The chemist who cracked the DNA code and created the first artificial gene was born into poverty 100 years ago in an Indian village
Khorana’s legacy has also suffered from neglect which may be the result of racial prejudice. But this neglect is changing, as a new generation of writers has begun to construct a more accurate and inclusive history of science.
2022 marks the 100th birthday of Nobel Prize-winning chemist Har Gobind Khorana – or so we think. The exact date of his birth is not known, as Khorana was born into poverty into a British Indian class that rarely recorded such dates. As a child, he had to beg a neighbor for a glowing ember so his mother could start their daily kitchen fire. He was 6 years old before owning his first pencil.
Khorana emerged from this background to receive a Nobel Prize in 1968 for deciphering the genetic code that translates DNA sequences into protein molecules that perform the functions of living cells.
I I am writing a biography of Khorana in the hope that her story will inspire young scientists from all walks of life to pursue their dreams of exploration and discovery.
Education and formation
Despite his family’s poverty, Khorana’s father insisted on educating his children. He taught them to read and write very early. The first four years of schooling of the young Khorana took place under a tree until her father helps establish a one-room school in their village.
Khorana attended the University of Punjab, where he obtained a master’s degree in chemistry in 1945. That same year, the Indian government launched a program that sent talented students abroad for training. Khorana belonged to the first cohort and obtained a doctorate in organic chemistry from the University of Liverpool in 1948.
Under the terms of his scholarship, he was to return to India. But the previous year, Khorana had met and been captivated by Esther Silber, a Swiss. He chose to do a postdoctoral year in Switzerland. Without funding, he lived on his meager savings to work with Vladimir Prelog, one of the world’s foremost organic chemists.
Khorana also began reading extensively about German-language chemistry, which led him to become interested in a family of little-known synthetic reagents called carbodiimides that help form larger organic molecules from smaller components. One of these chemicals in particular, diccyclohexylcarbodiimide or DCC, has become critical in Khorana’s future work on DNA.
In 1949, Khorana returned to India alone, but his promised government post never materialized as the newly independent country was bankrupt. He managed to get a scholarship to the University of Cambridge in England, which was emerging as a world center for molecular biology.
The groundbreaking work taking place there included the sequencing of protein molecules into their amino acid components as well as the determination of their structure. Francis Crick and James Watson would unravel the double helix structure of DNA there in 1953.
Khorana began using the chemical DCC to disassemble and assemble the amino acid components of protein molecules. DCC also allowed him to assemble chains of DNA, starting with their fundamental units, nucleotides.
In 1952, Khorana was offered his own laboratory at the University of British Columbia. Esther and Khorana got married and moved to Vancouver.
Solve the genetic code
In Vancouver, Khorana focused on using DCC to synthesize complex molecules, particularly protein molecules called enzymes that regulate metabolism. He succeeded in synthesizing ATPthe molecule responsible for energy production in cells.
In 1960, he had synthesized an even more complex molecule, coenzyme A, involved in digestion. This success made him one of the most important biological chemists of his time.
Because DCC also allowed a researcher to string together DNA sequences, Khorana came up with a surprisingly ambitious project – the creation of an artificial gene. Nothing like this had ever been attempted and it became the holy grail of Khorana’s lab.
Khorana moved to the University of Wisconsin at Madison in 1960. In 1961 biochemists Marshall Nirenberg and Heinrich Matthaei announced a way to translate DNA sequences into amino acid sequences outside of a living cell .
They first placed a variety of cellular components in a test tube. When they then fed short DNA sequences into the test tube, the system translated them into a sequence of amino acids which, in turn, became part of a protein.
The effect on Khorana was electrifying. The chemical DCC allowed him to create any DNA sequence he wanted, which was beyond what Nirenberg and Matthaei could do. Inserting synthesized sequences into a test tube could produce all the amino acid sequences encoded by DNA.
Several laboratories were competing to do the same thing. Khorana’s lab worked around the clock in double shifts to solve the code first. In 1966 it was complete.
Khorana and Nirenberg were awarded the 1968 Nobel Prize in Physiology or Medicine, which they shared with Robert Holley, who had discovered another molecule involved in protein formation.
Solving the genetic code was a detour in Khorana’s relentless pursuit of artificial genes. In 1970 Khorana moved his laboratory to the Massachusetts Institute of Technology, where he remained for the rest of his life. In 1972, he finally finished the total synthesis of a functional gene outside of a living organism. He also showed that he could function properly in a bacterium.
Despite her acknowledged success and notoriety, racism marred Khorana’s life for much of her career. His daughter told me that in the UK and Canada he was ridiculed as a “Paki” by white residents.
In Canada, he was paid less and expected to work more than his white colleagues. She also noted, in the United States, that their mixed-race family dared not travel down South together.
Khorana’s legacy has also suffered from neglect which may be the result of racial prejudice. When author Horace Freeland Judson conducted interviews with molecular biologists for his pioneering story of molecular biology in 1979, “The eighth day of creationhe ignored Khorana — though dozens of lesser white figures were interviewed and given their due. Even though Khorana and Crick were in constant contact during the years the genetic code was cracked, Khorana only gets a fleeting mention in Crick’s biography by Robert C. Olby.
But this neglect is changing, as a new generation of writers has begun to construct a more accurate and inclusive history of science.
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Sahotra Sarkarprofessor of philosophy and integrative biology, The University of Texas at Austin College of Liberal Arts
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