420 3 5,488 5,433 82 5'404
711 2"367 8.503 1,076 4,838 s2 4,'l6s 4,861 2,185 1'313 -- 18,108 -- 17'618 1'981 1,714 l;867
2,820
l9s 4
91 82 69 454
13.( 240.(
154 4,335
352 98 350 161 362 570 2'998 458 77 1,056 325 & 4,674 316 5'73e
I,918
ANNU ALIZ ED DA TA
Expen./ (Loss)
Assets
Total
Revs./ Emp. yr.
Current
Total Profit Current Total Revenue Asset/ Assetl /Asset Emp. /Emp. EmP' EtrP. yr. loyee loyee yr.
(Thousand of S per employee)
18.7
|
5
(Thousands of $)
(2,014) (417) (1.718)
1,939
*:: "!:
136
8,386 569
2,802
56.5
(13.4)
5.9
0.05
0 ,007)
(4,976) (7s8)
(873)
(109) (507)
495
2,845
15,522 1,813
11
2t1
(1,060)
180
1,427
16'7.5 136.s 7.8 30.6 85.8 (13.8) 51.2 103.6 (13.1) 57.0 92.2 (8.8) 15.3 6l.8 (11.6) 90.3 95.3 (1.2) 17.5 85.1 (16.9) 128.0 113.9 3.5 82.8 81.4 0.3 65.6 97.0 (7.8) 189.3 141.3 12.0
0.87 28.o
258.7 0.28
l8e.:
84,-5
t'76.4 60.4
123.4
94.8
t53.2
140.9 38.4
95.1
0.35
1.99
(2,921)
(6) (363) 461
85
23,608 26,582
a1a
8,381 4,713
1'r)
715 (101)
3,665
l?{
44,683
1,197
1,584
41,317
36,791 8,934
79,135 28j76
61,889
(r,2't6)
16.096
20,511
id
0,45e)
(45e) 55 (480)
9,02s 24,875
16,278 4,668
9,282
26.323 2,387
395 3,783
3t,597
3,979
(393) (2s4)
(18e)
I,504
5,513
(2,636)
(5e8)
lo,769
2,627 5,624
6,789
2,734
2,691
13,539
Q61)
(1,06')
u,zl2
58.9 0.96 56.6 74.7 (4.5) 33.+ 393.s 0.31 123.8 93.1 7.7 346.7 153.'t 0.63 96.7 94.7 0.5 82.9 330.5 0.36 201 .2 I 19.7 115.4 | .l 138.2 0.55 (7 8) 12t .8 76 .3 lO7 .4 223 .4 0.76 96.8 18.3 184.0 170.1 156.5 0.47 73.6 110.8 (9.3) 33.8 49.6 0.92 44.2 0.3 17.9 4s.4 69.8 1.31 91.2 96.6 (1.4) 51.3 103.2 0.19 81.3 78.9 0.6 s6.? 246.3 0.06 ts.1 189.9 (43.s) 205.s I 85.0 0.15 125 .e 86 8 (r4 .7) 28 .t 80.9 80.0 0.2 157.8 0.19 30.3 7s.2 (rr.2\ r2s.2 0.43 164. t 69.9 103.3 (8.3) 84.9 69.1 0.88 6t.0 ffi.4 0.1 25.8 246.9 0.30 73.1 88.1 (3.8) 205.7 39.8 1.53 61.0 76.7 (3.9) 23.e 60.2 0.26 15.7 s6.3 (10.2) 15.8 306.3 0.12 35.8 77.8 (10.5) 210.2 O.l4 291 t 39.1 324.1 ('71.2' | 83.5 32.1 74.1 (10.5) 39.2 . 46.1 0.70 432.6 0.05 19.7 100.0 (20.1) 207.0 100.9 0.77 77.9 95.7 14.4) 56.4
. .
