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Barbara McClintock

age chromosome genetic genetic gene transposition genes

Geneticist 1902-1992

Barbara McClintock was one of the most important geneticists of the twentieth century and among the most controversial women in the history of science. She made several fundamental contributions to our understanding of chromosome structure, put forward a bold and incorrect theory of gene regulation, and, late in her career, developed a profound understanding of the interactions among genes, organisms, and environments. She was born on June 16, 1902, in Hartford, Connecticut, the third of four children and the youngest daughter. She grew up in Brooklyn, New York, and in 1919 she enrolled in the agricultural college of Cornell University, where she received all her post-secondary education. She took a bachelor's degree in 1923, a master's in 1925, and a Ph.D., under the direction of the cytologist Lester Sharp, in 1927.

McClintock gravitated toward the cytology and genetics of maize, or Indian corn, and by 1929 she was a rising star in her field. Not quite single-handedly, she made possible the "golden age of maize genetics," from 1929 to 1935. During those years, McClintock published a string of superb papers identifying novel cytological phenomena and linking them to genetic events. Working with Harriet Creighton, she confirmed that chromosomes physically exchange pieces during the genetic phenomenon known as "crossing over." She was supported by a series of prestigious fellowships, from the National Research Council, the Guggenheim Foundation, and others, that took her from Cornell to the California Institute of Technology, and to Berlin and back. In 1935 she took a faculty position at the University of Missouri in Columbia. She was not happy there, however, and resigned in 1939, despite the apparent imminence of a promotion with tenure.

In 1941 she took a summer position at Cold Spring Harbor on New York's Long Island, at the Carnegie Institution of Washington's Department of Genetics. It was an ideal position for her, with no teaching or administrative duties. Within a year the post became permanent, and she remained there until her death. On arrival, she continued work that she had begun while at Missouri, investigating a phenomenon called the breakage-fusion-bridge (BFB) cycle. This is a repeating pattern of chromosome breakage she had discovered among strains of maize plants grown from X-rayed pollen. In 1944, during an experiment designed to use the BFB cycle to create new mutations, she discovered numerous "mutable" genes: genes that turned on and off spontaneously during development. In the cells of some of these new mutants lay her most important discovery, chromosome segments that move from place to place on the chromosome. That same year, the National Academy of Sciences honored a woman for only the third time in its eighty-year history when it elected McClintock a member.

During the rest of the 1940s McClintock developed a novel theory of how genes could control the development and differentiation of organisms.

The key to the theory was a new type of genetic element, not a gene but a gene-controller, that first appeared in her 1944 BFB experiment. These "controlling elements," she argued, inhibited or modulated the effects of the genes near them. She proposed that through coordinated movement from gene to gene (transposition) controlling elements executed the genetic program of development, much as the hammers on a player piano execute the program encoded on a piano roll.

Transposition in maize was confirmed immediately and repeatedly by other researchers. Few scientists, however, could accept her notion that the movements were coordinated. After about 1954, McClintock did little more with transposition, but she continued to work on genetic control for the rest of her long career. Her systems grew increasingly complex, and her thinking led her to comparisons between embryology and evolution.

During the 1970s transposition was discovered in bacteria, and its biochemistry was explained in terms of DNA sequences and enzymatic action. Soon transposition was found to be nearly universal in the living world and was linked to medical fields such as cancer, virology, and immunology. McClintock experienced a rare scientific renaissance. Her theories of genetic control, never widely accepted and by this time rejected outright, were forgotten, and she was reborn as the discoverer of transposition. She won, unshared, the 1983 Nobel Prize in physiology or medicine "for her discovery of transposable genetic elements."

Since then, the experiments of other researchers have provided at least qualified support for even some of her wilder ideas, such as her conception of the genome as a "sensitive organ of the cell"; and the idea that any organism has the genetic instructions to make any other. Some of these findings had appeared by the time she died, on September 2, 1992, but it has been the various genome projects, human and otherwise, that have lent the strongest support to McClintock's dynamic, interactive vision of nature. Had she lived to be one hundred, she might well have been considered for a second Nobel, this time for her insights into the workings of the genome.

Nathaniel Comfort

Bibliography

Comfort, Nathaniel C. The Tangled Field: Barbara McClintock's Search for the Patterns of Genetic Control. Cambridge, MA: Harvard University Press, 2001.

———. "Two Genes, No Enzyme: A Second Look at Barbara McClintock and the 1951 Cold Spring Harbor Symposium." Genetics 140, no. 4 (1995): 1161-1166.

Keller, Evelyn Fox. A Feeling for the Organism: The Life and Work of Barbara McClintock, 10th Anniversary Edition. New York: W. H. Freeman, 1993.

McClintock, Barbara. The Discovery and Characterization of Transposable Elements: The Collected Papers of Barbara McClintock. New York: Garland, 1987.

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