June 2012

Stark raving mad for science

George Stark’s enthusiasm for understanding
signaling pathways and developing
biochemical methods is infectious.

Photo of George Stark 
George Stark remains committed to developing methods and understanding the fundamentals of signaling pathways. Photo courtesy of George Stark 

George Stark of the Cleveland Clinic is as comfortable in a kitchen as he is in a laboratory. The son of a restaurant owner, Stark says, “learning how to handle myself in a restaurant was good training for how to be a good chemist.” In fact, an extremely good biochemist. Stark’s scientific accomplishments, such as the development of Northern blotting for detecting RNA and the discovery of the JAK-STAT signaling pathway, have garnered him many accolades, including the 2011 Herbert Tabor/Journal of Biological Chemistry Lectureship, awarded by the American Society for Biochemistry and Molecular Biology each year for excellence in biological chemistry and molecular biology (1).

As a boy in the 1940s, Stark spent hours working in his father’s eatery, Stark’s Beef and Beans, in Washington, D.C. Watching his father’s struggles made Stark decide at a young age that the restaurant business was not for him. His father agreed. His father, whom Stark describes as “a dominant personality … a go-out-and-get-’em business man,” had grand plans for his only son (Stark has two older sisters). “It was the typical ‘My son should be a doctor!’” says Stark with a laugh.

Stark’s mother was a quiet woman who worked as a bookkeeper to hold the family steady through the highs and lows of the restaurant business. His parents didn’t know much about science, Stark says, but, based on what they were aware of, they encouraged him to pursue medicine. To get the boy started, the family moved to New York City so Stark could attend the Bronx High School of Science for his senior year.

He went on to Columbia College for his undergraduate degree, but as he got more into his premedical school studies, Stark says, he realized he really wanted to do research, not medicine. A comparative anatomy class cemented the decision. “Looking at a bunch of pins stuck in a dissected frog and trying to remember the names of what was underneath each pin was daunting for me,” he says. “I can remember things very well if I can link them in a logical chain, but the names of all these nerves and so forth in the frog were not linkable in a logical chain for me!”

In what he calls an act of self-defense to avoid medical school, Stark stayed on at Columbia for graduate school in the laboratory of his undergraduate adviser, Charles Dawson, to study ascorbate oxidase from yellow crook-necked squash. In a Reflections article for The Journal of Biological Chemistry, Stark recalls spending happy hours in the cold room peeling mounds of the vegetable because the enzyme was concentrated in its skin (2).

Stark followed his graduate studies with a stint at The Rockefeller University as a postdoctoral fellow with soon-to-be Nobel laureates Stanford Moore and William Stein, who had invented the amino acid analyzer and sequenced bovine pancreatic ribonuclease. It was also during this time that Stark met a physicist who became his wife and, for several years, labmate. Stark has described Mary Beck as “the glue that holds one’s life together.”

Stark’s work on carbamylation to identify the amino-terminal residues of proteins and aspartate transcarbamylase attracted the attention of Arthur Kornberg, who recruited him to Stanford University in the early 1960s. There, in the 1970s, Stark’s group developed Northern blotting. At that time, RNA was detected by separating an RNA mixture in a tube gel, freezing the gel, and “putting it in a device like an egg slicer and cutting it into 100 or so pieces,” says Stark. Each gel piece was hybridized with a complementary RNA probe to see which gel piece contained the RNA in question. The method, Stark says, was “ridiculously cumbersome.” His group decided to do better.

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