2,006.2
0.13
ANNEXURE
III
Agencies Engaged
Biotechnology
in In
National Biotechnology Soard (NBftB) constituted in 1980 has identified the following priority areas] for research: Hormones, Antibodies, Antibiotic$, Enzymes and Genetherapy. It hopes to isolate a vaccine againsf leprosy and parasitic infection within a decade. UNIDO sponsored International Qentre for Genetic Engineering and Biotechnology would becorne a legal entity when at least 24 countries ratify the legal formalities. The Centre would have two components: one, the JNU Campus, New Delhi, and the other in Trieste, Italy. The major facilities for the Centre are: a fermentation plant and a Computer tre. Tbe Indian comoonent of the Centre will work .on related to the areas of agriculture and human and animal The Italian Centre would concentrate on industrial The Centre would have affiliated centres in different countri The International Biotechnology at Nerv Delhi is moving ahead fairly rapidly. The basic are to create a centre of excellence where scientists will be in research, training and development of technologies of relevance to developing
.
countries.
Other agencies engaged in l) At the Council of Scientific and Biochemicals a support facility restriction enzymes and other
dustrial Research Centre for been created to ensure that important materials are
Annexure
III
79
2) The Indian Agricultural Research Institute is studying characterization of translation and transcription process in Escherichia coli
during 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 of veterinary and animal science and with departments of animal
genetics and breeding. ICAR has set up several institutions for preserving animal genetic resources, including the National Bureau of Animal Genetic Resources
at Izzat Nagar, Arunachal Pradesh, the National Institute Breeding Centre for Camels at
Science, Bangalore, is working on gene in rinderpest virus, histogene, rice embryos structure, and expression 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-restriction
proteins in Escherichia coli and shigella dysentries as well as cloning of biocide gene. 6) National Chemical Laboratory, Pune, is working on immobilised enzymes and microbial whole cells (ethanol fermentation), develop-
ment
of
enzyme teagents
and other biochemicals for genetic 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 like pomegranate, and plantation crops like sugarcane' cardamom, turmeric and ginger. 7) The National Institute of Immunology is engaged in the construction of mycrobacteriumJeprees' DNA library' human chgrionic
80
Biotechnology-
gonadotorpin (HCG) and human tal lactogen. They have tried anti-fertilitv vaccines on and trials on human beinqs are expected to start in coming few onths. 8) Osmania University and Cen for Cellular and Molecular Hyderabad, as well as Bose Biology, titute of Nuclear Phvsics are working on the application of engineering techniques and studies of biological nitrogen fixation 9) The School of En Sciences, Jawaharlal Nehru Univemity is studying the transfer nitrogen fixing genes into the chromosomes of cereal bearins ts throush recombinant DNA
technology.
l0)
Research Centre are carrying on work of cloning of genes of agrobacterium and drosophila. Bhab Centre has introduced gene genetic engineering. Formerly, cloning streptomycete, a technique selecting strains of high quality used to take as much as ten
ll) Scientists at the Central have applied recombinant DNA antigens of cholera bacteria for have cloned genes involved in biod The first post-graduate biotechn at Aligarh Muslim University in 1 lakhs, the institute will train students compulers in genetic engineeriug. Five centres of biotechnology ha Nehru University, Benaras Hindu Poona University and Madurai power in biotechnology for institu batch has just graduated orit ir
biotechnology. Some private firms such as Hi
to fifteen vears.
Research Institute, Lucknow to identify protective development. They also n of cellulose. institute began functioning 6. Set up at a cost of Rs. 50 and researchers in the use of been started at Jawaharlal University, M S University, train manand industries. The first 987 with Master's degree in Lever Limited, Ranabuxy, engaged in biotechnology in Ahmedabad and the other ill be producing fructose. The f one tonne per day and will sweet". considerable success in oils terials of their business. They modified bacteria to
Hoechst and Tata Oil Mills are research. Besides, two companies, a joint sector project in Tamil Nadu Ahmedabad factory has a capacity
sell fructose under the trade name Hindustan Lever Ltd., has
"
and fats which are the maior raw have investigated the feasibility of
Annexure
III
8l
oil and glycerine for industrial use' Such a proposition is of great interest to a perennially oil-short country
produce edlble quality
Although the developments are at an early stage' the results are genes encouraging. Scientists in the laboratories have manipulated 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' 9,000Rs. 10,000 per tonne.
like India.
