±COVER STORY

Potential of
biotechnology
Dr. Manju Sharma
Secretary, Department of BT, Government of India

B
iotechnology can be broadly defined as “using living”
organisms or their products for commercial purposes.
As such biotechnology has been practiced by human
society since the dawn of history in which activities taking
place were baking bread, brewing alcoholic beverages or
breeding food crops or domestic animals were taking place.
These processes actually marked the beginning of what we
today call as biotechnology. large number of industrial and agricultural activities as well
The discoveries and innovations specially in industrialised as in the health sector. This would provide the impulse to
counties through the basic understanding and unravelling of radically transform the competitiveness and growth potential
the double helix structure of DNA by Watson and Crick in for a number of activities and open up new possibilities.
1953 and thereafter, developing a large number of Biotechnology promises a ‘golden age” in agricultural
biotechnological tools and techniques, the field of production, where no one goes hungry, customize foods
Biotechnology has assumed a prime position amongst all the contain added nutrients to enhance our health or ward
disciplines of science. off disease, and farmers produce the raw materials for
The Human Genome Project gives the completion of plant-based industrial stock, fuels, antibiotics and a myriad
the DNA sequence and analysis of human chromosome of other products as well as food.
6 comprising 167 million base pairs. This chromosome Biotechnology provides unique opportunities to
has tremendous significance from the medical research increase the quantity, quality and reliability of food
point of view including aspects of protection and supply. These gains can be achieved with potentially less
treatment for diseases like cancer, schizophrenia, arthritis need for pesticides and herbicides, less demand on scarce
and diabetes. The most important aspect is a region on water supplies and less pressure to use ecologically
the short arm of the chromosome which encodes the sensitive land.
Major Histocompatibility Complex (MHC). It is
To increase agricultural productivity, in an environmentally
absolutely essential for the human immune response. This
sustainable manner in the face of diminishing land and water
work is going to further light up the curiosity and desire
resources is a highly challenging task. Knowledge based
to speed up research in all aspects of genomics.
approaches including crop genomics can provide powerful
The challenges, the excitement, the curiosity and the solutions and enhance food security, by improving local
opportunities are limitless before the scientific community agricultural productivity, minimizing the use of chemical
pursuing modern biology and biotechnology research. inputs such as pesticides and fertilsers, insulating crops against
Equally important are the aspects of its application. losses from diseases and pests, curtailing post harvest loses
Modern biotechnology constitutes a growing range including food spoilage, improving food quality and nutrition,
of techniques, procedures and processes. The confluence increasing crop tolerance to stress factors such as drought
of classical and modern technologies enables the creation and salinity problem, and through the production of value
of new products and highly competitive processes in a added products.
KERALA CALLING December 2003 1 3
 We have been domesticating, breeding and
hybridising animals and plants since long. But while
doing so, we could not accomplish the most
desirable goals because of the natural constraints
imposed by species barriers and some built-in-
limits. Genetic engineering has by passed all the
species barrier and information between completely
unrelated species in a controlled manner and has
given birth to Precision Breeding.
Biotechnology can expedite the development
of new varieties and also enhance marginal crops
like millets, banana, grain legumes, cassava and
sweet potato all important staples in the developing
world. Introducing genes that increase by three-
fold are available iron levels in rice can be a
potential remedy for iron deficiency. Modern
biotechnology offers effective techniques to
address food safety concerns. Biotechnological
methods may be used to decrease the time necessary to detect
food borne pathogens, toxin and chemical contaminants as agriculture where biotechnology has shown significant
well as to increase detection sensitivity. Enzymes, antibodies achievement include transgenic crops, herbicide tolerance,
and micro organisms produced using rDNA techniques are insect resistant, virus tolerance, other engineered products,
being used to monitor food production systems for quality stress tolerance.
control. Biotechnology can compress the time frame required Vaccine Production from Plants
to translate fundamental discoveries into applications. Now An interesting development is the use of plants to produce
plants resistant to insect attack like Bt cotton, are a reality, no “edible oral vaccines”. The plants provide a natural
more the fantasies of science fiction. encapsulated environment for the proteinaceous vaccines
A case study compiled by National Centre for Food and which can be produced on a very large scale at cost, which is
Agriculture Policy (NCFAP) reveals that crops (maize, sugar lower as compared to using current technologies. Currently
beet and potato) developed through biotechnology can help edible crops such as bananas and corn are being used for
farmers reap an additional 7.8 billion kgs of yield and improve producing a variety of vaccines including vaccines against
farm income by 50 billion Rupees and reduce pesticide usage Hepatitis B, transmissible gastroenteritis and E. coli labile toxin.
by almost 10 million kg per year. Potential applications of this technology would include
It is amazing to know that three years of field trials of efficient immunisation of humans and animals against disease
genetically modified cotton in Australia particularly Bollgard and control of animal pests. For instance, antigens for the
II has shown that pesticide use can be reduced by as much as Hepatitis B virus have been successfully expressed in tobacco
75per cent compared with conventional cotton. plants and used to immunise mice.
