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Barbara McClintock

2007 Schools Wikipedia Selection. Related subjects: Human Scientists

      Barbara McClintock
   Born June 16, 1902
        Hartford, Connecticut
   Died September 2, 1992
        Huntington, New York

   Barbara McClintock ( June 16, 1902 – September 2, 1992) was a
   pioneering American scientist and one of the world's most distinguished
   cytogeneticists. McClintock received her PhD in botany from Cornell
   University in 1927, where she was a leader in the development of maize
   cytogenetics. The field remained the focus of her research for the rest
   of her career. From the late 1920s, McClintock studied chromosomes and
   how they change during reproduction in maize. Her work was
   groundbreaking: she developed the technique to visualize maize
   chromosomes and used microscopic analysis to demonstrate many
   fundamental genetic ideas, including genetic recombination by
   crossing-over during meiosis—a mechanism by which chromosomes exchange
   information. She produced the first genetic map for maize, linking
   regions of the chromosome with physical traits, and she demonstrated
   the role of the telomere and centromere, regions of the chromosome that
   are important in the conservation of genetic information. She was
   recognized amongst the best in the field, awarded prestigious
   fellowships and elected a member of the National Academy of Sciences in
   1944.

   During the 1940s and 1950s, McClintock discovered transposition and
   used it to show how genes are responsible for turning physical
   characteristics on or off. She developed theories to explain the
   repression or expression of genetic information from one generation of
   maize plants to the next. Encountering skepticism of her research and
   its implications, she stopped publishing her data in 1953. Later, she
   made an extensive study of the cytogenetics and ethnobotany of maize
   races from South America. McClintock's research became well understood
   in the 1960s and 1970s, as researchers demonstrated the mechanisms of
   genetic change and genetic regulation that she had demonstrated in her
   maize research in the 1940s and 1950s. Awards and recognition of her
   contributions to the field followed, including the Nobel Prize in
   Physiology or Medicine awarded to her in 1983 for the discovery of
   genetic transposition; to date, she has been the first and only woman
   to receive an unshared Nobel Prize in that category.

Early life

   Barbara McClintock was born in Hartford, Connecticut, the third of four
   children of physician Thomas Henry McClintock and Sara Handy
   McClintock. She was independent from a very young age, a trait
   McClintock described as her "capacity to be alone." From about the age
   of three until the time she started school, McClintock lived with an
   aunt and uncle in Massachusetts in order to reduce the financial burden
   on her parents while her father established his medical practice. The
   McClintocks moved to semi-rural Brooklyn, New York in 1908. She was
   described as a solitary and independent child, and a tomboy. She was
   close to her father, but had a difficult relationship with her mother.

   McClintock completed her secondary education at Erasmus Hall High
   School in Brooklyn. She discovered science at high school, and wanted
   to attend Cornell University to continue her studies. Her mother
   resisted the idea of higher education for her daughters on the theory
   that it would make them unmarriageable, and the family also had
   financial problems. Barbara was almost prevented from starting college,
   but her father intervened, and she entered Cornell in 1919.

Education and research at Cornell

   McClintock began her studies at Cornell's College of Agriculture in
   1919. She studied botany, receiving a BSc in 1923. Her interest in
   genetics had been sparked when she took her first course in that field
   in 1921. The course was the only one of its type offered to
   undergraduates in the United States at the time, and was taught by C.
   B. Hutchison, a plant breeder and geneticist. Hutchinson was impressed
   by McClintock's interest, and telephoned to invite her to participate
   in the graduate genetics course at Cornell in 1922. McClintock pointed
   to Hutchinson's invitation as the reason she continued in genetics:
   "Obviously, this telephone call cast the die for my future. I remained
   with genetics thereafter."

