fruit flies were used as experimental material by morgan as

The Context of Morgan's Discovery

Morgan's conclusion—that the white-eye trait followed patterns of sex chromosome inheritance—was at once very specific and very grand. A few years prior to these test crosses, Mendelian ideas of inheritance had been enthusiastically discussed by many researchers in the context of new findings about chromosomes. Indeed, after observing meiotic reductive divisions and correlating them to chromosome counts in male and female offspring, cytologists Walter Sutton, Nettie Stevens, and E. B. Wilson had all promoted the idea that sex was determined via chromosome-based inheritance . Morgan, however, had long resisted the idea that genes resided on chromosomes, because he did not approve of scientific data acquired by passive observation. Furthermore, Morgan was not convinced that traits couldn't morph into new forms in an organism based on the blending of parental contributions, an idea leftover from pre-Mendelian scientists. Morgan was sure that Wilson and the other researchers who promoted the chromosome theory of inheritance were looking for an easy answer as to how independent assortment occurred in gamete formation, because he believed they ignored counterevidence in the face of excited conviction. In fact, he thought that the concept of genes was at best an invention intended to link the mysterious paths of chromosomes and discontinuous inheritance patterns. Morgan formalized his derision in a well-known publication (Morgan, 1909), wherein he called for a more experimental approach to the understanding of inherited factors and insisted that germ plasm should not be cast aside as a putative carrier of inherited traits.

Interestingly, within a year of this public criticism of chromosome theory, Morgan set out to test the idea of inherited chromosomal factors using Drosophila . Because Morgan was particularly interested in experiments designed to test hypotheses, he turned to the fly system to maximize data acquisition over short periods of time. Soon after launching these experiments, Morgan saw his white-eyed fly peering back at him through his hand lens. Then, many crosses later, Morgan became convinced by his own empirical evidence that traits could in fact be passed on in the same manner predicted by the inheritance of sex chromosomes . Morgan never looked back, and he developed a huge following of accomplished students over the next few decades. Indeed, for his work with Drosophila , Morgan was awarded the Nobel Prize in 1933.

References and Recommended Reading

Benson, K. R. T. H. Morgan 's resistance to the chromosome theory. Nature Reviews Genetics 2 , 469–474 (2001) doi:10.1038/35076532 ( link to article )

Morgan, T. H. What are "factors" in Mendelian explanations? American Breeders Association Reports 5 , 365–368 (1909) ( link to article )

———. Sex-limited inheritance in Drosophila . Science 32 , 120–122 (1910) ( link to article )

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Understanding Evolution

Your one-stop source for information on evolution

The History of Evolutionary Thought

Chromosomes, mutation, and the birth of modern genetics: thomas hunt morgan.

In 1900 several scientists across Europe came to the same realization about heredity that  Mendel  had some 40 years before. But they arrived at the discovery from a very different direction.

Chromosomes contain genetic material

Nineteenth century cell biologists discovered that animal and plant cells had a central compartment known as the nucleus. Each nucleus contained a set of rod-shaped structures, and when a typical cell divided, a new nucleus complete with a new set of rods was created. These rods were named chromosomes for the way they absorbed colored stains. But sperm and eggs contained only half the normal set of chromosomes. When a sperm fertilized an egg, the chromosomes combined to create a full complement.

Scientists realized that the chromosomes stored the information necessary for building an individual, and heredity consisted of the transfer of that information from generation to generation. Each chromosome contained information for many different traits, and scientists dubbed each chromosomal chunk that was responsible for a particular trait a “ gene .”

Rediscovering Mendel

Dutch botanist  Hugo DeVries  and several other scientists carried out breeding experiments in the late 1890s and rediscovered Mendel’s three-to-one ratio. But this new generation could offer a clearer interpretation of what was happening in their experiments. We each carry two copies of the same gene, one from each parent, but in many cases only one copy produces a trait while the action of the other is masked. Here was the secret behind Mendel’s three-to-one ratio of smooth and wrinkled peas.

Mutated gene = new species?

Perhaps, scientists speculated, evolution took place as genes were altered. DeVries claimed that if a gene changed — if it “mutated” — it would create a new species in a single jump. But no one could say for sure what mutations  did until they could be studied up close. That became possible in the laboratory of a Columbia University biologist, Thomas Hunt Morgan (left).

Morgan bred fruit flies by the thousands, and his team tried to create mutant flies with x-rays, acids, and other toxic substances. Finally, in one unaltered lineage of flies, the researchers found a surprise. Every single fly in that line had been born with red eyes, until one day a fly emerged from its pupa with white eyes. Something had spontaneously changed in the white-eyed fly.

Mutation does not equal speciation

Morgan realized that one of its genes had been altered and it had produced a new kind of eye. Morgan bred the white-eyed fly with a red-eyed fly and got a generation of red-eyed hybrids. And when he bred the hybrids together, some of the grandchildren were white-eyed. Their ratio was three red to one white. Here was a mutation, but one that didn’t fit DeVries’s definition. DeVries thought that mutations created new species, but the fly that had acquired the white-eyed mutation remained a member of the same species. It could still mate with other fruit flies, and its gene could be passed down to later generations in proper Mendelian fashion.

Genetics is born

The work of scientists such as Morgan established a new science: genetics. It would not be until 1953 that the molecular structure of genes ( DNA ) would be discovered, and only later did scientists figure out how DNA’s code is used by cells to build proteins. But already by the 1920s, many of the paradoxes about genes that tormented previous biologists dissolved. Genes do not always come in simply two different versions, one dominant and one recessive. Mutations can create many different versions of the same gene (known as  alleles ). While a single mutation can sometimes create a drastic change to an organism, such as changing red eyes to white, most mutations cannot. That’s because most traits are based on many different genes working together. Mutating any one of those genes often only produces a subtle change, or none at all.

Fossil Hominids, Human Evolution: Thomas Huxley & Eugene Dubois

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Experiments in embryology

The work on drosophila.

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Thomas Hunt Morgan

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Thomas Hunt Morgan (born Sept. 25, 1866, Lexington , Ky., U.S.—died Dec. 4, 1945, Pasadena , Calif.) was an American zoologist and geneticist, famous for his experimental research with the fruit fly ( Drosophila ) by which he established the chromosome theory of heredity . He showed that genes are linked in a series on chromosomes and are responsible for identifiable, hereditary traits. Morgan’s work played a key role in establishing the field of genetics . He received the Nobel Prize for Physiology or Medicine in 1933.

Morgan’s father, Charlton Hunt Morgan, was a U.S. consul, and his uncle, John Hunt Morgan , had been a Confederate army general.

Early in life, Morgan showed an interest in natural history. In 1886 he received the B.S. degree from the State College of Kentucky (later the University of Kentucky) in zoology and then entered Johns Hopkins University for graduate work in biology . At Hopkins, Morgan studied under the morphologist and embryologist William Keith Brooks . After being awarded the Ph.D. in 1890, Morgan remained there a year before accepting a teaching post at Bryn Mawr College .

During the period 1893–1910, Morgan applied experimental techniques to fundamental problems of embryology . In order to identify causally related events during development, he analyzed such problems as the formation of embryos from separated blastomeres (early embryonic cells) and fertilization in nucleated and nonnucleated egg fragments. As examples of the effects of physical factors, he analyzed the way in which the spatial orientation of eggs affects their future development and the action of salt concentration on the development of fertilized and unfertilized eggs. In 1904 he married one of his graduate students at Bryn Mawr, Lillian V. Sampson, a cytologist and embryologist of considerable skill. The same year, he accepted an invitation to assume the professorship of experimental zoology at Columbia University , where, during the next 24 years, he conducted most of his important research in heredity.

Like most embryologists and many biologists at the turn of the century, Morgan found the Darwinian theory of evolution lacking in plausibility. It was difficult to conceive of the development of complex adaptations simply by an accumulation of slight chance variations. Moreover, Darwin had provided no mechanism of heredity to account for the origin or transmission of variations, except his early and hypothetical theory of pangenesis. Although Morgan believed that evolution itself was a fact, the mechanism of natural selection proposed by Darwin seemed incomplete because it could not be put to an experimental test.

Morgan had quite different objections to the Mendelian and chromosome theories. Both theories attempted to explain biological phenomena by postulating units or material entities in the cell that somehow control developmental events. To Morgan this was too reminiscent of the preformation theory—the idea that the fully formed adult is present in the egg or sperm—that had dominated embryology in the 18th and early 19th centuries. Although Morgan admitted that the chromosomes might have something to do with heredity, he argued in 1909 and 1910 that no single chromosome could carry specific hereditary traits. He also claimed that Mendelian theory was purely hypothetical: although it could account for and even predict breeding results, it could not describe the true processes of heredity. That each pair of chromosomes separates, with the individual chromosomes then going into different sperm or egg cells in exactly the same manner as Mendelian factors, did not seem to be sufficient proof to Morgan for claiming that the two processes had anything to do with each other.

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 (F 1 ) were red-eyed. Brother–sister matings among the F 1 generation produced a second generation (F 2 ) with some white-eyed flies, all of which were males. To explain this curious phenomenon, Morgan developed the hypothesis of sex-limited—today called sex-linked—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.

Among Morgan’s most important books are those dealing with (1) evolution: Evolution and Adaptation (1903), in which he strongly criticizes Darwinian theory; and A Critique of the Theory of Evolution, (1916), a more favourable view of the selection process; (2) heredity: Heredity and Sex (1913), his first major exposition of the Mendelian system in relation to Drosophila; and with A.H. Sturtevant, H.J. Muller, and C.B. Bridges, The Mechanism of Mendelian Heredity (1915; rev. ed., 1922); and The Theory of the Gene (1926; enlarged and revised ed., 1928); the latter two works firmly established the Mendelian theory as it applied to heredity in all multicellular (and many unicellular) organisms; and (3) embryology: The Development of the Frog’s Egg: An Introduction to Experimental Embryology (1897), a detailed outline of the developmental stages of frogs’ eggs; Experimental Embryology (1927), Morgan’s statement on the value of experimentation in embryology; and Embryology and Genetics (1934), an attempt to relate the theory of the gene to the problem of embryological differentiation and development.

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Article Contents

Early years: marine organisms, morphology, and experimental embryology, regeneration and artificial parthenogenesis: from earthworms to sea urchins, sex determination: insect studies, mendel and mutations: mice and fruit flies, acknowledgements.

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Thomas Hunt Morgan at the Marine Biological Laboratory: Naturalist and Experimentalist

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Diana E Kenney, Gary G Borisy, Thomas Hunt Morgan at the Marine Biological Laboratory: Naturalist and Experimentalist, Genetics , Volume 181, Issue 3, 1 March 2009, Pages 841–846, https://doi.org/10.1534/genetics.109.101659

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Anecdotal, Historical and Critical Commentaries on Genetics

IN the early 1910s, researchers at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, might have wondered why a colleague, Thomas Hunt Morgan ( Figure 1 ), began shipping fruit flies from his Columbia University lab to the MBL each summer. After all, the Woods Hole currents supplied the MBL with a rich variety of marine organisms and Morgan, an avid practitioner of experimental embryology, made good use of them.