Genetic engineering can be used to modify the genetic This technique promises to pave the way for inexpensive
compositions of plants, animals, and micro organisms. immunisation against several human diseases. Oral vaccines
The number of genes that have been isolated and are against cholera have already been expressed in plants.
available for transfer are growing daily. Some of the areas in Generation of antigens through plants is not only cost-
effective, but can also be mass produced, and easily recovered.
Plant biotechnology is stated to be an important R&D
‘Designer’ Foods business in our country, as India is regarded as the largest
Many plants are now being used to produce useful proteins. producer of milk and the second largest for fruits and
This has given birth to ‘Nutraceuticals’ - a word coined for vegetables. Analysts predict that by 2010 India can become
made up food. These foods are also known as functional the World’s largest exporter of agriculture.
foods. The nutraceuticals include all ‘designer’ foods from Biodiversity
the vitamin-enriched breakfast cereals to Benecol, a margarine Increased economic growth spurred by genetically
spread that actually lowers LDL cholesterol. A leading improved crops will provide much-needed resources in the
American company, Novartis Consumer Health, estimates efforts to conserve biodiversity.
the US market for functional foods is around ten billion dollars, India is one of the world’s 12 mega diversity areas, with
with an expected annual growth rate of ten per cent. over 45 000 wild plant species and 77000 wild animal species

1 4 December 2003 KERALA CALLING

registered, accounting for about 6.5 per cent of the world’s that help the body overcome infections and cancers, fight
known wildlife. The biological wealth of India is a valuable pain, encourage the growth and repair of tissues or carry out
asset to be managed prudently, particularly since the CBD other specific functions. The body itself during its normal
recognizes that the biodiversity present within the political functioning in fact produces many of these proteins.
frontiers of a country is the sovereign property of that country Vaccines
.The diversity of living forms in India is the result of climate
The vaccines produced by modern biotechnology consist
and soil variability and cultural and ethnic diversity. There
only of the antigen. This reduces the risk of the vaccines
are over 53 million tribal people in India, belonging to 550
transmitting the virus and allows for modification of the
communities.
vaccine to increase its effectiveness. We are at various stages
There are three megacentres of endemic biodiversity in of developing vaccines for dreadful killer diseases such as
India -the Western Ghats, the Eastern Himalayas and the Malaria, Cholera, Tuberculosis, Japanese Encephalitis Virus,
Western Himalayas -and 25 micro-endemic centers. HIV/AIDS etc.
We have the rich bioresources base which can provide Diagnostics
novel genes, molecules, enzymes for commercial exploitation
Diagnostics are used to detect diseases under normal and
etc. These would eventually generate a significant revenue
abnormal conditions of the human body. Many modern
for the state.
diagnostic kits are based on the use
Recently, the World Summit on of labelled antibodies. More recently
Sustainable Development held at DNA Vaccine : A boon to diagnostic kits based on the
Johannesburg once again reviewed the developing countries polymerase chain technology have
concept of sustainable development
and projected three dimensions as With DNA vaccines, the gene for a protein been developed.
Diagnostic kits produced through
integral part of this, namely: from a pathogen is inserted into a bacterial
biotechnology play an important role
environmental conservation and plasmid. The first clinical trials using
in the screening of blood for HIV and
enhancement of genetic resources; injections of DNA to stimulate immune hepatitis. Home pregnancy tests are
social security of the people; and
Economic security.
response against a foreign protein began for examples of commonly used
Human Health Care HIV in 1995. Since DNA is relatively diagnostic product.
