The fruit fly Drosophila melanogaster has the longest history of any model organism and has been

widely used to study genetics and developmental biology. The fruit fly (Drosophila melanogaster) is a small insect that feeds and breeds on spoiled fruit. It has been used as a model organism for over 100 years and thousands of scientists around the world work on it. Part of the reason for this is historical. Scientists today choose to study the fruit fly because so many others have done so before them. There are established methods for handling flies in the laboratory and an immense volume of data has accumulated about fly biology. But why was the fruit fly chosen in the first place? As with most of the long-established model organisms, the initial choice was for practical reasons. The fruit fly is small and has a simple diet. Therefore, large numbers of flies can be maintained inexpensively in the laboratory. The life cycle is also very short, taking about two weeks, so large-scale crosses can be set up and followed through several generations in a matter of months. Fruit flies also have large polytene chromosomes, whose barcode patterns of light and dark bands allow genes to be mapped accurately. Due to these advantages, fruit flies were extensively used in the early 20th century to work out the principles of genetics. Indeed, they are still used in this capacity to teach genetics in schools. Mutants are available for a large number of genes and new mutations can be induced very easily by exposing flies to radiation or adding mutagenic chemicals to their food. This ability to recover mutants means that flies can be used to investigate the genetic basis of any conceivable biological process. The fruit fly (Drosophila melanogaster) has been used as a model organism for nearly a century. The relevance of the fruit fly to the human genome project reflects the remarkable conservation among genes in different animals. The fly genome, which was sequenced in the year 2001, is 165 million base pairs in length (spread over four chromosomes) and contains approximately 14 000 genes. The human genome contains 3-4 times as many genes but most of these are thought to have arisen by two rounds of genome doubling during the evolution of vertebrates. Therefore, humans have more genes than flies but about the same number of gene families. Since it is easy to create mutants and carry out experiments on fruit flies, the functions of many fly genes have been established. The relationship between fly and human genes is so close that the sequences of newly discovered human genes, including disease genes, can often be matched against their fly counterparts. This provides a lead towards the function of the human gene and could help in the development of effective drugs. The analysis of fly embryonic development has made a particularly important contribution to the understanding of developmental processes in humans. The genetic basis of many human birth defects is now known thanks to experiments on developmental mutants in the fly. In acknowledgement of this, Ed Lewis, Christiane Nusslein-Volhard and Eric Wieschaus, who led early work on Drosophila developmental genetics, were awarded the Nobel Prize in Physiology or Medicine in 1995.

Morgan was a many-sided character who was, as a student, critical and independent. His early published work showed him to be critical of Mendelian conceptions of heredity, and in 1905 he challenged the assumption then current that the germ cells are pure and uncrossed and, like Bateson was sceptical of the view that species arise by natural selection. «Nature», he said, «makes new species outright.» In 1909 he began the work on the fruitfly Drosophila melanogaster with which his name will always be associated. It appears that Drosophila was first bred in quantity by C. W. Woodworth, who was working from 19001901, at Harvard University, and Woodworth there suggested to W. E. Castle that Drosophila might be used for genetical work. Castle and his associates used it for their work on the effects of inbreeding, and through them F. E. Lutz became interested in it and the latter introduced it to Morgan, who was looking for less expensive material that could be bred in the very limited space at his command. Shortly after he commenced work with this new material (1909), a number of striking mutants turned up. His subsequent studies on this phenomenon ultimately enabled him to determine the precise behaviour and exact localization of genes. The importance of Morgan's earlier work with Drosophila was that it demonstrated that the associations known as coupling and repulsion, discovered by English workers in 1909 and 1910 using the Sweet Pea, are in reality the obverse and reverse of the same phenomenon, which was later called linkage. Morgan's first papers dealt with the demonstration of sex linkage of the gene for white eyes in the fly, the male fly being heterogametic. His work also showed that very large progenies of Drosophila could be bred. The flies were, in fact, bred by the million, and all the material thus obtained was carefully analysed. His work also demonstrated the important fact that spontaneous mutations frequently appeared in the cultures of the flies. On the basis of the analysis of the large body of facts thus obtained, Morgan put forward a theory of the linear arrangement of the genes in the chromosomes, expanding this theory in his book, Mechanism of Mendelian Heredity (1915).

