(5 of 7)
Neat as it was, this scheme still left unanswered one more question: How could DNA or RNA choose from among 20 amino acids to produce complex proteins by using an informational system that had only four code letters—the four bases—at its disposal? An answer to this intriguing problem was suggested by Physicist George Gamow, who likened the four bases to the different suits in a deck of playing cards.
If the cards are dealt one at a time, disregarding the order of the cards within the suits, the player encounters only one of four possibilities on each draw (a heart, diamond, spade or club); clearly, if DNA's code worked this way, there would not be enough choices to encode 20 amino acids. If the cards are dealt in pairs, the number of combinations increases to 16 (since each card may combine with its own kind or one of three other suits). But such a two-unit system also would be inadequate. So Gamow reasoned that DNA's four bases had to be taken at least three at a time: this would yield 64 possible combinations (4 X 4 X 4), more than enough to code for the existing amino acids.
IN 1961, CRICK'S team at Cambridge proved Gamow's ingenious "triplet" theory. They demonstrated that RNA formed from only one or two base units could not effect the manufacture of proteins. But when they added a third base unit, protein formation began immediately. It remained, however, for an unknown young biochemist named Marshall Nirenberg, at the National Institutes of Health, to crack the code itself. That same year Nirenberg had succeeded in building up short, synthetic strands of RNA out of only one type of base. Invariably, this artificial RNA induced the manufacture of chains of proteins consisting of only one type of amino acid, phenylalanine. The conclusion was inescapable: in the genetic code, Nirenberg's triplet had to signify phenylalanine.
Using this clue as their Rosetta stone, Nirenberg and other researchers eventually found one or more three-letter code words, or codons, that could call up every single amino acid—plus other words that acted as punctuation, marking the start or completion of a message ordering the production of a protein. Even more remarkable, they learned that the code was universal: the same four letters, taken three at a time to form a single genetic word, code the same amino acids in all living things. Thus by the mid-1960s, scientists finally understood how DNA passes on genetic information with exquisite precision, and the way it orders up the fabrication of new cellular protein.
That process, shown in the accompanying color chart, was summarized by Crick in a series of rules that became known as the Central Dogma. Most scientists interpreted the key rule of that dogma to be that genetic information flowed in one direction: from DNA to RNA to protein. To the surprise of many molecular biologists, however, it has recently been shown that part of the process can sometimes be reversed. This finding, in the opinion of molecular biologists like Columbia's Sol Spiegelman, may offer an important clue to the workings of cancer cells (see box, page 44).