Gobind: an inspiring enigma

Abstract  

Gobind Khorana’s distinguished career spanned nearly six decades (1952–2011). His work resulted in remarkable achievements starting with the complicated synthesis of coenzyme A. He then pioneered the synthesis of DNA oligonucleotides, which enabled him to crack the genetic code. Using this experience, he ventured to accomplish the first complete synthesis of a gene. Not satisfied with elucidating the function of bacteriorhodopsin, Gobind took up another greater challenge, that of spearheading studies on visual rhodopsin, its mechanism of activation, and the consequent signal transduction pathway. This Editorial acts to introduce the articles appearing in this Issue Focus dedicated to celebrating the 100th anniversary of the year of his birth.

Almost all authors get into what is called a writer’s block when they are unable to write anything at all. When we had to write an editorial piece for this issue Focus, dedicated to Gobind (Fig. 1), one of us (GKA) was stuck in a similar situation. GKA read up a lot to check as to what it is that people do to get out of this “block.” The most common answer was, “Keep it simple,” and GKA decided to do just that. Gobind, for him, was like a god, possessing extraordinary tenacity, passion, and the talent to convert his vision into results (the only other similar people I can think of are Feynman and Pauling). We seriously wonder and doubt whether pedigree had anything to do with his extraordinary success. GKA talked to Prof. Robert Lefkowitz from Duke University (who works on G-protein-coupled receptors). He narrated a story that he had heard, first hand from Prof. Emil Smith. Apparently, when on the lookout for a post-doctoral fellowship, Gobind had written to Prof. Emil Smith but never heard back from him. Being Gobind, over dinner at a conference, he introduced himself to Emil, who in turn wondered and asked how they had not met before. To Emil’s surprise, Gobind replied that they do know each other and that Gobind had applied for a post-doctoral position to Emil. Emil never bothered to reply, assuming researchers from India were not good.

Fig. 1.

Drawing of Har Gobind Khorana: courtesy of Mr. Paras Gautam who is a first year PhD scholar in the structural biology lab, Department of Biotechnology, IIT Madras

The question really is: would it have made a difference if Gobind had joined Emil’s lab? I personally do not think so. Gobind won the “molecular biology race” when he discovered the genetic code. He would have flourished in the area of biochemistry and discovered something as important as the genetic code or even better, if he had started in Emil’s lab. Gobind was hardwired to be successful as is evident from the fact that in 30 odd years he had changed his area of research three times from oligonucleotide synthesis and cracking the genetic code to studying bacteriorhodopsin to visual rhodopsin and his group did well, every time. Gobind was beyond competition but an extraordinarily humble person — the trade mark of a genius. Gobind deeply affected people’s lives, especially those who worked with him. When I joined Prof. Thomas Sakmar’s lab as a post-doctoral fellow, I was told that the login password for all of the spectroscopy instruments was “gobind.” Someone once suggested that we should have a new password and snap came Toms reply, “dnibog.” Such was the depth of the impact Gobind had on people. In 2011, Tom Rajbhandary, his longtime friend put it correctly in a newspaper interview. He said, with Gobind’s death, an era has ended.

On the occasion of Gobind’s 100th birth anniversary, we have brought out a series of articles contributed by his colleagues and collaborators. For this, we solicited contributions personally and through an article published in this journal. Most people we approached accepted the task with great eagerness and only a couple backed out for personal reasons (COVID infection being one), bringing forth the love and affection they shared for him.

Among the articles is one written by Fahmy and Sakmar that details all the biophysical techniques that Gobind used in order to achieve his goals to understand the structure–function relationship of membrane proteins, both bacteriorhodopsin and the visual pigment, rhodopsin (Fahmy and Sakmar 2022). Through their article, they walk us through a span of three-and-a-half decades of Gobind’s work on various spectroscopic techniques that were used to elucidate the structures of these two proteins and the mechanism of their function. Gobind collaborated extensively and used more than a dozen biophysical techniques. The technical details of all these papers are beautifully brought by the authors. Greater details of the use of vibrational spectroscopy in understanding membrane proteins are presented by Kenneth Rothschild (Rothschild 2023). A combination of FTIR spectroscopy, proteolytic cleavage, and site-directed mutations lead to insightful understanding. Mutational analysis done by Ken and Gobind’s labs led to a model of the proton pump that has stood the test of time including what the crystal structures revealed, e.g., slightest of movements of an arginine side chain that was detected 15 years later by X-ray crystallography. Ken’s article also mentions Gobind’s passion to be a “hands-on” scientist and how he would work on the bench himself.

Articles by Judith Klein-Seetharaman and Sriram Subramaniam are excellent anecdotal memoirs of their stay in Gobind’s lab (Klein-Seetharaman 2023; Subramaniam 2023). Sriram, in narrating his personal experiences, successfully conveys how the tools and techniques were but a means for Gobind to get to the core of the mechanism involved in every biological system he was trying to understand. The article also subtly brings out how extraordinarily competitive Gobind was. All the articles in this issue clearly point to one thing — Gobind was hardwired with a desire to win. The strategically designed mutations in bacteriorhodopsin and rhodopsin enabled what most scientists thought was impossible: understanding the structure–function relationship at atomic level. Judith’s article adds a personal touch and brings out how caring Gobind was to people he knew. She starts her article with a picture of a birthday greeting card that Gobind had sent her with a box of donuts, one each for the lab members, and how his care was on display that Saturday. Her article brings out several such incidents in combination with Gobind’s habit of never switching off from science, whether he was in his lab, at home or as far as Japan, on a sabbatical.

The article by Philip Reeves brings out a new dimension of Gobind’s thought process (Reeves 2023). He explains how farsighted Gobind was. His goal was to solve the structure of rhodopsin and to get there. Gobind’s lab established large scale expression of the protein and worked their way around several problems, including efforts to get homogenously glycosylated protein. Enroute, Gobind showed what a true genius he was, eventually mastering NMR methodologies. The article also makes it clear that Gobind taught us all a lot of cell and molecular biology.

The final article reviews the structure–function relationships and physiological roles of the Apelin G-protein-coupled receptor and its agonist peptides apelin and elabela (Murali and Krishna 2023). Contributed by one of the two Issue Focus editors (AGP), this final article acts a personal tribute in honour of a Har Gobind Khorana.

We hope that this Issue Focus will serve as a source material for the readers of this journal to understand the current status and the future directions of the work that Gobind initiated long back. The completion and the success of an Issue Focus depend on the quality of articles (both reviews and personal anecdotes) from experts who share their knowledge and experience, and we are grateful to all of them. Thanks to all the reviewers also, for sparing their precious time in refereeing these articles. Finally, it is our pleasure to thank Damien Hall and the Editorial Board members for agreeing to bring out this special issue.

Author contribution

Both authors have contributed equally to write this article.

Data availability

No raw data has been presented/used in this article.

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Conflict of interest

The authors declare no competing interests.