The Great Genome Project

IT'S the El Dorado of modern times. In a multi-billion dollar enterprise, thousands of scientists in the US, Europe and Japan are busy charting out the human genetic landscape, so that they can then zero in on the 100,000-odd genes that, going by the most grandiose claims, will tell us who we are, where we came from, why we behave the way we do, and where we are going.

And so, hardly a month goes by without gene-hunters claiming to have progressed another step. A gene for breast cancer; a gene for haemophilia; a gene for cystic fibrosis; a gene for schizophrenia. And even a gene for obesity, for suicide, for alcoholism, for homosexuality.

But this treasure hunt is not aimed just at whetting intellectual curiosity; the International Human Genome Project is seeking to detect the defective genes that plague mankind, link them to diseases and then finally come up with a therapy. The project's apologists claim the future genetic medicine industry would be worth more than $100 billion, almost 10 times the current worth of the modern medicine market.

With liberalisation and globalisation now the new mantras of India's economic revival, Indian scientists too have jumped on to the gene-hunting bandwagon with the recent launch of 'Human Genome—the Indian Initiative' by the Department of Biotechnology (DBT). Says Manju Sharma, DBT secretary: "We thought it necessary that the Indian scientific community be ready to meet this new frontier. We expect to get about Rs 78 crore over five years for the project." The project's raison d'etre is twofold, explains geneticist Obaid Siddiqi, who is chairman of the DBT task force for human genetics: "to use information coming out of the International Human Genome project for diagnosis, prevention and therapy of genetic disorders peculiar to India. And to understand India's genetic diversity".

The arguments for the project are persuasive. For one, says Sameer Brahmachari of  the Indian Institute of Science, Bangalore, who is a member of the DBT task force on human genetics: "We have a very large population suffering from rare genetic disorders, so there will be no dearth of samples." For instance, 2 per cent of all newborns suffer from congenital disorders. Then there are instances of Down's syndrome, in which the child is born mentally retarded, and hereditary anaemias such as thala-ssemia and sickle-cell disease. Other disorders lie dormant till triggered off by provocateurs like diet, stress or a pollutant. These include coronary heart disease, hypertension, diabetes, schizophrenia and epilepsy.

The DBT plans to set up several centres to keep a record of the genetic disorders. Currently, only eight hospitals maintain a record. So far the DBT has set up three major centres—PGI (Chandigarh), Guru Nanak Dev University (Amritsar) and AIIMS (New Delhi)—to study genetic disorders. (See box.) Another justification for the project, explains Partha Mazumdar of the Indian Statistical Institute, Calcutta, who is studying the pattern of sickle-cell anaemia in two communities, is the fact that "we have remote groups with little contact with civilisation and high degree of inbreeding which could prove to be genetic goldmines".

Indeed, India is home to 465 communities and 75 endangered tribes. The DBT says the project may give special priority to vanishing tribes in the Andaman and Nicobar Islands, the Kadars in Kerala, one of the last few surviving hunter-gatherers, and the dwindling Parsi community.

Four laboratories are being set up for this project and a national bank of genetic material is going to be built, says Sharma. In fact, the DBT has already funded two studies under the project, one being Mazumdar's. In the other study, Indian Institute of Science researchers are studying the insular Sankethi community in Karnataka, among whom marriages between close relatives is probably the highest in the world. Having said that, the mapping of human genes has come under attack from scientists, sociologists, lawyers, among others. Mostly in the West, of course. While the DBT has been debating it in close-door meetings, many geneticists and social scientists are unaware of the criticism.

APART from its fantastic claims of offering a panacea for most human ailments and that it would provide a key to unravelling longstanding mysteries of human behaviour and existence, the human genome project has far-reaching legal, social and ethical implications.

Picture this. A young girl is told that she might develop breast cancer around the age of 30; or an insurance company discovers that his client has a genetic predisposition for Alzheimer's; or an employer finds out that his employee has a gene for hypertension; or a tribe in India discovers that its DNA has been sold, without consent, to a pharmaceutical company (a gene for obesity was actually sold to a drug firm for a $70 million); or a community is told that it is genetically less intelligent—refer to the controversial book Bell Curve which condemned American blacks as intellectually inferior. And then, the ghost of eugenics and ethnic cleansing can't be wished away.

This is just a trailer of the merlins in the Pandora's box the project is going to throw open. Alarmed, governments have initiated studies into the ethical, legal, social implications (ELSI) of the programme. This year alone, the US will spend about $11 million on ELSI studies. In the US, it's become an explosive issue and many scientists have decried the project proponents for garnering huge amounts of public money by telling them a tall story about its benefits. While scientists are debating the ethical implications of the project, are its scientific claims beyond dispute? No, say many critics. The first error, argues US biologist R.C. Lewontin, is in talking about the human genome sequence as if all human beings were alike. All individuals differ from one another appreciably in the amino acid  sequence of their proteins. Whose genome is going to act as the template? Incidentally, it was discovered that the DNA US scientists were busy deciphering belong to not more than three individuals, contrary to their belief that it came from diverse individuals.

Besides, many disorders may be caused by not one but several gene defects. So when the DNA from one person with a disease is compared to the DNA from a 'normal' person, it would be impossible to decide which of the multiple differences between the two DNAs is responsible for the disease. One such disease is thalassemia, a blood disorder triggered by haemoglobin deficiency and which afflicts Indians in large numbers. There are at least 17 different defects in different parts of the haemoglobin gene, all of which result in the disease. Another major problem with the human genome sequencing effort is the claim that once the genetic code has been cracked, we would know everything that is worth knowing about humans. It regards the gene as determining the individual, and the individual as determining the society. US social scientists Dorothy Nelkin, Laurence Tancredi and Evelyn Fox Keller suggest that the project may succeed less in ridding people of the 6,000-odd genetic diseases and more in validating the belief that human and social behaviour is rooted in genes.

 So why do scientists want to persist with this dream? The answer, says Lewontin, "is that they are so completely devoted to the ideology of simple single causes that they believe in the efficacy of the research and do not ask themselves more complicated questions". But in part the answer is a rather crass one, he adds: "The participation in and the control of a multi-billion dollar, 30-50 year research project that will involve the everyday work of thousands of technicians and lower-level scientists is an extraordinarily appealing prospect for an ambitious biologist." Besides, a large number of scientists involved with the project are also stockholders in biotech companies.

This is equally applicable to the Indian genome effort, despite the DBT's argument that the entire effort is to alleviate genetic suffering of Indians. It is unfortunate therefore that even as the DBT launches its human genome initiative, whose mandate, at least on paper, is as ambitious as genome programmes of other countries, there is hardly any public debate about its claimed benefits, let alone its implications. Biologists have warned that the project might disillusion many people. In Lewon-tin's words, "The public will discover that despite inflated claims of molecular biologists, people are still dying of cancer, that institutions are still filled with manic depressives, that the war against drugs has not been won." One hopes that the DBT, as and when it magnifies the scope of its human genome initiative, will keep these sobering thoughts in mind.