In 1945, as World War II came to an end, Britain was forced to accept decolonization, to wind down its empire, and India began preparing for independence. The country was at the time the fourth largest industrial economy in the world. In preparation for modernization after independence, the (British) Government of India initiated a new scheme for jump-starting scientific and technological development. Every year a number of gifted Indian students would be selected for training abroad in scientific and technological areas. They would be provided with full scholarships to study abroad for a higher degree or certificate. Under the terms of these scholarships, after the completion of their studies, they would be expected to return to India where the government promised that an appropriate job would be waiting for them.

A Surprise in London

Khorana was in the first cohort of students selected in 1945. Given his background in xanthone chemistry, he was specifically selected by the Ministry of Agriculture for further training in Britain on the chemistry of insecticides and fungicides. The hope was that, on returning to India, this training would benefit agricultural development through better pest control. He was assigned to an institute in Berkshire. The Indian High Commission in London was given the responsibility of securing his admission. Khorana set sail for Britain, expecting a future career in agricultural chemistry.

However, late in 1945, when Khorana arrived in London, he was shocked to find out that the expected position in Berkshire had not materialized. British institutions were overcrowded after the end of World War II from the return of ex-servicemen wanting to continue with their training. There were no slots left for others, especially candidates from the colonies, in most places. As a result, the Indian High Commission had failed to secure the expected position in Berkshire.

Instead, without consulting Khorana (who was in transit on a ship), because of his M.Sc. in organic chemistry, the High Commission had secured for him a regular Ph.D. studentship, that is, one dedicated to basic research, in Organic Chemistry at the University of Liverpool. Faced with no other choice, Khorana accepted the assignment and moved to Liverpool. He would later come to regard it as an extraordinarily lucky development and interpret it as yet another occasion when serendipity had favored him.

In 1950, Khorana and Kenner were reunited in Todd's laboratory at the University of Cambridge. Though neither could possibly have realized it at the time, Cambridge was emerging as one of the centers of a new molecular revolution that, during the next decade, would permanently transform biology. Central to the emergence of molecular biology was the “Unit for Research on the Molecular Structure of Biological Systems” set up in 1947 by the (British) Medical Research Council (MRC), originally to further the research of Max Perutz and John Kendrew in using X-ray diffraction to study proteins with the goal of determining their three-dimensional structure at an atomic resolution, a feat that had never before been attempted. Perutz and Kendrew would solve the myoglobin molecule in 1957 and hemoglobin in 1959 to be rewarded with the Nobel Prize in Chemistry in 1962.

In the early 1950s, the MRC Unit rapidly expanded its interest into other areas, including the structure of DNA, which would be elucidated on site by Francis H. C. Crick and James D. Watson using data from the work of Maurice Wilkins and Rosalind Franklin. The result was the double helix model for DNA, which was first published in 1953, and soon became the most visible icon of the new molecular biology. The unit was initially located in the Physics Department at the Cavendish Laboratory, indicating a perceived centrality of physics for the new molecular characterization of biological problems. Crick, who later became one of Khorana's closer intellectual interlocutors, had a background in physics and joined the MRC Unit in 1949, shortly before Khorana returned to Cambridge, but there is no evidence that they became acquainted at the time. The organic chemists lived in another world. Nevertheless, it was fortuitous that Todd also worked on nucleic acids. Khorana thus was kept aware of recent developments in that field.

Meanwhile, closer to Khorana's everyday work, in the Department of Biochemistry, Frederick Sanger was taking the chemical analysis of proteins to a new level of precision. That proteins consisted of polypeptides or amino acid residue chains (which means the same thing) had been known since the turn of the twentieth century.

Har Gobind Khorana did not know when he was born. “The correct date of my birth is not known,” he wrote in 1968, continuing: “that [the date] shown on documents is January 9, 1922.” We do not know where that date came from. Though the family owned some ancestral land, his parents were poor, and Indians of that era and from that economic background rarely kept exact records of births or other such events. Not unexpectedly, no childhood photograph of Khorana is known to exist, and the few stories that are known about his childhood may well be apocryphal rather than a record of facts.

