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Jan-Mar2002-10(1)
DISCUSSION
Responsibilities in the post
genome era: are we prepared?
S Kumar
Singh
The successful completion of the human genome
sequence can be counted as one of the most important scientific achievements in
biology in recent times. The analysis of the draft sequence by two groups, the
human genome consortium and a private company (1,2), has revealed astonishing
insights into the genetic blueprint of the human race. It has also provided
tantalising clues as to what makes us a unique species.
To cite a few examples, the analysis of the draft
human genome sequence has revealed that (a) humans have a total of only about
31,000-39,000 genes which is only fractionally higher than the 18,000 genes of
Caenorhabditis elegans - a worm - and 26,000 genes in Arabidopsis- a plant
(compare these with 6,000 genes in yeast and 13,000 in Drosophila - a fly). (b)
Less than 1.1-1.4% of the 3.2 billion basepairs codes for a functional gene
products while the rest 98% are mostly repetitive DNA with an as yet
unidentified function. (c) About 50 % of the genome consists of the four classes
of repetitive DNA segments, many of them interspersed as large islands
throughout the genome. (d) There are vast stretches of DNA deserts devoid of any
genes at all on certain chromosomes, while there are dense gene clusters on
others. (e) More than 1.42 million single nucleotide polymorphisms (SNP, these
indicate the degree of variability of an allele in a population) have been
identified in the draft version of the genome with many more likely to be
identified in the near future. These polymorphisms are likely to be the hotspots
of genetic variations and the probable cause of various genetic pathologies and
hence are likely to be the first search targets by medical
researchers.
Much of this knowledge was unheard of even a year
ago. New, mind-boggling facts are being unravelled about our genetic make-up
almost every day. New results and hypotheses on human genetics are being
proposed, tested and in some cases disproved (3). New technologies are
demonstrating their potential to unravel useful medical information from the
genetic data. The first glance at the raw sequence data has yielded important
insights on phenomena like addiction (4). Numerous key protein targets have been
identified for targeting by immunomodulatory treatments (5) and more than 10,000
of disease causing genes in humans and their causal mutation have been
catalogued (6, 7).
It is clear that even by conservative estimates,
the impact of this research on any field of human biology - especially medicine
- is likely to be staggering. While there may be little in terms of immediate
benefit to the general medical practitioner (especially in India), there is much
cause for optimism as the genome sequence is likely to provide a fertile hunting
ground for medical researchers to probe the molecular underpinnings of many
diseases. This is evident from the unprecedented increase (in the developed
world) in investment of manpower and financial resources in both academia and
commercial ventures in research projects that exploit the new information. Many
suspected cases of rare medical anomalies go unnoticed during routine
investigations in Indian hospitals. Cheap and rapid screening methods that are
likely to emerge in the near future could enable the 'doctor on the street' to
quickly screen the average patient with little investment in cost and
manpower.
There is however a darker side to this story. Led
by the prospects of untold riches and the urge to gain biotechnological
leadership, there has been a scramble among commercial ventures to patent DNA
sequences which are suspected to be involved in critical disease processes and
thus have potential commercial value. The rapidity with which this field has
advanced has given little time for legislatures to formulate laws on complex
genome related legal and ethical issues.
The Indian contribution to the genome endeavour has
been dismal from the beginning, almost non-existent. Like in most cases, Indian
science has adopted the wait-and-see approach even as the genomic gold mine lies
bare in front of us with all its prospects. Today India with its diverse
population base distributed over a vast geographical area is uniquely placed to
gain from these evolving technologies. The multicultural and multiracial nature
of our society has a rich and diverse genetic resource inherently embedded in
it.
One of the main reasons for the success of this
project was the tremendous advancement made in various technologies like
automated sequencing methods, increase in computational power and advanced
algorithms for sequence assembly and annotation. Many of these techniques were
unthinkable even five to six years ago. It is clear that if India is to benefit
from these technologies and realise the full potential of its vast genetic
resources, there must be a paradigm shift in the manner in which basic and
applied research is practised, be it in isolated labs or large collaborative
studies.
