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Obituaries / Seymour Benzer, 1921 - 2007

Pioneering biologist linked genes to behavior

December 02, 2007|Thomas H. Maugh II | Times Staff Writer

Seymour Benzer, the Caltech biologist who made key findings about the structure and function of genes and pioneered research linking genes to behavior, died from a stroke Friday at Huntington Hospital in Pasadena. He was 86.

Many of his colleagues felt that he should have been awarded a Nobel Prize for his achievements in elucidating the nature of genes and their links to everyday activities.

Although the prize was denied him, he did win several other major awards that are generally considered precursors of the Nobel, including the Albert Lasker Award for Basic Medical Research and the Albany Medical Center Prize in Medicine and Biomedical Research, the richest U.S. prize for scientific achievement.

"Seymour was one of the greatest scientists of our era and made fundamental contributions in several areas," said biologist Elliot Meyerowitz of Caltech. "He was an amazing person, a truly original scientific thinker, and an adventurous character both in and out of his scientific work."

Benzer had "that special imagination and view of the world that makes a great scientist," biologist Lewis Wolpert wrote in a New York Times review of Jonathan Weiner's 1999 biography of Benzer, "Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior."

When Benzer began his research in the early 1950s, geneticists thought that genes were indivisible units strung together on chromosomes like pearls on a necklace. Benzer, however, reasoned that each gene was composed of discrete segments that could reassemble in new combinations when two individuals mated.

Testing that theory was difficult, however, because such recombinations are extremely rare and can be difficult to identify. To overcome both problems, he focused on one of the smallest organisms known, called a phage. Phages are tiny viruses that infect bacteria and that reproduce remarkably rapidly, making 100 copies of themselves in 20 minutes.

Benzer mated two strains of a phage called T4, each with a discrete mutation that prevented it from growing on the bacterium Escherichia coli. When he spread the phage offspring on a culture dish where the E. coli was growing, he soon observed a clear spot where the bacteria had been killed by the phage -- indicating that the offspring had obtained healthy segments of the crucial gene from each parent.

The results confirmed that genes can be split into individual elements and verified James Watson and Francis Crick's model of the gene as consisting of many nucleotide pairs.

Benzer eventually identified a large number of mutants of the gene, called rII, and mapped their locations. One of his accomplishments was determining that certain key compounds could produce mutations in the phages. The chemical 5-bromouracil, for example, can replace thymine in the synthesis of DNA, creating a nonfunctional mutation at specific points. These points proved to be different from those at which spontaneous mutations most frequently occur.

Using thousands of mutations, he found that there was a mutation site that corresponded with each nucleotide along the DNA segment that composed the gene.

He also showed that there were short functional units within the gene that could function independently regardless of defects in other units. He named them cistrons.

In his search for mutations, he also studied mutant forms of transfer RNA, or tRNA, which binds to individual amino acids and connects them to the growing string that eventually becomes a protein. He discovered that there could be several different tRNAs that would each bind to the same amino acid while responding to different DNA codes -- a concept called degeneracy.

By attaching an amino acid to a tRNA molecule and then chemically altering the identity of the amino acid fragment, he verified Crick's prediction that the RNA controlled the fate of the molecule, not the amino acid.

Benzer later turned to studies of how genes affect behavior, using the fruit fly Drosophila melanogaster as a model. He said later that he was inspired by the birth of his second daughter, whose behavior was markedly different from that of his firstborn. "I wondered, 'Are my wife and I doing things that differently?' " he said.

He and his students identified flies with unusual behaviors -- a feat that often necessitated the invention of special equipment for screening the insects -- and bred them to form new strains. He found flies, for example, that had circadian rhythms of 14 hours and 28 hours rather than the normal period of 24 hours. Circadian rhythms govern waking and sleep cycles, as well as a variety of other functions.

The team eventually identified the genes that were associated with the altered behavior and tracked down the aberrant proteins they produced, shedding new light on the normal functions of the genes.

Other genes he tracked down governed courtship, memory and learning, among other things.

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