Khorana was born in Raipur, then a village of about a hundred people near the ancient city of Multan in Punjab in what is now Pakistan. The village was near what is now Kabirwala; otherwise, it has disappeared from maps though there are people still living in the area. None of Khorana's family remains there today. During the time of India's Partition in 1947 and the violent chaos that followed, they had all migrated to India, initially mainly to Delhi. Other than being Khorana's birthplace, nothing of significance has been recorded of Raipur.

According to his grandnephew, Alok Khorana: “family lore speaks of a mischievous child who liked to steal sugarcane from the sugarcane fields. Gobind described our ancestral home as consisting of a kitchen and bedrooms in one corner, with a courtyard housing cows and horses on the opposite end.” The family is believed to have owned that ancestral home for centuries. As far as can be told, the ancestral home does not survive. The family lost all their landed property during Partition as was typical for Hindus and Sikhs who fled Pakistan and Muslims who fled India.

Gobind's father, Ganpat Rai Khorana, was a patwari, that is, a village agricultural taxation clerk at the lowest level of the administrative system of British-ruled India. We know little about Ganpat Rai, except that he insisted on educating all his children. Khorana later recalled: “Although poor, my father was dedicated to educating his children and we were practically the only literate family in the village.”

On the evening of December 10, 1968, on the seventy-second anniversary of Alfred Nobel's death, a slightly built Indian American man, only 44 years old, stood before King Gustaf Adolf of Sweden on a stage in the Konserthuset Stockholm (the Stockholm Concert Hall). By the king's side were Princess Christina and Prince Bertil of Sweden. The slightly built man was Har Gobind Khorana, and he was there to receive his share of the Nobel Prize in Physiology or Medicine. Accompanying him was his Swiss-born wife, Esther Elizabeth.

The Prize ceremony was followed by a formal banquet with about 1,300 guests. The menu included lobster and avocados as a starter, lamb with creamed mushrooms as the main course, and pineapple ice cream and cake for dessert. To drink, they had a choice of Pommery & Greno Brut or Château d’Yquem 1962. Afterward the Khoranas sipped Courvoisier. It was a joyous occasion.

In 1968, as today, the Nobel Prize was the greatest honor that a scientist can receive. Khorana received his prize for his role in solving the most important problem of molecular biology of his era: the nature of the genetic code. By the mid-1950s it had become clear that a string of four DNA nucleotides (adenosine [A], cytosine [C], guanine [G], and thymine [T]) in genes determined, by the order of their occurrence, the string of amino acid residues in protein molecules that carried out most of life's activities. These amino acid residues were of 20 types. But which sequence of DNA nucleotides specified which amino acid residues? This translation was carried out according to the genetic code. It turned out, as Khorana definitively established, that a triplet “codon” of nucleotides specified each amino acid residue. He established exactly which triplet of nucleotides specified each amino acid residue.

The problem of the genetic code had moved to the center of attention in molecular biology in the late 1950s, shortly after Francis Crick and James D. Watson established that DNA had the structure of a double helix with nucleotides strung along the two backbones that faced each other along the central core of the double helix.

If 1979 had been a year of transcendental success because Khorana had finally succeeded in creating a synthetic gene that could function within a cell, it followed a year that had brought him great personal sorrow. His younger daughter, Emily Anne, succumbed to leukemia on July 12, 1978, after a protracted illness. She was 23 years old and her mortal remains were interred at Henniker Cemetery in Henniker, New Hampshire, where the Khoranas had bought a cabin.

The family was devastated, though they knew Emily's death was coming. Friends mourned with them across the world. In Liverpool, Gobind's old mentor, Roger Beer found it sadly ironic that Khorana, who had done so much to reveal the secrets of life, had been helpless when cancer attacked his young daughter. He could well have asked: What was the point of all this biological research?

