MCCLINTOCK, BARBARA

(b. Hartford, Connecticut, 16 June 1902; d. Huntington, New York, 2 September 1992),

genetics, maize, cytology, developmental regulation.

In her six-decade career, McClintock had three achievements of the sort that transform a field. First, in the late 1920s and early 1930s, she worked out the cytology of the maize plant, a problem that had stymied geneticists for years. This work made her reputation among geneticists. Second, twenty years later, she discovered transposable elements, genes that change position among the chromosomes. She won a Nobel Prize in the category of Physiology or Medicine for this discovery in 1983. Transposable elements made her world famous, but the way they were interpreted has obscured her third achievement: the development, in the 1960s and 1970s, of a vision, unique in its time, of the genome as dynamic and highly responsive to external stimuli. The reasons that this last achievement might have transformed developmental biology and genomics, but has not, revealed some of the social processes at play in the making of a scientific reputation.

Born in 1902 in Hartford, Connecticut, McClintock soon moved to Flatbush, Brooklyn, where she grew up. Although she was named Eleanor, very early she began to be called Barbara; as a young adult she changed her name legally. Her father, Thomas Henry McClintock, was a physician, respectable and middle class. Her mother, Sara Handy McClintock, descended from a long line of Boston bluebloods who traced their ancestry to the Mayflower. McClintock was a middle child, with two older sisters and one younger brother. Late in life, she recalled that her parents had allowed her the freedom to pursue her interests and did not pressure her to perform in school or to conform socially—she located this as a source of the fierce independence she showed throughout her adult life. She attended Erasmus Hall High School, graduating at age sixteen. Her father supported her intention to attend college and she was accepted to Cornell University in Ithaca, New York, which for its day had an impressive record of admitting women. McClintock entered the agriculture college, which is part of New York’s state university system, in the fall of 1919. All of McClintock’s degrees were from Cornell: a bachelor of science (1923), master of arts (1925), and PhD (1927).

Making Maize Cytogenetics . When McClintock arrived at Cornell, it was becoming a world center for the study of maize genetics. Harvard’s Edward Murray East and Cornell’s Rollins Emerson were the top two maize geneticists in the country. Through the late 1910s and the 1920s, Emerson built Cornell into a center of maize genetics research and a clearinghouse for data, methodological tips, and professional gossip. By the late 1920s, Cornell’s maize program boasted several professors and many brilliant graduate students and postdoctoral fellows, seminars and conferences, ample funding from the U.S. Department of Agriculture (USDA), and a world-class reputation. Maize was clearly the most vigorous, exciting specialty of genetics at Cornell in those years.

One of Emerson’s important early discoveries was a so-called mutable allele, which spontaneously mutated back and forth from the wild type form during the development of the plant. Its effects are evident in the colorful mottled and striped kernels on almost any ear of holiday “Indian corn.” For Emerson, this mutable allele suggested a key to the physiology of the gene. Yet maize geneticists felt hampered by their inability to map genes to specific sites on chromosomes, as the fruit fly geneticists had been doing since the midteens. Maize workers had identified genetic linkage groups—clusters of genes that tend to be inherited together—but had not been able to correlate them to individual chromosomes. At the end of the 1920s, maize genetics stood about where Drosophila genetics had been in the 1910s.

McClintock brought maize into its “classical” phase. While still a graduate student, she became the research assistant to the cytologist Lowell Fitz Randolph. Randolph drew her into his research on maize chromosomes. She quickly developed into a virtuoso of the microscope; she had that sense of the instrument scientists call “feel.” With this virtuosity added to a startling intelligence, candid personal style, and hot temper, McClintock was universally admired but not always liked. Her friends were intensely loyal, but she made enemies easily—particularly with those in positions of authority. A bitter skirmish with Randolph ended their collaboration and she began to work under Lester W. Sharp.

