SPEAKING
FREELY Genomics: Challenges and opportunities in
India By Kannan Sivaprakasam
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The Human Genome
Project A
genome is an organism's complete set of
deoxyribonucleic acid (DNA), and a unit of
hereditary. Genomes vary widely in size: the
smallest known genome, bacterium, contains about
600,000 DNA base pairs, while human and mouse
genomes have some 3 billion. Except for mature red
blood cells, all human cells contain a complete
genome. Begun in October 1990, the Human Genome
Project (HGP) was a 13-year, multinational effort
undertaken by 20 groups from six countries
coordinated by the US Department of Energy and the
National Institutes of Health. It is the largest
single biological project ever begun, and the
completion of the HGP marks the beginning of a new
era, and a major scientific milestone of the 21st
century. The main goals of the project were to
identify approximately 30,000 genes (a gene is a
sequence of DNA that corresponds to a protein) in
human DNA and to determine the sequences of the 3
billion chemical base pairs and make them freely
accessible for biological research. The human
genome holds an extraordinary trove of information
about human development, physiology, medicine and
evolution, and it is the largest genome to be
sequenced so far (about 25 times the longest
sequence previously sequenced and eight times the
sum of all other sequences). From Asia, only China
and Japan participated in the HGP. India, despite
having the necessary scientific and technological
infrastructure, did not join the HGP.
India stands to gain
immensely by actively encouraging investment in
genomics. Given India's vast and diverse ethnic gene
pool and varied climatic regions supporting rich flora
and fauna, there is an abundant bio-diverse basis for
genomics.
India, which let the Human Genome
Project (HGP) pass by deliberately overlooking it, has
joined the international rice genome project, and it can
vigorously participate in the interpretation phase of
genomics.
Genomic data provides information
about deoxyribonucleic acid (DNA) sequences, but it
doesn't reveal their function. Sequencing the human
genome is only the first step in the genomic revolution.
Transformation of the sequence data into useful
information is a gigantic task.
The
characteristics of the genome's downstream products,
such as ribonucleic acid (RNA) and proteins, and the
complex pathways in which these molecules function and
interact, must be elucidated in order to understand the
genetic basis of human disease and development.
But currently, the opportunities and challenges
in this information-driven sector revolve around mining
the large databases for new knowledge and converting
them into useful and commercially significant results.
It is here that India can contribute immensely,
with scientific manpower capabilities existing in both
life sciences and information technology (IT). It is
necessary to bear in mind that the progress and success
of the HGP was made possible by the seamless integration
of scientists from molecular biology, biophysics,
biochemistry, chemistry, genetics, etc.
An
analysis of the blueprint of life would need, in
addition to the above group, the active assistance of
experts in IT and computer science. IT majors such as
Intel, IBM, Sun and Wipro are getting into this segment,
spurred by genomics-driven drug discovery and
development.
Indian IT companies have a great
business opportunity by offering complete database
solutions to major pharmaceutical and genome-based
biotech companies around the world. Satyam Computers has
signed a five-year alliance with the Center for Cellular
and Molecular Biology to create, store and annotate
genetic databases, and it is angling for contracts from
big global pharmaceuticals to sequence genes and build
protein catalogs.
Strand Genomics, a
Bangalore-based bio-informatics start-up, is designing
tools to accelerate drug discovery. With an estimated
market size of US$4.5 billion in 2010, India's biotech
market is set to compete in the global market. The major
issue for India is its transition from a recognized
global leader in software development to areas of real
strength on which it can capitalize in genomics.
The identifiable areas are in computational
biology and bio-informatics (the integration of biology,
computer science and information technology), where a
substantial level of development skills are required to
develop custom applications to knot together and
integrate databases, simulations, molecular modeling,
docking programs, etc.
Bio-informatics is
crucial for the advancement of the genome-based industry
by cutting the timeframe and costs in developing a
product. India was one of the first countries in the
world to enter into bio-informatics in the mid-1980s.