T. H. Morgan in 1920. This portrait of Morgan was taken by A. F. Huettner. Courtesy of MBL Archives.

Yet those who knew Morgan well would not have been surprised by his insect stocks. A keen naturalist, Morgan studied a veritable menagerie of experimental animals—many of them collected in Woods Hole—as a student and later researcher at the MBL from 1890 to 1942. Moreover, Morgan always had a diversity of investigations going on simultaneously. “This was the way Morgan worked: he wasn't happy unless he had a lot of different irons in the fire at the same time,” wrote A. H. Sturtevant, Morgan's long-term collaborator ( Sturtevant 2001 , pp. 4–5). In Morgan's first 3 decades at the MBL, for instance, he studied at least 15 different species, including the now-famous fruit fly, while investigating a variety of problems related to his central interests in development and heredity ( Morgan 1888–1937 ; Marine   Biological   Laboratory 1909 ).

Morgan was also a vocal proponent of experimentalism, and at the MBL he (quite successfully) joined with Jacques Loeb in arguing for a quantitative, predictive foundation for biological studies ( Allen 1969 ). Morgan was interested only in scientific problems that could be experimentally tested. Deeply wary of ungrounded hypotheses, he sought not overarching theories, but experimental methods that would allow him to identify proximate causes. This stance would triumph in Morgan's work with the fruit fly, Drosophila melanogaster . Morgan initially began breeding this animal in his search for an experimental approach to evolution: he was testing an alternative to the theory of natural selection, which he felt was insufficient to explain the origin of new species. But when a sex-linked mutation appeared in his Columbia University stocks in 1910, Morgan's attention was diverted to analyzing the material basis of sex determination and inheritance. By 1912, he and his colleagues were mapping the location of genes on chromosomes. These epoch-making studies launched the field of experimental genetics.

Morgan's penchant for maintaining multiple, diverse lines of investigation paid off in important ways, as this review of his work at the MBL up through the mid-1920s shows. First, Morgan was able to synthesize his research on many different organisms in his book Regeneration ( Morgan 1901 ), which today provides a useful and insightful perspective on regenerative medicine. Second, evidence from originally distinct studies conceptually converged for Morgan. An example is his post-1910 work at the MBL on the insects phylloxeran and aphid, which confirmed his early Drosophila results on the relationship of the chromosomes to sex determination and inheritance.

Morgan's dual characteristics as a “naturalist and experimentalist” ( Figure 2 ) place him historically in an era when biology was transitioning from a descriptive and often speculative field to an experimental one ( Allen 1969 ). Yet they may indicate also why Morgan was a successful scientist, one who received the first Nobel Prize ever awarded in genetics in 1933 and became the first in a now-long list of Nobel Laureates affiliated with the MBL. Morgan's appreciation of natural diversity and his wide-ranging investigations, coupled with his skepticism toward a priori theories, could have left him flailing in a biological wilderness. What anchored him was his strict experimentalism, his insistence on choosing problems that could be analytically tested.

Naturalist, experimentalist, and trustee. This plaque in the lobby of Lillie Laboratory at the MBL commemorates T. H. Morgan's long-term and wide-ranging activities at the laboratory. Courtesy of Matthew Person.

In 1886, when T. H. Morgan was 20 years old and about to start graduate studies in zoology at Johns Hopkins, he attended the summer marine laboratory in Annisquam, Massachusetts, where he first learned how to collect and handle marine organisms for basic biological research. “Altogether, I am delighted with myself for being here and without doubt the work will be of the greatest assistance to me next winter,” he wrote to a friend ( Allen 1978 , p. 25). As it turned out, the Annisquam laboratory closed down after that summer, and its benefactors moved its glassware, apparatus, boats, furniture, and fixtures to Woods Hole, where they established the MBL in 1888 ( Lillie 1944 ). When Morgan died in 1945, he was “the last surviving personal link” between the MBL and its predecessor at Annisquam, wrote Edwin G. Conklin of Princeton University, Morgan's close friend and 45-year colleague at the MBL ( Conklin 1947 , p. 14).

At Johns Hopkins, Morgan trained with embryologist W. K. Brooks, who promoted the use of marine organisms for studies of early development, as was then practiced at the Naples Zoological Station and other European marine laboratories. Through Brooks' arrangement, Morgan spent the summer of 1889 at the U.S. Fish Commission Laboratory in Woods Hole, and the following summer Morgan was one of 20 investigators at the nascent MBL, which had opened in 1888. During these two summers, Morgan collected and studied sea spiders for his doctoral research. Morgan, like Brooks, was then working within the paradigm of descriptive morphology; in his thesis, he sought to trace the phylogenetic relations of sea spiders with other arthropods by studying their embryological development. In 1891, after defending his thesis and accepting an assistant professorship at Bryn Mawr College, Morgan returned to the MBL and did so again for the next two summers.

Morgan's activities in those years are not much noted in descriptions of the MBL written by his contemporaries. Yet Morgan's profile in Woods Hole rose significantly after he spent 10 months at the Naples Zoological Station in 1894–95, carrying out research with the German embryologist Hans Driesch. Through Driesch, Morgan came into direct contact with the European school of experimental embryology that had begun in the 1870s with Wilhelm His, who developed methods for sectioning embryos and argued for a cleaving of the field from phylogenetic studies. Morgan had already been attracted to these new methods and this approach and had devised experiments on teleost and echinoderm eggs at the MBL in 1893. Other MBL investigators were interested, too. A few months before Morgan left for Naples, W. M. Wheeler translated Wilhelm Roux's manifesto for an experimental and mechanistic approach to embryology, or Entwicklungsmechanik , and presented it as a Friday Night Lecture at the MBL ( Roux 1895 ; Maienschein 1991 ).

Morgan's Naples experiments, which were designed to identify causal factors controlling development of the egg cell, made a singular impression on his Woods Hole contemporaries. Edmund B. Wilson, Morgan's longtime friend and colleague at Columbia University and at the MBL, described a “beautiful experiment” Morgan conducted in Naples in which he manipulated the relative position of frog blastomeres and gave “most conclusive evidence that each of the (first) two blastomeres contains all the materials, nuclear and cytoplasmic, necessary for the formation of a whole body, and that these materials may be used to build a whole body or half-body, according to the grouping that they assume” ( Morgan 1895 ; Wilson 1897 , p. 319). In another experiment, Driesch and Morgan showed with ctenophore eggs that if part of the cytoplasm is removed, the remainder gives rise to incomplete larvae showing defects corresponding to the part removed ( Driesch and Morgan 1895 ). “Thus the way was prepared for theories of organ-forming germ regions in the egg and later of ‘organ-forming substances,’” wrote Frank R. Lillie in his history of the MBL. “The chapter in experimental embryology that immediately follows from this is a long one, with important contributions from Woods Hole investigators,” particularly Wilson, Conklin, Lillie, and Morgan himself ( Lillie 1944 , p. 128).

After his Naples stay, Morgan next returned to the MBL as an investigator in 1897. At that point, he also became deeply involved in organizational matters at the MBL and was named a trustee, a position he would hold for the rest of his life ( Conklin 1947 ). Over the next five years, Morgan's research interests at the MBL would dovetail closely with those of Jacques Loeb, whom MBL director C. O. Whitman had recruited to establish a department of physiology at the MBL in 1894. Loeb had also been influenced by Driesch and was even more adamant than Morgan in his experimentalist, mechanistic approach to biology. Together, Morgan and Loeb waged battle in Woods Hole against the descriptive, phylogenetic tradition. “Loeb has been here [in Woods Hole] … all summer and I have learned to know him so much better,” Morgan wrote to Driesch in 1899. “We agree on so many fundamental views (and differ on these points from most of the people here) that we have become very good friends and strong allies. We have done battle with nearly all the other good morphologists and still survive their united assaults” ( Allen 1978 , p. 326).

The first line of research Loeb developed at the MBL was regeneration ( Lillie 1944 ). Morgan, beginning in 1897, also pursued experiments on regeneration in a variety of organisms, including earthworms, hermit crabs, and teleost fish. By 1901 he had published more than 30 articles and a book on the topic, and much of this work was carried out at the MBL ( Marine   Biological   Laboratory 1909 ; Maienschein 1991 ). Morgan saw regeneration as essentially similar to normal development; he understood the value of using regenerative organisms to study both. One outcome of Morgan's extensive studies on regeneration was they led him to initially reject the Darwinian theory of natural selection, particularly the idea that adaptations have arisen due to their usefulness. How could the regenerative power have been slowly acquired through selection, Morgan argued, since it is useful to the animal only if the injured part entirely regenerates in a single generation? “The building up of the complete regeneration by slowly acquired steps, that cannot be decisive in the battle for existence, is not a process that can be explained by the theory (of natural selection),” he wrote ( Morgan 1901 , p. 129). These considerations would lead Morgan to explore alternative mechanisms for the origin of species, which later led to his experimental use of fruit flies.

In 1899, Morgan was at the front lines of Jacques Loeb's spectacular discovery of artificial parthenogenesis at the MBL, which brought the lab much publicity ( Loeb 1899 ). Morgan reported in 1896 and in 1898 on the induction of artificial asters in sea urchin eggs by the use of hypertonic seawater and in 1899 on the effects of various salt solutions on unfertilized sea urchin eggs, finding that they caused irregular cell division ( Morgan 1896 , 1898 , 1899 ). These latter experiments, carried out at the MBL, nearly “come to a complete anticipation of Jacques Loeb's famous discovery,” Lillie wrote ( Lillie 1944 , p. 133). According to A. H. Sturtevant, later Morgan's long-term collaborator, there was “at the time a rather general feeling that Loeb had taken more credit than was due him for his discovery of artificial parthenogenesis,” and Morgan “clearly felt that Loeb had been secretive about his own work and had used every opportunity to find out just what Morgan was doing”; however, Morgan “was not as resentful as were some other members of the Woods Hole group on his behalf” ( Sturtevant 1959 , p. 288). The artificial parthenogenesis episode seems not to have unduly troubled Morgan; he and Loeb remained friendly until Loeb's death in 1924.

Beginning about 1906, Morgan also pursued studies of sex determination in insects at the MBL, focusing on phylloxerans and on aphids that he later reported collecting from bearberry plants at nearby Quissett, Massachusetts ( Morgan 1915 ). The relationship of the chromosomes to sex determination was at that time a topic of vigorous investigation at the MBL, particularly by Thomas H. Montgomery, Edmund B. Wilson, and Nettie Stevens, a former student of Morgan's at Bryn Mawr ( Marine   Biological   Laboratory 1909 ). Parallel cytological studies by Wilson and Stevens in 1905 (not at the MBL) provided strong evidence that the X chromosome determined sex, but Morgan remained unconvinced, believing the cytoplasm and physiological development played a more important role.

The evolution of Morgan's thought on sex determination is apparent in his papers on the phylloxerans and aphids, both of which have a life-cycle phase in which parthenogenetic eggs produce both males and females. Morgan wanted to find out what in the egg determines what sex it will become. In 1906, Morgan reported finding no discernible difference between the chromosomes of the male-producing and the female-producing phylloxeran eggs, nor in their cytoplasm. In watching them develop, though, he noted one importance difference: “the precocious development of the relatively enormous reproductive organs of the male,” suggesting that “a pre-existing mass of cytoplasm from which the testis develops may be present in the egg.” This led him to suggest that “the immediate determination of the sex is a cytoplasmic phenomenon” ( Morgan 1906 , p. 206). In 1908, he reported having discovered that somatic cells in the female phylloxeran have six chromosomes, while those in the male have only five; thus at some point in the parthenogenetic egg the ones that will become male lose a chromosome. He was still considering cytoplasmic influences: “It follows that the egg as well as the sperm has the power of determining sex by regulating the number of its chromosomes,” he wrote ( Morgan 1908 , p. 57). In a 1909 study of both phylloxerans and aphids, Morgan concluded that the sex of the egg is determined to be male or female before any change in chromosome number. “Clearly, the egg as well as the sperm contains factors that determine sex,” he wrote ( Morgan 1909 , p. 235).

