Human Genome Project: Missed opportunities for India

This is the second in a three-part series. The first article appeared on October 26.

IT IS now well known that India is the only country in the world that has extensive scientific infrastructure and capabilities which was not a part of the international human genome sequencing project. This was very unfortunate because in 1988 - that is, about the time the U.S. had decided to invest in this project which subsequently became an international project with the participation of even countries such as China and Japan (but not India) - I wrote a letter to the then Prime Minister, Shri Rajiv Gandhi, suggesting that India should also invest in the human genome project. I stated that India can do it at a much lower cost than the U.S. that is Rs. 300 crores, which would mean, on an average, Rs. 20 crores each year over a 15-year period.

This letter was written after very careful deliberation. I have been one of the few privileged persons, especially from the East, who have had an occasion to watch the entire modern biological revolution from the early 1950s onwards from close quarters, and to know most of the actors in this fantastic drama. Many of them, including a score of Nobel Prize Winners and those who were intimately involved in the human genome project, have been in the CCMB (Centre for Cellular and Molecular Biology, Hyderabad) which I had the privilege of conceiving, building and directing for 13 years and which is regarded as the finest scientific research laboratories anywhere.

On the other hand, I also had the privilege of participating in our battle for Independence as a university student in Lucknow, and committing myself to contributing whatever an individual could (within my own limitations), to making our country a leader in my chosen area of science. It was this commitment that has been the driving force behind all my scientific endeavours. Thus a significant quantum of commitment, knowledge and experience went into the above mentioned letter to the Prime Minister.

The Prime Minister's Office referred my letter to the Department of Biotechnology (DBT) of the Government of India who shelved it. It seemed ironical to me that even though I had played a vital role in the setting up of this Department and was a Member of its high-power Scientific Advisory Committee for many years, not even an acknowledgement was sent to me as a matter of courtesy, leave aside communicating to me the reasons for the project being shelved.

My proposal to the Prime Minister was commented on in the national and international press, for example in Nature of 21st September 1988 under the title ``Sequencing Bargain in India''.

According to the report in Nature , the proposal was turned down by the DBT as ``the project would require equipment, reagents and enzymes which would need to be imported'' and that the DBT and many other scientists in the country supported by it and occupying positions of power or influence, not always on merit, disagreed with my estimate of the cost. The above reasons were, to say the least, ridiculous and no more than excuses.

All the reagents and chemicals required were either already available with us when I made the proposal, or have since then become available in the country, or could have been easily synthesised with the tremendous tradition we have of synthetic organic chemistry which has been at the base of the remarkably successful drug industry in the country.

The question of escalation in the cost estimate given by us would have never arisen. In fact, if anything at all, it was clear to the informed scientific community that the cost would come down, as has happened in respect of both the international project and the Celera Genomics human genome sequencing projects, the former in the public and the latter in the private sector, the latter project cost only 900 crores. It is well known that what can be done in 900 crores outside India when there is major expenditure on labour, can be done in India at one-fourth the cost. In any event, Rs. 300 crores meant only Rs. 20 crores a year for 15 years which is by no means big money for India. It is the yearly grant of a good laboratory.

Further, even in science in our country we waste at least thirty times that much money every year. The DBT has spent nearly 2000 crores in the last nearly 15 years. What good has it done to the country? Has it led directly to producing even one rupee worth of a useful product which would not have been produced, perhaps quicker, if DBT did not exist?

If we had initiated the human genome project in our country in the mid 1980's, our gains would have been the same for which Celera Genomics, a private company led by Craig Venter invested on parallel efforts for sequencing the human genome. They started later but finished at the same time as the international project and for much less cost. They expect returns on the investment by patenting a large number of STRs (short tandem repeats, which are specific stretches of sequences in DNA, the genetic material). We would have done the same. (The STRs would have a huge market in diagnosis).

Further, when you are a part of the discovery team in such a complex area as the sequencing of human genome, you have access to information that is not made available when the final results are put in the public domain; this information is often crucial for optimal utilisation of the final result.

Thirdly, experience of sequencing a part of the human genome would have made it easier for us to sequence other genomes of particular interest to us. Lastly, if we had invested in our own human genome project, the chances are that, at one point or another, we would have become integrated with the international effort but only after staking our right to leadership. As of now, at least for a long item, we would only be a follower. I don't have to tell the readers the difference between being a leader and a follower; a leader, for example, is always in a much better position in respect of bargaining.

Subsequently, Dr. Lalji Singh, one of India's most illustrious scientists of today, whom I had persuaded to return to the CCMB from the UK in 1987 and who is now the Director of CCMB, also submitted a project to the DBT when he was not its Director and after I had left the CCMB, suggesting that we should sequence at least a part of the human genome (the sex chromosomes). This project was also not approved by the DBT.