G loss
ry
Asscrsrc
leaves
: Any
mernber
of the
or by synthesis.
ine
insoluble in water arld physi r'fiwa AlrrNo Acn : Anv of the organic corir-rpounds that contain one or tnore basic amino groups and one or more acidic carboxyl groups that are polymerized to form peptides and proteins. Only 20 amino acids serve as building blocks for proteins. They are component molecules o[ proteins.
present in the serum
or
compound having a
quinine. Typically
of
an 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 infection by the same antigen. ANTrBIorrc : A chemical substance, produced by rnicro-organisms and synthetically that has the cApacity in dilute solutions to inhibit the growth of and even to destroy bacteria and other micro-organisms, e.g. penicillin pr streptomycin. Used in the treatment of infoctious' diseases. ANrtcnu : A protein or other molecu]e which when injected into a human or anirnal body will g$nerate the production of an antibody.
Glossar
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, phenylalanine and aspartic acid.
Assa,v
AuxtNs
A five membered heterocyclic compound that contains two or more cyclic atoms. Blcrerul : Extremely small, relatively simple micro-organism tradiAzotte,:
tionally classified with fungi. : 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 in protein 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 within the living organism. BrorEcuNolocv : The application of engineering and technological principles to the life sciences. Clr.lus (Tlsue) : A hard tissue that forms over a damaged plant
BIo-E\-GTNEERTNc
technique that measures a biological response. compound which promotes plant growth along the longitudinal axis when applied to shoots free from indigenous growth-promoting substances.
:A
: An organic
surface.
: Substance that alters the velocity of a chemical reaction and may be recovered essentially unaltered in form and amount at the end of the reaction. CslL: The microscopic functional or structur!1l unit of all living organisms consisting of a nucleus, cytoplasm and a limiting
CeTAlvst
membrane.
Cer"l CurrunE
of cells usually
isolated from
a 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 plant matter; 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 than one zygote (an organism produced by the union of two mature
B4
Biotechnology
germ cells).
used
or
in the
coagulating
milk
casein
of genetiqally i tical cells or organlsms from a common , by asexual production as by cuttings, graftings, etc., in Colr-oroel SYsruu : An intimate mi of two substances. one of (or colloid) is uniformlv which called the dispersed p distributed in a finely divided te through thc second substance called the dispersion medi or dispersed phase may be a gas, liquid or solid. Also kno as colloidal dispersion or colloidal susDension. CttroMosoNrs : Any of the complex, threadlike structures seen in animal and plant nuclei during karyokinesis, which carry the linearly arranged genetic units. are constant in number for any species. In the h cell there are 22 Dairs of chromosomes and 2 sex . (Karyokinesis-Nuclear division characteristic of exact uplication and separation of the chromosome threads so tha each of the two dauehter nuclei carries a chromosome identical to that of the parent nucleus). Curruns : Experimenthl growth micro-organisms such as bacteria, fungi in a nutrient Cvsrrc Frsnogs : A congenital c disease of the mucous gland which affects the pancreas and digestive and pulmonary
group
descended
disorders.
CyrostNn:
A white, crystalline,
rnetabolism.
DroxynrsoNuclErc ActD (DNA) : constituent of the chromosomes viruses), The DNA molecule chains in the form of double
f all
nucleic acid that is the main organisms (except some ists of two polynucleotide containing phosphate and
Glossary
85
the sugar deoxyribose and linked by hydrogen bonds between ano the complementary bases adenine and thymine or cytoslne plays a central role in protein guanine. DNA is self replicating, Jynthesis and is responsible for the transmission of hereditary characteristics from parents to offspring' on Dlncsosrlcs (IN Vrrno) : Diagnostic kits and systems ftrr use Included here are tests tissue or fluid samples in the laboratory' 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.
