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Seymour Benzer (October 15, 1921 – November 30, 2007) was an American
physicist A physicist is a scientist who specializes in the field of physics, which encompasses the interactions of matter and energy at all length and time scales in the physical universe. Physicists generally are interested in the root or ultimate cau ...
,
molecular biologist Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physic ...
and behavioral geneticist. His career began during the molecular biology revolution of the 1950s, and he eventually rose to prominence in the fields of molecular and behavioral genetics. He led a productive genetics research lab both at Purdue University and as the James G. Boswell Professor of Neuroscience, Emeritus, at the California Institute of Technology.


Biography


Early life and education

Benzer was born in the
South Bronx The South Bronx is an area of the New York City borough of the Bronx. The area comprises neighborhoods in the southern part of the Bronx, such as Concourse, Mott Haven, Melrose, and Port Morris. In the early 1900s, the South Bronx was orig ...
to Meir Benzer and Eva Naidorf, both Jews from Poland. He had two older sisters, and his parents favored him as the only boy. One of Benzer's earliest scientific experiences was dissecting frogs he had caught as a boy. In an interview at Caltech, Benzer also remembered receiving a microscope for his 13th birthday, “and that opened up the whole world.” The book '' Arrowsmith'' by Sinclair Lewis heavily influenced the young Benzer, and he even imitated the handwriting of Max Gottlieb, a scientist character in the novel. Benzer graduated from New Utrecht High School at 15 years old. In 1938 he enrolled at
Brooklyn College , mottoeng = Nothing without great effort , established = , parent = CUNY , type = Public university , endowment = $98.0 million (2019) , budget = $123.96 m ...
where he majored in physics. Benzer then moved on to
Purdue University Purdue University is a public land-grant research university in West Lafayette, Indiana, and the flagship campus of the Purdue University system. The university was founded in 1869 after Lafayette businessman John Purdue donated land and ...
to earn his Ph.D. in solid state physics. While there he was recruited for a secret military project to develop improved radar. He performed research that led to the development of stable
germanium Germanium is a chemical element with the symbol Ge and atomic number 32. It is lustrous, hard-brittle, grayish-white and similar in appearance to silicon. It is a metalloid in the carbon group that is chemically similar to its group neighbors ...
rectifiers and discovered a germanium crystal able to be used at high voltages, among the scientific work that led to the first
transistor upright=1.4, gate (G), body (B), source (S) and drain (D) terminals. The gate is separated from the body by an insulating layer (pink). A transistor is a semiconductor device used to Electronic amplifier, amplify or electronic switch, switch ...
.


Personal life

At
Brooklyn College , mottoeng = Nothing without great effort , established = , parent = CUNY , type = Public university , endowment = $98.0 million (2019) , budget = $123.96 m ...
, as a sixteen-year-old freshman, Benzer met Dorothy Vlosky (nicknamed Dotty), a twenty-one-year-old nurse. He later married her in
New York City New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the L ...
in 1942. They had two daughters, Barbie (Barbara) and Martha Jane. Benzer died of a stroke at the
Huntington Hospital Huntington Memorial Hospital is a 619-bed not-for-profit hospital in Pasadena, California. The official name of the hospital is Pasadena Hospital DBA (doing business as) Huntington Memorial Hospital, known locally as HMH, Huntington Memorial or ...
in
Pasadena, California Pasadena ( ) is a city in Los Angeles County, California, northeast of downtown Los Angeles. It is the most populous city and the primary cultural center of the San Gabriel Valley. Old Pasadena is the city's original commercial district. ...
.


