The discovery of the genetic code, the once-secret language of our DNA, was made independently by three research groups led by Har Gobind Khorana, Marshall W Nirenberg, and Robert W Holley. Decoding our DNA propelled us to link sequence to function in our proteins, which illuminates factors that dictate our health.

Because of the profound impact of the genetic code, this article highlights one of the three researchers, Har Gobind Khorana, to give you a glimpse into his life, work, and impact on our lives.

Who was Har Gobind Khorana?

Har Gobind Khorana was an Indian-American researcher who co-discovered the genetic code. His actual birthday is unknown but is documented as January 9, 1922. His education began amid unlikely circumstances in a small village in Punjab, now part of Pakistan, called Raipur. “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,” explained Khorana in a short autobiographical piece.

His education continued at Punjab University in Lahore, where he studied chemistry and received a bachelor’s and master’s degree. Then, Khorana moved to England in 1945 with the help of a Government of India Fellowship and completed his PhD in 1948 at the University of Liverpool, studying the chemistry of melanins in the lab of Roger JS Beer. His postdoctoral mentors were Vladimir Prelog in Zurich at Eidgenössische Technische Hochschule, where he focused on alkaloid chemistry, followed by Alexander Todd in Cambridge, where he studied the structure of nucleic acids.

Har Gobind Khorana
Figure 1. Har Gobind Khorana (left) and Donald S Fredrickson (right, then director of the National Institutes of Health [NIH]) hold an NIH lecture award in 1978. (photo source)

During his time in Cambridge, he married Esther Elizabeth Sibler in 1952. And then, he moved to Vancouver, where he took a position at the University of British Columbia from 1952–1959. During the next eleven years at the University of Wisconsin, he worked on the genetic code, became a naturalized US citizen in 1966, and won the Nobel Prize in 1968. The remainder of his career was spent at MIT from 1971 until 2007, when he retired. Khorana had a family of three children, Julia Elizabeth, Emily Anne, and Dave Roy. He passed away on November 9, 2011.

Deciphering the Genetic Code

What is the Genetic Code?

The genetic code is the way our DNA is interpreted to create proteins. Three-letter nucleotide combinations code for specific amino acids. DNA is transcribed into RNA, and RNA is translated into protein. The code tells us the amino acid that results from the three-letter RNA nucleotide combination. For example, UAC codes for tryptophan, and AUG codes for methionine. Codon tables that contain nucleotide and their resulting amino acids simplify the interpretation.

How the Genetic Code was Deciphered

The work required to figure out the genetic code began long before DNA's structure was even known. Parts of the code had already been determined at the time when Khorana worked on it. The first codon cracked was UUU for phenylalanine by Nirenberg. Khorana confirmed and decoded the remaining codons, including the start and stop codons, and established that the genetic code was, in fact, a three-letter code.

Khorana applied his chemistry knowledge to molecular biology, which greatly assisted him in deciphering the genetic code. The technology Khorana used was the chemical synthesis of nucleic acid sequences. For the experiments, he created short repeating sequences that could then be tested against specific amino acids.

Because of the tremendous impact of his work, Khorana was awarded The Nobel Prize in Physiology or Medicine in 1968 along with Marshall Nirenberg (Cornell University) and Robert Holley (National Institutes of Health).

The Significance of Khorana’s Research Contributions

Knowing how our DNA relates to RNA and protein is key to determining the function of our genes. It helps answer the question: what does our DNA mean? Khorana’s research provided the means to answer that question.

After he was awarded a Nobel prize, Khorana continued his research that led to additional scientific advances. His work on the synthesis of nucleic acid sequences eventually allowed him to create the first synthetic gene. And, he was a pioneer in describing the step-wise amplification of synthetic genes—a process that would be developed by Kary B Mullis into polymerase chain reaction (PCR) through the use of a thermostable DNA polymerase.

Ultimately, the field of biotechnology was significantly impacted by Khorana’s research. These contributions provided essential information and technology for genetics and molecular biology, helping to lay the foundation of the incredible development of gene therapy. Khorana dedicated his life to research and added much more than the gift of the genetic code.

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