: The formation and development of an embryo' : A protein which acts as a catalyst in biological reactions' Exzvun EnvnrnopotsirN (EPO) : A hormone thought to be produced by the kidneys, that regulates formation of red blood cells' It
EMBRYocENEsIs
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' water ETHANoL: Ethyl alcohol, a colourlcss liquid miscible with
and most organic solvents. Also known as alcohol' used as EtsvI-ENE : A cilcurless flammable gas, boiling at 102'7'C medicine, and for manufacture of an agricultural chemical, in organic chenricals and polyethylene; also known as ethene' Errreniore: Organisrn for plants and animals whose DNA is sequestered in a nucleus in the cell'
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 Used certain lrganisms to live and grow in the absence of air' manufacture of products such in variouslndustrial processes for Fnucross
in called fruit sugar' honey and many fruits. Also GrntNc : To form become a gel (gelatine), jelly-like' Ger,ltut'.1 AnsrNtos : A crystalline material, melting point 1238'C;
as alcohols, acids and cheese'
6()
Bioteclmology
Bus
frequently alloys
phosphide.
of this ma
are formed with gallium in the chromosonre that ry character. It is capable a fixed position on a parent to offspring during
grnes. e nitrogenous bases
Crrr:
The unit of heredity the development of of replication and mutation, chromosome and transmitted
con trols
Grxrrlc ; Of or relating to genetics, CeNrrc Coor : The order in which are arranged in the molecule amount of protein synthesised . arranged in groups of three i
of DNA ich determines the type and the cell. The four bases are a specific order, each group ' actjng as a unit which specifies z particular amino acid. ,GENErlc ENcrNrenrwc (Also known as Recombinant DNA) : Tho construction and maniDulation I hybrid DNA to introduce genes coding for desired proteint into specific organisms. GrNovs : The complernent cf haploi chromosomes contained in a single gamete or nucleus. Gtnsunnl-r-lxs : Any member of lr ily of naturally derived compounds which have a gibbane sleton and a broad spectrum of biological activity but are no as plant growth regulators. GnowrH HonN,roNs : A short of protein invotved in the regulation of grorvth. Secreti of endocrine glandd having growth promoting properties, e. pituitary growth hormone, in
plants called auxins.
: A colourless solid used ch Heploto (Trssurs) : Having half the chromosomes as in maturc serm Hnltcal : Spiral in shape or form li 'HruoplrrLrL: A rafe, hereditary ' tendency toward bleeding and of Factor VIII. Hpparrrs B : Inflammation of the Hr:nsrcroE : An agent (e.g. a plant growth; $pecifically, a injurious to crop plants. Hrnpns : An acute inflamrnation of
GunNrNe
to
deficiency
used
of groups of vesiclcs on
Glossary
81
HonuoNp : An internally secreted compound formed in endocrine organs whictr afects the functions of specifically receptive organs 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 in culture and is immortal, and lymphoeyte -antibody producing cell); the resulting cell grows in culture and produces monoclonal antibodies. Hvpnopor.llcs : A method of cultivating plants by growing them in gravel, etc. 'through which water containing dissolved inorganic nutrient salts is pumped INsur-tN: A hormone, produced by the islets of cells of the
pancreas, that regulates the metabolism
carbohydrates.
INTERFERoN
: A protein used by intact animal cells when infected with viruses acts to inhibit viral reproduction and to induce
resistance in host cells. INrsnI-EurtN (II): A type of immunomodulator which is being tested for anti-cancer efects. It stimulates T cell srowth in-vivo.
IN-VIrRo: Literally, in glass; pertaining to a biological reaction taking place in an artiflcial apparatus. In-vitro diagnostic products are products used to diagnose disease outside of the IN-VNo : Literally, in life. Pertaining to a biological reaction taking place in a living cell or organism. In-vivo products are
products used within the body. ISoMERASE: An enzyme that catalyses isomerization reactions (a process whereby a compound is changed into isomer; for example, conversion of butane into isobutane). Isoiopr : Any of two or more forms of a chemical eleme nt having the same number of protons in the nucleus but having diferent
numbers of neutrons.