Near the end of her work with Randolph, McClintock had discovered a triploid, a maize plant with a complete third set of chromosomes. In its offspring, she found a plant with a single extra chromosome, a phenomenon known as trisomy. McClintock used it to crack the greatest problem in maize genetics at the time. An extra chromosome alters the normal Mendelian inheritance pattern, giving instead a “trisomic ratio.” By technical innovation and careful observation, McClintock learned to distinguish among the ten maize chromosomes. She could therefore tell which chromosome was tripled in a given plant. If that plant showed a trisomic ratio for a gene in a known linkage group, then she could confidently locate that linkage group to that chromosome. In Science magazine in 1929, she published the first chromosome diagram for maize. By 1932, she had mapped eight of the ten linkage groups to their respective chromosomes, and colleagues had mapped the others.

Assigning linkage groups to chromosomes is based, of course, on the assumption that the genes lie on the chromosomes. An implication of the chromosome theory of heredity is that cytological crossing over, in which two chromosome arms physically cross one another and exchange segments, corresponds to genetic crossing over, in which an allele changes linkage groups. Still, no one had yet confirmed this correlation unequivocally. In 1931, McClintock and graduate student Harriet Creighton did so in “A Correlation of Cytological and Genetical Crossing-Over in Zea mays,” a paper considered a classic of cytogenetic technique and reasoning.

McClintock’s work helped usher in the golden age of maize genetics in the first half of the 1930s. In 1932, Cornell hosted the Sixth International Congress of Genetics. The Emerson and East schools were turning out superb

students who were colonizing other programs, predominantly at big land-grant universities in the midwestern Corn Belt. Knowledge of maize cytogenetics exploded, with large numbers of new genes discovered, characterized, and mapped to the chromosomes. For the international congress, the Cornell maize geneticists planted a living chromosome map: ten rows of corn, one for each chromosome, with a plant for each genetic locus in the correct order down the row. With her brilliant microscopic technique and cleverly designed, meticulously executed experiments, McClintock was one of the brightest lights of this era.

Golden age or no, it was the Great Depression. Jobs were few, jobs for women were fewer still, and jobs for “difficult” women fewest of all. Yet Emerson supported McClintock on his USDA grant after her PhD, and she then received two distinguished fellowships, from the National Research Council (1931–1933) and from the Guggenheim Foundation (1933–1934). The Guggenheim fellowship took her to Berlin, where she intended to work with the fruit fly geneticist Curt Stern. Stern, however, had been working in Thomas Hunt Morgan’s laboratory at the California Institute of Technology. When Adolf Hitler came to power in 1933, Stern, a Jew, wisely decided not to return to Germany. McClintock, however, was urged to go anyway.

In Berlin, she befriended Richard Goldschmidt, another notoriously prickly personality. Goldschmidt introduced her to the group of German geneticists who were exploring the physiology of the gene, cytoplasmic inheritance, and the relation of genes to embryological development. When Berlin, the capital of the Nazi state, grew too depressing for McClintock, he arranged for her to escape to Freiburg, where she worked in the laboratory of Friedrich Oehlkers, another member of the group. As Jan Sapp showed in his Beyond the Gene (1987), a central concern of this school was the “paradox of nuclear equivalence”: if, as everyone assumed, a gene is “on” all the time, and if each cell contains all the genes, how do different cell types arise? How do development and differentiation occur? The Germans’ answer was that some regulatory machinery must lie outside the nucleus, in the cytoplasm. McClintock returned early from Germany, but only after absorbing an interest in gene regulation that remained for the rest of her life.

In 1936, McClintock took her first and only regular university faculty appointment, at the University of Missouri. The head of the botany department was Lewis J. Stadler, a distinguished maize geneticist and longtime McClintock admirer and collaborator. At Missouri, from descendants of Stadler’s x-rayed strains, McClintock developed a strain of corn in which chromosomes would rip themselves apart. The chromosomes break at cell division, the broken ends find one another, and they fuse again. But if broken ends from different chromosomes fuse, they will be pulled apart again at the next division, breaking the chromosomes anew and repeating the cycle. She called this the breakage-fusion-bridge (BFB) cycle and published it in 1938. She quickly turned BFB into a research tool. When the chromosomes break, mutations are often produced. McClintock began to use BFB the way others used x-rays, as a tool for generating mutations. With x-rays, one generated random mutations over all the chromosomes and screened perhaps thousands of plants. But BFB occurs at a predictable site on a given chromosome, thus providing a means of producing directed mutations. This was a boon—especially for McClintock, who preferred to grow small numbers of plants and tend them all herself.

