Opinion The odd and inspiring case of Hargobind Khorana

The Nobel was only one of the milestones of his scientific career,which explored various new trails in molecular biology

Dhananjaya Dendukuri

November 16, 2011 02:43 AM IST First published on: Nov 16, 2011 at 02:43 AM IST

The improbable story of Hargobind Khoranas career and achievements is both inspiring and revealing. Born in 1922,the child of a patwari (village clerk) from Raipur in what is now Pakistani Punjab,Khorana progressed from a rural school and Punjab University through some of the best institutions in Europe and the US. An itinerant scientist,Khorana spent significant time as a professor at the University of British Columbia in Vancouver and the University of Wisconsin before finally staying put at the Massachussetts Institute of Technology for the last 40 years of his career. He apparently remarked that the occasional move was always good to keep him intellectually stimulated.

In Cambridge during his post-doctoral work in the early 50s,Khoranas time coincided with the most momentous discovery of biology in the 20th century the solving of the structure of DNA. Not surprisingly,work on genetic material remained a strong theme through his career. It was his work on showing how genetic material is converted to proteins that won him the Nobel Prize in 1968 along with two other scientists,Robert Holley and Marshall Nirenberg. While the genetic material is transferred from one cell to the daughter cell identically,proteins which perform many of the essential functions inside of us are synthesised from the genetic material on a continual basis. Deoxyribonucleic acid (DNA) and its counterpart genetic material riboxynucleic acid (RNA) are composed of only four building blocks. In the case of RNA,these are the four nucleic acids,U,G,C and A. Yet,it was already known that 20 different amino acids (the building blocks of proteins) and a vast diversity of resultant protein structures could be built from just these four building blocks.

How was this possible and what was the specific mechanism that could explain this? Through the 1960s,Khorana and his team painstakingly synthesised and catalogued short chains of DNA and RNA of known sequence. At a timewhen synthetic nucleic acid chemistry was still in its infancy,this was a laborious and challenging task.

Along with others in the field,Khorana was able to decode that specific tri-mers (like UGC or UAC) of RNA each coded for an individual amino acid. There are 64 unique combinations of tri-mers that can be built from the four building blocks (4 x 4 x 4 = 64). Khorana synthesised all of these combinations and was able to connect each of them to a single amino acid. Thus,a universal genetic code which extends across life forms was deciphered. This momentous discovery is now one of the central tenets of molecular biology that every student of biology learns.

A side benefit of Khoranas research,which is relatively less spoken about,is that his team accidentally discovered the way to amplify genetic material during the course of their work. This later was very useful in developing techniques that are now the basis of genetic testing (known as polymerase chain reaction or PCR). Importantly,Khoranas motivation did not end with his winning the Nobel Prize at the relatively young age of 46. His scientific journey saw him tackle a few different problems across his lifetime. Through the 70s,his lab worked on cutting-edge molecular biology techniques that led to the synthesis of artificial genes and the introduction of synthetic genes into life forms. Many of these have now become standard practice in labs all over the world. The last 30 years of his career saw him work a great deal on rhodopsin,a protein responsible for the sensation of light in living beings.

An extremely hard-working man,Khorana spent long hours in the lab and rarely took holidays,once remarked that he had gone without a vacation for 12 years! A self-effacing and humble human being,Khoranas willingness to give credit to others is amply reflected in his Nobel lecture. As careful in his credits as his science,he documents the contributions of his peers and predecessors,explaining how his work fits in the jigsaw puzzle of decoding the sequence of proteins. In good academic tradition,his students became like family,many of them going on to achieve fame in their own right,with one of them going on to win the Nobel as well. If a boy from the only literate family of 100 in rural Punjab could pull it off 80 years ago,surely we have a 100 Khoranas in our midst,waiting to find their place in the scientific spotlight.

The writer is CEO and co-founder of Achira Labs,a Bangalore-based start-up in the biotech space