JosEpHsoN JuucrroN
: If two superconductors were weakly coupled, one could have current through such a junction without drop in
voltage.
88
'
of
overall
equipments
MoNocLoNAL ANTIBoDIES (MAB) body produced bY a single only one antigenic site/chemt
a varietY of industrial
easily produced
specificity.
in
and large
spccific type of anti of cells which can recognize I structure. MAbs are useful in ical capacities since they are and have a remarkable
A highly
Gtossary
89
: A sudden appearance in the offspring of an organism of a characteristic not present in its parents. MvBroul : Antibody producing tumour cells usually in the marrow of several bones. NnrurnoqutNoNn : Greenish yellow powder soluble in organic solvents used as an antimycotic agent in synthesis. NITRocEN FIXATToN : The conversion of atmospheric nitrogen gas to a chemically combined form, ammonia which is essential to growth. Only a limited number of micro-organisms can fix
Mur.lTIoN
nitrogen. NucLErc Actps
tide bases. There are two kinds of nucleic acids; DNA, which
contains sugar deoxyribose, and RNA which contains the sugar
in protein synthesis
NucLEorIDEs: An ester (compound formed by elimination of water and the bonding of an alcohol and an organic acid) of a nucleoside and phosphoric acid; the structural unit of a nucleic
acid. ONcocBNE
and in the transmission of hereditary characteristics, since they embody the genetic code.
: A gene that
causes cancer
types
of
to
cancerous,
OnclNrc (ColrpouNps) : Of or relating to animal or plant constituents 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,
government allowing the inveltor of a new invention the right to exclude all others from making, using or selling the invention unless specifically approved by the inventor, for a specifred time period in return for full disclosure by the inventor about the invention. Persocnr : A parasite producing damage in its host. Any disease producing micro-organism or substance. PEcrrN : A purified carbohydrate obtained from the inner portion
of the rind of citrus fruits, or from apple pomace. hcrrNAsE : An enzyme that catalyzes the transformation of pectin
90
'PBprDss
Biotechnology
into sugars and galacluron ic : Substances resultins from A compound of two or more PH: A term used to describe the A sotution of pH 0 to 7 is aci over 7 to 14 is alkaline. PggxvrllNnsn : An essential amino by hydrolysis of proteins
body.
: breakdown of
acids.
proteins/
pH of 7 is neutral and pH
to
PnrnouoNrs
:d
hormonal
rts that competes with the PnmonssprRlrroN : Reaction in photosynthetic process. Instead of fixing COr, RUBPCASE ' (ribulosebiphosphatecarbc' can utilise oxygen, which results in a net loss of fixed CO'. out by plants where carbon PnotosvNrnssls : The reaction into sugars in the presence dioxide from the atmosphere is solar energy into biological of sunlight; the transformation
energy.
Pusurc : Combining form. Plesuro : An extrachromosomal etii element found among bacteria. various strains ol E.coli and precursor, br zymogen, of PLASMTNocEN Acrrv.rron : The plasma- the fluid portion of plasmin (a proteolytic enzyme blood or lymph). A factor whi causes activation of plasmin , which breaks down blood clots. Por,yunn : Substance made of eiant es formed bv the union ene (the unit of polythene). of simple molecules, such as plex cartrohydrates such as Pot-vslccnlntoes : A group of starch, cellulose, etc. They may regarded as derived lrom x
molecules of water.
Powornv Mtr-nnw :
funsus
cterized
bv
oroduction of
'Glossary
9.1
high molecular weight that occur in alt living cells and that are
required for all life processes in animals and plants. PnornN ENclNrrnrNc : The study of the relationship of protein structure and function with a view to designing proteins with
specifi c characteristics.
of a cell considered
as a unit;
includes the cytoplasm; the nucleus, and the plasma membrane. Cocking succeeded in obtaining protoplast by using enzymes
that dissolved the cell walls so that membrane bound living rnatter within the cells was released and formed., a suspension
of spherical, wall-less cells. Pnotoplest FusroN : The joining of two cells in ttre laboratory to achieve desired results; such as increased visibility or antibioticproducing cells. : A heterocyclic compound containing fused pyrimidine and imidazole rings; adenine and guanine are the purirte components of nucleic acids and co.enzylnes. RlotoncrtvE IsoropB : An isotope rvhich exhibits radio activity. Reco {urNlNr DN.A : (See Genetic Engineering).