Then, an event in Morgan's Drosophila research, which he had initiated in about 1908, catalyzed a distinct change of course in his thought. In May 1910, Morgan discovered a male fly with a white-eyed mutation in his Drosophila stocks at Columbia University. By June, he had done enough crosses to realize he had in his white-eyed fly “a splendid case of sex-limited inheritance,” as he wrote to a friend from Woods Hole ( Schwartz 2008 , p. 179). Morgan submitted his classic Science paper describing his new Drosophila results from Woods Hole, and it was published in July ( Morgan 1910 ). Although Morgan described the expression of the white-eyed mutation in males only, it is noteworthy that he did not mention chromosomes in this paper. Yet Morgan soon found additional sex-linked traits in Drosophila, which he first publicly reported in a lecture at the MBL in July 1910. These findings would lead him to accept the chromosomal theory of sex determination, as well as chromosomes serving as the physical basis for Mendelian inheritance ( Morgan 1911a ; Allen 1978 ; Maienschein 1984 ). In 1912, after his Drosophila discoveries and with new cytological evidence from the phylloxerans, Morgan unequivocally ascribed differences in the male and female parthenogenetic phylloxeran eggs to differences in their sex chromosomes. (Prior to this, he admitted in this paper, “the value of the chromosome hypothesis in sex determination” might have seemed to “hang in the balance.”) ( Morgan 1912 , p. 479).

Sturtevant considered Morgan's phylloxeran and aphid work, which he continued to pursue in Woods Hole until 1915, as very important in confirming the chromosome hypothesis. “[Morgan] showed that the facts, which at first seemed quite inconsistent with the chromosome interpretation of sex determination, were in fact intelligible only in terms of that interpretation,” Sturtevant wrote. “This was one of Morgan's most brilliant achievements, involving great skill and patience in the collecting and care of the animals, insight in seeing what were the critical points of study, and ability to recognize and to follow up on unexpected facts. The results were of importance in serving to demonstrate the role of the chromosomes in sex determination, at a time when that importance was seriously questioned by many biologists” ( Sturtevant 1959 , pp. 289–290).

The rediscovery of Gregor Mendel's work in 1900 brought questions of evolution and heredity to the fore in biological circles. Morgan began investigations of Mendelian inheritance in 1905, when he started breeding rats and mice ( Kohler 1994 ). In the summer of 1907, he caught a house mouse in Woods Hole with the “sport,” or mutation, of a pure white belly. “Later, I caught two more such mice and, in the same closet, another typical house mouse. In the neighborhood, I have caught a few other white-bellied mice,” Morgan reported (which summons a vision of an agile Morgan chasing mice around Woods Hole). Morgan then obtained white-bellied mice from Iowa and New York and began a series of breeding experiments crossing the wild sport with various domesticated races. “My intention was to familiarize myself at first hand with the process of Mendelian inheritance,” he wrote, by observing the varieties of coat color that his crosses produced ( Morgan 1911b , p. 88).

At some point in the midst of this work, probably in 1908, Morgan started breeding Drosophila, not for Mendelian studies, but as a foray into experimental evolution. Morgan's studies of regeneration had led him to reject Darwin's concept of new species arising by natural selection of minute, random, continuous variations. Instead, Morgan entertained Hugo de Vries' concept that species evolved through discrete jumps, which de Vries called mutations ( Allen 1978 ). De Vries had predicted that, under certain conditions, animals can enter “mutating periods.” With Drosophila, Morgan wanted to see if he could induce such a mutating period through intensive inbreeding ( Allen 1975 ; Kohler 1994 ).

The first researchers to use Drosophila experimentally were William E. Castle and his students at Harvard University ( Castle   et al . 1906 ) and Morgan was clearly influenced by this work. It is not certain who gave Morgan his first Drosophila stocks; but “certainly some of the early material was collected in grocery stores which existed then in Woods Hole,” Sturtevant wrote ( Sturtevant 2001 , p. 3). Morgan himself in a letter to A. F. Blakeslee in 1935, responding to whether he had obtained his first stocks of flies from F. E. Lutz, wrote “…if so, I have forgotten it” ( Carlson 2004 , p. 168).

For many months, Morgan's inbreeding experiments with Drosophila turned up nothing, and when Ross Harrison visited Morgan's Columbia University lab in January 1910, Morgan referred to it as “two years' work wasted” ( Kohler 1994 , p. 41). Yet, soon after, a stream of mutants began appearing in his stocks, starting with an atypical thorax pattern. Overjoyed, Morgan at first thought he had succeeded in inducing a de Vriesian mutating period in the fly ( Kohler 1994 ). But soon the sex-limited Mendelian ratios Morgan observed for white-eye and other mutations drew his attention from his original focus on experimental evolution to an analysis of the chromosomes in sex determination and inheritance, despite his prior skepticism toward the chromosomal theory. As Castle later wrote, “Morgan was too good a scientist to hold a conclusion after he believed it had been clearly disproved” ( Carlson 2004 , p. 163).

Beginning in 1913 and continuing through the 1920s, Morgan brought members of his Columbia University “fly room,” particularly A. H. Sturtevant and C. B. Bridges, to the MBL each summer, where they carried out their Drosophila research in the Crane Building ( Sturtevant 1959 ) ( Figure 3 ). “This did not mean any interruption in the Drosophila experiments,” Sturtevant later wrote. “All the cultures were loaded into barrels—big sugar barrels—shipped by express, and what you started in New York, you'd finish (in Woods Hole) and vice versa.” They traveled from New York by boat, lugging cages of chickens, pigeons, mice, and other animals Morgan was working on, and “when Morgan got to Woods Hole, he plunged deeply into work on marine forms, even while his work with Drosophila was actively going on,” Sturtevant wrote ( Sturtevant 2001 , p. 4). From 1917 to 1924, for example, Morgan conducted an extended study of regeneration and “intersex” mutations in the fiddler crab at the MBL ( Morgan 1920 , 1924 ). Also accompanying Morgan to Woods Hole since their marriage in 1904 was biologist Lilian Vaughan (Sampson) Morgan, who investigated amphibian breeding and development at the MBL in the 1890s and later transitioned into genetics. In 1913, Lilian Morgan cofounded what is now the Children's School of Science in Woods Hole ( Keenan 1983 ).

Morgan and friends: T. H. Morgan called this photo, taken at the MBL in the summer of 1919, “Solving the Problems of the Universe.” Clockwise from left: T. H. Morgan, Calvin Bridges (kneeling), Franz Schrader, E. E. Just, A. H. Sturtevant, and an unidentified person. Courtesy of MBL Archives.

Morgan's success with Drosophila in establishing a material basis for the Mendelian theory of inheritance was a triumph of the experimentalist approach, which would come to dominate biological research in the 20th century. Yet the diversity of Morgan's studies at the MBL over more than 50 years indicates he also appreciated the naturalist Louis Agassiz's dictum, which is still displayed in the MBL Library: “Study Nature, not Books.” In Morgan's time, the naturalist and the experimentalist traditions seemed to pose a dichotomy: descriptive vs . quantitative, holistic vs . reductionistic. Morgan did not choose either/or: he adopted, with great success, something of both.

The authors are grateful to Jane Maienschein and Garland E. Allen for helpful discussions about Morgan and for generously providing feedback and suggestions on the manuscript. The authors also thank Catherine N. Norton, library director, and Diane M. Rielinger, archivist, of the Marine Biological Laboratory Woods Hole Oceanographic Institution Library, Woods Hole, Massachusetts, for archival assistance.

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Castle , W. E., F. W. Carpenter , A. H. Clark , S. O. Mast and W. M. Barrows , 1906 The effects of inbreeding, cross-breeding, and selection upon the fertility and variability of Drosophila . Proc. Am. Acad. Arts Sci.   41 :   729 –786.

Conklin , E. G., 1947 Thomas Hunt Morgan: 1866–1945, in The Marine Biological Laboratory, forty-ninth report, for the year 1946. Biol. Bull.   93 (1): 14 –18.

Driesch , H., and T. H. Morgan , 1895 Zur analysis der ersten entwickelungstadien des ctenophoreneis. I. Von der entwickelung einzelner ctenophorenblastomeren; II. Von der entwickelung ungefurchter eier mit protoplasmadefekten. Arch. Entwicklungsmech.   2 :   204 –226.

Keenan , K., 1983 Lilian Vaughan Morgan (1870–1952): her life and work. Am. Zool.   23 :   867 –876.

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Maienschein , J., 1991 The origins of entwicklungsmechanik, pp. 43–61 in A Conceptual History of Modern Embryology , edited by S. F. Gilbert . The Johns Hopkins University Press, Baltimore.

Marine   Biological   Laboratory , 1909 The 11th annual report of the Marine Biological Laboratory, years 1907–1908. Biol. Bull.   17 :   56 –100.

Morgan , T. H., 1888–1937   Collected Reprints of T. H. Morgan, 1888–1937 . MBL Library Archives, Woods Hole, MA.

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Morgan , T. H., 1899 The action of salt-solutions on the unfertilized and fertilized eggs of Arbacia, and of other animals. Arch. Entwicklungsmech. Org.   8 :   448 –539.

Morgan , T. H., 1901   Regeneration . MacMillan, New York.

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Morgan , T. H., 1911 b The influence of heredity and of environment in determining the coat colors of mice. Ann. NY Acad. Sci.   21 :   81 –117.

Morgan , T. H., 1912 The elimination of the sex chromosomes from the male-producing eggs of phylloxerans. J. Exp. Zool.   12 :   479 –498.

Morgan , T. H., 1915 The predetermination of sex in phylloxerans and aphids. J. Exp. Zool.   19 :   285 –321.

Morgan , T. H., 1920 Variations in the secondary sexual characters of the fiddler crab. Am. Nat.   54 :   220 –246.

Morgan , T. H., 1924 The artificial induction of symmetrical claws in male fiddler crabs. Am. Nat.   58 :   289 –295.

Roux , W., 1895 The problems, methods and scope of developmental mechanics, pp. 149–190 in Biological Lectures Delivered at the Marine Biological Laboratory , translated by W. M. Wheeler (in 1894). Ginn and Co., Boston.

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1911: Fruit Flies Illuminate the Chromosome Theory

Morgan and his students made many important contributions to genetics. His students, who included such important geneticists as Alfred Sturtevant, Hermann Muller and Calvin Bridges, studied the fruit fly Drosophila melanogaster . They showed that chromosomes carry genes, discovered genetic linkage - the fact that genes are arrayed on linear chromosomes - and described chromosome recombination.

In 1933, Morgan received the Nobel Prize in Physiology or Medicine for helping establish the chromosome theory of inheritance.

More Information

References:.

