Barbara McClintock

Infobox Scientist
name = Barbara McClintock


image_width = 200px
birth_date = birth date|1902|6|16
birth_place = Hartford, Connecticut, USA
nationality = United States
death_date = death date and age|1992|9|2|1902|6|16
death_place = Huntington, New York, USA
field = Cytogenetics
work_institution = University of Missouri
Cold Spring Harbor Laboratory
alma_mater = Cornell University
doctoral_advisor =
doctoral_students =
known_for =
prizes = Nobel Prize in Physiology or Medicine (1983)
footnotes =

Barbara McClintock (June 16 1902 – September 2 1992), the 1983 Nobel Laureate in Physiology or Medicine, was an 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 for visualizing 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 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 for her contributions to the field followed, including the Nobel Prize, awarded to her in 1983 for the discovery of genetic transposition; she is the only woman to receive an unshared Nobel Prize in that category.

Early life

University of Missouri

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. [McClintock, Barbara. (1941) "The stability of broken ends of chromosomes in Zea Mays". "Genetics" 26:234–82.] 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 recalled being excluded from faculty meetings, and was not made aware of positions available at other institutions.Keller, Evelyn Fox. (1983) "A feeling for the organism". W. H. Freeman and Company, New York. ISBN 0-7167-1433-7] 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." [McClintock, Barbara. Letter from Barbara McClintock to Charles R. Burnham (16 September 1940) [http://profiles.nlm.nih.gov/LL/B/B/N/T/_/llbbnt.pdf .pdf]
] [http://profiles.nlm.nih.gov/LL/Views/Exhibit/narrative/missouri.html] Initially, McClintock's position had been especially created for her by Stadler and may have depended on his presence.Kass, Lee B. 2003. "Records and recollections: A new look at Barbara McClintock, Nobel Prize-Winning geneticist". "Genetics" 164 (August): 1251-1260. Kass, Lee B. 2005. "Missouri compromise: tenure or freedom. New evidence clarifies why Barbara McClintock left Academe". Maize Genetics Cooperation Newsletter 79: 52-71.] 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. [Comfort, Nathaniel C. (2002) "Barbara McClintock's long postdoc years". "Science" 295:440.] Recent evidence reveals that McClintock more likely decided to leave Missouri because she had lost trust in her employer and in the University administration. In early 1941 she was invited by the Director of the Department of Genetics at Cold Spring Harbor to spend her summer there. She took a leave of absence from Missouri in hopes of finding a position elsewhere. She also accepted a visiting Professorship at Columbia University, where her former Cornell colleague Marcus Rhoades was a professor. He offered to share his research field at Cold Spring Harbor on Long Island. In December 1941 she was offered a research position by Milislav Demerec, the newly appointed acting director, and she joined the staff of the Carnegie Institution of Washington's Department of Genetics Cold Spring Harbor Laboratory.

Cold Spring Harbor

After her year-long temporary appointment, McClintock accepted a full-time research position at Cold Spring Harbor. 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. [McClintock, Barbara. (1945) "Neurospora: preliminary observations of the chromosomes of Neurospora crassa". "American Journal of Botany". 32:671–78.]

Discovery of controlling elements

In the summer of 1944 at Cold Harbor Spring, McClintock began systematic studies on the mechanisms of the mosaic color 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-color 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 color 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 behavior of mutable loci in maize" published in the journal "Proceedings of the National Academy of Sciences". In summer 1951, when she reported on her work on gene mutability in maize at the annual symposium at Cold Spring Harbor, the paper she presented was called "Chromosome organization and genic expression". [McClintock, Barbara. (1950) "The origin and behavior of mutable loci in maize". Proceedings of the National Academy of Sciences. 36:344–55.]

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". [McClintock, Barbara. "Introduction" in "The discovery and characterization of transposable elements: the collected papers of Barbara McClintock".] 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. [McClintock, Barbara. (1953) "Induction of instability at selected loci in maize". "Genetics" 38:579–99.] 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 behavior. 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.Comfort, Nathaniel, C.(1999) ""The real point is control": The reception of Barbara McClintock's controlling elements". "Journal of the History of Biology" 32:133–6.]

