Making the Gradient

Ron Kaback didn’t believe that electrochemical gradients could power the transport of sugars and amino acids across cell membranes—until he proved that they do.

Written byKaren Hopkin
| 9 min read

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H. RONALD KABACK
Professor of Physiology
University of California, Los Angeles
F1000 Faculty Member: Neuronal Signaling Mechanisms
PHOTO © 2011 JIM CORBFIELD
Ron Kaback got hooked on membrane transport as a medical student at the Albert Einstein College of Medicine in the late 1950s. “I went to all the biochemistry seminars, and one of the first ones I heard was given by Werner Maas, a geneticist at NYU. He had discovered the first mutants that become antibiotic resistant by losing the ability to take up the antibiotic,” he says. These mutant strains of E. coli proliferated normally in the presence of certain growth-inhibitory amino acids. “And the way they became resistant to these amino acids is they lost the ability to transport them.” The experiments Maas described reminded Kaback of a talk he’d heard as an undergraduate at Haverford College, in which Arthur Kornberg described work done by his then postdoc Paul Berg on transfer RNA—the RNAs that move amino acids to growing proteins. “So I’m sitting there listening and a light bulb goes off in my head,” says Kaback. “And I think: there must be another species of RNA, located in the membrane, that’s involved in amino acid transport.”

The young Kaback obtained the mutant strains from Maas and, in his spare time, started working on preparing membranes from the bacteria. “I worked all my weekends and holidays on these membranes—all the way through med school,” he says. “I’d get a little bit of transport, and there was always a difference between wild-type E. coli and the mutants. So I was determined to stick with it.”

Not everyone was so enthusiastic about his idea. “I used to go to honors lectures on Saturday mornings at NYU where they would bring in these real big shots,” says Kaback. “And one week, Werner Maas arranged for me to have an audience with Francis Crick before the start of his lecture. I was ushered into the room, ...

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