Avadhesha Surolia on Har Gobind Khorana’s legacy of the genetic code, for which he was awarded the Nobel prize.
On November, 9, 2011 the world witnessed the silent departure of a great scientific revolutionary, Har Gobind Khorana, a man renowned for cracking the code to life. Born in a small village in Punjab (now a part of Pakistan), Khorana was the youngest of five siblings. Despite his poor financial condition, his father’s keen desire to educate his children laid the foundation of Khorana’s glorious academic career. As quoted by Khorana himself, “Although poor, my father was dedicated to educating his children and we were practically the only literate family in the village inhabited by about 100 people.”
Khorana was homeschooled after which he went to Punjab University, Lahore, for his graduation.
A shy village lad, he applied for admission in two departments, English literature and chemistry, but destiny had something else in store for him and despite a restricted admittance and his failure to attend the qualifying interview, Khorana managed to get admitted into the chemistry department and so he became a chemist. After postgraduation from the same university in 1945, he was awarded a studentship by the Government of India to study insecticides and fungicides in England, but instead destiny drove him to the Chemistry Department of the Liverpool University where he was trained as an organic chemist during his PhD, following which he went to the Eidgenössische Technische Hochschule in Zurich, Switzerland, for his postdoctoral studies and to work with Vladimir Prelog, a Croatian chemist and a Nobel prize winner in chemistry. During his stay at the Swiss Institute, he was fascinated by carbodiimides, chemical compounds formed after removal of water molecules from urea, which formed an essential part of his research work in later years.
Upon completion of his higher education abroad, Khorana returned to India, but the Partition-affected country did not have anything to offer him and the subsequent course of events took him back to Cambridge University, where he resumed his research career as a postdoctoral fellow in Alexander Todd’s laboratory, who was at the climax of solving the structures of nucleic acids, the main components of our genes. His stay at Cambridge allowed him to witness some of the greatest discoveries in science, from sequencing of the first protein-insulin by Frederick Sanger to determination of what DNA looks like by Watson and Crick. After spending two years in Cambridge, he went to the University of British Columbia, Vancouver in 1952 where he began his pioneering studies on nucleic acids with inspiration and constant encouragement from Gordon M Shrum. In the same year he married Esther Elizabeth Sibler, who formed the supporting pillar of his life. They were an exceedingly warm and hospitable couple. They invited guests to their cottage in north Hampshire and Khorana himself used to take pride in cooking and serving Punjabi delicacies to them, such was the loving and affectionate nature of this man.
In 1960, he joined the Institute for Enzyme Research at the University of Wisconsin-Madison, finally becoming the Alfred Sloan Professor of Biology and Chemistry at the Massachusetts Institute of Technology in 1970 till his retirement in 2007. His postdoctoral experiences at Switzerland and Cambridge had been highly instrumental in inculcating in him a deep interest in proteins and nucleic acids and shaping his overall perspective towards science. In his words “In my own scientific development, I was most fortunate in coming under the influence of a number of very great scientists: Vladimir Prelog made me see the beauty in chemistry, work and effort. Later, in biochemistry, I came under the influence of Fritz Lipmann, who was so gifted in integrating ideas, and Arthur Kornberg, who taught me stringency in biochemical experimentation. Association with Francis Crick during and since work on genetic code has been intellectually stimulating and inspiring. Much later, Efraim Racker introduced me to membrane biochemistry.”
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The 1960s have been regarded as the golden era of molecular biology and Khorana’s own contribution in the development of this field as an independent discipline is exceptionally outstanding. He began his scientific trysts by synthesising polymers of nucleic acids or oligonucleotides using carbodiimides and making short chains of amino acids (the building blocks of proteins) from them by a process of in vitro translation. His diligence bore fruit and he became the first person to synthesise oligonucleotides and construct the first artificial gene. The scientific field will always be grateful to him for this kind gift, which has acquired an immeasurable importance in biotechnology, beginning from cloning to engineering living beings. In 1961 he made another breakthrough by synthesising coenzyme A, a small molecule of immense biological relevance that participates in over 9 per cent of all the chemical reactions occurring within a living cell. He even devised a method to make several copies of DNA, which he termed “Repair Synthesis” that was later rediscovered by Kary Mullis and named as Polymerase Chain Reaction or PCR.
It was during this time that he deciphered the biological language of genes and demonstrated to the world how genes code for proteins that make life. This historic invention was duly recognised when he was awarded the Nobel Prize for medicine in 1968 along with Marshall W. Nirenberg and Robert W. Holley. His legacy of the genetic code to the world would be remembered and valued for times infinite.
Following the discovery of the genetic code his interests radically shifted and since then he had been working on mechanisms governing conversion of light energy to chemical energy by proteins bacteriorhodopsin and rhodopsin, a biological pigment of the retina, and had about 400 scientific publications to his name in leading journals. He mentored over 300 colleagues from all over the world in his lab and faithfully transferred his excellence to them. His first student, Michael Smith, was a recipient of the 1993 Nobel Prize in Chemistry for devising site-directed mutagenesis, a method of manipulating DNA.
Apart from Nobel, Khorana had been honored with several other prestigious awards which include the Merck Award from the Chemical Institute of Canada, the Dannie-Heinneman Prize, the American Chemical Society Award for Creative Work in Synthetic Organic Chemistry, the Lasker Foundation Award for Basic Medical Research, the Padma Vibhushan Presidential Award, the Ellis Island Medal of Honor, the National Medal of Science, and the Paul Kayser International Award of Merit in Retina Research.
The long and distinguished career of this great man came to an end with his death on November 9, 2011. He was 89 and is survived by his children, Julia Elizabeth and Dave Roy.
The remarkable contributions of the man who laid the stepping stone for the creation of artificial life and raised hope for treatment of genetic disorders with synthetic DNA will forever be cherished and we will always remain indebted for his endowments to us.
(Professor Avadhesha Surolia is director of the National Institute of Immunology, New Delhi)