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Present at the creation

Medicine@Yale, 2005 - June July

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Expert on gene swapping joined molecular biology at its very beginnings

Charles M. Radding, M.D., professor emeritus of genetics, did sculpture as a hobby in medical school, and his portraits demonstrated a natural aptitude for plastic surgery, according to an influential mentor who also happened to be his older brother, Philip. The elder Radding, an orthopaedic surgeon, hoped the two would someday practice in side-by-side offices. Although the scheme had some appeal, Charles already knew his passion was biochemistry, not medicine.

It was 1953, and Watson and Crick’s double-helix model of DNA had opened a new door to understanding for biologists, a door the fledgling biochemist Radding eagerly entered. Radding, who recently retired after 37 years at Yale, went on to become a leader in illuminating the theoretical and biochemical underpinnings of genetic recombination. Also known as gene swapping, recombination orchestrates the orderly transmission of genes from generation to generation in all organisms, and it is now recognized as an important anticancer defense that human cells use to repair tumor-causing mistakes in the genome.

In the mid-1970s, while traveling on a bus filled with fellow scientists through the Scottish Highlands, Radding and Matthew Meselson of Harvard University hatched a new theoretical model of recombination. The 1975 paper they co-authored describing the model formed the basis for much of the experimental work in recombination in the years that followed.

Radding’s experimental approach combined his expertise in enzymes with the latest techniques in DNA research. In 1979, he scored an experimental coup by enticing a bacterial enzyme to swap genes between two strands of DNA in a test tube. For decades thereafter, his lab in the Sterling Hall of Medicine was the source of progressively more detailed biochemical investigations of this swapping reaction.“Radding’s meticulous studies contributed greatly to understanding the individual steps involved in the recombination of DNA molecules,” says Meselson.

Franklin Stahl, Meselson’s partner in the landmark “Meselson-Stahl experiment” on DNA replication, also praised Radding as lecturer and teacher. “Charlie showed a lifelong dedication to understanding the enzymology of recombination and communicating that understanding to his colleagues and students,” says Stahl, now professor emeritus of biology at the University of Oregon.

A symposium to honor Radding drew Meselson, Stahl and other colleagues and former students from around the world to Yale last fall. “Charlie has trained so many successful people,” says Patrick Sung, D.Phil., professor of molecular biophysics and biochemistry, an expert on DNA repair. Sung joined other speakers at the vibrant daylong conference, which was followed by a celebration that lasted late into the evening.

In retirement, Radding looks forward to reading and writing poetry— and perhaps trying his hand at art once again.

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