McClintock hated the restrictions and tedium of academic life. She found the students dull, the faculty meetings stultifying, and the bureaucracy and arbitrary rules intolerable. A widespread anecdote has it that she shocked the faculty by climbing in the window of her locked laboratory after hours. True or not, it captures how she bridled at authority. As always, she concentrated her antipathy on the man in charge, in this case Stadler. She became almost paranoid about Stadler’s “machinations”; she became convinced that he was undermining her and was about to fire her. She told the story this way for years, and many accounts relate her version of the story. But in fact, she was offered a promotion with tenure and turned it down. When it became clear to Stadler that McClintock would leave Missouri, he strove to find her a place where she would be happier. He succeeded with Milislav Demerec, a former Emerson student who was in 1940 the interim (soon to be permanent) director of the Carnegie Institution of Washington’s Department of Genetics, at Cold Spring Harbor on New York’s Long Island.

Controlling Elements . McClintock joined the Carnegie staff at Cold Spring Harbor in 1941. The small research laboratory, tucked among the grand estates of Long Island’s Gold Coast, was not well suited to maize genetics. It could not provide the dozens of acres most corn geneticists required. Its annual rhythms—busy summers chocked with meetings and courses and quiet winters with only the small permanent staff to talk to—clashed with the routines of maize genetics. McClintock complained that summer visitors continually tramped through her cornfield, looking to chat, during the busiest time of her year. Yet the resources would suffice. McClintock could grow the one hundred to two hundred plants she needed each season on a sandy acre by the water’s edge. And Cold Spring Harbor, almost uniquely, offered what she needed more than land or privacy: freedom from teaching, administration, and grant writing. She had nothing to do but science. Though clashes with various directors prompted occasional thoughts of leaving, she remained at Cold Spring Harbor for fifty-one years, until her death.

In 1944, she crossed two strains of maize that underwent the BFB cycle. The experiment was designed as a straightforward exercise in gene mapping: she hoped to generate new mutations on chromosome 9 and locate them relative to known genes. But the plants fairly exploded with new mutations, including several new mutable alleles. McClintock saw immediately that she had disrupted something fundamental among the chromosomes. The entire set of chromosomes—what came to be called the genome—had become unstable and was throwing off mutations right and left. One mutable gene in particular caught her attention. At first it appeared to cause chromosome breakage. She called it Ds, for Dissociator. She later regretted the name, because she soon found that Ds did many things besides break chromosomes. A second locus, Activator (Ac), needed to be present in order for Ds to operate. Mapping the new loci proved unusually difficult. Whenever she thought she had one of them isolated to a particular location, it would appear somewhere else in the next generation. In the spring of 1948, she realized that both Ds and Ac were changing positions, physically moving from one site to another. When Ds inserted next to a gene, that gene would be silenced or altered. When Ds jumped away again, the gene would be restored to normal function. Dissociator seemed to create mutable alleles.

The term transposition had existed in the genetics literature for decades. Well-known events such as translocations and shifts resulted in the transposition of a gene from one location to another. McClintock used the word transposition to describe the action of Ds and Ac. Her transposition was novel in that only one gene seemed to be moving at a time; it was physically excising itself from the chromosome and reinserting at another location.

Transposition per se was never what interested McClintock most. It provided her with a mechanism for the genomewide disruption she had witnessed in the 1944 experiment. In a normal plant, she reasoned, the mobile elements must be under some sort of control, which enables them to regulate when genes turn on and off during the development of the plant. This was her answer to the paradox of nuclear equivalence. She imagined a massively coordinated system of thousands of mobile elements, turning genes on and off as the organism developed. Each cell type in the organism would be produced by a characteristic pattern of transpositions. McClintock imagined that in the 1944 experiment, she must have disrupted that control system, liberating masses of rogue mobile elements that transposed out of control and produced the welter of new mutations. By 1950 she was calling her mobile elements “controlling elements.”

The fact of transposition was immediately confirmed and rapidly accepted by the maize community. By the fall of 1950, transposition was confirmed by Robert Nilan and Royal Alexander Brink at the University of Wisconsin. In June 1951, McClintock gave what would become a famous talk on controlling elements at the Cold Spring Harbor Symposium, which Brink attended. In 1953 Peter Peterson, at the University of Iowa, independently isolated another mobile element. Through the 1950s, other researchers requested seeds from McClintock’s controlling-element strains. No one doubted that transposition occurred in maize.

