KATHERINE LAMBERT FOR TIME

The Pioneers of Molecular Biology: Tom Cech
	Ignoring the cult of DNA, he instead embraced the research possibilities of RNA
	By David Bjerklie

Posted Sunday, February 9, 2002; 10:31 a.m. EST
It was not the perfect way to begin graduate school. "I was in the uncomfortable position," remembers Tom Cech, "of entering the program in physical chemistry at U.C. Berkeley knowing only one thing: that I didn't like doing physical chemistry." Undergraduate research had convinced Cech that he lacked the patience required to perform the experiments. "There's a lot of very high-tech plumbing involved in gas-phase physical chemistry, a lot of work with wrenches and vacuum systems."

Luckily, Cech, who is now president of the Howard Hughes Medical Institute, met John Hearst, a professor in the department, who "was bouncing off the walls with excitement about chromosomes." Cech loved science and wasn't about to quit the field just because physical chemistry didn't fit his personality. He instead switched to a new area of research. "With molecular biology, you could go into the lab with an idea in the morning and in a day or two you'd get results to think about. It is a timescale appropriate for an impatient person such as myself."

After he got DNA religion, Cech admits he poked good-natured fun at colleagues who weren't working on DNA. "I felt that it was the source of all this information and everything else was derivative." But when Cech set up his own lab at the University of Colorado, he was in for another surprise: RNA was where the action was. Building on work done by Phillip Sharp at M.I.T. and researchers in Watson's Cold Spring Harbor Laboratory, Cech's team decided to explore how RNA, once thought of as merely a messenger molecule, had its discontinuous pieces spliced together to make a seamless, functional whole.

The mechanism was the mystery. "Everybody thought that protein enzymes would be the little machines that were cutting and pasting the RNA to accomplish the splicing. But we couldn't find such proteins. It turned out RNA was catalyzing its own splicing reaction." RNA was unexpectedly playing the roles of information molecule and enzyme workhorse at the same time.

Working on RNA, however, demanded different techniques than those used to manipulate DNA. And this meant another new learning curve for Cech. "For me personally, this was not an easy transition, both because the techniques were different and because I had brainwashed myself into thinking that DNA was the more important molecule." In fact, RNA had already eclipsed DNA as the focus for many researchers, including Watson and Crick.

Cech today says there's nothing he'd rather talk about than RNA. "I mean, frankly, DNA just sits there. And that's good. Because if you want a stable storehouse of genetic information, you don't want it doing things like rearranging itself; you want it to be very stable and static and therefore rather boring." Not that DNA isn't involved in a myriad of fascinating things," Cech is quick to add, giving his first passion its due, "but it's with all the players that interact with the DNA where the real excitement is." And, Cech hopes, further surprises.

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