Scientific career


Molecular biology

Upon receiving his Ph.D. in 1947, he was immediately hired as an assistant professor in physics at Purdue. However, Benzer was inspired by Erwin Schrödinger's book '' What Is Life?'', in which the physicist pondered the physical nature of the gene and a “code” of life. This catalyzed Benzer's shift in interest to biology, and he moved into the area of
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bac ...
genetics., spending two years as a postdoctoral fellow in Max Delbrück's laboratory at California Institute of Technology, and then returning to Purdue. At Purdue University, Benzer developed the T4 ''rII'' system, a new genetic technique involving recombination in T4 bacteriophage ''rII'' mutants. After observing that a particular ''rII'' mutant, a mutation that caused the bacteriophage to eliminate bacteria more rapidly than usual, was not exhibiting the expected phenotype, it occurred to Benzer that this strain might have come from a cross between two different ''rII'' mutants (each having part of the ''rII'' gene intact) wherein a recombination event resulted in a normal ''rII'' sequence. Benzer realized that by generating many ''r'' mutants and recording the
recombination frequency Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separ ...
between different ''r'' strains, one could create a detailed map of the gene, much as Alfred Sturtevant had done for
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
. Taking advantage of the enormous number of recombinants that could be analyzed in the ''rII'' mutant system, Benzer was eventually able to map over 2400 ''rII'' mutations. The data he collected provided the first evidence that the gene is not an indivisible entity, as previously believed, and that genes were linear. Benzer also proved that
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
s were distributed in many different parts of a single gene, and the resolving power of his system allowed him to discern mutants that differ at the level of a single
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...
. Based on his ''rII'' data, Benzer also proposed distinct classes of mutations including deletions, point mutations, missense mutations, and nonsense mutations. Benzer's work influenced many other scientists of his time (see Phage group). In his molecular biology period, Benzer dissected the fine structure of a single gene, laying down the ground work for decades of mutation analysis and genetic engineering, and setting up a paradigm using the ''rII'' phage that would later be used by
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical stru ...
and Sydney Brenner to establish the triplet code of DNA. In addition, Benzer's mapping technique was taken up by Richard Feynman. In 1967, Benzer left the field of phage genetics and returned to the California Institute of Technology to work in behavioral genetics.


Behavioral genetics


Benzer vs. Hirsch

Benzer was one of the first scientists to rise to prominence in the field of behavioral genetics. As the field began to emerge in the 1960s and 70s, Benzer found himself in scientific opposition to another of the field's leading researchers, Jerry Hirsch. While Hirsch believed that behaviors were complex phenomena irreducible to the level of single genes, Benzer advocated that animal behaviors were not too complex to be directed by a single gene. This translated to methodological differences in the two researchers' experiments with
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...
that profoundly influenced the field of behavioral genetics. Hirsch artificially selected for behaviors of interest over many generations, while Benzer primarily used forward genetic mutagenesis screens to isolate mutants for a particular behavior. Benzer and Hirsch's competing philosophies served to provide necessary scientific tension in order to accelerate and enhance developments in behavioral genetics, helping it gain traction as a legitimate area of study in the scientific community.


Research accomplishments

Benzer used forward genetics to investigate the genetic basis of various behaviors such as phototaxis, circadian rhythms, and learning by inducing mutations in a Drosophila population and then screening individuals for altered phenotypes of interest. To better identify mutants, Benzer developed novel apparatuses such as the countercurrent device, which was designed to separate flies according to the magnitude and direction of their phototactic response. Benzer identified mutants for a wide variety of characteristics: vision (''nonphototactic'', ''negative phototactic'', and ''eyes absent''), locomotion (''sluggish'', ''uncoordinated''), stress sensitivity (''freaked-out''), sexual function (''savoir-faire'', ''
fruitless The ''fruitless'' gene (''fru'') is a ''Drosophila melanogaster'' gene that encodes several variants of a putative transcription factor protein. Normal ''fruitless'' function is required for proper development of several anatomical structures nec ...
''), nerve and muscle function (''photoreceptor degeneration'', ''drop-dead''), and learning and memory ('' rutabaga'', ''dunce''). Benzer and student Ron Konopka discovered the first circadian rhythm mutants. Three distinct mutant types—arrhythmic, shortened period, and lengthened period—were identified. These mutations all involved the same functional gene on the X chromosome and influenced the eclosion rhythm of the population as well as rhythms in individual flies' locomotor activity. To monitor ''Drosophila'' locomotor activity, Benzer and postdoctoral researcher, Yoshiki Hotta, designed a system using infrared light and solar cells. All three mutations were mapped to the X chromosome, zero centimorgans away from each other, indicating that the mutant phenotypes corresponded to alleles of the same gene, which Konopka named '' period''. This was the first of several seminal studies of single genes affecting behavior, studies that have been replicated in other animal models and are now the basis for the growing field of molecular biology of behavior. In 1992 Benzer, working with Michael Rosbash, furthered this work by showing that the PER protein, which '' period'' codes for, is predominantly located in the nucleus. The work with Period mutants was catalytic in the study of circadian rhythms and served to propel the field forward. On 2 October 2017, Dr. Rosbash, along with Drs. Michael W. Young and Jeffrey C. Hall, were awarded the Nobel Prize in Physiology or Medicine in recognition of their cloning of circadian rhythm genes, and the elucidation of the biochemical mechanisms by which the circadian rhythm protein products regulated behavior. Benzer was at the forefront of the study of neurodegeneration in fruit flies, modeling human diseases and attempting to suppress them. He also contributed to the field of aging biology, looking for mutants with altered longevity and trying to dissect the mechanisms by which an organism can escape the inevitable functional downfall and its associated diseases. In 1998, Benzer and his colleagues Yi-Jyun Lin and Laurent Seroude published findings of a long-life mutant in ''Drosophila'', then named Methuselah. The mutant gene coded for a previously unknown member of the GPCR family. By testing against temperature stress, it is thought that these mutants have an increased ability to respond to stress and thus to live longer. One of Benzer's final research projects was on dietary restriction and longevity research. A paper was published, in ' 'Cell'', on the longevity effect of 4E-BP, a translational repressor, following dietary restriction. Although the research was done before his death, the paper was published afterwards and dedicated to his memory.