Biomedical and genomic technologies existing today
can tinker with the genetic makeup of reproductive cells. This can have profound
consequences on and affect lives of millions of people at a fundamental level.
Will this knowledge be used to benefit us in hitherto unforeseen ways? Or will
it unleash new ghosts from the Pandora's box? These are questions for the
future. Nonetheless, it is clear that new ethical and moral questions are likely
to be hotly debated in scientific circles.
The need of the hour is to create awareness, among
biomedical research personnel and practitioners, of the new opportunities - and
the dangers - in emerging technologies. There should be a concerted effort among
the academic scientific community and medical practitioners to rapidly (albeit
cautiously) apply the new technologies to problems of immediate national
concern. This has to be correlated by an appropriate increase in funds available
for projects which focus on the use of these methodologies for problems relevant
in the Indian context. The decision of the department of biotechnology, to fund
areas in stem-cell research on cataract and the brain is a step in the right
direction. The impressive strides made by indigenous academic research centres
and commercial laboratories in stem cell research are indeed commendable.
Regulatory bodies which monitor the ethical
practices of medical personnel, and those monitoring the preservation of
indigenous genetic material, will have additional responsibilities. They must
set up ethical and regulatory standards on experimental protocols so that the
interests of subjects are safeguarded. Ethical and responsible conduct is going
to be increasingly necessary in light of the power of the emerging technologies
(8).
This will go a long way in restricting the 'drain'
of the nation's valuable genetic resources while exploiting the full potential
of local resources, with which India is richly endowed.
References:
1. The Genome International Sequencing Consortium : Initial sequencing and analysis of the human genome. Nature 2001; 409: 860-921.
2. Venter JC et al; The sequence of the human genome. Science 2001; 291:1304-1350.
3. Michael J. Stanhope MJ, Lupas A, Italia MJ, Koretke KK, Volker C & Brown JR.: Phylogenetic analyses do not support horizontal gene transfers from bacteria to vertebrates. Nature 2001; 411; 940-944
4. Nestler EJ, Landsman D: Learning about addiction from the genome. Nature 2001; 409:834-835
5. Fahrer AM, Bazan JF, Papathanasiou P, Nelms KA, Goodnow CC: A genomic view of immunology. Nature 2001; 409: 836-838.
6. McKusick, V.A.: Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore: Johns Hopkins University Press, 1998 (12th edition).
7. Sanchez JA, Childs B and Valle D: Human disease genes. Nature 2001; 853-855. 8. Editorial: Defining a new bioethic. Nature Genetics 2001; 297-298.
1. The Genome International Sequencing Consortium : Initial sequencing and analysis of the human genome. Nature 2001; 409: 860-921.
2. Venter JC et al; The sequence of the human genome. Science 2001; 291:1304-1350.
3. Michael J. Stanhope MJ, Lupas A, Italia MJ, Koretke KK, Volker C & Brown JR.: Phylogenetic analyses do not support horizontal gene transfers from bacteria to vertebrates. Nature 2001; 411; 940-944
4. Nestler EJ, Landsman D: Learning about addiction from the genome. Nature 2001; 409:834-835
5. Fahrer AM, Bazan JF, Papathanasiou P, Nelms KA, Goodnow CC: A genomic view of immunology. Nature 2001; 409: 836-838.
6. McKusick, V.A.: Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore: Johns Hopkins University Press, 1998 (12th edition).
7. Sanchez JA, Childs B and Valle D: Human disease genes. Nature 2001; 853-855. 8. Editorial: Defining a new bioethic. Nature Genetics 2001; 297-298.
S. Kumar Singh, Ph.D,
Post-doctoral research scientist, Dept of Biochemistry, University of Texas
Southwestern Medical Center, Harry Hines Blvd, Dallas TX 75206 USA. Email:skumar@biochem.swmed.edu