Grinding its way through various government-funded laboratories is the mother of all scientific research projects -- the Human Genome Project (HGP) -- which is expected to revolutionise drug research and rewrite the future of healthcare across the globe in the new millennium.

The HGP is a 13-year effort coordinated by the US department of energy and the National Institutes of Health and involves around 350 labs across the globe. It aims at sequencing the entire genome (i.e. all the DNA in an organism). In the case of humans, that's works out to approximately 1,00,000 genes.

Rapid technological advances have accelerated the expected completion date of this project to 2003, while BusinessWeek International says that draft human genome project report will be ready in the next two months.

Yet another effort in decoding the human genome -- by Celera Corporation -- is on its last leg. Company president, Dr J Craig Venter has reportedly stated that Celera has analysed some 10 million fragments of human DNA, each about 500 chemical units in length. The Rockville-based Celera is now ready to assemble them into a human genome.

Experts say that many inborn errors of metabolism are a consequence of genetic dysfunction. DNA research aims at studying these "faulty" genes that cause ailments like cancer, diabetes, asthma etc. If it is possible to zero in on these genes, it may also be possible to determine disease susceptibility in an individual. That's why international pharma giants are pouring billions of dollars into genetic research and waiting for the final mapping of the human genome. Many of the top global healthcare companies, including Glaxo Wellcome, Sandoz (now Novartis) and Warner Lambert hold large stakes in biotech companies. Prominent among these are Sandoz's $295 million deal for Genetic Therapy and Glaxo Wellcome's acquisition of Spectra, essentially involved in central nervous system (CNS) genomics.

In India, such direct involment is near-absent. SmithKline Beecham (now in the midst of merging with Glaxo Wellcome) already has a multi-million dollar collaboration with Human Genome Sciences (HGS) Inc. The agreement gives SmithKline certain rights to develop and commercialise human and animal healthcare discoveries based on HGS Inc's data. SmithKline DNA researchers have already uncovered many new genes, apparently important in controlling signals in the brain.

Investigations are on to see if new medicines for treating depression, schizophrenia etc can be developed.

Indian drug companies are not much into genomics yet, but they are showing signs of seeking a share of the action. Three top-notch domestic companies -- Ranbaxy Labs, Dr Reddy's Labs and Cipla -- say that they would look at opportunities in gene researching in future. Cipla says it already has a specific team in place), but two others, Wockhardt and Lupin Labs, say they have not made concentrated efforts, yet, in this area.

The government initiative on this front is, however, rather striking. Says Ranbaxy Labs president (R&D) JM Khanna: "It appears that the department of biotechnology (DBT) has a five-year, $20-million Indian Genome Initiative (IGI) to study the genetic variations of the diverse Indian population. Two institutions are being set up for Genome Research in India -- the Plant Genomic Centre in New Delhi and the Centre for Human Genetics in Bangalore."

The dark-horse in the private sector appears to be the Ahmedabad-based Cadila Healthcare. Says Cadila Healthcare president Ganesh Nayak: "DNA sequencing is being carried out by a large number of research institutes, academic institutes and in our R&D labs at Zydus Research Centre. We at Zydus have developed the capability to do this. Presently, we do the sequencing of genes and are working on certain focused areas."

Nayak says that a laboratory (Dr Lalji Singh's) at the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, is involved in the international Human Genome Project. But Jayaram Chigurupati, senior vice-president (emerging businesses) of Dr Reddy's Laboratories, feels that India's involvement is grossly inadequate. "The situation in India as far as involvement in the human genome project is concerned leaves a lot to be desired. Some work is being initiated in the sequencing of plant and other genomes in various centres."

Khanna adds that none of the Indian pharma companies or even national research laboratories are into human genomics. "But some of our national research labs, under the aegis of the department of biotechnology (DBT), Indian Council of Medical Research (ICMR), and the department of science and technology (DST) are into gene sequencing of bacteria, virus, parasites etc," he said.

Compare this with the international scenario and Chigurupati's statement seems like a veiled warning for the domestic industry. Companies like Pfizer have an annual R&D budget of $1.7 billion largely focused on genetic research, while SmithKline Beecham spends $3 million a day towards DNA research. The price-controlled (or rather strangled) Indian industry (the top eight companies including Ranbaxy, Dr Reddy's, Cipla etc), in contrast, together spent only Rs 260 crore on R&D last year.

But there's no need for undue panic, say industry experts. The international Human Genome Project (its ultimate goal is to obtain the DNA sequence of the three billion DNA sub-units present in human DNA) will not have any short to medium term impact, though the long-term fallout can be far-reaching.

Says Nayak, "The immediate goals would be to harness genomic information for targeting any gene, any m-RNA or protein expressed in a given disease condition, by entering into alliances with small companies carrying out sequencing or to buy out sequences and enter the new drug discovery programme through pharmacogenomics."

Pharmacogenomic techniques can help predict which patient will be likely to respond to a specific treatment.

Adds Indegene Lifesystems director Rajesh Nair: "The long-term impact is substantial and a whole new sub-sector -- bioinformatics -- will emerge. This will merge biotech with IT."

Ranbaxy's Khanna claims that it is still a very long way to fully apply this knowledge (from the human genome project) in the discovery of drugs and healthcare programmes in general. "However, it will have implications in the long term if timely preparedness is not there in terms of (developing) research capabilities, conducive policies/systems, focussed and integrated fundamental/basic research approach of academia and judicious financial mechanism," he said.

Genomics, Nayak adds, would lead to identification of new targets, target validation, lead generation and to rational drug design and computer aided design. Put simply, genomics offers innumerable targets for the study of drug-disease interaction. This would, in turn, enable a quantum jump in healthcare.

And for those with an eye for numbers, savour this. Nair says that a calculation by PricewaterhouseCoopers indicates that even if five per cent of the proteins encoded in the human genome have therapeutic value and a further 20,000 represent possible biological targets, there will be 25,000 new targets.

Even if 25 per cent of these have genuine potential, this would translate into a 14-fold increase over the present position, he says. Over the past 50 years, the pharma industry has been focussed on finding treatments for less than 500 targets.

Lest anyone should have any doubts about the enormity of the genome project, here's what Graham T.T. Molitor, vice-president of the World Future Society, had to say in a speech last July: "Mapping the human genome opens up epoch-setting potentials.

Gene-mapping provides a blueprint for biological sciences akin to the periodic table of the chemical elements. Once laid out, the ability to comprehend and manipulate combinations become clearer. The secret of life itself, one of the most sought after mysteries of all time, is beginning to be revealed and understood." Little wonder then, pharma companies are scenting the opportunity of a lifetime in the Human Genome Project.