Rubin, G.M., Lewis, E.B., A Brief History of Drosophila's Contributions to Genome Research. Science , 287(5461):2216-8. 2000. [ PubMed ]

Morgan, Thomas Hunt, et. al., "The mechanism of Mendelian heredity", (New York: Henry Holt and Co., 1915)

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Last updated: April 22, 2013

Thomas Hunt Morgan and the Chromosome Theory of Heredity

Thomas Hunt Morgan (1866-1945)

On September 25 , 1866 ,  American evolutionary biologist , geneticist , embryologist , and science author Thomas Hunt Morgan was born. He is famous for his experimental research with the  fruit fly by which he established the chromosome theory of heredity . Thomas Hunt Morgan was awarded the  Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that the chromosome plays in heredity .

“Except for the rare cases of plastid inheritance, the inheritance of all known cooacters can be sufficiently accounted for by the presence of genes in the chromosomes. In a word the cytoplasm may be ignored genetically.” — Thomas Hunt Morgan, ‘Genetics and the Physiology of Development’, The American Naturalist (1926),  60 , 491

Thomas Hunt Morgan – Early Years

Thomas Hunt Morgan was born in Lexington, Kentucky. He joined the State College of Kentucky, today known as the University of Kentucky. Morgan mostly studied natural science and worked with the U.S. Geological Survey during the summer. Morgen started his graduate studies at the recently founded Johns Hopkins University. Under William Keith Brooks, Morgan was able to complete his thesis on the embryology of sea spiders he collected at the Marine Biological Laboratory in Woods Hole, Massachusetts. In 1890, Morgan was awarded his Ph.D. from Johns Hopkins and was also awarded the Bruce Fellowship in Research. He used his scholarship to travel to Jamaica, the Bahamas and Europe where he conducted further research.

Morphological Research

Also in 1890, Thomas Morgan was appointed associate professor at Johns Hopkins’ sister school Bryn Mawr College. There he taught all morphology-related courses and studied sea acorns, ascidian worms and frogs. Through the years, Morgan got enthusiastic for experimental biology, influenced by the German biologist Hans Driesch in Naples. Back then, there was a considerable scientific debate over the question of how an embryo developed. Basically, the two sides evolved around Wilhelm Roux who believed that hereditary material was divided among embryonic cells, which were predestined to form particular parts of a mature organism, and Hans Driesch who (among his followers) thought that development was due to epigenetic factors, where interactions between the protoplasm and the nucleus of the egg and the environment could affect development. Morgan collaborated with Driesch and they demonstrated that blastomeres isolated from sea urchin and ctenophore eggs could develop into complete larvae, contrary to the predictions of Roux’s supporters. Further, Thomas Morgan was able to show that sea urchin eggs could be induced to divide without fertilization by adding magnesium chloride.

Regeneration

Thomas Morgan returned to Bryn Mawr in 1895 and was appointed full professor upon his arrival. His first book ‘ The Development of the Frog’s Egg’ was published two years later. He further started a series of studies on different organisms’ ability to regenerate, which he published in 1901 with the title ‘ Regeneration ‘.

In a typical Drosophila genetics experiment, male and female flies with known phenotypes are put in a jar to mate; females must be virgins. Eggs are laid in porridge which the larva feed on; when the life cycle is complete, the progeny are scored for inheritance of the trait of interest., image: cudmore, CC BY-SA 2.0 <https://creativecommons.org/licenses/by-sa/2.0>, via Wikimedia Commons

Evolutionary Theories

Morgan joined Columbia University in 1904 in order to focus fully on his experimental work. His research shifted more and more towards the mechanisms of heredity and evolution. Like many biologists back then, he did see evidence for biological evolution but rejected Darwin’s proposed mechanism of natural selection acting on small, constantly produced variations. However, while Morgan was skeptical of natural selection for many years, his theories of heredity and variation were radically transformed through his conversion to Mendelism. Around 1900, Carl Correns ,[ 6 ]  Erich von Tschermak and Hugo De Vries rediscovered Gregor Mendel ‘s work and with it the foundation of genetics.[ 4 ] As Morgan had dismissed both evolutionary theories, he was seeking to prove De Vries’ mutation theory with his experimental heredity work.

Working with the Fruit Fly

Just like C. W. Woodworth and William E. Castle , Thomas Morgan started to work on the fruit fly Drosophila melanogaster around 1908. Together with Fernandus Payne , he mutated Drosophila through physical, chemical, and radiational means and started cross-breeding experiments to find heritable mutations. After no significant finding during their two years of work, a series of heritable mutants appeared, some of which displayed Mendelian inheritance patterns. For instance, Morgan noticed a white-eyed mutant male among the red-eyed wild types. When white-eyed flies were bred with a red-eyed female, their progeny were all red-eyed. A second generation cross produced white-eyed males — a sex-linked recessive trait, the gene for which Morgan named white. He also found a pink-eyed mutant that showed a different pattern of inheritance. In 1911, Morgan published a paper concluding that some traits were sex-linked, the trait was probably carried on one of the sex chromosomes, and other genes were probably carried on specific chromosomes as well.

Genetic Linkage

Morgan and his students whom he had motivated to study flies as well counted the mutant characteristics of thousands of fruit flies and studied their inheritance. The observation of a miniature-wing mutant, which was also on the sex chromosome but sometimes sorted independently to the white-eye mutation, led Morgan to the idea of genetic linkage and to hypothesize the phenomenon of crossing over. Morgan proposed that the amount of crossing over between linked genes differs and that crossover frequency might indicate the distance separating genes on the chromosome.

Mendelian Chromosome Theory

During the following years more and more biologists accepted the Mendelian chromosome theory, which was independently proposed by Walter Sutton and Theodor Boveri , and elaborated and expanded by Morgan and his students. However, the details of the increasingly complex theory, as well as the concept of the gene and its physical nature, were still controversial. Still, due to Thomas Morgan’s success on fruit flies, numerous labs across the globe took up fruit fly genetics and Columbia became the center of an informal exchange network, through which promising mutant Drosophila strains were transferred from lab to lab. Drosophila became one of the first, and for some time the most widely used, model organisms.

Inheritance of eye color in fruit flies according to Morgan

Later Years

During his later career, Morgan returned to embryology and worked to encourage the spread of genetics research to other organisms and the spread of the mechanistic experimental approach to all biological fields. He also became a critic of the growing eugenics movement, which adopted the ideas of genetics in support of racism. Thomas Morgan’s fly-room at Columbia became famous, and he found it easy to attract funding and visiting academics. In 1927 after 25 years at Columbia, and nearing the age of retirement, he received an offer from George Ellery Hale to establish a school of biology in California.[ 5 ] In 1919 he was elected a Foreign Member of the Royal Society, which awarded him the Darwin Medal in 1924 and the Copley Medal in 1939. From 1927 to 1931 he was president of the National Academy of Sciences, of which he had been a member since 1909. In 1928 Morgan was elected to the American Academy of Arts and Sciences. In the same year he was elected a foreign member of the Göttingen Academy of Sciences. In 1933 he received the Nobel Prize for Medicine . In 1935 he was accepted as a corresponding member of the Prussian Academy of Sciences. From 1923 he was Corresponding Member and from 1932 Honorary Member of the Soviet Academy of Sciences.

Thomas Hunt Morgan had throughout his life suffered with a chronic duodenal ulcer. In 1945, at age 79, he experienced a severe heart attack and died from a ruptured artery.

References and Further Reading:

• [1]  Thomas Hunt Morgan at nature
• [2]  Thomas Hunt Morgan at the Nobel Prize Foundation Webpage
• [3]  Thomas Hunt Morgan at Britannica Online
• [4]  Gregor Mendel and the Rules of Inheritance , SciHi blog
• [5]  George Ellery Hale – Large Telescopes and the Spectroheliograph , SciHi Blog
• [6]  Carl Correns and the Principles of Heredity , SciHi Blog
• [7] Thomas Hunt Morgan via Wikidata
• [8]  Thomas Hunt Morgan and fruit flies , 2016,  Khan Academy  @ youtube
• [9]  Kenney, D. E.; Borisy, G. G. (2009).  “Thomas Hunt Morgan at the Marine Biological Laboratory: Naturalist and Experimentalist” .  Genetics .  181  (3): 841–846.
• [10]  Morgan, Thomas Hunt; Alfred H. Sturtevant, H. J. Muller and C. B. Bridges (1915).  The Mechanism of Mendelian Heredity . New York: Henry Holt.
• [11]  Timeline for Thomas Hunt Morgan, via Wikidata

Tabea Tietz

Related posts, norman borlaug and the green revolution, sidney fox and his research for the origins of life, frederick william twort and the bacteriophages, wilhelm pfeffer – a pioneer of plant physiology, one comment.

Morgan was also in 1928, a Life Member of the Marine Biological Laboratory, a fraternal organization of scientists across the country. (It was located in Woods Hole, MA) along with George Papanicolaou, MD, PhD, who was a regular member of the MBL. Morgan quoted Papanicolaou’s PhD thesis in his 1913 “Heredity and Sex” book. pages 183-85. Morgan was responsible for opening the doors for Dr. Pap to get his first job at Cornell Medical College/NY Hospital in 1914. So in a sense, Morgan was a catalyst to the Pap Test for cervical cancer that Papanicolaou is know for. He (Pap) was born on May 13, 1883, a Friday. So much for being a unlucky day.

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The Natural History of Model Organisms: The secret lives of Drosophila flies

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Introduction

Where did d. melanogaster come from and how do these flies live, what is different in the lab and field, untapped potential of drosophila, combining genomics and natural history, conclusions, article and author information.

Flies of the genus Drosophila , and particularly those of the species Drosophila melanogaster , are best known as laboratory organisms. As with all model organisms, they were domesticated for empirical studies, but they also continue to exist as wild populations.

Decades of research on these flies in the laboratory have produced astounding and important insights into basic biological processes, but we have only scratched the surface of what they have to offer as research organisms. An outstanding challenge now is to build on this knowledge and explore how natural history has shaped D . melanogaster in order to advance our understanding of biology more generally.

From its first use in the laboratory in the early 1900s until the present day, Drosophila melanogaster has been central to major breakthroughs in genetics. The use of this fruit fly as a model organism began with the pioneering work of Thomas Hunt Morgan, who was awarded the 1933 Nobel Prize in Physiology or Medicine for ‘his discoveries concerning the role played by the chromosome in hereditary’ . Morgan's former student, Herman J Muller, subsequently received the prize in 1946 ‘for the discovery of the production of mutations by means of X-ray irradiation’. In 1995, the Drosophila researchers, Edward B Lewis, Christiane Nüsslein-Volhard and Eric F Wieschaus shared the prize ‘for their discoveries concerning the genetic control of early embryonic development’. Most recently, Jules Hoffman shared the 2011 prize for ‘discoveries concerning the activation of innate immunity’ in Drosophila .

How did one species of Drosophila , D. melanogaster , come to be a model system? Harvard entomologist Charles Woodworth was the first to rear D. melanogaster , just after the turn of the 20th century . It is not clear why or how he came to breed them, but their short generation time and ease of rearing were probably very appealing attributes. Woodworth then recommended them to his colleague William Castle, who initially worked on mammals but utilized the flies to study inbreeding. During this same period, another entomologist, Frank Lutz at the American Museum of Natural History, also began studying this fly's basic biology, publishing more than a dozen papers about them ( Davenport, 1941 ; Carlson, 2013 ). It was from Lutz that Thomas Hunt Morgan introduced them into his laboratory at Columbia University. At the time Morgan began his work, the basic principles of heredity were still under debate. Morgan's discoveries and the fact that he attracted a highly talented group of graduate students no doubt fuelled the use of D. melanogaster as a model system.