Gene Therapy
In a report published in nature inexpensive and is easier to produce than
the isolated proteins or attenuated organisms Gene therapy involves
genetics it was revealed that 10 most
modification, deletion or addition of
promising biotechnologies for on which conventional vaccines are based,
genes. to cure a disease. Theoretically,
improving health in developing this technology may enhance the availability a single successful application of gene
countries in the next five to ten years
include: modified molecular
of vaccines to developing countries and therapy will cause the body to
technologies for affordable, simple enable timely immunization against permanently cure the disease. Gene
therapy is currently being evaluated
diagnosis of infectious disease, emerging infectious diseases. In India
for its ability to treat wide range of
recombinant technologies to develop significant progress has been made to
diseases such as cancers, diabetes,
vaccines against infectious diseases,
develop DNA rabies vaccine at IISc heart disease, arthritis and neuro-
technologies for more efficient drug
Bangalore. degenerative diseases. Gene therapy
and vaccine delivery systems,
has been used, for example, to treat
technologies for environmental
severe combined immunodeficiency
improvement (sanitation, clean water,
disease (SCID), commonly known as the “bubble body
bioremediation), sequencing pathogen genomes to
disease”. Gene therapy requires the identification and cloning
understand their biology and to identify new antimicrobials,
of the relevant human genes. The data generated from the
female-controlled protection against sexually transmitted
completed Human Genome Project will therefore prove to
diseases, both with and without contraceptive effect,
be a cornerstone of gene therapy.
Bioinformatics to identify drug targets and to examine
pathogen -host interactions, genetically modified crops with Stem cells have an enormous potential for repairing
increased nutrients to counter specific deficiencies, damage to the body caused by disease, injury, or aging. Stem
recombinant technology to make therapeutic products (for cells also offer the prospect of treating many inherited diseases
example, insulin, interferons) more, affordable, combinatorial caused by a single, defective gene.
chemistry for drug discovery. DNA Fingerprinting
Biopharmaceuticals The development of DNA fingerprinting technique has
Many of the biotechnology based therapeutics under proved to be extremely significant in identifying criminals
development or which have been approved for use are proteins and establishing parentage.
KERALA CALLING December 2003 1 5
 Prenatal Diagnosis of Inherited
Diseases
Molecular genetics has a
significant application in prenatal
diagnosis of inherited disorders like
haemoglobinopathies. For instance,
the technique for analysing DNA to
diagnose sickle cell anaemia from the
amniotic fluid cells was devised in
1978.
Pharmacogenomics
The intervention of molecular
tools in the pharmaceutical domain
has given birth to a new area of Dolly and Polly from species like pigs are believed to be
Pharmacogenomics. This upcoming promising sources of donor organs for
field holds great promise of the day, The development of Dolly and Polly by humans. This practice is referred to as
when it will be possible to tailor drugs Dr. Ian Wilmutt of PPL Therapeuticals, ‘Xenotransplantation’. The first
for individual patients keeping in view xenotransplantation experiment was
their genetic architecture. London, the first cloned animals created waves conducted in 1905, when a French
Animal Health allover the world. This feat is indeed significant, surgeon transplanted slices of a rabbit
kidney into a human patient.
Using biotechnology, scientists are as it not only marks a great scientific
developing fast, accurate diagnostic achievement, but also paves the way for the Bovine embryo transfer is another
tests for many of the most common generation of many other cloned animals, which technique of genetic manipulation. The
live stock diseases. Recombinant DNA carry valuable human proteins. principal advantage of embryo transfer
technology has made it possible to is that it increases the reproductive
breed animals with great precision and In addition to producing new diagnostic tests capacity of useful cattle like cows and
accuracy. Specific genes can be inserted and therapeutic proteins, animal scientists are buffaloes. Such transfer can also decrease
into an animal embryo without causing using biotechnology to develop vaccines to the generation interval between selection
a shift in other genes present in the steps by having a large percentage of
same animal.
prevent disease. A safe, effective vaccine for progeny of young donors.
One of the major applications of
swine pseudorabies, is already in use. Another Industrial Biotechnology
genetic engineering is the development advantage of recombinant vaccines is the speed The most successful application of
of new breeds of productive cows that with which they can be developed. industrial biotechnology outside the
can produce more nutritious milk. The pharmaceutical industry to date has been
“Conventional vaccine development can take 20
milk of an ordinary cow lacks the production of industrial enzymes
lactoferrin, an iron-containing protein, or 30 years, may be even 100 years”, through fermentation - a process with
which is significant for infant growth. Recombinant vaccines are being developed for leading market applications in textiles,
Scientists at Gen Pharm International, foot-and-mouth disease, a highly contagious food, and detergents. Techniques for
California, have now developed the removing hazardous chemicals from the
viral disease that infects cattle, sheep, and other
transgenic bull Herman, which has environment are also gaining interest.
been microinjected with the human animals. Food and Beverage Industry
gene for lactoferrin. The breeding of Enzymes are biological molecules
Herman and its progeny will prove to be a new source of present in various organisms. Microorganisms have been
nutritious milk. found to be a rich source of industrially important enzymes.
