December 24, 1961 New Horizons in Science By Earl Ubell Science Editor Bruecke and I have sworn to make the truth prevail: no forces are effective in the organism other than the purely physical-chemical—-Emil Du Bois-Reymond, 1847. Eventually, physiology must completely dissolve into or- ganic physics and chemistry— Emil Du Bois-Reymond, 1848. * » * When Du Bois-Reymond set those brave words down as a thirty-year-old biologist in .|Berlin.more than a century ago, they seemed as revolutionary as the Communist Manifesto of those same years. His call for a physical-chemical basis for life hammered at the prevailing theory of vitalism:. the “old men” believed an unseen, im- measurable vital force gave the spark to life. In typical revolutionary fashion and in keeping with the times, the young men in science rallied to the young Berliner’s side. Bruecke was Ernst Bruecke, who later became Sigmund Freud’s physiology teacher in Vienna. Hermann von Helmholtz, then twenty- seven and a founder of the law of conservation of energy, and Karl Ludwig, thirty-two, a physiologist, joined the fight. Of course, with their methods they failed) to prove their biological manifesto. Last week another groyp of! Predoninatitly” young ~ men} announced they had come closer than ever to prov- ing the Germans right. They had tapped one of the inner- lmost. secrets of living things. They had found the key to the chemical code of life: they had learned the basic ‘chemical language of heredity and of the living chemistry by which protoplasm regenerates itself. They had given more reason than ever to believe that at bottom the life force is chem- istry and physics. Credit for the fundamental crack in the code goes to Dr. Marshall W. Nirenberg, thirty- two, of the National Institute of Arthritis and Metabolic Diseases, Bethesda, Md. Work- ing with Dr. J. Heinrich Matthaei, Dr. Nirenberg six months ago deciphered the first “word” of that code. The News Leaks Out When Dr. Nirenberg an- nounced his achievement in Moscow at the International Biochemical Congress last August, he set the world of biochemistry abuzz. However, the news did not leak into the newspapers until last week. A group of four researchers from New York University announced they had taken Dr. Nirenberg’s code-breaking procedure several steps further and deciphered fourteen out of twenty words of the code of life, and had thus effectively broken it. After this announcement by the NYU group headed by Nobel Prize winner Dr. Servo Ochoa, Dr. Nirenberg’s insti- tute announced that he and Dr. Matthaei had also de- ciphered as many words. At week’s end, it seemed it would be only a short time before the full code was known, now that its basic secret was revealed. What is this code? What is the “language” involved? What are the “words?” These are but metaphorical ways of ex- pressing the great modern question in biology: how does a living thing transmit its char- acteristic to its offspring? The Code of Life Finally Cracked In the mood of 1848 trans- ferred to today, biologists and chemists know the transfer is chemical. They know that when sperm ‘unites with . egg, chemicals are joined. When an amoeba or a cell or a germ splits in two, chemicals are distributed. It was only a few generations ago that biologists traced the site of those important chemi- cals to the nucleus, the central core of the cell; and in the nucleus to the chromosomes, microscopic rods. Twenty years ago, they iden- tified the chemical that carries the hereditary. information—it was called - deoxynucleic’ acid (dee-OXY-NOO-KLEE-ik), and known as DNA for short. The past two decades have been spent trying to understand its chemistry. and its role in the hereditary mechanism. Composed of two long strings of four basic molecules, per- muted thousands of times, the DNA holds the information for the‘manufacture of proteins in cells. The type and variety of proteins make an animal the size, shape and color if is. The proteins, composed of twenty different aminoacids, carry on the basic life chemistry.’ | Stull Unknown But the biologists did not know how the information from the DNA moves from the nucleus of the.cell. inte the pro- tein manufacturing region, the | cytoplasm, and into the ribo- somes, the microscopic protein factories. Recently they found the role of the transfer agent played, by. another chemical, ribonucleic acid (RYE-bo- NOO-KLEE-ik), a cousin to DNA and known as RNA. Unknown: What sequence of submolecules in RNA (as trans- ferred from the DNA) produced the proper sequence of amino acids in the proteins? The whole sequence of RNA sub- molecules—identified by letters representing the 4 chemicals, G, C, U, A—is the language of life; eaeh three-letter combina- tion is a “word.” Each word— UUU, UAA, CUA, etc.—controls the addition of a particular amino acid to a particular pro- tein. Dr. Nirenberg fed artificial RNA to the ribosomes. ‘This artificial RNA had but one word —UUU—UUU---UUU—repeated over and over. The ribosomes read the code and produced a protein containing only one amino acid, phenylalanine. This was the news last August in — Moscow. The NYU group tried other RNAs and worked out—with some ambiguities still—the code words for fourteen of the twen- ty amino acids. Dr. Nirenberg has also done so. Future Uses. This work has great practical implications. If biologists know the whole hereditary code and learn how to change it at will, they. may be able to. control. heredity by chemical means. They could raise plants and animals of almost any desired character, and do it in a hurry. In human beings, it could lead to control of hereditary diseases like diabetes and gout, to name but two. Some scien- tists are even worried that it could be applied to control the intelligence of large human populations wholesale; i. e., breed @ super-race. But all this is in the distant future. At the moment, the biological manifesto of 1848 looks very good indeed. ‘