Cech, Thomas R. (1947- )

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Cech, Thomas R. (1947- )

American biochemist

The work of Thomas R. Cech has revolutionized the way in which scientists look at RNA and at proteins. Up to the time of Cech's discoveries in 1981 and 1982, it had been thought that genetic coding, stored in the DNA of the nucleus , was imprinted or transcribed onto RNA molecules. These RNA molecules, it was believed, helped transfer the coding onto proteins produced in the ribosomes . The DNA/RNA nexus was thus the information center of the cell, while protein molecules in the form of enzymes were the workhorses, catalyzing the thousands of vital chemical reactions that occur in the cell. Conventional wisdom held that the two functions were separatethat there was a delicate division of labor. Cech and his colleagues at the University of Colorado established, however, that this picture of how RNA functions was incorrect; they proved that in the absence of other enzymes RNA acts as its own catalyst. It was a discovery that reverberated throughout the scientific community, leading not only to new technologies in RNA engineering but also to a revised view of the evolution of life. Cech shared the 1989 Nobel Prize for Chemistry with Sidney Altman at Yale University for their work regarding the role of RNA in cell reactions.

Cech was born in Chicago, Illinois, to Robert Franklin Cech, a physician, and Annette Marie Cerveny Cech. Cech recalled in an autobiographical sketch for Les Prix Nobel, he grew up in "the safe streets and good schools" of Iowa City, Iowa. His father had a deep and abiding interest in physics as well as medicine, and from an early age Cech took an avid interest in science, collecting rocks and minerals and speculating about how they had been formed. In junior high school he was already conferring with geology professors from the nearby university. Cech went to Grinnell College in 1966; at first attracted to physical chemistry, he soon concentrated on biological chemistry, graduating with a chemistry degree in 1970.

It was at Grinnell that he met Carol Lynn Martinson, who was a fellow chemistry student. They married in 1970 and went together to the University of California at Berkeley for graduate studies. His thesis advisor there was John Hearst who, Cech recalled in Les Prix Nobel, "had an enthusiasm for chromosome structure and function that proved infectious." Both Cech and his wife were awarded their Ph.D. degrees in 1975, and they moved to the east coast for postdoctoral positionsCech at the Massachusetts Institute of Technology (MIT) under Mary Lou Pardue, and his wife at Harvard. At MIT Cech focused on the DNA structures of the mouse genome, strengthening his knowledge of biology at the same time.

In 1978, both Cech and his wife were offered positions at the University of Colorado in Boulder; he was appointed assistant professor in chemistry. By this time, Cech had decided that he would like to investigate more specific genetic material. He was particularly interested in what enables the DNA molecule to instruct the body to produce the various parts of itselfa process known as gene expression. Cech set out to discover the proteins that govern the DNA transcription process onto RNA, and in order to do this he decided to use nucleic acids from a single-cell protozoa , Tetrahymena thermophila. Cech chose Tetrahymena because it rapidly reproduced genetic material and because it had a structure which allowed for the easy extraction of DNA.

By the late 1970s, much research had already been done on DNA and its transcription partner, RNA. It had been determined that there were three types of RNA: messenger RNA, which relays the transcription of the DNA structure by attaching itself to the ribosome where protein synthesis occurs; ribosomal RNA, which imparts the messenger's structure within the ribosome; and transfer RNA, which helps to establish amino acids in the proper order in the protein chain as it is being built. Just prior to the time Cech began his work, it was discovered that DNA and final-product RNA (after copying or transcription) actually differed. In 1977, Phillip A. Sharp and others discovered that portions of seemingly noncoded DNA were snipped out of the RNA and the chain was spliced back together where these intervening segments had been removed. These noncoded sections of DNA were called introns.

Cech and his coworkers were not initially interested in such introns, but they soon became fascinated with their function and the splicing mechanism itself. In an effort to understand how these so-called nonsense sequences, or introns, were removed from the transcribed RNA, Cech and his colleague Arthur Zaug decided to investigate the pre-ribosomal RNA of the Tetrahymena, just as it underwent transcription. In order to do this, they first isolated unspliced RNA and then added some Tetrahymena nuclei extract. Their assumption was that the catalytic agent or enzyme would be present in such an extract. The two scientists also added small molecules of salts and nucleotides for energy, varying the amounts of each in subsequent experiments, even excluding one or more of the additives. But the experiment took a different turn than was expected.

Cech and Zaug discovered instead that RNA splicing occurred even without the nucleic material being present. This was a development they did not understand at first; it was a long-held scientific belief that proteins in the form of enzymes had to be present for catalysis to occur. Presenting itself was a situation in which RNA appeared to be its own catalytic motivator. At first they suspected that their experiment had been contaminated. Cech did further experiments involving recombinant DNA in which there could be no possibility of the presence of splicing enzymes, and these had the same result: the RNA spliced out its own intron. Further discoveries in Cech's laboratory into the nature of the intron led to his belief that the intron itself was the catalytic agent of RNA splicing, and he decided that this was a sort of RNA enzyme which they called the ribozyme.

Cech's findings of 1982 met with heated debate in the scientific community, for it upset many beliefs about the nature of enzymes. Cech's ribozyme was in fact not a true enzyme, for thus far he had shown it only to work upon itself and to be changed in the reaction; true enzymes catalyze repeatedly and come out of the reaction unchanged. Other critics argued that this was a freak bit of RNA on a strange microorganism and that it would not be found in other organisms. The critics were soon proved wrong, however, when scientists around the world began discovering other RNA enzymes. In 1984, Sidney Altman proved that RNA carries out enzyme-like activities on substances other than itself.

The discovery of catalytic RNA has had profound results. In the medical field alone RNA enzymology may lead to cures of viral infections. By using these rybozymes as gene scissors, the RNA molecule can be cut at certain points, destroying the RNA molecules that cause infections or genetic disorders. In life sciences, the discovery of catalytic RNA has also changed conventional wisdom. The old debate about whether proteins or nucleic acids were the first bit of life form seems to have been solved. If RNA can act as a catalyst and a genetic template to create proteins as well as itself, then it is rather certain that RNA was first in the chain of life.

Cech and Altman won the Nobel Prize for chemistry in 1989 for their independent discoveries of catalytic RNA. Cech has also been awarded the Passano Foundation Young Scientist Award and the Harrison Howe Award in 1984; the Pfizer Award in Enzyme Chemistry in 1985; the U. S. Steel Award in Molecular Biology ; and the V. D. Mattia Award in 1987. In 1988, he won the Newcombe-Cleveland Award, the Heineken Prize, the Gairdner Foundation International Award, the Louisa Gross Horwitz Prize, and the Albert Lasker Basic Medical Research Award; he was presented with the Bonfils-Stanton Award for Science in 1990.

Cech was made full professor in the department of chemistry at the University of Colorado in 1983. Cech and his wife have two daughters. In the midst of his busy research career, Cech finds time to enjoy skiing and backpacking.

See also Viral genetics