Subject: Nobel Prize in Chemistry Cites Discovery That Spawned New Genetic Engineering Date: Published: 10/13/89 (111 lines) Source: Wall Street Journal. Copyright Dow Jones & Co. Inc. Technology: Nobel Prize in Chemistry Cites Discovery That Spawned New Genetic Engineering ---- By Jerry E. Bishop Staff Reporter of The Wall Street Journal A new kind of genetic engineering is being built on the biochemical discovery that won two Americans the Nobel Prize. The Nobel Prize in chemistry was shared by Thomas R. Cech, 41 years old, of the University of Colorado, and Sidney Altman, 50, of Yale University, for their discovery that RNA, one of the two vital genetic materials in every living cell, could actively engage in chemical reactions. The discovery, made in the late 1970s and early 1980s, astonished molecular biologists who had thought RNA was a more or less passive element in the cell's genetic machinery. As a result of the discovery and the subsequent research of Messrs. Cech and Altman, genetic engineers are learning to manipulate RNA with the same dexterity as they manipulate DNA, the other vital genetic material in the cell. It was the ability to manipulate DNA that led to the founding of the genetic engineering industry. The new-found ability to manipulate RNA is leading to new, potentially commercial means of fighting viruses, such as those that cause AIDS, cancer and other scourges, and of altering the genetics of plants and other organisms. Already one company, U. S. Biochemical Corp. in Cleveland, which has exclusive rights to patents being sought by the University of Colorado on Mr. Cech's discoveries, is working on a host of new products. And a government-backed agency in Australia recently announced it formed a 67.5 million Australian dollar (US$52.4 million) joint venture with a French seed company to exploit the new RNA-based technology. The chemistry award was announced simultaneously with the Nobel Prize in physics, which was shared by two Americans and one German. Norman F. Ramsey of Harvard University was honored for his discovery of how to "excite" atoms of hydrogen to higher energy levels. The discovery led to the atomic clock, in which the flicker of atoms from one energy level to another ticks off time with millionths-of-a-second accuracy. The phenomenon ultimately led to the development of so-called masers and, later, lasers. Honored for their discoveries on trapping electrically charged atoms, called ions, were Hans G. Dehmelt of the University of Washington in Seattle and Wolfgang Paul of the University of Bonn. In their discovery of RNA's chemical activity, Messrs. Cech and Altman overturned a basic tenet of molecular biology that developed in the mid-1950s when the double-helix structure of DNA was discovered. The DNA structure showed the sequence of the simple bead-like molecules along a stretch of DNA constitute a "message" that dictates the production by the cell of a protein. The DNA message for a complete protein comprises a gene. The DNA message, however, stays secluded in the chromosomes in the center of the cell. To get the message to the outer reaches of the cell, a second necklace-like strand of simple molecular beads is assembled on the DNA, copying the message. This second copy-cat strand is messenger RNA, which carries the message out to the cell's protein-making factories. There other types of RNA bring in the raw materials for the protein and assemble it. In 1977, biologists discovered that the DNA message -- the gene -- isn't a continuous "sentence." Instead, it is interrupted every few "words" by long, meaningless stretches of DNA. This meant that when the RNA copied the message the nonsense stretches had to be cut out of the message. The biochemists had assumed that this RNA editing was done by enzymes, chemically active proteins that, as far as any one knew, carried out all chemical reactions in living matter. In 1978, Mr. Altman discovered that the cutting-and-pasting of the RNA message was done by a piece of RNA at the tip of a protein. That RNA could have such enzyme-like activity astonished biologists. In 1981, Mr. Cech discovered that RNA was actually editing itself. Each nonsense stretch of RNA was actually cutting itself out and splicing the two remaining ends together to form a complete, uninterrupted sentence for the making of a protein. Because these self-splicing nonsense stretches of RNA acted like enzymes they were dubbed "ribozymes" (RNA stands for ribonucleic acid). This is now opening up a fledgling industry in which ribozymes are being developed that can cut-and-paste RNA at almost any desired point. A hint of their potential might be gained by noting that the entire genetic engineering industry, as it currently exists, is based on the use of enzymes that can cut-and-paste DNA. In a paper published late last year, Mr. Cech speculated on how ribozymes are likely to be used. Many viruses, including the AIDS virus and cancer viruses, do their damage by inserting either their own DNA or their RNA into a cell's genetic machinery. The inserted virus "message" has to be copied at some point by RNA for the virus to do its dirty work. "Ribozymes targeted against such viral RNAs might cleave and thereby inactivate them," Mr. Cech wrote in the Journal of the American Medical Association. In some cases, viruses like the hepatitis virus do their damage by inserting a viral ribozyme into the cell that disrupts the cell's RNA functioning. It's likely, he suggested, that drugs could be developed that inactivated such viral ribozymes. 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