   Women could not major in genetics at Cornell, and therefore her MA and
   PhD — earned in 1925 and 1927, respectively — were officially awarded
   in botany. During her graduate studies and her postgraduate appointment
   as a botany instructor, McClintock was instrumental in assembling a
   group that studied the new field of cytogenetics in maize. This group
   brought together plant breeders and cytologists, and included Rollins
   Emerson, Charles R. Burnham, Marcus Rhoades, and George Beadle (who
   became a Nobel laureate in 1958 for showing that genes control
   metabolism). McClintock's cytogenetic research focused on developing
   ways to visualize and characterize maize chromosomes. This particular
   part of her work influenced a generation of students, as it was
   included in most textbooks. She also developed a technique using
   carmine staining to visualize maize chromosomes, and showed for the
   first time that maize had 10 chromosomes. By studying the banding
   patterns of the chromosomes, McClintock was able to link to a specific
   chromosome groups of traits that were inherited together. Marcus
   Rhoades noted that McClintock's 1929 Genetics paper on the
   characterization of triploid maize chromosomes triggered scientific
   interest in maize cytogenetics, and attributed to his female colleague
   10 of the 17 significant advances in the field that were made by
   Cornell scientists between 1929 and 1935.

   In 1930, McClintock was the first person to describe the cross-shaped
   interaction of homologous chromosomes during meiosis. During 1931,
   McClintock and a graduate student, Harriet Creighton, proved the link
   between chromosomal crossover during meiosis and the recombination of
   genetic traits. They observed how the recombination of chromosomes and
   the resulting phenotype formed the inheritance of a new trait. Until
   this point, it had only been hypothesized that genetic recombination
   could occur during meiosis. McClintock published the first genetic map
   for maize in 1931, showing the order of three genes on maize chromosome
   9. In 1932, she produced a cytogenetic analysis of the centromere,
   describing the organization and function of the centromere.

   McClintock's breakthrough publications, and support from her
   colleagues, led to her being awarded several postdoctoral fellowships
   from the National Research Council. This funding allowed her to
   continue to study genetics at Cornell, the University of Missouri -
   Columbia, and the California Institute of Technology, where she worked
   with Thomas Hunt Morgan. During the summers of 1931 and 1932, she
   worked with geneticist Lewis Stadler at Missouri, who introduced her to
   the use of X-rays as a mutagen. (Exposure to X-rays can increase the
   rate of mutation above the natural background level, making it a
   powerful research tool for genetics.) Through her work with
   X-ray-mutagenized maize, she identified ring chromosomes, which form
   when the ends of a single chromosome fuse together after radiation
   damage. From this evidence, McClintock hypothesized that there must be
   a structure on the chromosome tip that would normally ensure stability,
   which she called the telomere. She showed that the loss of
   ring-chromosomes at meiosis caused variegation in maize foliage in
   generations subsequent to irradiation resulting from chromosomal
   deletion. During this period, she demonstrated the presence of what she
   called the nucleolar organizers on a region on maize chromosome 6,
   which is required for the assembly of the nucleolus during DNA
   replication.

   McClintock received a fellowship from the Guggenheim Foundation that
   made possible six months of training in Germany during 1933 and 1934.
   She had planned to work with Curt Stern, who had demonstrated crossover
   in Drosophila just weeks after McClintock and Creighton had done so;
   however, in the meantime, Stern emigrated to the United States.
   Instead, she worked in Germany with geneticist Richard B. Goldschmidt.
   She left Germany early, amid mounting political tension in Europe, and
   returned to Cornell, remaining there until 1936, when she accepted an
   Assistant Professorship offered to her by Lewis Stadler in the
   Department of Botany at the University of Missouri - Columbia.

University of Missouri - Columbia

   During her time at Missouri, McClintock expanded her research on the
   effect of X-rays on maize cytogenetics. McClintock observed the
   breakage and fusion of chromosomes in irradiated maize cells. She was
   also able to show that, in some plants, spontaneous chromosome breakage
   occurred in the cells of the endosperm. Over the course of mitosis, she
   observed that the ends of broken chromatids were rejoined after the
   chromosome replication. In the anaphase of mitosis, the broken
   chromosomes formed a chromatid bridge, which was broken when the
   chromatids moved towards the cell poles. The broken ends were rejoined
   in the interphase of the next mitosis, and the cycle was repeated,
   causing massive mutation, which she could detect as variegation in the
   endosperm. This cycle of breakage, fusion, and bridge, also described
   as the breakage–rejoining–bridge cycle, was a key cytogenetic discovery
   for several reasons. First it showed that the rejoining of chromosomes
   was not a random event, and secondly it demonstrated a source of
   large-scale mutation. For this reason, it remains an area of interest
   in cancer research today.