Few, however, accepted McClintock’s interpretation of these findings, their putative role as controllers of development. Brink, for example, preferred to call them transposable elements rather than controlling elements, believing his term less interpretive than hers. The question hinged on whether or not the transpositions were random. McClintock hurt her own case by refusing to publish more than a tiny fraction of her mountains of data; she relied instead on enigmatic talks and elliptical reviews. When, in 1961, François Jacob and Jacques Monod published their operon theory of gene control in bacteria, she followed immediately with review in the American Naturalist of the parallels between bacterial operons and maize-controlling elements. The bacterial operon, she argued, was merely a simpler, cruder mechanism in a simpler, cruder organism.

With the discovery of transposition in bacteria in 1967 and 1968, the accretion of accepted knowledge began to bury McClintock’s theory of genetic control. Meanwhile, the operon model was firmly established as the model of gene regulation. Transposition began to be seen as universal—and as not being a challenge to the operon. With a bacterial model for transposition, molecular studies of the phenomenon took off. Transposition is widespread and complex and has had a large impact on genome structure. Later, molecular studies of transposition led to a new interpretation of mobile elements as genomic parasites, very important in evolution, but not the driving force of development McClintock had believed them to be.

McClintock was recognized as the founder of a new and important field. She began to win science’s big prizes, and in 1983 was awarded an unshared Nobel Prize in Physiology or Medicine. But that prize was bittersweet, because it codified transposition as her major discovery and buried the concept that was most important to her: the genetic control of development.

The Dynamic Genome . McClintock worked little with transposition after 1953. In her controlling element work, she labored to keep the elements stationary, so she could better study their effects. Through the late 1950s and the 1960s, she probed ever-stranger phenomena but resolutely retained a language and methodology of classical genetics that was increasingly unable to cope with her findings. She invented new terminology—such as presetting and erasure—that had no correlates in the rest of the genetics literature. She explored the evolution of domestic corn, devising a novel method of mapping the evolutionary distribution of strains or “races” of maize throughout the Americas.

The last phase of her career was devoted to integrating genetics, development, and evolution into a sweeping vision of organic change on different time scales. That vision was at odds with the prevailing view of the nucleus as a hereditary vault, in which genetic information is stored and protected from the random insults of daily life. In the 1970s, McClintock made a series of brief “natural history” studies of the reprogramming of the developmental-genetic program by tadpoles metamorphosing into frogs, gall wasps on trees, and local plants. How could one set of genes make two such different organisms or tissues? The genes do not change—only the pattern of their activity changes. She understood that both internal and external forces could shape that pattern. In her Nobel Prize speech, she referred to the genome as a “sensitive organ of the cell,” responsive to the environment. In the years since, the vision of the genome as dynamic, not static, has become mainstream. In experimental biology, the field of evolutionary developmental biology (evo-devo) uses molecular tools to answer questions McClintock posed about patterns and timing of gene expression—and looks back to the German physiological geneticists as forerunners. In biomedicine, multi-gene and gene-environment interactions have become an intense field of study. Each of these fields might have acknowledged McClintock as a pioneer, but to date neither one has.

McClintock thus became a victim of her own reputation. In interviews, she told her story as one of scientific neglect and ideas ahead of their time. Because she was famous for transposition, it seemed it must have been transposition that was neglected. As a canonical narrative emerged, her reputation was cemented: she would be remembered as the discoverer of transposition, not of genetic control.

BIBLIOGRAPHY

McClintock’s papers are collected at the American Philosophical Society Library, in Philadelphia. This collection includes several boxes of correspondence, her reprint collection, and a large, challenging, and rewarding set of her laboratory and field notes. The archives at Cold Spring Harbor Laboratory, Cornell University, the Carnegie Institution of Washington, and the Guggenheim Foundation also contain small McClintock collections. In addition, several collections at the Lilly Library of Indiana University, in Bloomington, and the George Beadle collection at the California Institute of Technology Archives in Pasadena contain McClintock-related material.

