Obaid Siddiqi (1932-2013)

Man of science

Print edition : August 23, 2013

Obaid Siddiqi, photographed by the Nobel laureate Venkatraman Ramakrishnan in December 2011. Photo: By Special Arrangement

Siddiqi at his electrophysiology rig at the TIFR circa 1975. Photo: By Special Arrangement

Siddiqi with Alan Garen (centre) and Francis Crick at a symposium on nucleic acids in Hyderabad in January 1964. Photo: By Special Arrangement

Obaid Siddiqi (1932-2013): Pioneering scientist, institution builder and teacher par excellence.

OBAID SIDDIQI died on July 26 in Bangalore, succumbing to injuries from a road accident.

All too often we hear the refrain that Indian science has failed to produce scientists of quality and science leaders similar to the many stars of the pre-Independence era. The challenge to do better falls as a cloak on the extraordinary successes of some scientists in the post-Independence period. Yet, we are reticent in our public acknowledgement of these scientist-leaders: Their own modesty and our culture do not allow fulsome praise of those who are alive. With the tragic passing of Professor Obaid Siddiqi, we need to show no such restraint and we must fully praise this great man.

Venkatraman Ramakrishnan, the Nobel laureate from Cambridge, was absolutely right when he wrote in an e-mail: “It is not so difficult to do first-rate work at the LMB [Laboratory of Molecular Biology in Cambridge], but to do it in India while building up institutions with a good tradition is truly remarkable.”

The late 1950s was a period of dramatic breakthroughs in the understanding of life itself. Advances in genetics had started informing us about how characteristics of cells and organisms, including ourselves, are transmitted from generation to generation. Yet, the nature of the gene remained elusive and led some to speculate that it was impossible to fathom how anything material could encode the diversity that genes “controlled”.

This dualist view fell apart with the advent of molecular biology and with the discovery of the structure of DNA (deoxyribonucleic acid). To the new group of scientists in this field, the nature of the gene and the genetic code allowed them to fathom how the making of life forms was regulated. Obaid Siddiqi was part of an elite group and made his scientific mark early in experiments on the nature of the gene. His contributions are widely acknowledged and were key in his election to the Fellowship of the Royal Society.

Thereafter, the leaders of the molecular biology revolution, amongst them Francis Crick, Sydney Brenner and Seymour Benzer, moved on to the next big challenge: Understanding how the brain works. All were close friends of Siddiqi, who himself went on to tackle how nerves process smell and taste. Here, too, his work and the school he developed are recognised the world over.

Siddiqi was not only an accomplished scientist but was also widely praised as an institution builder. The Molecular Biology Unit and the National Centre for Biological Sciences (NCBS) of the Tata Institute of Fundamental Research (TIFR) are recognised internationally and have had a transformational impact on Indian science.

Govind Swarup, who founded the TIFR’s National Centre for Radio Astrophysics, had this to say: “… a great loss to science, as he continued to contribute new ideas. …an outstanding scientist… also a great human being. He inspired a large number of young talented students…. The excellent buildings and surroundings of NCBS are a tribute to his legacy, which will inspire scores of young students and scientists for decades to come.”

Hailstorm and a new turn

Studying at Aligarh Muslim University, Siddiqi was introduced to plant genetics and embryology and then went to the Indian Agricultural Research Institute, New Delhi. A hailstorm destroyed his crop and he had to wait for the next season to restart. Instead, he gave up his experimental plot and hatched a new one; the Indian Council of Agricultural Research lost a future star. Interested by the possibilities of genetics at a faster pace than what wheat allowed, Siddiqi wrote to Guido Pontecorvo, at the University of Glasgow. Pontecorvo asked him to come for an interview. Reaching Glasgow in 1958, Siddiqi was taken to the laboratory. Puzzled, he asked when the interview would be held. Pontecorvo replied that Siddiqi had passed the test by coming to Glasgow: He just wanted to see that the applicant was interested enough to come all the way from India despite the risk of being turned down. Siddiqi’s work as a graduate student on the fine structure of the gene became a classic that opened the best doors of science to him.

One of the visitors to Pontecorvo’s laboratory was Alan Garen, who worked in Al Hershey’s lab in Cold Spring Harbor Laboratory, Long Island, New York. In 1961, Siddiqi moved to Garen’s lab at the University of Pennsylvania, and worked on how genes exchanged genetic material. In elegant and brilliant experiments, Siddiqi and Garen discovered the mechanisms underlying how synthesis of proteins was terminated. This work directly stimulated the discovery of stop signals in the genetic code.

At this time, the study of gene regulation through bacteriophage and bacterial genetics was at its zenith and the new term molecular biology was coined. Siddiqi was a regular in meetings at Cold Spring Harbor and elsewhere where the new biology was being invented. Siddiqi, being a recognised comrade, brought these stars to India later on during his next avatar as an institution builder, thereby transmitting the culture of scientific excellence more effectively and linking young Indian scientists to the best in the world.

In Philadelphia, Siddiqi was looking to come back to India. These were times when relatively ordinary people did good work, but brilliant people did extraordinary work because of the interactions they had with each other. Siddiqi was right in the midst of this as one of the really brilliant people. It was very unusual, while at this centre of intellectual ferment, to decide to return to India and start at a laboratory, but that is what Siddiqi wanted to do. Siddiqi had contacts with P.C. Mahalanobis, who started the Indian Statistical Institute, and with Shanti Swarup Bhatnagar, who started the Council of Scientific and Industrial Research. It was a real possibility that he would come back to one or the other of these institutions.