   Although her research was progressing at Missouri, McClintock was not
   satisfied with her position at the University. She was excluded from
   faculty meetings, and was not made aware of positions available at
   other institutions. In 1940 she wrote to Charles Burnham, "I have
   decided that I must look for another job. As far as I can make out,
   there is nothing more for me here. I am an assistant professor at
   $3,000 and I feel sure that that is the limit for me." She was also
   aware that her position had been especially created for her by Stadler
   and may have depended on his presence. McClintock believed she would
   not gain tenure at Missouri, although according to some accounts she
   knew she would be offered a promotion by Missouri in the Spring of
   1942. In the summer of 1941 she took a leave of absence from Missouri
   to visit Columbia University, where her Cornell colleague Marcus
   Rhoades was a professor. He offered to share his research field at Cold
   Spring Harbour on Long Island. In December 1941 she was offered a
   research position by Milislav Demerec, and she joined the staff of the
   Carnegie Institution of Washington's Department of Genetics Cold Spring
   Harbour Laboratory.

Cold Spring Harbour

   After her year-long appointment, McClintock accepted a full-time
   research position at Cold Spring Harbour. Here, she was highly
   productive and continued her work with the breakage-fusion-bridge
   cycle, using it to substitute for X-rays as a tool for mapping new
   genes. In 1944, in recognition of her prominence in the field of
   genetics during this period, McClintock was elected to the National
   Academy of Sciences — only the third woman to be so elected. In 1945,
   she became the first woman president of the Genetics Society of
   America. In 1944 she undertook a cytogenetic analysis of Neurospora
   crassa at the suggestion of George Beadle, who had used the fungus to
   demonstrate the one gene–one enzyme relationship. He invited her to
   Stanford to undertake the study. She successfully described the number
   of chromosomes, or karyotype, of N. crassa and described the entire
   life cycle of the species. N. crassa has since become a model species
   for classical genetic analysis.

Discovery of controlling elements

   In the summer of 1944 at Cold Spring Harbour, McClintock began
   systematic studies on the mechanisms of the mosaic colour patterns of
   maize seed and the unstable inheritance of this mosaicism. She
   identified two new dominant and interacting genetic loci that she named
   Dissociator (Ds) and Activator (Ac). She found that the Dissociator did
   not just dissociate or cause the chromosome to break, it also had a
   variety of effects on neighboring genes when the Activator was also
   present. In early 1948, she made the surprising discovery that both
   Dissociator and Activator could transpose, or change position, on the
   chromosome.

   She observed the effects of the transposition of Ac and Ds by the
   changing patterns of coloration in maize kernels over generations of
   controlled crosses, and described the relationship between the two loci
   through intricate microscopic analysis. She concluded that Ac controls
   the transposition of the Ds from chromosome 9, and that the movement of
   Ds is accompanied by the breakage of the chromosome. When Ds moves, the
   aleurone-colour gene is released from the suppressing effect of the Ds
   and transformed into the active form, which initiates the pigment
   synthesis in cells. The transposition of Ds in different cells is
   random, it may move in some but not others, which causes colour
   mosaicism. The size of the colored spot on the seed is determined by
   stage of the seed development during dissociation. McClintock also
   found that the transposition of Ds and the is determined by the number
   of Ac copies in the cell.

   Between 1948 and 1950, she developed a theory by which these mobile
   elements regulated the genes by inhibiting or modulating their action.
   She referred to Dissociator and Activator as "controlling units"—later,
   as "controlling elements"—to distinguish them from genes. She
   hypothesized that gene regulation could explain how complex
   multicellular organisms made of cells with identical genomes have cells
   of different function. McClintock's discovery challenged the concept of
   the genome as a static set of instructions passed between generations.
   In 1950, she reported her work on Ac/Ds and her ideas about gene
   regulation in a paper entitled "The origin and behaviour of mutable
   loci in maize" published in the journal Proceedings of the National
   Academy of Sciences. In summer 1951, she reported on her work on gene
   mutability in maize at the annual symposium at Cold Spring Harbour, the
   paper she presented was called "Chromosome organization and genic
   expression".

