Har Gobind Khorana: Nucleic Acid Synthesis and Synthetic Gene Pioneer

Har Gobind Khorana
Dr. Har Gobind Khorana.

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Har Gobind Khorana (January 9, 1922 - November 9, 2011) demonstrated the role of nucleotides in the synthesis of proteins. He shared the 1968 Nobel Prize for Physiology or Medicine with Marshall Nirenberg and Robert Holley. He is also credited with being the first researcher to produce the first complete synthetic gene.

Fast Facts: Har Gobind Khorana

  • Full Name: Har Gobind Khorana
  • Known For: Research showing the role of nucleotides in the synthesis of proteins and the first artificial synthesis of a complete gene.
  • Born: January 9, 1922 in Raipur, Punjab, British India (now Pakistan) 
  • Parents: Krishna Devi and Ganpat Rai Khorana
  • Died: November 9, 2011 in Concord, Massachusetts, USA 
  • Education: Ph.D., University of Liverpool
  • Key Accomplishments: Nobel Prize for Physiology or Medicine in 1968 
  • Spouse: Esther Elizabeth Sibler
  • Children: Julia Elizabeth, Emily Anne, and Dave Roy

Early Years

Har Gobind Khorana was likely born to Krishna Devi and Ganpat Rai Khorana on January 9, 1922. While that is his officially recorded date of birth, there is some uncertainty as to whether or not that was his exact date of birth. He had four siblings and was the youngest of the five children.

His father was a taxation clerk. While the family was poor, his parents realized the value of educational attainment and Ganpat Rai Khorana ensured that his family was literate. By some accounts, they were the only literate family in the area. Khorana attended the D.A.V. High School and then matriculated to Punjab University where he earned both a Bachelor's (1943) and a Master's degree (1945). He distinguished himself in both instances and graduated with honors for each degree.

Subsequently he was awarded a fellowship from the government of India. He used the fellowship to earn his Ph.D. in 1948 from the University of Liverpool in England. After earning his degree he worked in a postdoctoral position in Switzerland under the tutelage of Vladimir Prelog. Prelog would greatly influence Khorana. He also completed additional post-doctoral work at Cambridge University in England. He studied both nucleic acids and proteins while at Cambridge.

During his time in Switzerland, he met and married Esther Elizabeth Sibler in 1952. Their union produced three children, Julia Elizabeth, Emily Anne, and Dave Roy.

Career and Research

In 1952, Khorana moved to Vancouver, Canada where he took a job with the British Columbia Research Council. The facilities were not expansive, but the researchers had freedom to pursue their interests. During this time he worked on research involving both nucleic acids and phosphate esters.

In 1960, Khorana accepted a position at the Institute for Enzyme Research at the University of Wisconsin, where he was the co-director. He became the Conrad A. Elvehjem Professor of the Life Sciences at the University of Wisconsin in 1964.

Khorana became an American citizen in 1966. In 1970, he became the Alfred P. Sloan Professor of Biology and Chemistry at the Massachusetts Institute of Technology (MIT), in Cambridge, Massachusetts. In 1974, he became the Andrew D. White Professor (at-large) at Cornell University in Ithaca, New York.

Order of Nucleotides Discovery

The freedom that began in Canada at the British Columbia Research Council in the 1950's was instrumental to Khorana's later discoveries related to nucleic acids. Along with others, he helped to explain the role of nucleotides in the construction of proteins.

The fundamental building block of DNA is the nucleotide. The nucleotides in DNA contain four different nitrogenous bases: thymine, cytosine, adenine, and guanine. Cytosine and thymine are pyrimidines while adenine and guanine are purines. RNA is similar but uracil is used instead of thymine. Scientists realized that DNA and RNA were involved in amino acid assembly into proteins, but the exact processes by which it all worked were not yet known.

Nirenberg and Matthaei had created a synthetic RNA that always added the amino acid phenylalanine to a linked amino acid strand. If they synthesized RNA with three uracils together, the amino acids produced were always just phenylalanine. They had discovered the first triplet codon.

By this time, Khorana was an expert in polynucleotide synthesis. His research group availed themselves of his expertise to show which combinations of nucleotides form which amino acids. They proved that the genetic code is always transmitted in a set of three codons. They also noted that some codons tell the cell to start making a protein while others tell it to stop making a protein.

Their work explained a number of facets of how the genetic code works. In addition to showing that three nucleotides specified an amino acid, their work showed what direction mRNA was read, that the specific codons do not overlap, and that RNA was the 'intermediary' between the genetic information in DNA and the amino acid sequence in specific proteins.

This was the basis of the work for which Khorana, along with Marshall Nirenberg and Robert Holley, was awarded the 1968 Nobel Prize for Physiology or Medicine.

Synthetic Gene Discovery

In the 1970's, Khorana's lab completed the artificial synthesis of a yeast gene. It was the first artificial synthesis of a complete gene. Many hailed this synthesis as a major hallmark in the field of molecular biology. This artificial synthesis paved the way for more advanced methods that would follow.

Death and Legacy

Khorana received a great number of awards during his lifetime. The foremost was the aforementioned Nobel Prize for Physiology or Medicine in 1968. He was also awarded the National Medal of Science, the Ellis Island Medal of Honor and the Lasker Foundation Award for Basic Medical Research. He was awarded the Merck Award and the American Chemical Society Award for Work in Organic Chemistry.

He earned a number of honorary degrees from universities in India, England, Canada, as well as in the United States. Over the course of his career, he authored or co-authored over 500 publications/articles in various scientific journals.

Har Gobind Khorana died of natural causes in Concord, Massachusetts on November 9, 2011. He was 89 years old. His wife, Esther, and one of his daughters, Emily Anne preceded him in death.

Sources

  • “The Nobel Prize in Physiology or Medicine 1968.” NobelPrize.org, www.nobelprize.org/prizes/medicine/1968/khorana/biographical/.
  • Britannica, The Editors of Encyclopaedia. “Har Gobind Khorana.” Encyclopaedia Britannica, Encyclopaedia Britannica, Inc., 12 Dec. 2017, www.britannica.com/biography/Har-Gobind-Khorana.