An Interview with Manuel F. Varela and Ann F. Varela: Seymour Benzer: What happens to people who read atomic physics in the synagogue?

Sep 30, 2020 by

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Michael F. Shaughnessy –

1) Professor Varela, we know that Seymour Benzer is one of the most interesting scientists ever. Where was he born and when?

Seymour Benzer was a truly remarkable scientist. Benzer has been called “a Renaissance man of modern science.” He was a physicist and a pioneer of molecular biology who studied phage biology, mapped phage genes, studied DNA recombination, and biological effects of DNA mutations. He was also a fly geneticist and neurobiologist. He coined the molecular biological term “cistron,” meaning a segment of DNA that encodes a single polypeptide.

Benzer was born in the neighborhood of Bensonhurst in Brooklyn, New York, on October 15, 1921. Benzer met Dorothy Vlosky at Brooklyn College when he was a 15-year-old freshman, and she was a 21-year-old nurse. In 1942, the two wed. The couple has two daughters, Barbara and Martha Jane. Dorothy died of breast cancer, and Benzer later married Carol Miller, with whom he had one son, Alexander.

2) I heard dozens of stories about his childhood—can you relate a few?

Benzer’s parents, Meyer B. and Eva Naidorf were Jewish immigrants from Poland. He had two older sisters. Benzer created a laboratory in the basement of his home in Brooklyn, in which he studied and dissected flies, and was gifted a microscope for his thirteenth birthday. Some sources say the gift was a bar mitzvah gift, which apparently “opened up the whole world.” During synagogue, Benzer was also well known for reading books regarding atomic physics.

3) His early education—where did he go to school?

Benzer attended Brooklyn College and took his B.S. in physics in 1938. He earned his M.S. and Ph.D. in solid-state physics from Purdue University in 1947. His knowledge of this subject matter led him to be actively recruited by the military, during World War II, to work on a covert project to develop improved radar. His discovery of a germanium crystal applied at high voltages, in part, led to the first transistor. His 1947 Ph.D. thesis title was “Photoelectric Effects in Germanium.

At Purdue University, Benzer became a professor of physics, though he spent a lot of his time traveling and collaborating with other molecular biologists in their labs performing experiments. As a professor of biology at California Institute of Technology (Caltech), Benzer and his graduate student, Ronald Konopka, performed revolutionary work in genes and fly behavior.

4) Fruit flies and genetics of the brain—what did they seem to have in common?

According to biographers, Benzer’s entry into studies involving the fruit fly, starting in 1967, would lead to a blockbuster of discovery. The work established a new research field, now known as neurogenetics. His children had inspired Benzer’s new interest away from molecular biology and towards behavioral genetics. Benzer had noticed complete differences in the personalities of his two children, Martha and Barbara. On the one hand, Martha, Benzer had observed, was extraordinarily composed, while on the other hand, Barbara was sprightly. Benzer had become curious about the genetic basis for the behavior of organisms. Roger Sperry at Caltech had also inspired Benzer’s move to neurogenetics. Sperry taught Benzer as a visiting Caltech scientist about neurobiology.

Importantly, Edward B. Lewis had influenced Benzer on the usefulness of the laboratory fruit fly called Drosophila melanogaster. Lewis had shared his technical expertise on making fly mutants and an unending supply of fruit flies with Benzer. The inspiration of Lewis upon Benzer would be profound, and it would lead to a remarkable new insight regarding neurogenetics. Benzer had thought about the relationship between behavior and the burgeoning field of neurobiology. In an unprecedented moment of perceptiveness, Benzer reasoned behavior could be studied in populations of fruit flies, rather than at the level of individual laboratory animals, as had been done up to then.

Furthermore, Benzer realized that individual fruit flies could be observed as part of an overall collective from which minor behavioral characteristics could be distinguished. These subtle behavioral traits, such as fly movement in response to changes in light versus dark, i.e., phototaxis, could be discerned with fruit fly populations. Lastly, Benzer astutely envisaged that phototactic behavior due to a mutation in a single gene could be readily studied using the fruit fly as his paradigm.

This historical insight, i.e., the discovery of neurogenetics, by Benzer would culminate in the groundbreaking publication in the prestigious journal of the Proceedings of the National Academy of Sciences in 1967. In the article, Benzer described his method and experimental evidence for behavioral genetics using fruit fly mutants.

In the laboratory, Benzer cultured his fruit flies by feeding them a cornmeal-sugar mixture and letting them develop under total light conditions. Next, he exposed the growing flies to chemical DNA mutagens supplemental in their cornmeal-sugar medium, to generate new fruit fly mutants. He let the mutants produce new progeny, which he had permitted to mate in various combinations. Next, Benzer placed his mated progeny into a so-called countercurrent distribution apparatus. The countercurrent apparatus consisted of two test tubes connected, with a light source placed near it. The fruit flies were placed in one end of the experimental device and allowed to move to the other end if they so desired. Those fruits flies who moved to the other end were collected and transferred to another apparatus, separating those fruits flies who remained stationary from those who had moved to the other end. Then, the process was started over again and repeated for a large number of times. The experiment was performed in either total darkness or the presence of the nearby light source. The movement towards or away from light was the basis of the countercurrent apparatus.

While in the dark, flies tended to migrate towards the other side of the apparatus at a constant rate. With light applied, however, fruit flies moved toward the light at a faster rate than that in the dark. The flies sought out the light. If the light source was placed near their starting point, at the original end of the apparatus, the flies would tend to stay with the light. At the end of 15 cycles in which the moving flies were transferred to new test tubes each time, Benzer separated two behaviorally distinct flies. One group of fruit flies moved to the light at a high rate of speed, and the other fly group tended to move from light at a slow rate of movement.

Benzer was able to purify a type of fruit fly mutant, called vestigial (vg), which lacked wings. The vg fly mutants also showed an inability to move towards the light, moving at rates much slower than their wild-type parents did. When the phototactic-deficient mutants were mated to normal fruit flies, the slow-moving behavior transferred to the next generation. That is, Benzer discovered fly mutants with heritable traits that affected behavior—the movement towards or away from light. The blockbuster discovery was in the artificial production of a fruit fly mutant that lost its ability to move towards the light! It was the first time in scientific history that neurobiological behavior was experimentally connected to genetic elements.

5) Benzer and Richard Feynman crossed tracks—what happened there?

Richard Feynman was a 1965 physics Nobel Prize Laureate who discovered the quantum electrodynamics (QED) field of physics. See Figure below. Particularly famous are Feynman’s diagrams, which depict the behavior of sub-atomic particles. One incident holds that in 1985 Feynman was once asked to explain QED so that non-physicists could understand it. Feynman was said to reply, “If I could explain it to the average person, I wouldn’t have been worth the Nobel Prize.

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Figure Professor Richard Feynman at the California Institute of Technology.

Biographers have described Feynman as an extraordinarily curious and adventurous character, if not an incorrigible one. In line with this account is the story of Feynman’s foray into the study of molecular genetics of bacteriophages as sort of a hobby. See Figure below.

Feynman enjoyed his new adventure with the bacteriophage. He would come extremely close to discovering a major molecular phenomenon called intragenic suppression!

Benzer’s connection to this remarkable story is that Feynman was said to have adopted the “Benzer Mapping” method of studying phage mutants. Likewise, Feynman would invoke a method of his own for problem-solving. As described by his colleague Murray Gell-Mann, Feynman’

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