WORKS BY MCCLINTOCK

“Chromosome Morphology in Zea mays.” Science 69 (1929): 629. The first published ideogram, or chromosome diagram, of maize.

With Harriet Creighton. “A Correlation of Cytological and Genetical Crossing-Over in Zea mays.” Proceedings of the National Academy of Sciences of the United States of America 17 (1931): 492–497. A classic paper correlating genetic and cytological crossing-over.

With Marcus M. Rhoades. “The Cytogenetics of Maize.” Botanical Review 1 (1935): 292–325. An excellent review of maize cytogenetics at the end of the “golden age.”

“Chromosome Organization and Gene Expression.” Cold Spring Harbor Symposia on Quantitative Biology 16 (1951): 13–47. Her most-cited article; the published version of her famous Cold Spring Harbor talk, reportedly but implausibly received with disbelief and jeering.

“Some Parallels between Gene Control Systems in Maize and in Bacteria.” American Naturalist 95 (1961): 265–277.

With T. Angel Kato Y. and Almiro Blumenschein. Chromosome Constitution of Races of Maize: Its Significance in the Interpretation of Relationships between Races and Varieties in the Americas. Chapingo, Mexico: Colegio de Postgraduados, Escuela National de Agricultura, Mexico, 1981. The result of a twenty-five-year effort to understand the evolution of cultivated maize.

“The Significance of Responses of the Genome to Challenge.” Science 226 (1984): 792–801. Her Nobel lecture.

The Discovery and Characterization of Transposable Elements: The Collected Papers of Barbara McClintock. Edited by John A. Moore. New York: Garland, 1987. Collects many, but not all, of McClintock’s papers from the late 1930s to the mid-1960s.

OTHER SOURCES

Barahona, A. “Barbara McClintock and the Transposition Concept.” Archives Internationales d’Histoire des Sciences (Paris) 46, no. 137 (1997): 309–329.

Coe, Edgar, and Lee B. Kass. “Proof of Physical Exchange of Genes on the Chromosomes.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 19 (2005): 6641–6646. An analysis of Creighton and McClintock’s famous article of 1931.

Comfort, Nathaniel C. “Two Genes, No Enzyme: A Second Look at Barbara McClintock and the 1951 Cold Spring Harbor Symposium.” Genetics 140, no. 4 (1995): 1161–1166.

_____. “‘The Real Point Is Control’: The Reception of Barbara McClintock’s Controlling Elements.” Journal of the History of Biology 32 (1999): 133–162.

_____. “From Controlling Elements to Transposons: Barbara McClintock and the Nobel Prize.” Trends in Biochemical Sciences 26, no. 7 (2001): 454–457. How McClintock came to be known for transposition.

_____. The Tangled Field: Barbara McClintock’s Search for the Patterns of Genetic Control. Cambridge, MA: Harvard University Press, 2001.

Kass, Lee B. “Current List of Barbara McClintock’s Publications.” Maize News Letter 73 (1999): 42–48. Also available from http://www.agron.missouri.edu/mnl/73/

_____. “Records and Recollections: A New Look at Barbara McClintock, Nobel Prize–Winning Geneticist.” Genetics 164, no. 4 (2003): 1251–1260.

_____, and Christophe Bonneuil. “Mapping and Seeing: Barbara McClintock and the Linking of Genetics and Cytology in Maize Genetics, 1928–1935.” In Classical Genetic Research and Its Legacy: The Mapping Cultures of Twentieth-Century Genetics, edited by Hans-Jörg Rheinberger and Jean-Paul Gaudillière. London and New York: Routledge, 2004. Covers McClintock’s career prior to controlling elements.

Keller, Evelyn Fox. Reflections on Gender and Science. New Haven, CT: Yale University Press, 1985. Chapter 9, “A World of Difference,” is a philosophical look at McClintock’s role in science.

_____. A Feeling for the Organism: The Life and Work of Barbara McClintock. Tenth Anniversary Edition. New York: W. H. Freeman, 1993.