But what do we know about the biology of this fly in nature? Here, I review what we know of its origins, its biology in the wild and how this differs from what we see in the laboratory, its natural history, and why its natural history matters for laboratory studies, as well as its advantages as a model organism. I also discuss why, even after so many years of intensive investigation, D. melanogaster and its relatives are in an important position to help us address central questions about biology.

D. melanogaster, described by Meigen in 1830, appears to have originated in sub-Saharan Africa ( Lachaise et al., 1988 ). The first out-of-Africa habitat expansion of D. melanogaster is thought to have occurred between 10,000 and 15,000 years ago, when it moved to Europe and Asia ( David and Capy, 1988 ). North America and Australia were colonized more recently ( David and Capy, 1988 ). Subsequent colonization events, especially as human travel has accelerated, have continued to move populations around the globe. Its current distribution is worldwide, being found on every continent and most islands ( Markow and O'Grady, 2005b ).

A human commensal associated primarily with rotting fruits, D. melanogaster is also associated with a wide array of decaying vegetables and other plant matter. The fact that this fly is an ecological generalist no doubt contributed to the facility with which it was initially propagated in the laboratory, rapidly becoming a popular model system. Drosophila are found worldwide, and their extensive distribution has allowed studies of adaptations to different latitudes.

D. melanogaster do not live alone. Their decaying host resources are also home to many microbes, as well as to other arthropods, including other Drosophila species, all of which they interact with (see Video 1, 2 ). Some microbes in the decaying material themselves provide food for D. melanogaster , being selectively consumed by larvae or adults. Other microbes are essential for decomposing fruit and other plant matter into substances, such as volatiles, that attract other adult flies to the food source, or for decomposing organic matter into new material, which in turn is consumed by the flies. Along with Drosophila simulans, Drosophila hydei, Drosophila immigrans , and Drosophila busckii , D. melanogaster forms part of what is known as the ‘cosmopolitan guild’ of Drosophila ( Atkinson and Shorrocks, 1977 ) . While found in association with these other species, D. melanogaster colonizes the rotting fruits at a particular time during the decay trajectory. First to arrive is D. simulans, followed by D. melanogaster, and then the other species ( Nunney, 1990 , 1996 ): this is consistent with D. melanogaster having a higher ethanol tolerance than its relative D. simulans ( McKenzie and Parsons 1972 , 1974 ), which arrives earlier, when fewer volatiles have been produced by fermentation. Other arthropods, especially beetles, are also common in the substrate and are predators of the developing flies.

This video cannot be played in place because your browser does support HTML5 video. You may still download the video for offline viewing.

Three members of the cosmopolitan guild of Drosophila feeding.

D. hydei (the larger, dark flies) and D. melanogaster and D. simulans (the smaller, lighter flies) quietly feeding on the juice of a rotting tomato and on the microbes present on it. D. melanogaster and D. simulans are sibling species and are morphologically indistinguishable in the video. Video credit: Therese Ann Markow.

Three members of the cosmopolitan guild of Drosophila interacting at a food source.

Drosophila : D. hydei (the larger, dark flies) and D. melanogaster and D. simulans (the smaller, lighter flies) interacting at a food source. Although there is little sexual dimorphism between males and females of the D. hydei species, males can be distinguished in the video because they approach other flies to court. In the D. melanogaster and D. simulans species , males are smaller than the females and have darker abdomens. These males can also be seen approaching other flies and attempting to court. Attempted courtships are brief and often end when females extrude their ovipositors. Notice that males will approach flies of different sexes and species, and that flies of D. hydei are much less active than those of D. simulans and D. melanogaster. D. melanogaster and D. simulans are sibling species and are morphologically indistinguishable in this video. Video credit: Therese Ann Markow.

D. melanogaster is holometabolous, meaning it undergoes a metamorphosis from its larval to adult form ( Figure 1 ). Females lay their eggs in necrotic material, and the larvae develop and pupate there. Two life stages are completely immobile: the egg and the pupa. Larvae can move within the resource patch, while adults can fly between patches. Given the sessile status of eggs and larvae, we expect these stages to exhibit adaptations against predation, parasitism and environmental stressors, such as temperature extremes, ultraviolet light and desiccation. Natural selection on behaviors such as oviposition and pupation site selection is therefore expected to be strong.

The life cycle of Drosophila melanogaster .

Egg and pupa stages are sessile, larvae move within the substrate, and adults are highly vagile as their ability to fly enables their dispersal. Different species of Drosophila vary in their larval development times, as well as in the ages at which females and males attain reproductive maturity. Image credit: Therese Ann Markow.

In the laboratory, life is simple. Much is constant. Flies are grown in one or more standardized culture media, usually treated with mould inhibitors, such as propionic acid or methylparaben, and antibiotics. While these culture conditions keep flies ‘healthy’ by laboratory standards, they do not represent the conditions that D. melanogaster experience in nature. The fungal, bacterial and viral pathogens ( Magwire et al., 2012 ; Keebaugh and Schlenke, 2014 ) flies encounter in nature are absent in the laboratory. In the wild, larvae and flies are also exposed to predators, such as ants, beetles, pseudoscorpions and lizards, as well as to parasites, such as wasps and phoretic mites. Encountering food of different types and ages in nature also differs from the benign consistency of the laboratory environment. In the laboratory, flies tend to be reared at a constant temperature and humidity level, while these abiotic variables fluctuate in nature. Laboratory adults also don't need to disperse to find a resource for the next generation.

What is different then, about the flies themselves, when found in nature? Few studies of D. melanogaster have been done in the wild, but those that have reveal a different picture of wild flies. For one thing, they tend to be larger than laboratory reared flies, possibly owing to some, as yet unknown, micronutrients and/or to the fact that in nature, temperatures fluctuate and growth is slower than in culture ( Chown and Gaston, 2010 ). The microbes that associate with D. melanogaster in the laboratory are also far less diverse than those that associate with these flies in the wild ( Chandler et al., 2011 ).

Reproductive behavior and biology, while extensively studied in the laboratory, is less well-understood in the wild. From the few studies conducted in nature, a different picture emerges. For example, in nature, virgins are not separated upon eclosion and stored until used in experimental pairings. Instead, they tend to be mated early and often ( Markow et al., 2012 ). In fact, many D. melanogaster females in the wild appear to have been force-mated by males waiting for them to emerge from their pupa cases ( Markow, 2000 ; Seeley and Dukas, 2011 ). In addition, while laboratory mated females tend to die earlier than do virgins, the well known ‘cost of mating’ ( Fowler and Partridge, 1989 ), in nature the opposite seems to be true ( Markow, 2011 ). Courtship itself is also different in nature compared to that observed in the laboratory. Laboratory experiments almost universally reveal an advantage to large males when placed with smaller males in ‘choice’ experiments ( Alcock, 2013 ). In nature, however, sexual interactions do not take place in small chambers. Males appear to sort themselves out by size at the mating site, with smaller males often being found in parts of the fruit where there are fewer females and thus fewer matings ( Markow, 1988 ). The mating advantage to larger males is not as apparent in wild populations ( Partridge et al., 1987 ; Markow, 1988 ). Furthermore, when courted by an undesirable male in nature, where there is ample space to escape, female D. melanogaster rarely decamp, instead, extruding their ovipositor to discourage the suitor ( Gromko and Markow, 1993 ; Video 2 ).

Our extensive foundational knowledge of the biology of D. melanogaster places these flies in a very strong position to contribute to our understanding of outstanding issues and questions in biology, supported by the availability of a sequenced genome ( Adams et al., 2000 ) and an array of genomic resources. While a number of future discoveries will concern basic processes in gene action and development, the natural history of D. melanogaster can also inform and guide discoveries relevant to contemporary and pressing problems in human health and environmental change.

Reproduction and biocontrol

The reproductive systems of Drosophila species are among the most variable of any organism ( Markow, 1996 , 2002 ; Markow and O'Grady, 2005a ). Some of this variability is behavioural. For example, in some species, such as D. hydei and Drosophila nigrospiracula, females will mate multiple times in a single morning, while in others, such as Drosophila subobscura, females will mate once in their lifetime. Some species, such as Drosophila pachea, require weeks for an adult fly to become sexually mature, while in others, such as Drosophila mettleri, either sex can be ready to mate within hours of emerging from the pupa case. The genes that control these behavioural differences can hold clues to controlling the reproduction of economically and medically important insects, such as testse flies and mosquitoes (see Box 1 ). Morphological variation can also influence the reproductive success of ‘problem’ species. Drosophila suzukii , for example, is an exceptional species that has recently invaded America and Europe from Asia ( Rota-Stabelli et al., 2013 ) and attacks agricultural produce (in particular, by laying its eggs into soft fruits). A sequenced genome ( Chiu et al., 2013 ) and comparative morphological studies of its females' sharp ovipositor ( Atallah et al., 2014 ) provide insights into the basis for its rapid invasion.

Outstanding questions about the natural history of Drosophila

Why can some Drosophila species feed and breed in certain resources while other species cannot?

Why can some Drosophila species tolerate extreme environmental conditions while others cannot?

What accounts for the particular microbial communities found inside the guts of D. melanogaster and of other species?

What accounts for the astounding variability in the reproductive biology of Drosophila species?

An additional aspect of biocontrol is to understand the neurobiological mechanisms by which insects identify their hosts. Here again, discoveries made in D. melanogaster can be applied to economically important species. These discoveries include the first functional mapping of olfactory responses ( Hallem and Carlson, 2004 ), and the use of multiple species' genomes to reveal the ecological and behavioural significance of the evolution of various olfactory receptors ( McBride, 2007 ; Guo and Kim, 2007 ; Goldman-Huertas et al., 2015 ). As such, the D. melanogaster toolbox can now be used to disrupt host-seeking behaviors in insects of medical and economic importance ( Carey and Carlson, 2011 ).

Human health

D. melanogaster has played an increasingly important role in the creation of animal models of human disease. Approximately 65% of human disease genes are estimated to have counterparts in D. melanogaster ( Chien et al., 2002 ), most of which are available in the Homophila database ( http://superfly.ucsd.edu/homophila/ ). The number of investigators using D. melanogaster as a model for studying human disease is steadily rising ( Pfleger and Reiter, 2008 ), especially for more complex disorders, such as heart disease ( Piazza and Wessells, 2011 ), mental and neurological illness ( Pandey and Nichols, 2011 ), and obesity ( Trinh and Boulianne, 2013 ).

Complex health problems tend to be rooted in the interaction between multi-factorial genotypes and the environment. What role can natural history play in our ability to understand these interactions with a view towards disease mitigation and treatment? In the past few decades, the importance of the gut microbiome for models of human health has grown. The D. melanogaster microbiome, under laboratory conditions, turns out to be quite simple, with an average of ten culturable bacterial species ( Lee and Hase, 2014 ), and has provided insights into the relationship between gut microbiota and processes such as intestinal function ( Lee and Lee, 2014 ) and insulin signaling ( Shin et al. 2011 ). Of considerable interest is that the microbiome of wild D. melanogaster is much more complex ( Cox and Gilmore, 2007 ) than that found in laboratory reared flies, comparable to the differences observed between non-westernized human populations and urban populations that consume highly processed diets ( De Filippo et al., 2010 ) (see Box 1 ). This similarity between flies and humans reveals the importance of host-microbiota homeostasis for human health ( David et al., 2014 ; Kostic et al., 2013 ). For example, Shin et al. (2011) demonstrated how the Drosophila gut microbiome regulates the metabolic homestasis of the fly.