Emily's death dominated 1978, but was not the only tragedy that year. On June 26, 1978, George Kenner, who had had a history of depression, died by suicide. After teaching at Cambridge for a number of years, he had moved to the University of Liverpool in 1957, where he became Heath Harrison Professor of Organic Chemistry and, after 1976, Royal Society Professor. When the Khoranas visited Beer at Liverpool over the years, they had also kept up with George and his wife, Jill. While Kenner had had a superb research career studying protein synthesis, eventually he succumbed to his depression and took his own life in a remote area in the hills of Wales where he loved to hike.

Following Kenner's death, the University of Liverpool Department of Chemistry instituted the George Kenner Prize and Lectures. The first of these lectures was held on October 28, 1980. Todd introduced the lecturer who, appropriately, was Khorana, speaking on the final complete synthesis of a functional gene (“Synthesis in the study of biological function of nucleic acids”). Todd also presented Khorana with an engraved bowl designed by Denis Mann of Caithness Glass, a well-known glass artist (see Figure 8.1). Khorana stayed with the Beers as usual. It must have been a bittersweet reunion: Kenner had been a friend to all of them.

The Nobel Prize brought Khorana fame, but it also brought even higher expectations. Though he may not have minded the fanfare, psychologically, all the attention took its toll. A short time after returning to Madison from Stockholm, he suddenly disappeared from his laboratory apparently in a state of mental exhaustion, possibly depression. For several months he was unavailable. Laboratory members tracked him to Vancouver, where he was recuperating, but showed little interest in an immediate return. Friends said that he sat by the water for hours every day staring into the distance. But, soon, a crisis emerged within the laboratory as a dispute burst open between two factions that refused to work together. RajBhandary duly reported the problem to Khorana and it finally had the effect of making him return to establish peace. The laboratory could start functioning again.

Laboratory members also recall that wherever Khorana went—and he gave many seminars in the late 1960s—he was repeatedly asked whether he had finished synthesizing a gene. Was it done yet? When would it be done? He must have felt immense pressure though, after that initial retreat to Vancouver, it would not manifest itself publicly.

He had brought the pressure on himself. In the early 1960s, when not even the sequence of a single gene was known, he had announced his goal of the total synthesis of a functional gene. He was always explicit that the drive to decipher the genetic code was a mere detour from that pursuit even though it had brought him fame and a share of a Nobel Prize. Synthesizing the gene was a much more challenging—and, therefore, intellectually satisfying—problem:

On August 15, 1947, India gained independence from the British who left it almost bankrupt after centuries of colonial plunder, most recently to finance its war against Germany and the Axis powers. The following spring, Khorana completed his Ph.D. at the University of Liverpool. The terms of his scholarship, because it had been funded by the Government of India, required him to return to India. But Khorana did not want to return, at least not immediately. He wanted a year's postdoctoral stay in Europe. Ostensibly, this wish was motivated by a desire to learn German well enough to navigate effortlessly the vast German scientific literature on organic chemistry. He later claimed: “I wanted very much to spend a period of time in a laboratory in a German-speaking region of Europe.”

In the chaos in continental Europe that followed World War II, laboratories in Germany or Austria were not viable options. That only left Switzerland as a possible destination in German-speaking regions. It is probably not a coincidence that this was where Esther lived. In fact, there is ample reason to believe that learning German alone does not explain Khorana's preference for Switzerland over India in 1948. It was mostly an excuse or, at best, a rationalization.

The Eidgenössische Technische Hochschule in Zürich

As his intended destination, Khorana chose the Eidgenössische Technische Hochschule (ETH) in Zürich which, as he later correctly noted, had “had a great tradition in organic chemistry.” He then applied for a year's funding from the new Government of India but, given its dire financial straits, he was not surprised when the application was turned down. However, according to him: