Barbara McClintock was a pioneering American geneticist whose discovery of transposable or jumping genes in the 1940s baffled most of her contemporaries for nearly three decades. McClintock spent nearly fifty years working apart from the mainstream of the scientific community. Yet her colleagues had such a high regard for her as an adherent to rigid scientific principles that they accepted her discovery of transposable genes decades before others could confirm her observations. McClintock was eventually awarded the Nobel Prize in medicine or physiology in 1983 for this prescient discovery.
McClintock was born on June 16, 1902, in Hartford, Connecticut. After graduating from Erasmus High School in Brooklyn, McClintock enrolled at Cornell University in 1919. McClintock became interested in the study of the cells, known as cytology, under the tutelage of Lester Sharp, a professor who gave her private lessons on Saturdays. She was invited to take graduate-level genetics courses while still in her junior year. She received her B.S. in 1923 and entered graduate school, where she majored in cytology and minored in genetics and zoology. At that time, geneticists favored studies of the fruit fly Drosophila that produces a new offspring every ten days. This rapid production of successive generations offered geneticists the opportunity to see quickly the results of genetic traits passed on through crossbreeding. It was studies of Drosophila that produced much of the early evidence of the relationship between genes and chromosomes. Chromosomes are strands of DNA (deoxyribonucleic acid) that contain the genes that pass hereditary traits from one generation to the next. At Cornell, the main focus of genetic research was corn, or maize, whose varicolored kernels, relatively long life spans, and larger chromosomes (which could be more easily viewed under the microscope) offered geneticists the opportunity to identify specific genetic processes.
While still in graduate school, McClintock had refined and simplified a technique originally developed by John Belling to prepare slides for the study of chromosome structures under a microscope. McClintock made modifications to this technique that enabled her to apply it to detailed chromosomal studies of maize. She obtained her M.A. degree in 1925 and her Ph.D. two years later and then was appointed an instructor in Cornell's botany department. McClintock's research at that time focused on linkage groups, the inherited sets or groups of genes that appear on a chromosome. Geneticists had already discovered these linkage groups in Drosophila and McClintock set out to relate specific linkage groups to specific chromosomes in maize.
In 1931, McClintock and Harriet Creighton published a landmark study proving a theory geneticists had previously believed without proof: that a correlation existed between genetic and chromosomal crossover. Their study revealed that genetic information was exchanged during the early stages of meiosis, the process of cell division. They found that this exchange occurred when parts of homologous chromosomes (chromosomes on which particular genes are identically located) were exchanged in the same division that produced sex cells. This groundbreaking work and McClintock's successive studies further establishing this relationship eventually led to her election to the National Academy of Sciences in 1944 and presidency of the Genetics Society of America in 1945.
In 1936, she received an appointment to the University of Missouri as an assistant professor of botany, her first faculty appointment. During this time, she performed further experiments delineating the cellular processes of chromosomal interactions and their effects on large-scale mutations. Although this appointment provided a base for McClintock to continue her work, the university decided that after five years McClintock did not fit into its future plans.
In the summer before the bombing of Pearl Harbor in December 1941, Marcus Rhoades obtained an invitation for his out-of-work friend and colleague to spend the summer at the Cold Springs Harbor Laboratory in New York. Run by the Carnegie Institute of Washington, the laboratory was a self-contained facility that had its own summerhouses for researchers. On the first of December 1941, McClintock was offered a one-year position at Cold Springs, where she would spend the remainder of her career. By the summer of 1944, McClintock had initiated the studies that would lead to her discovery of genetic transposition. She had noticed different colored spots that did not belong on the green or yellow leaves of a particular plant. She surmised that the larger the discoloration patch, the earlier the mutation had occurred, believing that many large patches on the leaves meant the mutation had occurred early in the plant's development. From this observation, McClintock determined that mutations occurred at a constant rate that did not change within a plant's life cycle, which led her to the concept of regulation and control in the passing on of genetic information. Investigating how this passing on of genetic information could be regulated, McClintock next noticed that in addition to these regular mutations there also occurred exceptions, in which there were different types of mutations not normally associated with the plant. Convinced that something must occur at the early stages of meiosis to cause these irregular mutations, McClintock worked with maize to identify what it might be.
McClintock discovered kernels on a self-pollinated ear of corn that had distinctive pigmentation but should have been clear, suggesting a loss of some genetic information that normally would have been passed on to inhibit color. Finally, after two years, she found what she called a controlled breakage in the chromosome and in 1948, she coined the term transposition to describe how an element is released from its original position on the chromosome and inserted into a new position. As a result of this jumping gene, plant offspring could have an unexpected pattern of heredity due to a specific genetic code that other offspring did not have. In fact, two transposable genes were involved in the process: one, which she called a dissociator gene, allowed the release of the activator gene that could then be transposed to a different site.
In 1950, McClintock published her research on transposition, but her work was not well received. Her discovery went against the genetic theory then current that genes were stable components of chromosomes. It wasn't until the 1970s, after technology had been developed that enabled geneticists to study genes on the molecular, rather than cellular, level--that McClintock's ideas were truly understood by the scientific community. Her discovery presaged many later discoveries, such as genetic imprinting or the presetting of genetic activity. Her work also would eventually be used to explain inheritance patterns that seemed to lie outside the strict Mendelian law based on simple ratios of dominant and recessive genes. In 1983, McClintock was awarded the Nobel Prize for physiology or medicine for her discovery of mobile genetic systems.
McClintock spent the remainder of her life at Cold Spring Harbor, studying transposition. She was acknowledged as a true pioneer in every sense of the word, and many of her fellow scientists believe that her accomplishments came from an intense desire for knowledge and the commitment to keep working on a problem.
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