   Her work on controlling elements and gene regulation was conceptually
   difficult and was not immediately understood or accepted by her
   contemporaries; she described the reception of her research as
   "puzzlement, even hostility". Nevertheless, McClintock continued to
   develop her ideas on controlling elements. She published a paper in
   Genetics in 1953 where she presented all her statistical data and
   undertook lecture tours to universities throughout the 1950s to speak
   about her work. She continued to investigate the problem and identified
   a new element that she called Suppressor-mutator (Spm), which, although
   similar to Ac/Ds displays more complex behaviour. Based on the
   reactions of other scientists to her work, McClintock felt she risked
   alienating the scientific mainstream, and from 1953 stopped publishing
   accounts of her research on controlling elements.

The origins of maize

   McClintock's microscope and ears of corn on exhibition at the National
   Museum of Natural History.
   Enlarge
   McClintock's microscope and ears of corn on exhibition at the National
   Museum of Natural History.

   In 1957, McClintock received funding from the National Science
   Foundation, and the Rockefeller Foundation sponsored her to start
   research on maize in South America, an area that is rich in varieties
   of this species. She was interested in studying the evolution of maize,
   and being in South America would allow her to work on a larger scale.
   McClintock explored the chromosomal, morphological, and evolutionary
   characteristics of various races of maize. From 1962, she supervised
   four scientists working on South American maize at the North Carolina
   State University in Raleigh. Two of these Rockefeller fellows, Almeiro
   Blumenschein and T. Angel Kato, continued their research on South
   American races of maize well into the 1970s. In 1981, Blumenschein,
   Kato, and McClintock published Chromosome constitution of races of
   maize, which is considered a landmark study of maize that has
   contributed significantly to the fields of evolutionary botany,
   ethnobotany, and paleobotany.

Rediscovery of McClintock's controlling elements

   McClintock officially retired from her position at the Carnegie
   Institution in 1967, and was awarded the Cold Spring Harbour
   Distinguished Service Award; however, she continued to work with
   graduate students and colleagues in the Cold Spring Laboratory as
   scientist emerita. In reference to her decision 20 years earlier no
   longer to publish detailed accounts of her work on controlling
   elements, she wrote in 1973:

     Over the years I have found that it is difficult if not impossible
     to bring to consciousness of another person the nature of his tacit
     assumptions when, by some special experiences, I have been made
     aware of them. This became painfully evident to me in my attempts
     during the 1950s to convince geneticists that the action of genes
     had to be and was controlled. It is now equally painful to recognize
     the fixity of assumptions that many persons hold on the nature of
     controlling elements in maize and the manners of their operation.
     One must await the right time for conceptual change.

   The importance of McClintock's contributions only came to light in the
   1960s, when the work of French geneticists Francois Jacob and Jacques
   Monod described the genetic regulation of the lac operon, a concept she
   had demonstrated with Ac/Ds in 1951. Following Jacob and Monod's paper
   1961 Nature paper "Genetic regulatory mechanisms in the synthesis of
   proteins", McClintock wrote an article for American Naturalist
   comparing the lac operon and her work on controlling elements in maize.
   McClintock's contribution to biology is still not widely acknowledged
   as amounting to the discovery of genetic regulation.

   McClintock was widely credited for discovering transposition following
   the discovery of the process in bacteria and yeast in the late 1960s
   and early 1970s. During this period, molecular biology had developed
   significant new technology, and scientists were able to show the
   molecular basis for transposition. In the 1970s, other scientists Ac
   and Ds were cloned and were shown to be Class II transposons. Ac is a
   complete transposon that can produce a functional transposase, which is
   required for the element to move within the genome. Ds has a mutation
   in its transposase gene, which means that it cannot move without
   another source of transposase. Thus, as McClintock observed, Ds cannot
   move in the absence of Ac. Spm has also been characterized as a
   transposon. Subsequent research has shown that transposons typically do
   not move unless the cell is placed under stress, such as by irradiation
   or the breakage, fusion, and bridge cycle, and thus their activation
   during stress can serve as a source of genetic variation for evolution.
   McClintock understood the role of transposons in evolution and genome
   change well before other researchers grasped the concept. Nowadays,
   Ac/Ds is used as a tool in plant biology to generate mutant plants used
   for the characterization of gene function.