Global environmental change: detoxification and stress resistance

Environmental change is actually a complex of changes, both abiotic and biotic. Abiotic challenges include changing temperature and humidity, and biotic challenges, often fomented by abiotic shifts, include changes in available habitat, presence of pathogens, parasites, competitors and invaders. Understanding adaptation to global environmental change thus also is a complex problem, and one that requires us to monitor natural populations, as well as to conduct laboratory studies to discover the bases of adaptations or the lack thereof. Natural populations and laboratory strains of D. melanogaster have been successfully exploited in examining responses to changing environments ( Rodríguez-Trelles and Rodríguez, 2007 ; Hoffmann, 2010 ). The susceptibility of D. melanogaster to global environmental change is well documented in the clinal or seasonal changes in the frequencies of alleles at particular loci ( Umina et al., 2005 ) and in changes in chromosomal inversion frequencies ( Anderson et al., 2003 ). Several thousand Drosophila species, some with highly specialized ecologies, are limited in their distributions to very cold or very hot climates. For example, D. pachea is endemic to the Sonoran Desert of North America, where it depends on the sterols in the cactus Lophocereus schottii, which has alkaloids that other Drosophila species cannot tolerate. Because of its obligate association with its cactus host, it is exposed to temperatures that often approach 50°C. Such species provide unprecedented opportunities to understand the genetic bases of adaptations to extreme situations (see Box 1 ) and to recruit these species to address problems of species loss in the face of global warming and other anthropogenic changes.

Another product of anthropogenic change is the evolution of pesticide resistance in a wide range of insects of economic and medical importance. Natural and laboratory populations of D. melanogaster have played key roles in our understanding of the roles of the cytochrome P450-encoding genes and the glutathione S -transferases in resistance to the insecticide, dichlorodiphenyltrichloroethane (better known as DDT) ( Ffrench-Constant, 2013 ). Various other Drosophila species have specialized on resources (such as cacti or Morinda fruit) that contain a range of allelochemicals, or secondary metabolites, many of which are toxic to other organisms and thus serve as defense against herbivory. The genetic bases of these specializations, as they relate to phenomena such as the evolution of pesticide resistance ( McDonnell et al., 2012 ; Miyo, 2012 ) and detoxification ( Gloss et al., 2014 ; Mitchell et al., 2014 ), are already being investigated through comparative genomics.

In 2003, the fly community submitted a white paper for the whole-genome sequencing of additional Drosophila species. The resultant 2007 publication by the Drosophila 12 Genomes Consortium et al., 2007 , of 12 genomes and their analysis, has rapidly revolutionized and expanded the utility of the Drosophila system for studies ranging from computational biology and embryology, to evolution and human disease. In the short time since these genomes were made available, insights have been gained into the emergence and loss of new pathways, the gain and loss of pathway complexity ( Salazar-Jaramillo et al., 2014 ), and the changes in the regulatory network of complex genomes ( Coolon et al., 2014 ; McManus et al., 2014 ). At this point in time, over 30 Drosophila genomes have been sequenced, further expanding the importance of and opportunities provided by these flies. These species, their evolutionary relationships and ecological features, are presented in Figure 2 .

Evolutionary and ecological relationships of Drosophila species.

Phylogenetic relationships (based on Markow and O'Grady, 2005b ) are shown for species with available assembled whole-genome sequences. Within the subgenus Sophophora, D. sechellia has specialized to consume and breed on Morinda fruit and D. erecta has similarly specialized on fruits of various Panandus species, as has D. yakuba although to a lesser degree. Within the subgenus Drosophila, D. buzzatii and D. mojavensis breed in cacti, while D. virilis and D. americana breed in the slime fluxes of deciduous trees. Even among specialists, adult flies may feed more broadly while larvae are more specialized. Arrows indicate substrate specialization by these species. Image credit: Therese Ann Markow.

The natural histories of these species are diverse. Some are highly specialized and live under extreme climatic conditions. Others are adapted to diets high or low in protein or carbohydrates. Their microbiomes differ ( Chandler et al., 2011 ) as does their genomic machinery for dealing with various environmental challenges ( Low et al., 2007 ; McDonnell et al., 2012 ).

The expanding number of sequenced Drosophila species' genomes offers a tremendous opportunity to learn from the ways in which different species have solved the challenges of living in different niches. But laboratory studies alone, in the absence of an understanding of the natural history, the challenges and lifestyles of these flies, will never allow us to fully exploit what they have to offer. By characterizing the natural history of not just D. melanogaster but also of those other Drosophilids with contrasting ecologies, we will be able to detect and exploit such phenomena as novel resistance mechanisms and novel dietary adaptations and reproductive strategies.

This knowledge can then be employed to advance our understanding of basic biological principles, thus building a more robust toolbox to apply to human problems. For example, the efficacy of anticancer therapeutic agents depends not only on their effects on the tumor but also on the ability of the host to tolerate the toxic effects of the drug. The many ways in which fly species have dealt with detoxification and tolerance could inform and refine drug discovery. It's not difficult, as one might imagine, to study a large number of different Drosophila species in the wild. But it's time to do more of it.

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Author details

Contribution, for correspondence, competing interests, national science foundation (nsf) (dbi-1351502), consejo nacional de ciencia y tecnología (national council of science and technology, mexico), university of california institute for mexico and the united states (uc mexus).

The funders supported the gathering of many of the observations reported in this paper.

Publication history

• Received: February 2, 2015
• Accepted: May 2, 2015
• Version of Record published : June 4, 2015

© 2015, Markow

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The Natural History of Model Organisms: New opportunities at the wild frontier

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A rapid phylogeny-based method for accurate community profiling of large-scale metabarcoding datasets

Environmental DNA (eDNA) is becoming an increasingly important tool in diverse scientific fields from ecological biomonitoring to wastewater surveillance of viruses. The fundamental challenge in eDNA analyses has been the bioinformatical assignment of reads to taxonomic groups. It has long been known that full probabilistic methods for phylogenetic assignment are preferable, but unfortunately, such methods are computationally intensive and are typically inapplicable to modern Next-Generation Sequencing data. We here present a fast approximate likelihood method for phylogenetic assignment of DNA sequences. Applying the new method to several mock communities and simulated datasets, we show that it identifies more reads at both high and low taxonomic levels more accurately than other leading methods. The advantage of the method is particularly apparent in the presence of polymorphisms and/or sequencing errors and when the true species is not represented in the reference database.

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Anecdotal, Historical and Critical Commentaries on Genetics

Thomas hunt morgan at the marine biological laboratory: naturalist and experimentalist.

IN the early 1910s, researchers at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, might have wondered why a colleague, Thomas Hunt Morgan ( Figure 1 ), began shipping fruit flies from his Columbia University lab to the MBL each summer. After all, the Woods Hole currents supplied the MBL with a rich variety of marine organisms and Morgan, an avid practitioner of experimental embryology, made good use of them.

T. H. Morgan in 1920. This portrait of Morgan was taken by A. F. Huettner. Courtesy of MBL Archives.

Yet those who knew Morgan well would not have been surprised by his insect stocks. A keen naturalist, Morgan studied a veritable menagerie of experimental animals—many of them collected in Woods Hole—as a student and later researcher at the MBL from 1890 to 1942. Moreover, Morgan always had a diversity of investigations going on simultaneously. “This was the way Morgan worked: he wasn't happy unless he had a lot of different irons in the fire at the same time,” wrote A. H. Sturtevant, Morgan's long-term collaborator ( S turtevant 2001 , pp. 4–5). In Morgan's first 3 decades at the MBL, for instance, he studied at least 15 different species, including the now-famous fruit fly, while investigating a variety of problems related to his central interests in development and heredity ( M organ 1888–1937 ; M arine B iological L aboratory 1909 ).

Morgan was also a vocal proponent of experimentalism, and at the MBL he (quite successfully) joined with Jacques Loeb in arguing for a quantitative, predictive foundation for biological studies ( A llen 1969 ). Morgan was interested only in scientific problems that could be experimentally tested. Deeply wary of ungrounded hypotheses, he sought not overarching theories, but experimental methods that would allow him to identify proximate causes. This stance would triumph in Morgan's work with the fruit fly, Drosophila melanogaster . Morgan initially began breeding this animal in his search for an experimental approach to evolution: he was testing an alternative to the theory of natural selection, which he felt was insufficient to explain the origin of new species. But when a sex-linked mutation appeared in his Columbia University stocks in 1910, Morgan's attention was diverted to analyzing the material basis of sex determination and inheritance. By 1912, he and his colleagues were mapping the location of genes on chromosomes. These epoch-making studies launched the field of experimental genetics.

Morgan's penchant for maintaining multiple, diverse lines of investigation paid off in important ways, as this review of his work at the MBL up through the mid-1920s shows. First, Morgan was able to synthesize his research on many different organisms in his book Regeneration ( M organ 1901 ), which today provides a useful and insightful perspective on regenerative medicine. Second, evidence from originally distinct studies conceptually converged for Morgan. An example is his post-1910 work at the MBL on the insects phylloxeran and aphid, which confirmed his early Drosophila results on the relationship of the chromosomes to sex determination and inheritance.

Morgan's dual characteristics as a “naturalist and experimentalist” ( Figure 2 ) place him historically in an era when biology was transitioning from a descriptive and often speculative field to an experimental one ( A llen 1969 ). Yet they may indicate also why Morgan was a successful scientist, one who received the first Nobel Prize ever awarded in genetics in 1933 and became the first in a now-long list of Nobel Laureates affiliated with the MBL. Morgan's appreciation of natural diversity and his wide-ranging investigations, coupled with his skepticism toward a priori theories, could have left him flailing in a biological wilderness. What anchored him was his strict experimentalism, his insistence on choosing problems that could be analytically tested.

Naturalist, experimentalist, and trustee. This plaque in the lobby of Lillie Laboratory at the MBL commemorates T. H. Morgan's long-term and wide-ranging activities at the laboratory. Courtesy of Matthew Person.

EARLY YEARS: MARINE ORGANISMS, MORPHOLOGY, AND EXPERIMENTAL EMBRYOLOGY

In 1886, when T. H. Morgan was 20 years old and about to start graduate studies in zoology at Johns Hopkins, he attended the summer marine laboratory in Annisquam, Massachusetts, where he first learned how to collect and handle marine organisms for basic biological research. “Altogether, I am delighted with myself for being here and without doubt the work will be of the greatest assistance to me next winter,” he wrote to a friend ( A llen 1978 , p. 25). As it turned out, the Annisquam laboratory closed down after that summer, and its benefactors moved its glassware, apparatus, boats, furniture, and fixtures to Woods Hole, where they established the MBL in 1888 ( L illie 1944 ). When Morgan died in 1945, he was “the last surviving personal link” between the MBL and its predecessor at Annisquam, wrote Edwin G. Conklin of Princeton University, Morgan's close friend and 45-year colleague at the MBL ( C onklin 1947 , p. 14).

