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“A lot of scientists would consider their careers a success if they'd done just one of them,” says Peter Moore, Steitz's long-time friend and Yale colleague who also played a key role in determining the structure of the large ribosomal subunit.
Later, Joan Steitz—herself a Yale professor and HHMI investigator—lists the structures her husband solved before the ribosome. “A lot of regulatory proteins, polymerases, transposases, all these different kinds of proteins. And the ultimate peak on the horizon was the ribosome. It was a very logical progression of his life's work,” she says.
There's a theme to all those molecules. Each is a cog in the central dogma put forth by Francis Crick in 1958 that explains how information flows in organisms: from DNA to RNA to proteins. Early in Steitz's career, exposure to some of the great minds in biology helped trigger the notion of mapping every cog in the machine.
An audacious goal, but one Steitz has largely fulfilled, says Moore. “When you look at what he's contributed to fundamental aspects of information transfer in organisms, it's just enormous. The ribosome is the capstone, but it's by no means his only big contribution.”
Steitz was born in Milwaukee and through high school considered a career in music, earning gold medals playing his saxophone. In the fleeting summers he bunched radishes at his grandfather's truck farm outside of town, the dirt imbuing a love of green things that has carried to his ever-expanding garden on the Connecticut coast.
Steitz headed to Harvard for graduate school, where he hung around the laboratory of James Watson who was poking into ribosomes. While Steitz developed an interest in cellular structures, he also grew interested in one of Watson's students, a Minnesotan named Joan Argetsinger. Joan and Tom soon married, and, in 1969, Joan became the first in the family to publish key discoveries about the ribosome, figuring out how the molecular machine initiates its protein-making cycle. (Joan Steitz was profiled in the February 2006 HHMI Bulletin.)
The new couple moved to the other Cambridge, in England, in 1967 and began work in the same institution where Watson and Crick had puzzled out the structure of DNA. Steitz thrived in the all-science-all-the-time environment, where the lunchtime conversation rarely strayed from the laboratory business of the day. Here an idea seeded at Harvard germinated: Steitz wanted to take apart the central dogma, piece by piece, like a clock.
He set to the task soon after the couple both landed faculty slots at Yale in 1970. In 1980, he tackled one of the enzymes that copies DNA, a polymerase, and solved it, the first polymerase structure published. Then “he marched through,” as he puts it. Over the next 25 years, he published a staggering number of structures.