The great biologist Seymour Benzer passed away yesterday. If you know Benzer, it’s probably through Jonathan Weiner’s masterful book, Time, Love, Memory, which focused on how Benzer discovered the influence of genes on behavior in fruit flies. But Benzer was one of those rare scientists who had enough time in his life for more than one great project. Before Benzer turned to fruit flies, he studied E. coli. And in studying that wonderful microbe, he helped to figure out what genes are in the first place.
In the early 1950s Benzer gave up a career in physics for biology after reading Erwin Schrodinger’s provocative book, What Is Life? At the time, molecular biology was in its infancy, and much of the inner workings of the cell was a mystery. Benzer took up molecular biology right around the time that James Watson and Francis Crick discovered the structure of DNA. Scientists were beginning to accept that DNA, not proteins, were the stuff of genes. Some scientists had even started to map the location of genes in chromosomes, particularly in E. coli. But those maps couldn’t reveal the structure within a gene.
Benzer discovered a tool to dissect genes–the viruses that infect E. coli. When a virus infects E. coli, it may soon find itself with another invader from a different viral strain. In 1946 scientists discovered that co-infecting viruses can mingle their genes. The new viruses that emerge from these hosts sometimes carry traits from both parental strains. A virus carrying a crippling mutation may be able to pick up a working copy of the gene from the other strain. It appeared that the chromosomes of viruses split apart when these recombinations took place. Benzer wondered if individual genes were sometimes torn in two in the process. Benzer realized he could test that possibility. He needed viruses that carried mutant versions of the same gene. The viruses might be able to swap parts of that gene to make a working copy. It would be like taking a pair of scissors to XIFE and LIFQ and pasting together LIFE.
Benzer chose a well-studied mutation that prevented viruses from infecting the K-12 strain of E. coli. He isolated viruses that carried the mutation, and allowed them to coinfect another strain of Escherichia coli. Once they had produced new viruses, he tried their offspring on K-12 again. As he had predicted, the mutant viruses could mix parts of the same gene to make a working version. Benzer then began to map the gene by crossing thousands of viruses and calculated the locations of dozens of its mutations. Just as physicists split the atom, Benzer split the gene.
As the geneticist Guido Pontecorvo wrote in 1958, “The analogy of the genetic material with a written message is a useful commonplace. The important change is that we now think of the message as being in handwritten English rather than in Chinese.” In Chinese, words are single pictograms. In English, words are not the fundamental unit–they are made from letters. Likewise, genes are made up of nucleotides of DNA. That may seem like an obvious truth today, but only thanks to Benzer.