October 2010

Science Focus: Mina J. Bissell

Berkeley, Calif., in the 1970s was abuzz with oncogenes. Numerous discoveries during that time, including important work done by Peter Deusberg and G. Steve Martin at Berkeley and Peter Vogt at the University of California, Los Angeles had demonstrated how viruses (Rous sarcoma virus) could use their genetic material to turn normal cells into tumor cells, and Michael Bishop, Harold Varmus and colleagues had shown that even some host genes had inherent potential to promote cancer if mutated. Many scientists believed these discoveries would win Richard Nixon’s recently declared war on cancer.

Bissell, however, was a bit more skeptical about the oncogene revolution at that time. In reading some literature about cancer, Bissell had been more intrigued by another, older concept: the Warburg hypothesis, which suggested that altered metabolism could induce cancer.

“Of course, by then, most scientists had discredited the Warburg theory, so no one was really pursuing it,” she says, then, adding adamantly, “but I was interested in it.”

Bissell notes that the main issue she discovered was that researchers who had measured metabolism and cancer cells often did not regulate various external factors like temperature, cell density and pH, which led to inconsistent results in the literature.

Science-Focus---machine

A steady-state apparatus developed by Mina J. Bissell and Al Bassham used to more accurately quantify metabolism in a variety of cell types.

So, together with Al Bassham, a protégé of legendary chemist Melvin Calvin (of Calvin cycle fame), she devised a unique steady-state machine that could keep the environment of cultured cells constant. Then, they adapted some kinetic techniques Calvin and Bassham had employed in studying photosynthesis to animal cells and tracked glucose metabolism in various cell types.

“Everyone thought glucose metabolism was a housekeeping function that should be the same in all cells, but we found that glucose metabolites had tissue-specific expression patterns,” she says proudly. “Furthermore, we found that glycolysis was always higher in cells infected and transformed by RSV once all factors were properly controlled, but the increases were not necessarily due to defects in cellular respiration, which Warburg had believed.”

The real intrigue came in further studies in which Bissell manipulated the glucose levels in normal and transformed cells; when she lowered the glucose concentration in RSV-infected cells, they began to appear more normal, whereas increasing the glucose concentration in normal cells could induce them to begin looking transformed.

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