PuntNr
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
synthesis.
agent in
Slltcou : A non-metallic eiement occt rring in a combined state in minerals and rocks and constituting rnore than one-fourth of
the earth's crust.
Sorrw.ltr : The totality of programmes usable on a particular kind of computer together with doculnents associated with a computer or a programme, such as manuals, diagrams and
operating instructions. : Of the body as distinguished from the mind. Sotrt.qtosr,qtrN: A brain hormone. Spncrelry CHErvlrcAL : Low-volume, high value chemicals such
Sorrr,trtc
enzymes.
a^s
Srnetrs : A group of organisms of the sarne species having distinctive characteristics but not usually considered a separate breed
or variety.
92
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 a
state.
SvNonorrar:
A
:
concurrence
of
discases.
Tnrog.qcrlr-uu
genus
of
recovering 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 that deals with strubture and form $f an organism at any stage of its life history. in artificial media. Trssur Cur,runn : Growth of tissue Ttsus PlmurxocEN AcrrvAron (TPA) : A substance which causes activation of plasmin which is involved in the breakdown of and strokes. blood clots, that cause heart a produced protein which Tulroun Necno$s FlcroR : A of tumour cells. lt has about exhibits in vitro and in vivo 30 per cent homology of amino trlcid sequence with lymphotoxin. involved in breakdown of UnorrNlss : A thrombolvtrc blood clots. It occurs in human or virus for introV.tcctxn : A preparation of any stimulate the production of duction into the body in order introduced, in order to antibodies to the mi infection by the same confer immunity against any type of micro-organisn. foreign DNA into host VEcroRs : DNA molecule used to i and other forms of DNA. cells. Vectors include plasmids' ting autonomously and A vector must be capable of ion of foreign DNA. must have cloning sites for the in companies with which VBNrurn Ceptrel : Money that is a high level of risk is associated from the periwinkle plant VTNBLAsTINE : An alkaloid (vinca rosga) and used as salt as antineoplaslic drug. periwinkle plant and used
93
Vnus : Submicroscopic infectious agent, smaller than bacteria, capable of passing through filters that will retain bacteria and multiplying only within a living susceptible host cell. Viruses differ from all other living entities by possessing only one kind of 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 information but 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 with
ZvlroonN
Xanthomonas campestris. : The inactive precursor of an enzyme. A non-catalytic substance formed by plants and animals as a stage in tbe development of an enzyme. Also called pro-enzyme.
Index
Biotechnology Investment Trust 66 Boots (Coy) 66 Bose Institute of Nuclear Phlsics 80 Boyer, Herbert 5
Brazil
79
Breeding Centre
for
Camels, Bikanel
68
Antibiotic 2, 3, 5,20,26
Antibody 5, 20, ZZ,23,24, 32, 66 Antigen 22 Antisera 5 Aspartame l7
Assay 26 A. tum<faciens Auxins 8, 9
12
Lzolla
16
