SEYMOUR BENZER: A TRAIL BLAZER IN THE BIRTH OF MOLECULAR BIOLOGY
Seymour Benzer died in December 2007. He was 86 and did most of his work in genetics at Caltech. Benzer approached genetics with the outlook of a physicist. He greatly admired Max Delbrück, a physicist turned biologist who founded the field of bacteriophage genetics. Benzer’s first great contribution to that field, beginning in 1955, was his discovery of genetic fine structure. He used viral mutants that caused the plaques or holes in the bacterial lawn of food to change size or texture. By using mixtures of these mutants (some arising spontaneously and others induced chemically) he mapped the position of each mutant lesion to produce a map of the gene he was using.
At the same time his work was appearing, I was just starting a similar approach on fruit flies in Muller’s laboratory at Indiana University (Benzer at that time was at Purdue University). His work had an electrifying effect on me and other geneticists because it brought together classical genetics and molecular biology. It was like being there when the west coast and east coast railroad lines were joined at Promontory, Utah in 1869 to form the first transcontinental railroad. Benzer used operational philosophy, developed by physicist Percy Bridgman, to define his gene as a unit of mutation (muton), recombination (recon), and function (cistron). The fine structure of his muton map corresponded to the number of nucleotides in the inferred gene’s DNA. Each of his cistrons had one hundred or more sites that could be mapped. His mutons were mostly single nucleotide pairs in a DNA molecule. Today those terms have largely disappeared as the focus of interest shifted from the structure of genes to the functions of them. Benzer had gone as far it was possible to go without using DNA itself to analyze gene structure and function.
Benzer shifted his work to the nervous system using fruit flies. He induced mutations for behavioral traits, starting with the ability of flies to move to light (think of moths swarming towards light on a summer night). He analyzed these and sorted out those with defects associated with flying, with recognition of light, and with defects in the eyelets of their compound eyes. The fly’s brain, essentially a ganglionic mass of cells, was sophisticated and Benzer could distinguish many behaviors, including courtship rituals (which are innate in flies) and gender recognition (he even isolated genes for same sex preference in fruit flies). Benzer mapped these genes and studied their anatomical and physiological activities.
I do not know why Benzer did not win a Nobel Prize for his work. His ideas and findings had enormous influence on other biologists throughout the last half of the twentieth century. He was witty, passionately committed to experimental science, and a brilliant lecturer. His only rivals for creativity and generating new ways to think about life were Linus Pauling and Francis Crick.