At Johns Hopkins, Morgan trained with embryologist W. K. Brooks, who promoted the use of marine organisms for studies of early development, as was then practiced at the Naples Zoological Station and other European marine laboratories. Through Brooks' arrangement, Morgan spent the summer of 1889 at the U.S. Fish Commission Laboratory in Woods Hole, and the following summer Morgan was one of 20 investigators at the nascent MBL, which had opened in 1888. During these two summers, Morgan collected and studied sea spiders for his doctoral research. Morgan, like Brooks, was then working within the paradigm of descriptive morphology; in his thesis, he sought to trace the phylogenetic relations of sea spiders with other arthropods by studying their embryological development. In 1891, after defending his thesis and accepting an assistant professorship at Bryn Mawr College, Morgan returned to the MBL and did so again for the next two summers.

Morgan's activities in those years are not much noted in descriptions of the MBL written by his contemporaries. Yet Morgan's profile in Woods Hole rose significantly after he spent 10 months at the Naples Zoological Station in 1894–95, carrying out research with the German embryologist Hans Driesch. Through Driesch, Morgan came into direct contact with the European school of experimental embryology that had begun in the 1870s with Wilhelm His, who developed methods for sectioning embryos and argued for a cleaving of the field from phylogenetic studies. Morgan had already been attracted to these new methods and this approach and had devised experiments on teleost and echinoderm eggs at the MBL in 1893. Other MBL investigators were interested, too. A few months before Morgan left for Naples, W. M. Wheeler translated Wilhelm Roux's manifesto for an experimental and mechanistic approach to embryology, or Entwicklungsmechanik , and presented it as a Friday Night Lecture at the MBL ( R oux 1895 ; M aienschein 1991 ).

Morgan's Naples experiments, which were designed to identify causal factors controlling development of the egg cell, made a singular impression on his Woods Hole contemporaries. Edmund B. Wilson, Morgan's longtime friend and colleague at Columbia University and at the MBL, described a “beautiful experiment” Morgan conducted in Naples in which he manipulated the relative position of frog blastomeres and gave “most conclusive evidence that each of the (first) two blastomeres contains all the materials, nuclear and cytoplasmic, necessary for the formation of a whole body, and that these materials may be used to build a whole body or half-body, according to the grouping that they assume” ( M organ 1895 ; W ilson 1897 , p. 319). In another experiment, Driesch and Morgan showed with ctenophore eggs that if part of the cytoplasm is removed, the remainder gives rise to incomplete larvae showing defects corresponding to the part removed ( D riesch and M organ 1895 ). “Thus the way was prepared for theories of organ-forming germ regions in the egg and later of ‘organ-forming substances,’” wrote Frank R. Lillie in his history of the MBL. “The chapter in experimental embryology that immediately follows from this is a long one, with important contributions from Woods Hole investigators,” particularly Wilson, Conklin, Lillie, and Morgan himself ( L illie 1944 , p. 128).

REGENERATION AND ARTIFICIAL PARTHENOGENESIS: FROM EARTHWORMS TO SEA URCHINS

After his Naples stay, Morgan next returned to the MBL as an investigator in 1897. At that point, he also became deeply involved in organizational matters at the MBL and was named a trustee, a position he would hold for the rest of his life ( C onklin 1947 ). Over the next five years, Morgan's research interests at the MBL would dovetail closely with those of Jacques Loeb, whom MBL director C. O. Whitman had recruited to establish a department of physiology at the MBL in 1894. Loeb had also been influenced by Driesch and was even more adamant than Morgan in his experimentalist, mechanistic approach to biology. Together, Morgan and Loeb waged battle in Woods Hole against the descriptive, phylogenetic tradition. “Loeb has been here [in Woods Hole] … all summer and I have learned to know him so much better,” Morgan wrote to Driesch in 1899. “We agree on so many fundamental views (and differ on these points from most of the people here) that we have become very good friends and strong allies. We have done battle with nearly all the other good morphologists and still survive their united assaults” ( A llen 1978 , p. 326).

The first line of research Loeb developed at the MBL was regeneration ( L illie 1944 ). Morgan, beginning in 1897, also pursued experiments on regeneration in a variety of organisms, including earthworms, hermit crabs, and teleost fish. By 1901 he had published more than 30 articles and a book on the topic, and much of this work was carried out at the MBL ( M arine B iological L aboratory 1909 ; M aienschein 1991 ). Morgan saw regeneration as essentially similar to normal development; he understood the value of using regenerative organisms to study both. One outcome of Morgan's extensive studies on regeneration was they led him to initially reject the Darwinian theory of natural selection, particularly the idea that adaptations have arisen due to their usefulness. How could the regenerative power have been slowly acquired through selection, Morgan argued, since it is useful to the animal only if the injured part entirely regenerates in a single generation? “The building up of the complete regeneration by slowly acquired steps, that cannot be decisive in the battle for existence, is not a process that can be explained by the theory (of natural selection),” he wrote ( M organ 1901 , p. 129). These considerations would lead Morgan to explore alternative mechanisms for the origin of species, which later led to his experimental use of fruit flies.

In 1899, Morgan was at the front lines of Jacques Loeb's spectacular discovery of artificial parthenogenesis at the MBL, which brought the lab much publicity ( L oeb 1899 ). Morgan reported in 1896 and in 1898 on the induction of artificial asters in sea urchin eggs by the use of hypertonic seawater and in 1899 on the effects of various salt solutions on unfertilized sea urchin eggs, finding that they caused irregular cell division ( M organ 1896 , 1898 , 1899 ). These latter experiments, carried out at the MBL, nearly “come to a complete anticipation of Jacques Loeb's famous discovery,” Lillie wrote ( L illie 1944 , p. 133). According to A. H. Sturtevant, later Morgan's long-term collaborator, there was “at the time a rather general feeling that Loeb had taken more credit than was due him for his discovery of artificial parthenogenesis,” and Morgan “clearly felt that Loeb had been secretive about his own work and had used every opportunity to find out just what Morgan was doing”; however, Morgan “was not as resentful as were some other members of the Woods Hole group on his behalf” ( S turtevant 1959 , p. 288). The artificial parthenogenesis episode seems not to have unduly troubled Morgan; he and Loeb remained friendly until Loeb's death in 1924.

SEX DETERMINATION: INSECT STUDIES

Beginning about 1906, Morgan also pursued studies of sex determination in insects at the MBL, focusing on phylloxerans and on aphids that he later reported collecting from bearberry plants at nearby Quissett, Massachusetts ( M organ 1915 ). The relationship of the chromosomes to sex determination was at that time a topic of vigorous investigation at the MBL, particularly by Thomas H. Montgomery, Edmund B. Wilson, and Nettie Stevens, a former student of Morgan's at Bryn Mawr ( M arine B iological L aboratory 1909 ). Parallel cytological studies by Wilson and Stevens in 1905 (not at the MBL) provided strong evidence that the X chromosome determined sex, but Morgan remained unconvinced, believing the cytoplasm and physiological development played a more important role.

The evolution of Morgan's thought on sex determination is apparent in his papers on the phylloxerans and aphids, both of which have a life-cycle phase in which parthenogenetic eggs produce both males and females. Morgan wanted to find out what in the egg determines what sex it will become. In 1906, Morgan reported finding no discernible difference between the chromosomes of the male-producing and the female-producing phylloxeran eggs, nor in their cytoplasm. In watching them develop, though, he noted one importance difference: “the precocious development of the relatively enormous reproductive organs of the male,” suggesting that “a pre-existing mass of cytoplasm from which the testis develops may be present in the egg.” This led him to suggest that “the immediate determination of the sex is a cytoplasmic phenomenon” ( M organ 1906 , p. 206). In 1908, he reported having discovered that somatic cells in the female phylloxeran have six chromosomes, while those in the male have only five; thus at some point in the parthenogenetic egg the ones that will become male lose a chromosome. He was still considering cytoplasmic influences: “It follows that the egg as well as the sperm has the power of determining sex by regulating the number of its chromosomes,” he wrote ( M organ 1908 , p. 57). In a 1909 study of both phylloxerans and aphids, Morgan concluded that the sex of the egg is determined to be male or female before any change in chromosome number. “Clearly, the egg as well as the sperm contains factors that determine sex,” he wrote ( M organ 1909 , p. 235).

Then, an event in Morgan's Drosophila research, which he had initiated in about 1908, catalyzed a distinct change of course in his thought. In May 1910, Morgan discovered a male fly with a white-eyed mutation in his Drosophila stocks at Columbia University. By June, he had done enough crosses to realize he had in his white-eyed fly “a splendid case of sex-limited inheritance,” as he wrote to a friend from Woods Hole ( S chwartz 2008 , p. 179). Morgan submitted his classic Science paper describing his new Drosophila results from Woods Hole, and it was published in July ( M organ 1910 ). Although Morgan described the expression of the white-eyed mutation in males only, it is noteworthy that he did not mention chromosomes in this paper. Yet Morgan soon found additional sex-linked traits in Drosophila, which he first publicly reported in a lecture at the MBL in July 1910. These findings would lead him to accept the chromosomal theory of sex determination, as well as chromosomes serving as the physical basis for Mendelian inheritance ( M organ 1911a ; A llen 1978 ; M aienschein 1984 ). In 1912, after his Drosophila discoveries and with new cytological evidence from the phylloxerans, Morgan unequivocally ascribed differences in the male and female parthenogenetic phylloxeran eggs to differences in their sex chromosomes. (Prior to this, he admitted in this paper, “the value of the chromosome hypothesis in sex determination” might have seemed to “hang in the balance.”) ( M organ 1912 , p. 479).

Sturtevant considered Morgan's phylloxeran and aphid work, which he continued to pursue in Woods Hole until 1915, as very important in confirming the chromosome hypothesis. “[Morgan] showed that the facts, which at first seemed quite inconsistent with the chromosome interpretation of sex determination, were in fact intelligible only in terms of that interpretation,” Sturtevant wrote. “This was one of Morgan's most brilliant achievements, involving great skill and patience in the collecting and care of the animals, insight in seeing what were the critical points of study, and ability to recognize and to follow up on unexpected facts. The results were of importance in serving to demonstrate the role of the chromosomes in sex determination, at a time when that importance was seriously questioned by many biologists” ( S turtevant 1959 , pp. 289–290).

MENDEL AND MUTATIONS: MICE AND FRUIT FLIES

The rediscovery of Gregor Mendel's work in 1900 brought questions of evolution and heredity to the fore in biological circles. Morgan began investigations of Mendelian inheritance in 1905, when he started breeding rats and mice ( K ohler 1994 ). In the summer of 1907, he caught a house mouse in Woods Hole with the “sport,” or mutation, of a pure white belly. “Later, I caught two more such mice and, in the same closet, another typical house mouse. In the neighborhood, I have caught a few other white-bellied mice,” Morgan reported (which summons a vision of an agile Morgan chasing mice around Woods Hole). Morgan then obtained white-bellied mice from Iowa and New York and began a series of breeding experiments crossing the wild sport with various domesticated races. “My intention was to familiarize myself at first hand with the process of Mendelian inheritance,” he wrote, by observing the varieties of coat color that his crosses produced ( M organ 1911b , p. 88).

At some point in the midst of this work, probably in 1908, Morgan started breeding Drosophila, not for Mendelian studies, but as a foray into experimental evolution. Morgan's studies of regeneration had led him to reject Darwin's concept of new species arising by natural selection of minute, random, continuous variations. Instead, Morgan entertained Hugo de Vries' concept that species evolved through discrete jumps, which de Vries called mutations ( A llen 1978 ). De Vries had predicted that, under certain conditions, animals can enter “mutating periods.” With Drosophila, Morgan wanted to see if he could induce such a mutating period through intensive inbreeding ( A llen 1975 ; K ohler 1994 ).