Morgan apparently began breeding Drosophila in 1908. In 1909 he observed a small but discrete variation known as white-eye in a single male fly in one of his culture bottles. Aroused by curiosity, he bred the fly with normal (red-eyed) females. All of the offspring (F1) were red-eyed. Brother–sister matings among the F1 generation produced a second generation (F2) with some white-eyed flies, all of which were males. To explain this curious phenomenon, Morgan developed the hypothesis of sex-limited—today called sexlinked—characters, which he postulated were part of the X-chromosome of females. Other genetic variations arose in Morgan’s stock, many of which were also found to be sex-linked. Because all the sex-linked characters were usually inherited together, Morgan became convinced that the X-chromosome carried a number of discrete hereditary units, or factors. He adopted the term gene, which was introduced by the Danish botanist Wilhelm Johannsen in 1909, and concluded that genes were possibly arranged in a linear fashion on chromosomes. Much to his credit, Morgan rejected his skepticism about both the Mendelian and chromosome theories when he saw from two independent lines of evidence—breeding experiments and cytology—that one could be treated in terms of the other. In collaboration with A.H. Sturtevant, C.B. Bridges, and H.J. Muller, who were graduates at Columbia, Morgan quickly developed the Drosophila work into a large-scale theory of heredity. Particularly important in this work was the demonstration that each Mendelian gene could be assigned a specific position along a linear chromosome “map.” Further cytological work showed that these map positions could be identified with precise chromosome regions, thus providing definitive proof that Mendel’s factors had a physical basis in chromosome structure. A summary and presentation of the early phases of this

work was published by Morgan, Sturtevant, Bridges, and Muller in 1915 as the influential book The Mechanism of Mendelian Heredity. To varying degrees Morgan also accepted the Darwinian theory by 1916. In 1928 Morgan was invited to organize the division of biology of the California Institute of Technology. He was also instrumental in establishing the Marine Laboratory on Corona del Mar as an integral part of Caltech’s biology training program. In subsequent years, Morgan and his coworkers, including a number of postdoctoral and graduate students, continued to elaborate on the many features of the chromosome theory of heredity. Toward the end of his stay at Columbia and more so after moving to California, Morgan himself slipped away from the technical Drosophila work and began to return to his earlier interest in experimental embryology. Although aware of the theoretical links between genetics and development, he found it difficult at that time to draw the connection explicitly and to support it with experimental evidence. In 1924 Morgan received the Darwin Medal; in 1933 he was awarded the Nobel Prize for his discovery of “hereditary transmission mechanisms in Drosophila”; and in 1939 he was awarded the Copley Medal by the Royal Society of London, of which he was a foreign member. In 1927–31 he served as president of the National Academy of Sciences; in 1930 of the American Association for the Advancement of Science; and in 1932 of the Sixth International Congress of Genetics. He remained on the faculty at Caltech until his death.

Morgan apparently began breeding Drosophila in 1908. In 1909 he observed a small but discrete variation known as white-eye in a single male fly in one of his culture bottles. Aroused by curiosity, he bred the fly with normal (red-eyed) females. All of the offspring (F1) were red-eyed. Brother–sister matings among the F1 generation produced a second generation (F2) with some white-eyed flies, all of which were males. To explain this curious phenomenon, Morgan developed the hypothesis of sex-limited—today called sexlinked—characters, which he postulated were part of the X-chromosome of females. Other genetic variations arose in Morgan’s stock, many of which were also found to be sex-linked. Because all the sex-linked characters were usually inherited together, Morgan became convinced that the X-chromosome carried a number of discrete hereditary units, or factors. He adopted the term gene, which was introduced by the Danish botanist Wilhelm Johannsen in 1909, and concluded that genes were possibly arranged in a linear fashion on chromosomes. Much to his credit, Morgan rejected his skepticism about both the Mendelian and chromosome theories when he saw from two independent lines of evidence—breeding experiments and cytology—that one could be treated in terms of the other. In collaboration with A.H. Sturtevant, C.B. Bridges, and H.J. Muller, who were graduates at Columbia, Morgan quickly developed the Drosophila work into a large-scale theory of heredity. Particularly important in this work was the demonstration that each Mendelian gene could be assigned a specific position along a linear chromosome “map.” Further cytological work showed that these map positions could be identified with precise chromosome regions, thus providing definitive proof that Mendel’s factors had a physical basis in chromosome structure. A summary and presentation of the early phases of this work was published by Morgan, Sturtevant, Bridges, and Muller in 1915 as the influential

book The Mechanism of Mendelian Heredity. To varying degrees Morgan also accepted the Darwinian theory by 1916.

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