Nobel Prize: The Code-Breakers

One of the most remarkable characteristics of living beings is their ability to pass inherited features from one generation to the next. And one of the greatest of man’s scientific triumphs has been the discovery of the method by which the genes transmit and translate the message of heredity. Last week, for their ingenious work in breaking the genetic code, U.S. Molecular Biologists Marshall Nirenberg, 41, Har Gobind Khorana, 46, and Robert Holley, 46, were jointly awarded the 1968 Nobel prize for physiology and medicine.

Long before the three new Nobel laureates began their experiments, scientists had learned that the message of heredity is carried by large molecules of deoxyribonucleic acid (DNA) in the chromosomes. Researchers had deduced that somehow DNA directs the cells to assemble amino acids into the proteins that form the basic structural material of all living beings and impart their characteristics. Then, in 1953, James Watson (author of The Double Helix] and Francis Crick put together more of the puzzle; they discovered that DNA consists of twin helices that are held together by regularly spaced links similar to the stairs of a spiral staircase.

Three-Letter Words. It was Watson and Crick who clarified the nature of the genetic code. They demonstrated that each stair of the double helix consists of a pair of chemical compounds called nucleotides. There are only four different kinds of nucleotides in DNA, but the order in which they appear along the length of the helix varies considerably, suggesting that they are arranged in a coded sequence. To be able to call up one of the 20 different amino acids using only four nucleotide “letters,” scientists decided, each genetic code “word” has to be three letters long. But how to break the code?

In 1961, Nirenberg, then an obscure young scientist at the National Institutes of Health, provided the biological Rosetta stone. After synthesizing a single helix with half-stairs that were the equivalent of only one of DNA’s nucleotides—adenine (A)—he added it to a solution containing all 20 amino acids. Only one protein was produced in the solution. It consisted entirely of a chain of amino-acid molecules called phenylalanine. Thus, Nirenberg concluded, a three-letter code word made up of adenine nucleotides (AAA) was nature’s instruction to the cell to use phenylalanine in building a protein.

Punched-Tape Message. Nirenberg refined his technique and began to match other three-letter combinations of nucleotides with particular amino acids. The task was also taken up independently by Khorana at the University of Wisconsin. Other scientists pitched in, and by 1965 the genetic code had been largely deciphered. Khorana was also able to determine that each of the three-letter words is always read separately and does not share any of its letters with another word. The words are read off continuously along a strand of DNA, much as a punched-tape message is read by a teletype machine. Among the 64 possible three-letter combinations of the four nucleotides, it was later discovered, there were several that served to direct the cell to start or stop manufacturing a protein. Nirenberg and Khorana also found some redundancy in the code: some of the amino acids were called up by several different three-letter combinations.

At Cornell, Holley studied both the genetic code and its function in building proteins by analyzing “transfer RNA,” a form of ribonucleic acid. RNA collects amino acids floating in the cell and, like a tug towing a barge, pulls them to an assembly site where, in the sequence dictated by the master DNA molecule, they are combined into the appropriate protein. Holley worked out the complete structure of a transfer RNA molecule, demonstrating how it attaches to a particular amino acid and brings it to the growing protein chain at the proper time and place.

By their accomplishments the three new U.S. Nobelmen have not only provided a clearer understanding of the nature of life, they have brought closer the day when molecular biologists will be able to correct genetic defects, control heredity, and perhaps even create life itself.