Bacteria 2, 3,4, 11,14, 16, 11, 19, 21, 35, 43, 60, 62, 80
Becton, Dickinson,
BeU Lab 46
BARC 80
Centre
Molecular
Biolosy 32, 33, 80 Cetus (Coy) 21 ,25, 67, 73. 74, 76 Chakraborty, Anand IU. 19, 36,37,
54
Biochip
Chesterfield 3 Chemotherapy 25
China l7 Chiron 47
Chromosome 10, 80 Chymosin (Renin) 28, 73
'96
,
City of
Centre
40
or VIII20, .A.O. 15
69, 7J
69
Council
of
70
Research 78
Crick, Francis I
Culture 2, 8, 9, 10, 16, Cystic fibrosis 39
61
cytokinin 8,
4,20,21,55,72
rance 42,53, 57
17, 18, 67, 80
Denmark 68
Deoxyribonucleic Acid (DNA) 1, 3' 5' 6,8, 11, 12, 13,20,21,24,32 Diagnostics 20, 21, 4'1,50,66,67
7Z
61,65
R-oger 9
arsenide
35
32,
M,
67
,68
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 I
Programme
Screening 37, 50
variety 4l
engineered
Erythropoietin (EPO) 22 Escherichia <oli (E. coli) 1,2' 3, 5, 39, 43,79 Established firms 51 Ethanol 30, 35, 79
Ethylene 8
Eukaryote
36,47,49,69,75 1,2
)J
Index
Gestation period 50
International Centre
56,78
for
Cenetic
Guidoboni
31
Haploid l3
Hardy, Ralf W.F. 3l Hawaii 64
In-vitro 47,
Ln
60
18
Helical I
Hemophilia 20, 36, 69, 73 Hepatitis B 20, Zl, 36, 60, Hrbicide I l, 29 flerpes 20, 23, 36, 60
67
Ilewlett Packard
69
56'
,70
Humulin
36, 68
Ilybridization 12,
16, ZO, 79
Maizo sweet
18, 80
I.8.M.43
t.Q.r. 49
Immunex 25, 76 India 18, 54,55,78 Indian 54, 55,78,79
search 61, 79
Malaysia 63, 64
Mallinckrodt 40
Meristem 8, 9,
11
(Dr')
33
Microbe 3, 19,34,35,39
Microbiological Resource
(MIRCEN)
11
Centre
Eiotechnology
l
18, 30
M.I.T. 40,
53
M,I.T.I.56
Mitosis l0 Molecular biology 40
ngineering 28 Molecule 5, 35
on
16
34, 54, 62
t,
43
Monoclonal antibodies (MAB) 5, 6, 20, 2t, 22,26, 33, 50, 59, 66, 72, 73
Monsanto 3, 40, 71 Morel 8 Mutation I l, 3t
activator 26, 69
arides 29
mildew
13
NABARD
79
Naito (Dr.) 7l
National Biotechnology Board 54, 55,
78
National Bureau
Resources 79
of Animal
(usA)
24
National Chemical Laboratory 79 National Enterprise Board (UK) 66 National Institute for Goats 79 National Institute of Irnmunology 79 Native Plants Inc. (USA) 7l N.B.F. (New Biotchnology firm) 42,
44, 48, 49, 50
67,
DNA 5,
osenberg 24 oya,lty 61 , 69
'r,
t Lake city an Diego 22
66
1')
71
4, 44
N. & M. Rothschild
Norman 16 Northern Africa t7
of Environmenlal Sciences 80
21
l1 ilicon 35
o.E.c.D.
34
rz,79
tostanin 69 East Asia 15
Pacific 7 chemicals 2, 5,28, 44, 49, 69,13
56
Organism 1,2,3, 5,
3L
1, 16, 30
55
, 57
te
5,7
4,7l
Inde
x
T.I.F.R.80
16
oo
Suspension 9, 11, 66
ll,
16,
Tamil Nadu
Tapioca
18
Tata Oil Mills 80 Tax 40 Tax allowance 57 Tax at capital gains rate 56 Tax exemplion 56 Technology
Agricultural l4
Breakthrough 45
4,7' ll.
Clonal
61
14, 17, 23, 25, 26,29, 32, 37' 42' 45' 46, 48, 50, 53, 54, 55, 56, 57' 59' 62,
Aligarh Muslim 80
Benares
3
llindu
80
California I
Cambridge 5 European 4
Illinois
36
High
,10
Hybridoma 5, 6
Immuno 54
ImmunoassaY 44
Infrastructural Laboratory 2
Mechanical
16
53
Stanford I, 5
Washington
,10
New 52
Process
7l
Proprietary product 45
Protein engineering 70 Recombinant DNA 3, 26, 40, 43, 67 Second generation 5l
Tissue culture 61, 7l Unproven 43
Thiobacillum 35
17
World Bank
17