Cancer research

In 1978, Dotty was in the hospital with breast cancer, and Seymour's friend, colleague, and mentor Max Delbrück was diagnosed with cancer. Consequently, Seymour Benzer took interest in cancer biology and attended several conferences on breast cancer. Benzer later remarried with Carol Miller, a neuropathologist. Together, in the early 1980s, they used antibody staining techniques to find nearly identical genes between flies and humans.


Honors and awards

* Fellow of the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, a ...
(1959) * Gairdner Foundation International Award (1964) *
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
(1971) *
Louisa Gross Horwitz Prize The Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers who have made an outstanding contribution in basic research in the fields of biology or biochemis ...
from
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
(1976), * Harvey Prize (1977) * Dickson Prize in Science (1978) * National Medal of Science (1982) * Rosenstiel Award (1985) * Thomas Hunt Morgan Medal (1986) *
Ralph W. Gerard Prize in Neuroscience The Ralph W. Gerard Award of the Society for Neuroscience (SfN) is an award in neuroscience awarded annually since 1978 for Lifetime Achievement. It is the highest recognition conferred by the SfN. As of 2018, the prize winner receives US$25,000. ...
(1989) *
Wolf Prize in Medicine The Wolf Prize in Medicine is awarded annually by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The ...
(1991) * Crafoord Prize (1993) * Feltrinelli Prize (1994) * International Prize for Biology (2000) *
NAS Award in the Neurosciences The NAS Award in the Neurosciences is awarded by the U.S. National Academy of Sciences "in recognition of extraordinary contributions to progress in the fields of neuroscience, including neurochemistry, neurophysiology, neuropharmacology, develop ...
from the National Academy of Sciences (2001) * March of Dimes Prize in Developmental Biology (2002) * Gairdner Foundation International Award (2004) (second award) * Bower Award and Prize for Achievement in Science (2004) * Albany Medical Center Prize (2006) He was a member of the
French Academy of Sciences The French Academy of Sciences (French: ''Académie des sciences'') is a learned society, founded in 1666 by Louis XIV at the suggestion of Jean-Baptiste Colbert, to encourage and protect the spirit of French scientific research. It was at ...
, the U.S. National Academy of Sciences, the
American Philosophical Society The American Philosophical Society (APS), founded in 1743 in Philadelphia, is a scholarly organization that promotes knowledge in the sciences and humanities through research, professional meetings, publications, library resources, and communit ...
and the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
.


Books

Benzer is the subject of the 1999 book ''
Time, Love, Memory ''Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior'' is a book by American non-fiction writer Jonathan Weiner, published in 1999. The book is a biography of California Institute of Technology biologist Seymour Be ...
: A Great Biologist and His Quest for the Origins of Behavior'' by Pulitzer laureate
Jonathan Weiner Jonathan Weiner (born November 26, 1953) is an American writer of non-fiction books based on his biological observations, focusing particularly on evolution in the Galápagos Islands, genetics, and the environment. His latest book is ''Long for ...
, and ''Reconceiving the Gene: Seymour Benzer's Adventures in Phage Genetics'' by Lawrence Holmes.


See also

* Phage group * T4 rII system


References


External links


Obituary in ''The Times''
12 December 2007
Interview with Seymour Benzer
conducted by the Oral History Project of the Caltech Archives
National Academy of Sciences Biographical Memoir
{{DEFAULTSORT:Benzer, Seymour 1921 births 2007 deaths American geneticists American people of Polish-Jewish descent 20th-century American physicists Behavior geneticists California Institute of Technology faculty Fellows of the American Academy of Arts and Sciences Foreign Members of the Royal Society History of genetics Jewish American scientists Jewish physicists Members of the French Academy of Sciences Members of the United States National Academy of Sciences American molecular biologists National Medal of Science laureates Phage workers Purdue University alumni Wolf Prize in Medicine laureates Recipients of the Albert Lasker Award for Basic Medical Research People from Bensonhurst, Brooklyn Scientists from New York (state) New Utrecht High School alumni Brooklyn College alumni 20th-century American Jews