The origins of maize

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, Almiro 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 made a Distinguished Service Member of the Carnegie Institution of Washington. This honor allowed her to continue working 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. [McClintock, Barbara. Letter from Barbara McClintock to J. R. S. Fincham (1973) [http://profiles.nlm.nih.gov/LL/B/B/G/C/_/llbbgc.pdf .pdf] ]

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 1961 "Journal of Molecular Biology" 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, Barbara. (1961) "Some parallels between gene control systems in maize and in bacteria". "American Naturalist" 95:265–77.] 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, "Ac" and "Ds" were cloned by other scientists 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.

Honors and recognition

McClintock was awarded the National Medal of Science by Richard Nixon in 1971. Cold Spring Harbor named a building in her honor 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 from Columbia University 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 Harbor 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 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, whereas Comfort asserts that McClintock was well regarded by her professional peers, even in the early years of her career. [cite book
last =Comfort | first =Nathaniel C. | authorlink =Nathaniel C. Comfort
title =The Tangled Field: Barbara McClintock's search for the patterns of genetic control
publisher =Harvard University Press
month =June | year =2001 | location =Cambridge, MA
isbn=0-674-00456-6] Although Comfort argues that McClintock was not a victim of gender 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". A recent biography for young adults by Naomi Pasachoff, "Barbara McClintock, Genius of Genetics", provides a new perspective, based on the current literature. [Pasachoff, Naomi. 2006. "Barbara McClintock, Genius of Genetics". Enslow Publishers, Inc.]

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 and a laboratory building at Cold Spring Habor Laboratory bear 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 behavior 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

Footnotes

References

*Coe, Ed and Lee B. Kass. 2005. "Proof of physical exchange of genes on the chromosomes". Proceedings of the National Academy of Science 102 (No. 19, May): 6641-6656. PMID 15867161
*Comfort, Nathaniel C. (1999) ""The real point is control": The reception of Barbara McClintock's controlling elements". "Journal of the History of Biology" 32:133–62. PMID 11623812
*Comfort, Nathaniel C. (2001) "The tangled field: Barbara McClintock's search for the patterns of genetic control". Harvard University Press, Cambridge, MA. ISBN 0-674-00456-6
*Kass, Lee B. 2003. "Records and recollections: A new look at Barbara McClintock, Nobel Prize-Winning geneticist". "Genetics" 164 (August): 1251-1260.
*Kass, Lee B. 2005. "Harriet Creighton: Proud botanist". "Plant Science Bulletin". 51(4): 118-125. Available online, December 2005: [http://www.botany.org/PlantScienceBulletin/PSB-2005-51-4.php#HARRIET Botanical Society of America]
*Kass, Lee B. 2005. "Missouri compromise: tenure or freedom. New evidence clarifies why Barbara McClintock left Academe". Maize Genetics Cooperation Newsletter 79: 52-71; article without footnotes or photographs; available, online April 2005: [http://www.agron.missouri.edu/mnl/79/05kass.htm Maize Genetics Cooperation Newsletter]
*Kass, Lee B. and Christophe Bonneuil. 2004. "Mapping and seeing: Barbara McClintock and the linking of genetics and cytology in maize genetics, 1928-1935". Chapt 5, pp. 91-118, in Hans-Jörg Rheinberger and Jean-Paul Gaudilliere (eds.), "Classical Genetic Research and its Legacy: The Mapping Cultures of 20th Century Genetics". London: Routledge.
*Keller, Evelyn Fox (1983) "A feeling for the organism". W. H. Freeman and Company, New York ISBN 0-7167-1433-7