Nathaniel C. Comfort

McClintock, Barbara

American Botanical Geneticist 1902-1992

Barbara McClintock, a pioneering botanical geneticist, was awarded the Nobel Prize in physiology or medicine in 1983 for her investigations on transposable genetic elements. She was born on June 16, 1902, in Hartford, Connecticut, and with her family soon moved to Brooklyn, New York, where she attended public schools. After graduating high school at age sixteen, McClintock attended the New York State College of Agriculture at Cornell, where she excelled in the field of plant genetics and graduated, in 1923, with a Bachelor of Science (B.S.) in Agriculture, having concentrated in plant breeding and botany.

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.

McClintock, Barbara

(b. 16 June 1902 in Hartford, Connecticut; d. 2 September 1992 in Huntington, New York), geneticist whose groundbreaking work in the field using maize made her the sole winner of the 1983 Nobel Prize in physiology or medicine for the discovery of ’mobile genetic elements.’

McClintock was the third of four children of Thomas Henry McClintock, a physician, and Sara Handy, a home-maker. From McClintock’s earliest years her relationship with her mother was strained, so between the ages of three and six she was sent to live with an aunt and uncle in rural Massachusetts. There she acquired a love of nature that lasted throughout her lifetime. In 1908 McClintock and her family moved to Brooklyn, New York, where her father forbade his children’s teachers to assign them homework. Consequently McClintock was able to pursue many outside interests, including playing the piano and ice-skating.

In 1919 after graduating from Erasmus Hall High School in Brooklyn, New York, McClintock enrolled at Cornell University in Ithaca, New York. She became the president of the freshmen women and also played the tenor banjo in a jazz group until she found that those activities took too much time away from her studies. At that time she also realized that her independent spirit could only be kept alive if it were unfettered by close emotional relationships, and she decided that marriage did not fit into her plans.

McClintock developed a keen interest in cytology while working privately with Professor Lester Sharp (who would later become her thesis advisor) on Saturdays. Her performance was noticed and, as a result, she was invited to take graduate-level genetics courses during her junior year. In 1923 she received a B.S. degree and began graduate school at Cornell. Her major was cytology with minors in genetics and zoology. Although the fruit fly (Drosophila melanogas-ter) was the organism of choice for experiments in many laboratories at that time, corn or maize (Zea mays) was selected at Cornell. While a graduate student, McClintock modified a technique originally developed by John Belling, a botanist at the Florida Agricultural Experiment Station, that permitted her to apply the preparation of slides to detailed chromosomal studies of maize.

After she earned an M.A. degree in 1925 and a Ph.D. in 1927, McClintock was appointed as an instructor in Cornell’s botany department. Remaining in this position until 1931, she was particularly concerned about the relationship between linkage groups and specific chromosomes in corn. At that time McClintock’s mentor Rollins A. Emerson, along with Charles R. Burnham and other young scientists such as Marcus Rhoades, George Beadle, and Harriet Creighton, formed a small but important group of individuals studying the sequence of genes.

In 1931 McClintock and Creighton, who had been McClintock’s student, published a study proving that a correlation existed between genetic and chromosomal cross-over.

This work later became the cornerstone of modern genetic research. From approximately 1931 to 1933 McClintock was a fellow of the National Research Council. For the next year or so after that she was a fellow with the Guggenheim Foundation, which enabled her to go to the Kaiser Wilhelm Institute in Berlin. She soon returned, however, because she was concerned about Adolf Hitler’s rise to power. McClintock’s next position was as a research associate with Cornell from 1934 to 1936. During this time she became interested in the mutagenic effects of X-rays on corn that had been demonstrated by Lewis Stadler at the University of Missouri at Columbia. Stadler sent her some irradiated strains of corn, and McClintock identified ring chromosomes and hypothesized the existence of a tel-omere, a structure at the tip of a chromosome that ensured its stability. As a result of this association, Stadler brought McClintock to the University of Missouri, where she remained from 1936 to 1941 as an assistant professor of botany.

In 1942, under the auspices of the Carnegie Institution of Washington and with an invitation obtained by Rhoades, McClintock became a staff member at Cold Spring Harbor, the institution’s center for genetics research, on the North Shore of Long Island in New York, There she conducted the work that led to her discovery of “jumping genes,” which decades later, in 1983, earned her the prestigious Nobel Prize in physiology or medicine for her pioneering work with “mobile genetic elements.”