Animal Nutrition One such enzyme is xylanase. Different types of xylanases
Natural proteins called somatotropins, or growth have been identified and isolated by genetic manipulation.
hormones, help animals convert feed into muscle or milk. These include digestive enzymes for natural fibres like wood,
Using recombinant DNA technology, scientists have been pulp and cellulose.
able to develop bacteria that produce commercial quantities Environmental Biotechnology
of somatotropins. One of the major concerns today is the preservation of
Organ transplantation the existing flora and fauna including plants, animals and
microbes. Molecular applications have opened up new and
The latest biotech feat, has proved to be a cost-efficient
improved methods of preserving plant and animal genetic
treatment for heart, kidney, lung and other diseases. Organs
resources and have accelerated the collection and evaluation
1 6 December 2003 KERALA CALLING
of germplasm for specific traits. We have gene banks, both applications. These are used as food, fertilizers, industrial
ex situ and in situ. A new generation of genetically engineered gums, medicinal use. cosmetics industry etc. Farming of
organisms is being developed to convert toxic materials into seaweeds has resulted in production of biopolymers with
benign substances. Scientists are also using genetically many industrial applications. For instance carrageen an is
engineered fungi, bacteria, and algae as “biosorption” systems widely used in food and cosmetic industries. This is a million
to capture polluting metals and radionuclides including dollar industry since India has a large coastline of 7000 km
mercury, copper, cadmium, uranium cobalt etc. Some of the and nearly 770 species have been reported from India. Of
areas where biotechnological tools have made c dent include late few Indian companies also have started seaweed
land fill technologies, bioremediation, biosensors, cultivation, which eventually would create nearly 50,000 job
biodegradation of Xenophobic Compounds, oil eating bugs, in coastal states especially for women.
designer bugs for biomining, pollution control, cleaning of Bio informatics
industrial, dairy, dye and industry wastes, restoration of
One of the main applications of bio informatics in
denuded ecosystems etc.
addition to its enormous use is the data mining and analysis
Maintenance of a wide genetic base, which is an important of the data gathered in genome projects. Other applications
element of biodiversity, is essential. The global scientific are sequence alignment. protein structure prediction.
community agrees that biotechnology gives us an important metabolic networks. morphometrics and virtual evolution.
additional tool towards meeting these needs. Plant tissue Protein structure prediction is another important application
culture has been regarded as a key technology for increasing of bio informatics. The amino acid sequence of a protein,
the production capability of many plants of selected varieties, the so-called primary structure, can be easily determined from
and to prevent their extinction. Biotechnological tools have the sequence on the gene that codes for it.
thus paved a new pathway for restoring and preserving our
There are many successful examples of structure based
biodiversity in multidimensional ways.
drug design. Development of anti-retroviral therapy for the
Aquaculture and Marine treatment of AIDS or the development of anti-cancer drugs
Biotechnology have been significantly accelerated by the knowledge of the
We all know that oceans cover 70 per cent of the earth three dimensional structure of the target proteins. Today,
and these house millions of marine organisms each of which structure based drug design is an undertaking in every major
offer unique qualities and uses. Reports suggest that marine pharmaceutical set up.
biotechnology can help utilize more than 30 thousand known Bio informatics can help in Characterising targets, such
species of marine organisms to develop new products as the classification and subclassification of protein families;
including the biochemical capabilities of marine organisms Understanding targets, such as their behaviour in a larger bio-
to generate new classes of pharmaceuticals, polymers, chemical and/or cellular context; Developing targets, such
enzymes and many other as production, detoxifica-
chemical products. This tion, the stratification on
technology can boost the Intellectual Property Rights and BT patient population and
development of vaccines, Due to increased costs of research and development all over the globe, it other gene-based varia-
diagnostics and analytical
became necessary in the interest of public, to provide adequate incentives tions.
agents, and genetically
to the inventors for carrying out research. This thought eventually gave It can be said that the
modified organisms for
genome projects gave us
aquaculture and seafood birth to what is called Patent, the Patent Law and IPR regime.
long lists of letters and
industry. IPR’s related to biotechnology are mostly covered under plant breeders with bio informatics I we
Biotechnology has made rights, trade secrets, trade marks and copy rights. Depending upon the can determine words,
significant contributions to
the field of marine nature of the invention, the patent may be granted for a product, a process grammar, sentences and,
finally their meaning.