The Szilard moment

But there was an extraterrestrial intervention. A visiting “Martian”, Leo Szilard, the famous nuclear physicist, ran into Garen. (Szilard was one of the five Hungarians who changed science in the United States, and they were so unusual that it was felt that they must be extraterrestrial.) Siddiqi met Szilard, who wrote to Homi Bhabha after talking to Garen: “The enclosed letter of a distinguished colleague of mine, Alan Garen of the University of Pennsylvania, is self-explanatory. The second enclosed letter is from Pontecorvo, a distinguished geneticist whom you may know and relates to the same subject matter. I should be grateful to you for reading these two letters and following it up which such action, which appears appropriate in the circumstances. I regret that our paths haven’t crossed for a long time....”

Bhabha wrote to Siddiqi saying: “I’ve received a letter regarding you from a friend, Szilard. I am very interested in personally supporting work in molecular biology.… We should give you an appropriate offer of appointment either at the Tata’s Institute of Fundamental Research or the Atomic Energy Establishment of Bombay, the biology division. I should be grateful if you send your CV. We usually ask for several letters of recommendation but those have already arrived so don’t bother too much about that and if you want to know anything, just let me know.”

So that is an interesting way of getting a job; the letters came in first, and all Bhabha wanted was Siddiqi’s CV for the record because Bhabha, quite rightly, trusted the judgment of people like Szilard, and Szilard trusted the judgment of people like Garen and Pontecorvo.

But that is not all, in Pontecorvo’s letter to Bhabha about Siddiqi, there is a statement about what is important for a scientist: “I think it would be very important for the progress of biology in India that he should go back to a job in which his abilities would be fully expressed. In fact, I’m really baffled as to why India continues to promote mediocre scientist politicians and does nothing to maintain the really good scientists.”

This prompted Bhabha to write to Prime Minster Jawaharlal Nehru, saying: “I actually agree with this and we really should make sure that people who work in the lab are highly regarded and it’s not scientist politicians who are highly regarded.”

Siddiqi came back to India to the TIFR. Bhabha had presented his application to the faculty asking for their opinion. The view was, we are told, uniformly negative and the feeling was that there should be no biology at the TIFR. Bhabha responded by thanking the faculty for their view but apologetically said he had already made Siddiqi an offer.

Siddiqi joined the TIFR in 1962. Using genetics to infer the molecular nature of inheritance and of cellular function was new, elegant, thrilling and informative. Its effective practitioners could be forgiven their deserved pride and self-confidence. At the Molecular Biology Unit, Siddiqi established a small but strong bacterial genetics group. Their work, delinking DNA transfer, DNA replication and recombination in bacteria, was again widely recognised. Under Siddiqi’s influence, Pabitra Maitra introduced yeast genetics to the institute, and he and Zita Lobo became leaders in the dissection of the genetics of sugar metabolism. P. Babu was another pioneer in the genetics of the worm C. elegans, and other areas also blossomed in Colaba by the sea.

Work on drosophila

Just when the ease of bacterial genetics could have become addictive, Siddiqi worked with his friend Seymour Benzer in the 1970s to change his scientific direction into using genetics to understand the nervous system and behaviour. Here, too, Siddiqi struck gold with his study of temperature-sensitive paralytic mutants in the fly Drosophila: work that has pioneered our understanding of how nerve signals are generated and transmitted.

Starting with his student Veronica Rodrigues in 1976, and until his death, Siddiqi pioneered yet again, this time studying the chemical senses of Drosophila. While his work led to an improved understanding of how olfactory information is encoded in the brain of the fly, his study of chemosensory genetics inspired others to address this challenging field.

In 1984, the Nobel Prize-winning geneticist E.B. Lewis asked me: “How does one person do such wonderful work in Aspergillus, E. coli, Drosophila physiology and behaviour? I can barely deal with one (gene) complex locus in a lifetime.” I did not have an answer as I did not know too many scientists then and I had not appreciated how unusual Siddiqi was. That meeting with Lewis, and each of several others with the best, showed me how Siddiqi’s name made you good friends. They came with praise for the Molecular Biology Unit and the TIFR.

As students, we seemed to have taken it for granted and as “normal” that we would have the best courses conducted by the best. Going out of the country, we realised how privileged we had been and what a wonderful culture and environment the Molecular Biology Unit and the TIFR had given us, a culture of questioning and one that defines purpose in science by the quality of the question and its answer, and not by the volume of herd opinion. That this culture lives on at the TIFR today is testimony to the effectiveness of Siddiqi and others like him.

With the same culture, Siddiqi developed a vision for, and founded, the National Centre for Biological Sciences (NCBS), which celebrated 20 years of existence along with his 80th birthday. As Siddiqi’s vision crystallised into reality, one theme stood out at every stage: The refusal to be hurried, to compromise on quality or in the NCBS’s core culture in the interests of speed. Well-meaning bureaucrats and friends offered advice, or sometimes insisted, that something counter to Siddiqi’s understanding of good sense be done. Siddiqi would work hard to persuade them to change. If they did not, he would simply wait for their successor, hopefully of a different persuasion: “They will all retire,” he famously said, somehow implying that he himself would never age or go away.

Obaid Siddiqi had many students, collaborators and admirers. They were all his friends, to be questioned in his piercing crystal-clear style. His wonderful family enveloped his professional circle as its own and bears his imprint of fierce independence and gentle inclusiveness. He is survived by his wife, the well-known historian Asiya Siddiqi, and his children—Imran, Yumna, Diba and Kaleem.

( This is modified from a post on the NCBS website from an article published by K. VijayRaghavan in Journal of Neurogenetics to commemorate Siddiqi’s 80th birthday.)

Dr K. VijayRaghavan is Secretary, Department of Biotechnology. He was a doctoral student of Obaid Siddiqi and P. Babu at the TIFR (1978-83). He joined the TIFR again in 1988, moved to the NCBS in 1991 and succeeded Siddiqi as its director (1997-2013).