In 1967 McClintock became a distinguished service member at Cold Spring Harbor, a position she held until her death in 1992. She also served as a visiting professor at the California Institute of Technology in Pasadena, California, in 1954, as a special consultant to the Agricultural Science Program of the Rockefeller Foundation from 1963 to 1969, and as Andrew D. White Professor-at-Large at Cornell from 1965 to 1974.

McClintock’s life was filled with accolades, including the American Association of University Women Achievement Award in 1947 and honorary degrees from over fifteen colleges and universities. She also received the Kimber Genetics Award presented by the National Academy of Sciences in 1967; the National Medal of Science in 1970; the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research in 1978; the Thomas Hunt Morgan Medal from the Genetics Society of America in 1981; the Wolf Prize in Medicine in 1981; the Albert Lasker Basic Medical Research Award in 1981; the MacArthur Prize in 1981; the Louisa Gross Horwitz Prize for Biology or Biochemistry from Columbia University in 1982; the Charles Leopold Mayer Prize from the Académie des Sciences, Institut de France, in 1982; the Albert A. Michelson Award in 1984; and the National Women’s Hall of Fame Award in 1986.

McClintock was a member of many learned societies as well, including the American Association for the Advancement of Science; the American Academy of Arts and Sciences; the American Philosophical Society; the American Society of Naturalists; the Genetics Society of America (of which she was vice president in 1939 and the first female president in 1945); the National Academy of Sciences; and Sigma Xi. McClintock was chosen as the honorary vice president of the Sixteenth International Congress of Genetics held in Ontario, Canada, in 1988; a foreign member of the Royal Society of London; and an honorary fellow with the Indian Society of Genetics and Plant Breeding among other memberships and honors. On 2 September 1992 McClintock died of natural causes at the age of ninety.

Enthusiastic, intense, dedicated, and shy, McClintock was a very private person in what became her very public world. While not working in the field that won her renown, she enjoyed playing the banjo, studying Eastern religions and forms of meditation, and while she worked in Cold Spring Harbor accompanying the local children home from the school bus speaking to them about nature. Her closest friends believed her mystical insight and “touch of genius, alloyed with sheer grit, determination and tenacity” made her “short in size, but great in stature” in a field that did not gladly receive women.

McClintock’s papers are at the Kroch Library of Cornell University and at the Archives of Cold Spring Harbor Laboratory. She is mentioned in the papers of Lewis John Stadler 1927-1955 (C#2429), Ernest R. Sears 1928–1991 (C#3892), and Lewis E. Atherton 1865–1974 (C#3603, folders 559 and 561), all archived at the University of Missouri at Columbia; and in the University of Missouri at Columbia Citations from 1966 to 1968 (C#2549). Evelyn Fox Keller, A Feeling for the Organism (1983), and Mary Kittredge, Barbara McClintock (1991), focus on all facets of McClintock’s life. Sharon Bertsch McGrayne, ed., Nobel Prize Women in Science (1993); Martha J. Bailey, American Women in Science: A Biographical Dictionary (1994); Emily). McMurray, ed., Notable Twentieth-Century Scientists (1995); and Pamela Proffitt, ed., Notable Women Scientists (1999), contain short biographies. Robert Cooke, “Nobel Winner Remembered,” Newsday (18 Nov. 1992), pays tribute to McClintock. Obituaries are in Newsday (3 Sept. 1992), the New York Times (4 Sept. 1992), and Nature (24 Sept. 1992).

Adriana C. Tomasino

McClintock, Barbara

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.

see also Chromosomal Aberrations; Chromosomal Theory of Inheritance, History; Gene; Maize; Mutation; Transposable Genetic Elements.

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.

Barbara McClintock

Geneticist Barbara McClintock (1902-1992) received the Nobel Prize in Physiology for her discovery that genes could move from place to place on a chromosome.

Barbara McClintock was born in Hartford, Connecticut, on June 16, 1902. She had two older sisters and gained a brother when she was two. Her father, Thomas Henry McClintock, was a physician. Upon the birth of their son, the McClintocks sent Barbara off to live with relatives in the country, where she lived on and off until she was of school age. It was here that she developed the deep love of nature that lasted her lifetime. In 1908, the family moved to the Flatbush section of Brooklyn where her father had taken a job with Standard Oil. McClintock rejoined the family and attended the local school. Her love of nature, however, persisted.