aquaculture. The tremendous or both {product-process patents). However, live forms may or may not
Advances in genomics
potential of marine resources be patentable though majority of the industrialized countries have and DNA analysis are
are still untapped. As extended patent protection to living organisms. Among the leading to new develop-
overexploitation of natural
biotechnological innovations, patents are granted for products like ments in molecular elec-
resources takes its toll on
these natural reserves, the antibiotics, new microorganisms, new gene(s) sequences, new substances tronics and bio comput-
ing.
development of transgenic with no previously recognized existence etc. Patentable processes include
fish will playa key role in the Biomolecules or mac-
method for new organisms, for example enhancing biological utility, romolecules like carbohy-
aquaculture industry in the
reducing disease incidence due to pathogenecity, construction of new drates, lipids, nucleic ac-
near future.
organisms by genetic recombination or cell fusion, etc. ids and proteins form an
Seaweeds have numerous
important area of re-
KERALA CALLING December 2003 1 7
search with application in Biosensors and DNA chips and
Dr.D. Karunagaran ,
Bio-chips.
Rajiv Gandhi Centre for BT,Thiruvannanthapuram
Nanobiology

W
hile the medical treatment strategies in general use
Over the years, we have seen the convergence of various
diverse fields and, this has led to development of new frontier now (i.e., surgery, chemotherapy, and radiation) are
successful in some cancers, they all have limitations.
inter-disciplinary areas, such as Nanobiology. It involves the
For example, surgery has been used successfully for many
expertise of physicists, as it deals with cooperative systems
years to remove cancerous tumors. However, not all cancers
of many subunits, which undergo structural changes also
can be surgically removed and even when they can be, some
computational methods, chemistry etc. Nanobiology is a blend
cancerous cells may have been missed. Conventional
of physics and biology -the study of biological entities at
treatments don’t always kill every cancer cell, or they kill
Nanometer scale levels.
normal cells as well as cancer cells. The use of cytotoxic
The emergence of nanobiology depends on the drugs and radiation against cancer is limited by a number of
development of Nanotechnology. The concept of factors, including toxicity, tumor resistance and lack of
nanobiology was first proposed in a group study named targeted cell death. Now, scientists are developing better ways
“Biological Nano- Mechanisms”. to target therapies directly to the tumor while protecting
healthy cells. New strategies are based on increasing and
improved knowledge of the molecular events responsible for
disordered cellular growth and include antibodies to block
receptors, small molecules that inhibit receptor tyrosine kinase
(RTK) mediated cell signaling, agents directed at suppressing
growth of blood vessels that feed cancer growth, vaccines to
stimulate immune recognition of cancer cells, cell cycle
inhibitors, and gene therapy to turn off signaling pathways
or provide a missing tumor suppressor. Novel agents are
already in the clinic, including antibodies such as Herceptin
to treat advanced breast cancer and the small molecule RTK
inhibitor Gleevec for the treatment of chronic myelogenous
leukemia. Herceptin is a monoclonal antibody directed against

Cancer treatment:
the HER2/neu receptor, one of the epidermal growth factor
receptor (EGFR) family members, and is the only growth
factor receptor inhibitor approved for clinical use (to treat
metastatic breast cancer with or without chemotherapy). Some
of the novel therapeutic approaches are outlined below.
Some of the areas where nanobiology can make impact are The goal of gene therapy for cancer is to inhibit the
development of improved chemical separations using non- constitutive signals that drive tumor growth. One area of
porous material, combine engineered and self assembled research is replacement of the missing function of a mutated
components into useful devices ranging from sensors to tumor suppressor gene, P53. Various approaches have been
photocatalysts for splitting, assessing the properties of used and are in clinical trials. Results from this and other
nanobiological systems such as enzymes, other proteins, and agents are limited by a variety of problems, including difficulty
biochemical processes for better understanding, of delivering the agent, identifying tumors that lack P53 or over
fundamental life processes and for developing new and useful express other targets, and production of the novel agent.
products from these technologies
Two radio labeled antibodies in clinical trials treating
Looking at the enormous potential of biotechnology, it patients with relapsed or transformed low-grade non-
seems quite apparent that our way of life is likely to be more Hodgkin’s lymphoma, are tositumomab (Bexxar), and
fundamentally transformed in the next several decades than ibritumomab tiuxetan (Zevalin}. Both are antibodies
in the previous one thousand years. By the year 2025, our
I to CD20, tositumomab is linked to 131I and ibritumomab
children and we may be living in a world very different from
is linked to 90Y. (An antibody against CD33 linked to the
anything human beings have ever experienced in the past.
l toxin calicheamycin has been effective in the treatment of
1 8 December 2003 KERALA CALLING