McClintock, Barbara

Career at Cornell

Awarded Cornell's graduate scholarship in botany for 1923-24, which supported her during the first year of her graduate studies, McClintock concentrated on cytology, genetics, and zoology. She received her master's degree (A.M.) in 1925 and a doctoral degree (Ph.D.) in 1927. Her master's thesis was a literature review of cytological investigations in cereals, with particular attention paid to wheat. In the summer of 1925, as a research assistant in botany, she discovered a corn plant that had three complete sets of chromosomes (a triploid). Then she independently applied a new technique for studying the chromosomes in the pollen of this plant and published these findings the following year. McClintock investigated the cytology and genetics of this unusual triploid plant for her dissertation.

Upon completing her doctorate in June 1927, McClintock became an instructor at Cornell and continued to pursue her studies on the triploid corn plant and its offspring. When triploid plants are crossed to plants with two normal sets of chromosomes, called diploids, they can produce offspring known as trisomics. Trisomics have a diploid set of chromosomes plus one extra chromosome. Plants with extra chromomes could be used for correlating genes with their chromosomes if one could distinguish the extra chromosome in the microscope. McClintock's continued investigations on the chromosomes of corn led her to devise a technique for distinguishing the plants' ten individual chromosomes.

In 1929, in the journal Science, McClintock published the first description of the chromosomes in corn. She knew that having the ability to recognize each chromosome individually would now permit researchers to identify genes with their chromosomes. Using a technique of observing genetic ratios in her trisomic plants and comparing the ratios with plants having extra chromosomes, McClintock cooperated with and guided graduate students to determine the location of many genes grouped together (linkage groups) on six of the ten chromosomes in corn.

Around the same time McClintock devised a way to cytologically observe pieces of one chromosome attached to another chromosome. These translocation or interchange chromosomes stained darkly in the microscope and could be easily observed during cell division (meiosis) to produce pollen grains. The interchange chromosomes were then used to locate the remaining four linkage groups with their chromosomes. They were also used to explain how some corn plants become sterile. In 1931 McClintock guided graduate student Harriet Creighton in demonstrating cytological "crossing over," in which chromosomes break and recombine to create genetic changes. It was the first cytological proof that demonstrated the genetic theory that linked genes on paired chromosomes (homologues) did exchange places from one paired chromosome to another. It confirmed the chromosomal theory of inheritance for which Thomas Hunt Morgan would be awarded a Nobel prize in 1933.

McClintock hoped for a research appointment commensurate with her qualifications. By 1931, however, the country was suffering from the Great Depression and research jobs at universities were not abundant, particularly for women. However, because of McClintock's excellent work and reputation, in 1931 she was awarded a National Research Council (NRC) fellowship to perform research with two leading corn geneticists, Ernest Gustof Anderson at the California Insititute of Technology (Caltech) and Lewis Stadler of the University of Missouri. Stadler, who was studying the physical changes (mutations) in plants caused by X rays, invited McClintock to study the chromosomes of his irridiated plants. She discovered that observable changes in the plant were due to missing pieces of chromosomes in the cell. At Caltech she employed interchange chromosomes to investigate the nucleolar organizer region in cells.

After a short period in Germany in 1933 studying on a Guggenheim fellowship, McClintock returned to Cornell, where she continued her research of the cytology of X-rayed plants that she had first examined at Missouri. This research led her to clarify and explain how some chromosomes became ring shaped, were lost during cell replication, or resulted in physical differences in plant tissues. These investigations led to her studies of the breakage-fusion-bridge cycle in corn chromosomes and would eventually lead, in 1950, to her revolutionary proposal that genes on chromosomes moved (transposed) from one place to another on the same chromosome and that they could also move to different chromosomes.

Career at Cold Spring Harbor

In 1936 McClintock, at Stadler's urging, accepted a genetics research and teaching position at the University of Missouri, which she held for five years, until she seized an opportunity to be a visiting professor at Columbia University and a visiting investigator in the genetics department of the Carnegie Institution of Washington (CIW), working at Cold Spring Harbor on Long Island in New York. She was offered a permanent job at Cold Spring Harbor in 1943 and spent the rest of her life working there with brief visiting professor appointments at Stanford University, Caltech, and Cornell.

In the winter of 1944 McClintock was invited by a former Cornell colleague, George Beadle, to go to Stanford to study the chromosomes of the pink bread mold Neurospora. Within ten weeks she was able to describe the fungal chromosomes and demonstrate their movement during cell division. This work was important to an understanding of the life history of the organism, and the fungus would be employed by Beadle and his colleagues to illucidate how genes control cell metablolism. In 1958 Beadle shared a Nobel Prize for that work.

Returning to Cold Spring Harbor in 1945, McClintock traced genes through the changes in colored kernels of corn. In that same year she was elected president of the Genetics Society of America. Over the next few years, using genetic and cytological experiments in the corn plant (Zea mays), she concluded that genetic elements (transposable elements, or transposons) can move from place to place in the genome and may control expression of other genes (hence called controlling elements). She published her findings in the 1950s, and more than thirty years later, in 1983, she was honored with the Nobel Prize for her remarkable discovery.

Many have wondered why it took so long for McClintock's work in transposition to be recognized by the leaders in the scientific community. One reason could be that although she studied corn chromosomes employing cytogenetic techniques, other researchers studied simpler organisms (bacteria and their viruses) and used molecular techniques. McClintock's experiments were complex and laborious, taking months or even years to yield results. Molecular studies in simpler organisms gave almost immediate answers, thus providing their researchers with instant celebrity. Additionally, McClintock's findings contradicted the prevailing view that all genes were permanently in a linear sequence on chromosomes.

Further, although McClintock's conclusion that genes could move from place to place in the corn genome was accepted, the idea was considered peculiar to corn, probably not universally relevant to all organisms. It was not until the 1970s when transposons were found in a number of other organisms, first in bacteria and then in most organisms studied by geneticists, that the value of McClintock's initial studies realized. Research on transposable elements, or transposons, led to the revolution in modern recombinant deoxyribonucleic acid (DNA) technology that has played a significant role in medicine and agriculture. When McClintock's work was rediscovered, she was recognized and rewarded with the Nobel Prize for her great insights. McClintock died on September 2, 1992, in Huntington on Long Island, New York.

SEE ALSO CHROMOSOMES; GENETIC MECHANISMS AND DEVELOPMENT; POLYPLOIDY.

Lee B. Kass

Bibliography

Creighton, Harriet B., and Barbara McClintock. "A Correlation of Cytological and Genetical Crossing-over in Zea mays." Proceedings of the National Academy of Sciences 17 (1931): 492-97.

Dunn, L. C. A Short History of Genetics: The Development of Some of the Main Lines of Thought, 1864-1939. New York: McGraw-Hill, 1965.

Fedoroff, N. V. "Barbara McClintock (1902-1992)." Genetics 136 (1994): 1-10.

Keller, Evelyn Fox. A Feeling for the Organism: The Life and Work of Barbara McClintock. San Francisco: W. H. Freeman and Co., 1983.

McClintock, Barbara. The Discovery and Characterization of Transposable Elements: The Collected Papers of Barbara McClintock, ed. John A. Moore. New York: Garland Publishing, 1987.