The Making of a Gene

Like the sages of his native India, Organic Chemist and Nobel Laureate* Har Gobind Khorana is an extremely patient man. Nine years ago, he began working on the chemical synthesis of a single gene--the basic unit of heredity. By 1970 he had constructed a yeast-cell gene identical to the original--except for one thing: it lacked the vital "start" and "stop" signals to make it function in a living cell. Last week members of Khorana's team at the Massachusetts Institute of Technology disclosed that his goal had finally been achieved. At an American Chemical Society meeting in San Francisco, they announced that using only off-the-shelf chemicals, they had made an artificial gene that does all the work of its natural counterpart.

Like Beads. Khorana's creation is a duplicate of one of the thousands of genes in the spiral-staircase structure of the DNA molecule in the common intestinal bacterium E. coli. Unlike human genes, which include millions of chemical "steps" along much larger DNA molecules, this bacterial gene contains only 199 full steps, each a pair of letters in the genetic code. Consisting of chemicals called nucleotides, these letters make up words in the gene's message--in this case, instructions to transfer the amino acid tyrosine to the cell's protein-manufacturing centers.

Duplicating the gene's basic structure, which had been determined earlier by British researchers, was extremely tedious, trial-and-error work. Each scientist on Khorana's team was assigned to assemble 1% segments of DNA. This involved chemically linking one nucleotide to another, like beads of a necklace, until a chain ten to 12 nucleotides long had been created. Eventually the team built up 40 segments, all of them single stranded. These had to be paired to form double-stranded DNA segments that had to be connected end to end in proper sequence to duplicate the bacterial gene. In the course of their work, Khorana and his colleagues built not only the basic gene but the hitherto elusive start and stop signals at either end. When the synthetic gene was inserted into an E. coli cell with the help of a carrier virus known as a bacteriophage, it performed perfectly.

Unlike other experiments in "genetic engineering" (TIME, July 19), Khorana's work apparently does not pose dangers. For one thing, the gene is assembled with control signals, which enables scientists to prevent runaway activity. Also, there is no attempt to produce new gene combinations from different organisms that could accidentally breed mutants against which humans or other life have no natural defenses. Indeed, some scientists see in gene synthesis enormous potential for good. It could, for example, eventually be used to replace defective genes in ailing humans--in hemophiliacs, say. It may also bring new understanding--and possibly control--of cancer by explaining why the genes suddenly order the rampages of cell growth characteristic of the killer disease.

*For his role in deciphering the genetic code.

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