Friday, Nov. 15, 1963

How Nature Reads the Code

Although geneticists agree that the giant molecules of DNA (deoxyribonucleic acid) contain the coded information that controls the development of living organisms, they have yet to decipher the message. But the varieties of experimental attack seem almost unlimited as stubborn scientific cryptologists continue to study one of nature's most intractable secrets.

German Chemists Peter Karlson and Adolf Butenandt of the University of Munich collected three tons of silkworm pupae, ground up the little animals, then carefully processed the mess to extract 100 milligrams (one three-hundredth of an ounce) of a hormone called ecdysone. They knew ecdysone played a large part in the silkworm's life cycle, and when they discovered that it was remarkably similar to human sex hormones, they were fascinated. But what, if anything, did it have to do with DNA's genetic code?

Karlson dipped into his tiny supply of pure ecdysone and sent a five-milligram test sample to Ulrich Clever, a young biochemist at the Max Planck Institute in Tuebingen. Clever had been investigating the appearance of puffy swellings on microscopic, DNA-carrying chromosomes in the salivary glands of fly larvae. The puffs appear just before the larvae mature and change into pupae, and the tiny swelling seems to cause the metamorphosis. Karlson wondered how ecdysone would affect that transformation.

Chemist Clever soon had his answer. Within 20 minutes after a larva got an injection of ecdysone, its chromosomes grew puffs. Shortly after that, the larva turned into a pupa.

On this one phenomenon Karlson has built a sweeping theory of how DNA controls the development of an organism, and how nature reads its own code. The great store of hereditary information that DNA contains, says Karlson, is not needed all at once. It comes into play gradually, as if it were being looked up, item by item, in a book of instructions. When the time comes for a larva to turn into a pupa, ecdysone secreted by its glands circulates among the cells and comes in contact with the long, ropelike molecules of the DNA in the chromosomes. The hormone affects only those parts of the DNA molecule that contain a few items of chemical instructions needed for metamorphosis. The parts become suddenly active; they swell up, forming visible puffs which show that the hormone has told them to do their stuff. Dutifully they release their information by forming "messenger RNA" (ribonucleic acid) that diffuses into the body of the cell and manufactures the protein enzymes that bring about metamorphosis. Then the puffs disappear, and the chromosomes wait for other hormones to come along and tell them to release other items of information.

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