The Biotechnology Information System Network in India
has covered the entire country by connecting the 57 key
research centers with a supercomputer-based network that
provides researchers with access to genomics and
proteomics (protein sequence, structure and activity)
databases. According to the Confederation of Indian
Industry, the global bio-informatics industry clocked an
estimated turnover of $2 billion in 2000, which is
expected to become $60 billion by 2005.
The
pharmaceutical industry is still faced with a growing
need for new informatics tools to help manage the influx
of data from genomics, and turn that data into
tomorrow's drugs. With an increase in sequencing
efficiency, there is now an accumulation of genomic
databases, but the tools to analyze them are lagging
behind: there are no effective genome comparison tools.
The astounding growth in genomic databases and
the massive parallel measurement/data acquisition
strategies has resulted in an information explosion
("Big Bang"). The total global market size for bio-IT
solutions is pegged at $25 billion and is growing at 20
percent annually. In India, the market is pegged at $15
million and is poised to grow to $120 million by 2006.
Aventis, Dr Reddy's Lab, Nicholas Piramal, SmithKline
Beecham, Bharat Biotech, Biocon India and Wockhardt are
the key players in the biopharma sector.
In a
patent-filled world, developing new drugs is more
enumerative. But the cost involved in the discovery and
development of new drugs is prohibitive. Hence, Indian
pharmaceutical companies have started going in for
symbiotic ventures with multinationals whereby the
latter can use the resources of the Indian counterparts
to accelerate the discovery/development process.
DNA underlies almost every aspect of human
health, both in function and dysfunction. Gene tests can
be used to diagnose disease, provide prognostic
information about the course of disease and predict the
risk of future disease in healthy individuals or their
progeny.
Genomic knowledge of the genes involved
in diseases, disease pathways and drug-response sites
will lead to the discovery of thousands of new targets.
But gene-targeting/gene-transfer still faces many
scientific obstacles before it can become a practical
approach for treating disease.
In the cell, the
biological transformation takes place in the following
direction, DNA->RNA->protein. Most of the current
drugs are chemical compounds that target the function of
protein. To attack the malfunction associated with the
DNA or RNA requires substantial scientific data, as any
side effects can cause unacceptable consequences.
According to the American Society of Human Genetics'
statement on gene therapy, effective progress will be
achieved only through continued rigorous research on the
most fundamental mechanisms underlying gene delivery and
gene expression in animals.
India has all the
ingredients required to conduct clinical trials to tap
the $70 billion opportunity in clinical trials and
clinical data management systems. However, India lacks
the records of clinical information about patients;
sequence data without clinical information will have
little meaning, and hence, partnerships with clinicians
are essential. But care must be taken so that India does
not end up merely as a testing ground for most of the
drugs.
A systematic and comprehensive
exploration of the sequence data of many organisms will
enable us to shift our view of biology from a
descriptive science into an informative and predictive
one. Francis Collins, director of the National Human
Genome Research Institute, a division of the National
Institutes of Health that is responsible for the HGP,
calls it building the periodic table of the elements for
human biology.
Sequencing projects on the
genomes of many microbes, as well as the honeybee, cow
and chicken, are in progress. Perhaps the most daunting
challenge is to begin to understand how all the "parts"
of cells' genes, proteins and many other molecules work
together to create complex living organisms. The
codebook of life is slowly emerging for many organisms,
but to understand the instructions will take some time.
Truly, the results of the HGP will serve as a
foundation of biomedical research in the years ahead.
India, being host to a vast bio-reservoir and a pool of
competent scientific and technical manpower, can really
make a mark in the post-genomics era if there is an
organized and directed private/public partnership, a la
a mini-HGP.
Kannan Sivaprakasam is a
Research Associate in Cornell University, Ithaca, NY,
USA.
Speaking Freely is an Asia Times
Online feature that allows guest writers to have their
say. Please click hereif you are
interested in contributing.
Mar 11, 2004
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