Further reading

*Bogdanov, Yu. F. (2002) A life devoted to science. In "Commemoration of the 100th anniversary of the birth of Barbara McClintock". "Russian Journal of Genetics" 38:984–87. PMID 12430570
*Fedoroff, Nina V. (1995). Barbara McClintock. " [http://books.nap.edu/html/biomems/bmcclintock.html Biographical Memoirs of the National Academy of Science] ". 68:211–36.
*Fedoroff, Nina V. 2002. "The well mangled McClintock myth". "Trends in Genetics" 18 (7): 378-379.
*Kass, L. B. 1999. "Current list of Barbara McClintock's publications". Maize Genetics Cooperation Newsletter 73: 42-48. Available online, 1998: [http://www.agron.missouri.edu/mnl/73/110kass.html Maize Genetics Cooperation Newsletter]
*Kass, Lee B. 2000. "McClintock, Barbara, American botanical geneticist, 1902-1992". Pp. 66-69, in Plant Sciences. edited by R. Robinson. Macmillan Science Library, USA.
*Kass, L. B. 2002. "The Tangled Field, by N. Comfort". "Isis". 93 (4): 729-730.
*Kass, L. B., 2004. Identification of photographs for the Barbara McClintock papers on the National Library of Medicine website. Maize Genetics Cooperation Newsletter 78: 24-26, available online, 2003: [http://www.agron.missouri.edu/mnl/78/04kass.html Maize Genetics Cooperation Newsletter]
*Kass Lee, B. 2007. Harriet B. Creighton (1909-2004), on Women Pioneers in Plant Biology, American Society of Plant Biologists website, edited by Ann Hirsch. Published online, February 2007: [http://www.aspb.org/committees/women/pioneers.cfm#Creighton American Society of Plant Biologists]
*Kass Lee, B. 2007. Barbara McClintock (1902-1992), on Women Pioneers in Plant Biology, American Society of Plant Biologists website, Ann Hirsch editor. Published online, March 2007: [http://www.aspb.org/committees/women/pioneers.cfm#McClintock American Society of Plant Biologists]
*Kass, L. B. and R. P. Murphy. 2003. "Will the real Maize Genetics Garden please stand up?" Maize Genetics Cooperation Newsletter. 77: 41-43. Available online, 2003: [http://www.maizegdb.org/mnl/77/79kass.html Maize Genetics Cooperation Newsletter]
*Kass, L. B and W. B. Provine. 1999 (&1998). Formerly restricted interview with Barbara McClintock, now available at Cornell University Archives. Maize Genetics Cooperation Newsletter. 73: 41. Available online, 1998: [http://www.agron.missouri.edu/mnl/73/11kass.html Maize Genetics Cooperation Newsletter]
*Kass, Lee B. Chris Bonneuil, and Ed Coe. 2005. "Cornfests, cornfabs and cooperation: The origins and beginnings of the Maize Genetics Cooperation News Letter". "Genetics" 169 (April): 1787-1797. Available online, May 6, 2005: [http://www.genetics.org/cgi/content/full/169/4/1787 Genetics Society of America]
*Jones, R.N. 2005. "McClintock's controlling elements: the full story". "Cytogenetics Research" 109:90–103 PMID 15753564
*Lamberts, William J. (2000) "McClintock, Barbara". "American National Biography Online". Oxford University Press
*McClintock, Barbara. (1987). "The discovery and characterization of transposable elements: the collected papers of Barbara *McClintock", ed John A. Moore. Garland Publishing, Inc., ISBN 0-8240-1391-3.
*Fedoroff, Nina V and Botstein, David (1993) "The Dynamic Genome: Barbara McClintock's Ideas in the Century of Genetics." Cold Spring Harbor Laboratory Press, New York. ISBN 0-87969-396-7

Archives and research collections

* [http://profiles.nlm.nih.gov/LL/ The Barbara McClintock Papers] at the National Library of Medicine.
* [http://www.amphilsoc.org/library/mole/m/mcclintock.htm Barbara McClintock Papers, 1927-1991] at the American Philosophical Society

External links

* [http://www.osti.gov/accomplishments/mcclintock.html Biography and Bibliographic Resources] , from the Office of Scientific and Technical Information, United States Department of Energy
* [http://library.cshl.edu/archives/archives/bmcbio.htm Cold Spring Harbor Laboratory Archives, Barbara McClintock:A Brief Biographical Sketch]
* [http://www.arabidopsis.org/info/springer.jsp Enhancer and Gene Trap Transposon Mutagenesis in Arabidopsis] , comprehensive article on the use of "Ac/Ds" and other transposons for plant mutagenesis
* [http://www.cumc.columbia.edu/horwitz/ The Official Site of Louisa Gross Horwitz Prize]

Persondata
NAME= McClintock, Barbara
ALTERNATIVE NAMES=
SHORT DESCRIPTION= cytogeneticist
DATE OF BIRTH= June 16 1902
PLACE OF BIRTH= Hartford, Connecticut
DATE OF DEATH= September 2 1992
PLACE OF DEATH= Huntington, New York