B McClintock research overview

BARBARA McCLINTOCK:Research Overview
Cold Spring Harbor Laboratory Archives

Even before her discovery of transposable elements in maize, Barbara McClintock was among the world's most respected cytogeneticists. She trained at Cornell with Rollins Emerson, one of the two foremost maize geneticists in the country (the other being Louis Stadler). Her colleagues at Cornell under Emerson included George Beadle and Marcus Rhoades. She may also have met Milislav Demerec, who received his Ph.D. under Emerson in 1923. Shortly after receiving her doctorate, McClintock began work with Harriet Creighton. Together they demonstrated that genetic crossing over was accompanied by physical crossing over of the chromosomes (the formation of chiasmata was made by Janssens in 1909). With this, McClintock and Creighton beat by a matter of weeks the German Drosophila geneticist Curt Stern, who made a similar finding in flies independently.

McClintock grew interested in the responses of the genome to traumatic events. She formed an association with Lewis Stadler at the University of Missouri. Stadler had shown the mutagenic effects of X rays on corn (at about the same time as Hermann Muller did with fruit flies) and sent McClintock irradiated strains of maize. With these, McClintock identified ring chromosomes, which she soon realized were a special case of chromosomes broken by radiation; the broken ends sometimes fused to one another and formed a ring. This led McClintock to hypothesize the existence of a special structure at the chromosome tip, which she called the telomere, that would maintain chromosome stability.

Stadler brought McClintock to the University of Missouri in 1936, where she continued work on broken chromosomes. There she described the breakage-fusion-bridge (bfb) cycle, a repeating pattern of chromosome behavior that was sometimes triggered by an initial breakage. In the bfb cycle, broken chromosomes might fuse to the other member of the pair, forming a bridge that was then ripped apart at meiosis (or, in another form of the bfb cycle, at mitosis), thus beginning the cycle again. For a variety of reasons, not least being McClintock's rivalry with Missouri geneticist Mary Guthrie, a tenured position was not forthcoming at Missouri. McClintock spent the summer of 1941 at Cold Spring Harbor as the guest of summer investigator Marcus Rhoades. McClintock never left. Demerec, by now director of the CIW Department of Genetics, arranged a temporary, and then a full-time appointment for her.

At Cold Spring Harbor, McClintock discovered in some of her bfb strains some bizarre genetic behavior. Certain mutable genes appeared to be transferred from cell to cell during development of the corn kernel. As she later said, "one cell gained what the other cell lost." Though her initial discovery was made in 1944, McClintock confirmed, controlled, and extended her observations for six years, publishing at last in 1950.

Her first public presentation of transposable elements was at the 1951 Cold Spring Harbor Symposium. McClintock expected recognition and acceptance, but instead was greeted with silence and derision. Almost certainly, much of this response resulted from the mutual admiration of McClintock and Richard Goldschmidt. The cantankerous Goldschmidt was a gadfly of genetics, known for denying the status quo. Since 1938 he had been arguing against the standard theory of the gene, promoting instead a holistic, chromosomal theory in which a gene's position relative to other genes determined its function. Goldschmidt fought one of the main advocates of the gene theory, George Beadle. He saw in McClintock's data new support for his theory; in return, McClintock saw that Goldschmidt's concept of the chromosome as the basic unit of heredity was more consonant with her transposable "controlling elements" than was the standard Beadle and Tatum model of the gene. With McClintock making her allegiance to Goldschmidt so plain, it is little wonder many scientists denied or ignored her! In reality, scientists had immense respect for McClintock's data; it was her conclusions they doubted.

The development of molecular techniques that allowed isolation of transposable elements, as well as their discovery in other organisms, including fruit flies and yeast, led to the eventual acceptance of transposable elements as a general and important phenomenon. Today, they are known to be widespread, occurring even in humans. Beginning in the late 1950s, McClintock spent many seasons in South America and Mexico, studying the "evolution" of agricultural maize by Indians. This represented an early and exhaustive example of ethnobotany, and was work McClintock was quite proud of, though less known for.

For more specific information on the availability of materials or to arrange an appointment to use the Archives please contact (516)367-8414 or archives@cshl.edu.

References

Nathaniel C. Comfort, "Two genes, no enzyme: a second look at Barbara McClintock and the 1951 Cold Spring Harbor Symposium. Genetics 140: 1161-1166 (1995).

Evelyn Fox Keller, A Feeling for the Organism, New York, WH Freeman 1983.

David Botstein and Nina Fedoroff, eds., The Dynamic Genome, Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 1993

written by Nathan Comfort