Seymour
Benzer
1921 – 2007
Seymour Benzer, the Boswell Professor of Neuroscience, Emeritus, a founder
of modern genetics, and one of the giants of 20th-century science, died
from a stroke on November 30, 2007, in Pasadena. He was 86.
In a series of elegant experiments, Benzer made groundbreaking discoveries
about the structure of genes, finding that they were not indivisible units
of inheritance, as many scientists had believed. He also pioneered the
field of behavioral genetics, in which he probed the connection between
genes and behavior.
Benzer was born to Polish immigrants in New York City, growing up on
a street nestled between Jewish and Italian neighborhoods in Brooklyn.
During the Depression, his parents, who worked in the garment district,
managed to shield him and his three sisters from most of the era’s
hardships. To make ends meet, Benzer’s parents brought clothes home
to work on late into the night.
Benzer had an interest in science from an early age. During summer trips
to the Catskill Mountains in upstate New York, he caught and dissected
frogs. A whole new world opened up when his brother-in-law bought him
a microscope for his 13th birthday, he said in his oral history. He looked
at everything he could find, and did experiments in his basement laboratory—such
as making frog legs twitch with electric wires. Although never a religious
person, Benzer said he respected his parents’ faith, and followed
his father to synagogue on holy days. There, he would slip a physics book
on top of the Torah; his father looked the other way while he read.
Benzer was the first in his family to go to college, enrolling in Brooklyn
College in 1938. Although he was interested in biology, he eschewed the
introductory classes and instead graduated with a physics degree in 1942.
He went on to earn his PhD at Purdue University, developing a special
type of germanium crystal for a secret military project. His work led
to the first transistor and a Nobel Prize for William Shockley (BS ’32),
John Bardeen, and Walter Brattain in 1956. The researchers who developed
the transistor came to him and told him, “You should have done this,”
he recalled. He said, “It escaped me, and it was under my nose.”
By then, however, he was an assistant professor in physics at Purdue
with a renewed interest in biology. Inspired by Erwin Schrödinger’s
book What is Life?, Benzer attended a summer course in 1948 on
bacteriophages, viruses that attack bacteria, at Cold Spring Harbor—organized
by Caltech biology professor Max Delbrück. “Three weeks of
that, and I was converted,” Benzer said. He continued studying bacteriophages
during a year at Oak Ridge National Laboratory in Tennessee before joining
Delbrück’s lab at Caltech for two years as a postdoc. He then
went to the Pasteur Institute in Paris for a year, before returning to
Purdue. Back in Indiana, he started what would become some of his most
well-known work on the structure of the gene.
At the time, molecular biology was in its embryonic stage. James Watson
and Francis Crick had just discovered the double-helix structure of DNA
in 1953. But until Benzer’s experiments, the physical nature of
the gene was a mystery.
He worked with mutant strains of a bacteriophage that infected Escherichia
coli. When two strains of the virus infected E. coli, their
offspring contained new genes that combined elements of the same gene
from both progenitors. Benzer analyzed tens of thousands of these so-called
recombination events, in which portions of the gene called rII
swapped places. By comparing the length of these portions, he mapped rII’s
fine structure, showing that it was not an indivisible unit of heredity,
but many smaller units strung together. His map was on a scale large enough,
in fact, to see changes the size of a single nucleotide—the letters
that make up the DNA code and formed the double helix. This work bridged
the gap between classical genetics and molecular biology.
As molecular biology exploded in popularity, Benzer went in a different
direction. In the 1960s, partly inspired by the divergent personalities
of his daughters, he became interested in behavior and the “nature-versus-nurture”
debate. He began experiments with the fruit fly Drosophila melanogaster
while on sabbatical from 1965 to 1966 in the lab of Roger Sperry, Caltech’s
Hixon Professor of Psychobiology, and stayed on to become a professor
of biology in 1967. At Caltech, Benzer developed a novel device that allowed
him to separate flies according to behavior and isolate mutant strains.
Benzer treated the flies as if they were particles, bits of statistical
data from hundreds of individuals that he could collect in minutes, rather
than taking weeks to prepare a handful of rats. His lab first studied
the flies’ response to light, creating strains that failed to go
toward a light, as normal flies do. Benzer, his students, and his postdocs
also developed strains that slept and woke at random intervals, flies
that died early, and mutant females that brushed away males. By finding
these kinds of mutants, they identified the genes responsible for the
flies’ circadian rhythms—the natural biological clocks of
organisms—and other genes responsible for courtship, memory, and
learning.
His research was controversial at the time, as many scientists were skeptical
as to whether the small and simple fruit fly could be used to dissect
the complexities of behavior. His first seminar in Sperry’s lab
outlining some of his initial fly research was met with a divided reaction.
“They were pretty much split down the middle between those who thought
that this was great stuff and others who thought this was pure crap,”
he recalled. “They were really screaming at each other.”
Nevertheless, Benzer was highly respected, and he pursued his interests
with freedom. His work with fruit flies grew into the new field of neurogenetics,
showing that much of behavior is hardwired and not the result of one’s
environment.
He became Caltech’s Boswell Professor in 1975 and officially retired
in 1992, although he remained an active researcher afterward. In the late
1990s, Benzer and colleagues identified the famous “Methuselah”
gene in fruit flies. Named after the Biblical character who supposedly
lived 969 years, the gene is key to longevity. The mutants lived 35 percent
longer, tolerated higher temperatures, survived longer without food, and
were more resistant to poison than normal flies.
Over his career, Benzer accumulated more than 40 honors, including membership
in the National Academy of Sciences, the Royal Society, and the American
Academy of Arts and Sciences. He won the National Medal of Science, the
Wolf Prize in Medicine from Israel, the Crafoord Prize of the Royal Swedish
Academy of Sciences, the International Prize for Biology from Japan, the
Albert Lasker Award for Basic Medical Research, and the Albany Medical
Center Prize. He also won the Gairdner International Award twice. In 2000
he became the subject of the book Time, Love, Memory: A Great Biologist
and His Quest for the Origins of Behavior, by Jonathan Weiner. Although
many colleagues said his work deserved a Nobel Prize, the award eluded
him. “My mother always regarded me as a failure because I didn’t
get the Nobel Prize,” he remarked.
Benzer savored gastronomical experiences, whether it was discovering
sushi in Japan or, upon encountering a dearth of good restaurants in Cambridge,
England, forming a gourmet club with friends to prepare their own meals.
Colleagues in his lab recalled him offering them bizarre food such as
rotten fish or
chocolate-coated grubs.
His enthusiasm for trying diverse cuisine paralleled his passion for
reaching across scientific disciplines, having gone from physics to molecular
biology to neurogenetics. Colleagues remembered him as a visionary and
scientific maverick, following wherever his curiosity took him. But his
science was more than mere interest—it was an extension of who he
was. Often waking up just before noon, he would work deep into the early
morning hours, prompting colleagues to wonder if his own biological clock
was the inspiration behind his research on circadian rhythms. He relished
starting afresh in a new field in which he was ignorant and could ask
basic questions. “Ask stupid questions,” he said, “and
you often get amazing answers.”
Benzer is survived by his wife, Carol Miller; two daughters, Barbara Freidin and Martha Goldberg; a son, Alexander Benzer; two stepsons, Renny and Douglas Feldman; and four grandchildren. His first wife, Dorothy Vlosky, died in 1978. —MW
