Most Nobel laureates in medicine come out of laboratories that already had a name. Har Gobind Khorana came out of a village of roughly a hundred people where, by his own account, his family was the only one that could read. He would go on to explain, in the flattest possible scientific prose, how a cell reads the four-letter alphabet of nucleic acid and turns it into the twenty-letter alphabet of protein — the central operating instructions of every living thing — and he shared a Nobel Prize for it in 1968. It is a large distance to travel, and Khorana rarely made much of having travelled it.
Raipur
He was born on 9 January 1922 in Raipur, a small village then counted as part of Multan district in undivided Punjab, and now in Khanewal district, Pakistan. His father worked as a patwari, a village-level clerk who kept the land and tax records for the area — a modest post, but a literate one, and he seems to have treated his children's education as the one asset he could reliably give them. "Although poor," Khorana wrote decades later in his Nobel autobiography, "my father was dedicated to educating his children, and we were practically the only literate family in the village inhabited by about 100 people." The first years of his schooling were conducted under a tree, the closest thing the village had to a classroom.
That early education was enough to get him into D.A.V. High School in Multan, and from there to Punjab University in Lahore, where he took a BSc and then an MSc in chemistry, finishing in 1945. A Government of India fellowship sent him to the University of Liverpool for a doctorate, and postdoctoral years followed at the Swiss Federal Institute of Technology in Zurich, under the chemist Vladimir Prelog, and at Cambridge, where he worked with the Nobel laureate Alexander Todd and first developed a serious interest in nucleic acids — the molecules that would occupy the rest of his career.
Reading the Code
By the 1950s, biology knew that DNA carried hereditary information and that it did so through the sequence of four bases along its strands. What nobody yet knew was the code itself: which sequences of bases specified which amino acids in a protein. Khorana, first at the British Columbia Research Council in Vancouver and from 1960 at the University of Wisconsin–Madison's Institute for Enzyme Research, took an approach that was as much a triumph of chemistry as of biology. Rather than working from natural samples, his laboratory chemically synthesized nucleotide chains of exactly known, controlled sequence, then used them to test which combinations of bases — codons — directed a cell's protein-building machinery to add which amino acid.
That painstaking, synthesis-driven method complemented the more biologically-derived work coming out of Marshall Nirenberg's laboratory at the US National Institutes of Health, and Robert Holley's determination of the structure of transfer RNA at Cornell. Between the three research programs, the genetic code was worked out triplet by triplet. In 1968 the Nobel Prize in Physiology or Medicine was awarded jointly to Khorana, Nirenberg and Holley "for their interpretation of the genetic code and its function in protein synthesis." Khorana had become a naturalized US citizen two years earlier; the prize made him, among other things, one of the first scientists of Indian birth to win a Nobel in the sciences.
After the Prize
The Nobel did not end his most consequential work. In 1970 Khorana moved to MIT as the Alfred P. Sloan Professor of Biology and Chemistry, and in 1976 his laboratory reported the first total synthesis of a gene, built up piece by piece from simple chemical starting materials, that functioned correctly when introduced into a living bacterial cell. It was proof, in the most literal sense, that a gene was not a mystical unit but a chemical object that could be built to specification — a foundational result for what later became synthetic biology and genetic engineering, fields that now routinely do at industrial scale what Khorana's group first managed by hand. He spent much of his later career on the biochemistry of vision, studying how the retinal protein rhodopsin responds to light, and remained at MIT, eventually as professor emeritus, until his retirement in 2007.
Concord
Khorana died on 9 November 2011 in Concord, Massachusetts, at 89. Colleagues who worked with him over the decades routinely described a man who did not trade on his own reputation; one remembered him, simply, as "one of the most modest people I have known," which sits oddly with a career that reshaped how biology understands its own machinery, and not at all oddly with a man whose earliest memory of ambition was a tree, a teacher, and a father determined that his children would be able to read.