Eventually, on account of the high reputation Dr. Lalji Singh enjoyed and the obvious importance of silk to the country, a project that he had submitted to the DBT on sequencing of the silk genome, was approved by the DBT, but it was subsequently taken away by the DBT from Dr. Lalji Singh, just because he changed his institution! This kind of project transfer in basic science is really never done in any respectable organistion.

In essence, lack of our involvement in the human genome sequencing project has been on account of the lack of vision, of commitment to the country, of professional competence, and of integrity on part of the DBT and of those on whom it has largely depended. This Department was set up in February 1986 to develop and pursue biotechnology, and I had a major role in setting it up. The history of DBT has been documented by me and Chandana Chakrabarti elsewhere (Current Science, 1991, vol. 61, pp. 549- 552; Economic and Political Weekly, Dec. 2, 1999, pp. 3049- 3050)0. However, everything that has happened in biotechnology in the country such as the marketing of the country's first genetically engineered product, the Hepatitis B vaccine by Shantha Biotech, has happened outside of the DBT and inspite of it with the DBT putting all kinds of hinderances in the success of the project.

In fact, most of what DBT has been doing would legitimately come under the purview of better-run and better-equipped departments and agencies, such as the DST (Department of Science and Technology), the UGC (University Grants Commission), the CSIR (Council of Scientific & Industrial Research), the ICAR (Indian Council of Agricultural Research), and the ICMR (Indian Council of Medical Research).

Perhaps, the only worthwhile accomplishment of DBT has been the setting up of the Bioinformatics Centres at various places in the country, but even in there much remains to be done. I was the Chairman of a Committee which reviewed the performance of these Centres but out report has been gathering dust in the DBT.

I have been in the past a Member of the Scientific Advisory Committee (SAC) of the DBT and of some of its other Committees; and have been amazed at the ease with which even the minutes have been wrongly recorded or manipulated. I remember that some years ago there was a report in the newspapers that the Government of India was planning to wind up the DBT.

I had then as a Member of the SAC of the DBT, asked for a one- page write-up as to why this department should not be wound up; with such a note, if it had merit in it, one could fight the case with support of other scientists and informed public. No such note was ever prepared and the matter was obviously taken up behind closed doors at the political level.

One may ask as to why such a situation has arisen in the country. A part of the answer lies in the evolution of a scientific mafia (see P. M. Bhargava, TheHindu, 28th March 1993) in the country since the late 1960s. The present Secretary of the DBT would probably have not been there and certainly for not so long, if it was not for the support of this mafia.

It is, of course, heartening that the influence of this mafia has declined remarkably in the last few years but, unfortunately, its role has now been taken up by sections of the Government. Let me give an example.

The following Starred Question (Dy. No. 1857) was asked on the floor of the Parliament on 4th August, 2000:

(a) Whether it is a fact, the former Director of CCMB, Hyderabad, had submitted to the Department of Biotechnology, in 1989 the human genome sequencing project by our scientists?

(b) Whether it is also a fact that the Department has confined the proposal to the cold storage; and

(c) If so, the reason for not approving the proposal in 1989?

In reply to this question - on which we believe there was a heated debate on the floor of the House - according to a report appearing in the Indian Express of 5th August, 2000, the Minister of Science, Dr. Murli Manohar Joshi, made the following statements:

(1) 10,000 scientists were working (presumably in India) round the clock on the human genome sequencing project.

(2) India had entered into collaboration with the United States and France and had made headway in the genome project.

Both these statements are absurd. For example, if 10,000 scientists have been working in India on this project, as it would cost at least Rs. 2 lakh per scientist, it would mean an expenditure of Rs. 200 crores per year on this project. I have asked Dr. Joshi in a letter dated the 8th August to let me have the list of the 10,000 scientists, and details of the collaboration with the USA and France. I have also asked him to confirm if the report in The Indian Express is correct.

I have received no reply from his nor do I expect any. Not only the above, the Minister of Science, who, perhaps, made the statement on the advice of the Secretary, DBT, tried to confuse the Parliamentarians by mixing up in his statement detection of genetic disorders with the human genome project. Thus, in ways more than one, the sanctity of the Parliament was violated.

The question in the Parliament was an opportunity to take the DBT to task for its continuing failures but, in our country we defend the indefensible and scuttle what is good for the country as much in science as in any other activity. This has been the bane of our science, and the denial of our participation in the human genome project was just one consequence of it. But who cares what damage has been done, what the country has lost? Surely not the Government and the concerned scientists holding the reigns of power whose only concern has been themselves and themselves.

Pushpa M. Bhargava

Former Director

Centre for Cellular and Molecular

Biology, Hyderabad.

(To be concluded)

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