Honours and recognition

   McClintock was awarded the National Medal of Science by Richard Nixon
   in 1971. Cold Spring Harbor named a building in her honour in 1973. In
   1981 she became the first recipient of the MacArthur Foundation Grant,
   and was awarded the Albert Lasker Award for Basic Medical Research, the
   Wolf Prize in Medicine and the Thomas Hunt Morgan Medal by the Genetics
   Society of America. In 1982 she was awarded the Louisa Gross Horwitz
   Prize for her research in the "evolution of genetic information and the
   control of its expression." Most notably, she received the Nobel Prize
   for Physiology or Medicine in 1983, credited by the Nobel Foundation
   for discovering "mobile genetic elements", over thirty years after she
   initially described the phenomenon of controlling elements.

   She was awarded 14 Honorary Doctor of Science degrees and an Honorary
   Doctor of Humane Letters. In 1986 she was inducted into the National
   Women's Hall of Fame. During her final years, McClintock led a more
   public life, especially after Evelyn Fox Keller's 1983 book A feeling
   for the organism brought McClintock's story to the public. She remained
   a regular presence in the Cold Spring Harbour community, and gave talks
   on mobile genetic elements and the history of genetics research for the
   benefit of junior scientists. An anthology of her 43 publications The
   discovery and characterization of transposable elements: the collected
   papers of Barbara McClintock was published in 1987. McClintock died
   near Cold Spring Harbour in Huntington, New York, on September 2, 1992
   at the age of 90; she never married or had children.

Legacy

   Since her death, McClintock has been the subject of the biographical
   work by science historian Nathaniel C. Comfort, in The tangled field :
   Barbara McClintock's search for the patterns of genetic control.
   Comfort's biography contests some claims about McClintock, described as
   the "McClintock Myth", which he claims was perpetuated by the earlier
   biography by Keller. Keller's thesis was that McClintock was long
   ignored because she was a woman working in the sciences, while Comfort
   notes that McClintock was well regarded by her professional peers, even
   in the early years of her career. While Comfort argues that McClintock
   was not a victim of sex discrimination, she has been widely written
   about in the context of women's studies, and most recent biographical
   works on women in science feature accounts of her experience. She is
   held up as a role model for girls in such works of children's
   literature as Edith Hope Fine's Barbara McClintock, Nobel Prize
   geneticist, Deborah Heiligman's Barbara McClintock: alone in her field
   and Mary Kittredge's Barbara McClintock.

   On May 4, 2005 the United States Postal Service issued the American
   Scientists commemorative postage stamp series, a set of four 37-cent
   self-adhesive stamps in several configurations. The scientists depicted
   were Barbara McClintock, John von Neumann, Josiah Willard Gibbs, and
   Richard Feynman. McClintock was also featured in a 1989 four stamp
   issue from Sweden which illustrated the work of eight Nobel Prize
   winning geneticists. A small building at Cornell University bears her
   name to this day.

Key publications

     * McClintock, Barbara (1929) A cytological and genetical study of
       triploid maize. Genetics 14:180–222
     * Creighton, Harriet B., and McClintock, Barbara (1931) A Correlation
       of Cytological and Genetical Crossing-Over in Zea Mays. Proceedings
       of the National Academy of Sciences 17:492–497
     * McClintock, Barbara (1931) The order of the genes C, Sh, and Wx in
       Zea Mays with reference to a cytologically known point in the
       chromosome. Proceedings of the National Academy of Sciences
       17:485–91
     * McClintock, Barbara (1941) The stability of broken ends of
       chromosomes in Zea Mays, Genetics 26:234–82
     * McClintock, Barbara (1945) Neurospora: preliminary observations of
       the chromosomes of Neurospora crassa. American Journal of Botany.
       32:671–78
     * McClintock, Barbara (1950) The origin and behaviour of mutable loci
       in maize. Proceedings of the National Academy of Sciences.
       36:344–55
     * McClintock, Barbara (1953) Induction of instability at selected
       loci in maize. Genetics 38:579–99
     * McClintock, Barbara (1961) Some parallels between gene control
       systems in maize and in bacteria. American Naturalist 95:265–77
     * McClintock, Barbara. , Kato, T. A. & Blumenschein, A. (1981)
       Chromosome constitution of races of maize. Its significance in the
       interpretation of relationships between races and varieties in the
       Americas.. Colegio de Postgraduados, Chapingo, Mexico

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