After graduating from Erasmus High School in 1918, she took a job rather than go on to college, in part because of lack of parental support. She did so well at private studies, however, that the following year she was allowed to enter Cornell University as a biology major in the College of Agriculture. During her freshman and sophomore years, she had a normal college life, including dating and playing tenor banjo in a jazz band. She was elected president of the freshman class and was asked to join a sorority. Upon discovering that the sorority would not accept Jews, McClintock refused the invitation. She never hesitated to snub the social conventions of her time. Upon receiving her B.A. in 1923 she pressed on to take her M.A. in 1925 and her Ph.D. in 1927, studying cytology. She was appointed an instructor in Cornell's botany department.

The faculty at Cornell's agricultural school during those years was pioneering the development of hybrid corn, and McClintock soon discovered a way to identify individual chromosomes of maize. Between 1929 and 1931 she published, with others, nine papers describing her work. Then, in August 1931, the National Academy of Sciences published a paper on the subject, done jointly with Harriet Creighton, which has been described as "the cornerstone of experimental genetics."

Despite the world wide recognition for her work and temporary teaching positions as well as grants from such major foundations as the Guggenheim Fellowship and the Rockefeller Foundation, Cornell University refused her a tenured faculty position. She accepted one from 1939 to 1941 at the University of Missouri but it turned out badly. It was clear that while she might have gotten a regular appointment at a women's college, other doors were closed to her because of her gender. In 1941 her friend fellow geneticist Marcus Rhoades obtained an invitation for her to spend the summer at the Cold Spring Harbor Laboratory, run by the Carnegie Foundation of Washington on Long Island. The laboratory was a self contained facility that had its own summer houses for researchers. She was offered a one-year position December 1, 1941 and she remained there for the rest of her career well into the mid-1980s. During her first decade at the laboratory she won many honors, including presidency of the Genetics Society of America and election to the National Academy of Sciences, only the third woman to be admitted to that body.

It was during the decade of the 1940s that she began the work which was later to result in the Nobel Prize. Essentially, it was her discovery that genes "jumped" from place to place in a chromosome, what she called transposable genetic elements. Since accepted opinion had it that genes were static, rather like beads on a string, her theory was generally received with either hostility or a lack of understanding. Soon after she presented these findings at a symposium in 1951, she stopped publishing her work, so disappointed was she at its reception. Furthermore, the discovery of the double helix structure of DNA in 1953 turned many geneticists away from the "old-fashioned" technique of McClintock (careful experiment, observation, and recording) to the more mechanistic models of James Watson, Francis Crick, and their associates. Partly because of her solitary nature, but also partly because she wanted to stay in close touch with her experiments, McClintock chose to work alone rather than as part of a large research team. As a result, she was in physical and intellectual control of all aspects of her work. As one colleague put it, "she has a feeling for the organism."

The rediscovery of McClintock's work began in the mid-1960s with the study of aspects of bacteria and became unavoidable in the 1980s with the growth of genetic engineering. In 1981 she was awarded the prestigious Wolfe Prize in Medicine for her work, as well as the Lasker Award. The MacArthur Foundation appointed her its first Prize Fellow Laureate; then in 1983 she received the Nobel Prize for Physiology or Medicine.

A deeply private person, McClintock continued to pursue her work alone and with the same holistic perspective she used throughout her career. Although the basics of her experimental work were not only accepted but honored, some of her larger hypotheses were yet to find an audience.

McClintock spent the remainder of her life studying transposition at Cold Spring Harbor. She died on September 2, 1992 shortly after her friends had celebrated her ninetieth birthday. In her obituary, Gerald R. Finks notes that her "burning curiosity, enthusiasm and uncompromising honesty serve as a constant reminder of what drew us all to science in the first place." In 1996 Cold Spring Harbor's DNA Learning Center held an exhibit in her honor featuring a replica of her original 1942 laboratory.

Further Reading

A good short sketch of McClintock's life and work may be found in Science, 222 (October 28, 1983). A full-length biography is Evelyn Fox Keller, A Feeling for the Organism: The Life and Work of Barbara McClintock (1983). Also see Long Island Business News, October 21, 1996. □