The first researchers to use Drosophila experimentally were William E. Castle and his students at Harvard University ( C astle et al . 1906 ) and Morgan was clearly influenced by this work. It is not certain who gave Morgan his first Drosophila stocks; but “certainly some of the early material was collected in grocery stores which existed then in Woods Hole,” Sturtevant wrote ( S turtevant 2001 , p. 3). Morgan himself in a letter to A. F. Blakeslee in 1935, responding to whether he had obtained his first stocks of flies from F. E. Lutz, wrote “…if so, I have forgotten it” ( C arlson 2004 , p. 168).

For many months, Morgan's inbreeding experiments with Drosophila turned up nothing, and when Ross Harrison visited Morgan's Columbia University lab in January 1910, Morgan referred to it as “two years' work wasted” ( K ohler 1994 , p. 41). Yet, soon after, a stream of mutants began appearing in his stocks, starting with an atypical thorax pattern. Overjoyed, Morgan at first thought he had succeeded in inducing a de Vriesian mutating period in the fly ( K ohler 1994 ). But soon the sex-limited Mendelian ratios Morgan observed for white-eye and other mutations drew his attention from his original focus on experimental evolution to an analysis of the chromosomes in sex determination and inheritance, despite his prior skepticism toward the chromosomal theory. As Castle later wrote, “Morgan was too good a scientist to hold a conclusion after he believed it had been clearly disproved” ( C arlson 2004 , p. 163).

Beginning in 1913 and continuing through the 1920s, Morgan brought members of his Columbia University “fly room,” particularly A. H. Sturtevant and C. B. Bridges, to the MBL each summer, where they carried out their Drosophila research in the Crane Building ( S turtevant 1959 ) ( Figure 3 ). “This did not mean any interruption in the Drosophila experiments,” Sturtevant later wrote. “All the cultures were loaded into barrels—big sugar barrels—shipped by express, and what you started in New York, you'd finish (in Woods Hole) and vice versa.” They traveled from New York by boat, lugging cages of chickens, pigeons, mice, and other animals Morgan was working on, and “when Morgan got to Woods Hole, he plunged deeply into work on marine forms, even while his work with Drosophila was actively going on,” Sturtevant wrote ( S turtevant 2001 , p. 4). From 1917 to 1924, for example, Morgan conducted an extended study of regeneration and “intersex” mutations in the fiddler crab at the MBL ( M organ 1920 , 1924 ). Also accompanying Morgan to Woods Hole since their marriage in 1904 was biologist Lilian Vaughan (Sampson) Morgan, who investigated amphibian breeding and development at the MBL in the 1890s and later transitioned into genetics. In 1913, Lilian Morgan cofounded what is now the Children's School of Science in Woods Hole ( K eenan 1983 ).

Morgan and friends: T. H. Morgan called this photo, taken at the MBL in the summer of 1919, “Solving the Problems of the Universe.” Clockwise from left: T. H. Morgan, Calvin Bridges (kneeling), Franz Schrader, E. E. Just, A. H. Sturtevant, and an unidentified person. Courtesy of MBL Archives.

Morgan's success with Drosophila in establishing a material basis for the Mendelian theory of inheritance was a triumph of the experimentalist approach, which would come to dominate biological research in the 20th century. Yet the diversity of Morgan's studies at the MBL over more than 50 years indicates he also appreciated the naturalist Louis Agassiz's dictum, which is still displayed in the MBL Library: “Study Nature, not Books.” In Morgan's time, the naturalist and the experimentalist traditions seemed to pose a dichotomy: descriptive vs . quantitative, holistic vs . reductionistic. Morgan did not choose either/or: he adopted, with great success, something of both.

Acknowledgments

The authors are grateful to Jane Maienschein and Garland E. Allen for helpful discussions about Morgan and for generously providing feedback and suggestions on the manuscript. The authors also thank Catherine N. Norton, library director, and Diane M. Rielinger, archivist, of the Marine Biological Laboratory Woods Hole Oceanographic Institution Library, Woods Hole, Massachusetts, for archival assistance.

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How the Humble Fruit Fly Changed Science

Tracing the journey of the fruit fly from its entry into science to its current position as an important tool for genetic research.

By National Centre for Biological Sciences, Tata Institute of Fundamental Research

curated by Nithila Madhu Kumar and Kailas Honasoge

Veronica Rodrigues observes the behaviour of Drosophila in the fly maze. (circa 1979) Original Source: Department of Biological Sciences, Tata Institute of Fundamental Research

This is a picture of Veronica Rodrigues , a biologist. The photograph was taken around 1979 when she was a PhD student at the Tata Institute of Fundamental Research (TIFR) in Bombay, India. Wondering what she’s looking at so intently?

Drosophila melanogaster with visible proboscis (2017-11-03) by Sanjay Acharya Original Source: Wikimedia Commons

Well, fruit flies .

By Fritz Goro LIFE Photo Collection

Lab animals

Think about animals in a lab, and lab mice come to mind immediately. But there is another creature that has made its mark significantly in the labs of science: Drosophila melanogaster. Or, the common fruit fly.

Two red eyed Drosophila (2017) Original Source: Drosophila Facility, National Centre for Biological Sciences

Model organisms

Our interactions with Drosophila are limited to swatting them away when they're hovering around ripe bananas. In the world of science, however, the humble fruit fly is a model organism – a creature that is studied with the hope that learnings may be applied to other species as well.

Drosophila melanogaster (2009-07-05) by Thomas Wydra Original Source: Wikimedia Commons

Drosophila has been used in research since the early 20th century. In this story, we look at fruit flies and their fascinating journey over the years, across countries, generations, and cultures.

Guinea Pigs (1961) by Paul Schutzer LIFE Photo Collection

Drosophila's debut into science

Up until the late 19th century, guinea pigs and rats were scientists’ lab animals of choice. In the early 1900s, American geneticist William E Castle realised that fruit flies were easier to study since they bred at a much higher rate than guinea pigs or mice. Fruit flies also cost considerably less and were smaller.

Thomas Hunt Morgan (1891) Original Source: Wikimedia Commons

Castle’s decision greatly influenced Thomas Hunt Morgan , an evolutionary biologist and geneticist whose work on inheritance (around 1910) helped put the fruit fly on the map as a model organism.

LIFE Photo Collection

Putting Darwin and Mendel to the test

The early 20th century was a time when radical ideas were spurring radical science. Charles Darwin’s theory of evolution and Gregor Mendel’s rules of heredity were widely accepted. But Morgan was not convinced by them because he thought they lacked experimental verification. His research with Drosophila, however, engineered a curious turn of events, and he went on to win the Darwin Medal in 1924 for his work on inheritance.

Columbia University Fly Room with a bunch of ripe bananas. Original Source: American Philosophical Society

The Fly Room

A bunch of overripe bananas was a permanent fixture in Morgan’s lab at Columbia University. While working in his famous ‘Fly Room’, Morgan observed something. 

A white eyed Drosophile next to a red eyed one (2017) Original Source: Drosophila Facility, National Centre for Biological Sciences

Most images of Drosophila will show you that it has bright red eyes. What Morgan noticed, however, was a male fruit fly with pale white-ish eyes. These eyes were the result of a random mutation of a gene, a fairly common occurrence.

DNA and gender (creative art) (2018) by Anmol Venkatesh Original Source: Archives, National Centre for Biological Sciences

Morgan was able to identify that the gene with the random mutation was located in the flies’ sex chromosomes (think X and Y). This was a groundbreaking discovery because up until then, no one really knew where our genes were. Connecting these dots would prove to be the foundation of modern genetics.

By Herbert Gehr LIFE Photo Collection

There was a small cascade of influences in the Drosophila world. Castle influenced Morgan. And Morgan, in turn, influenced his students to study the fruit fly further. One of them was Herman J Muller.

In the mid 1920s, Muller exposed fruit flies to a healthy dose of radiation. He discovered that ionizing radiation causes mutations in genes, and could be potentially harmful.

Interactions between physics and biology (creative art) (2018) by Anmol Venkatesh Original Source: Archives, National Centre for Biological Sciences

Muller’s discovery sent shockwaves through the scientific community. His work connecting radiation and mutations connected physics and biology, two subjects that had not mingled much until this point. This acted as a trigger that eventually led to many physicists shifting over to biology.

Seymour Benzer (1974) Original Source: Archives, California Institute of Technology

Seymour Benzer and the fly

One of these converted biologists was Seymour Benzer, a man best described by this picture (note the fruit fly tie). Benzer made the shift to biology in the late 1940s, and initially worked on bacteriophage, a type of virus, but was later inspired to take up a new area of study: genetics and behaviour.

Genetic Family by Herbert Gehr LIFE Photo Collection

Strange behaviour

Observing his daughters' acutely different personalities, Seymour Benzer grew interested in behaviour and the role of genetics and environment in determining it. In 1966, he joined Caltech under Robert Sperry, a neurobiologist, where he decided to study behaviour with Drosophila as his model organism.

White-eyed Drosophila (2006-11-16) by Paul Reynolds Original Source: Wikimedia Commons

What Benzer really liked about fruit flies was their small size, short life span and statistically large populations. His lab studied the flies’ circadian rhythms and observed the effects of genetic mutations on behaviour. One particular mutation they studied was called, "drop-dead," because it caused perfectly healthy flies to suddenly, well, you know, drop dead.

The "I'm Not Dead Yet" or "INDY" mutation (2017) Original Source: Drosophila Facility, National Centre for Biological Sciences

Incidentally, there is also the "Kumbhakarna" gene that causes flies to take forever to snap out of induced-paralysis, as well as the “cheap date” gene that increases a fruit fly’s susceptibility to alcohol. But the topper must be the “I’m Not Dead Yet” gene that increases the longevity of flies. Who would’ve guessed that geneticists had a thing for Monty Python references?

Obaid Siddiqi and Seymour Benzer in Pasadena Original Source: Courtesy of Siddiqi Family

Fruit fly paralysis

For a few years in the early 1970s, a lanky Indian from Aligarh worked in Benzer's lab. Before joining the lab, Obaid Siddiqi, a microbiologist who worked on bacteria, spent a year at MIT learning neurobiology. In Benzer's lab, he worked on certain mutants of Drosophila that were temperature-sensitive—high temperatures would paralyse them. Siddiqi's interest in paralysed mutants had interesting origins. Listen to him in the next slide as he recalls a lecture from his MIT days...

Obaid Siddiqi Original Source: Archives, National Centre for Biological Sciences

"When I was at MIT, there was a man, a Japanese scientist, David Suzuki . He came to MIT to give a lecture. David Suzuki had discovered the first temperature-paralyzed mutants of Drosophila. So I read David Suzuki's papers and David came to give a lecture at MIT and I remember that he had a test tube of Drosophila mutant paraTS, it is called paralyzed temperature sensitive, in his coat pocket. When he was lecturing, he took out the tube and held it in his hand and when he removed the hand, of course, all the flies were paralyzed and fell to the bottom. I was fascinated by this lecture, because anybody could see that this paralysis might involve the blocking of the nervous system. So I actually made up my mind right then that that was what I was going to work on-- to look at paralyzed mutants."

Obaid Siddiqi in the TIFR Molecular Biology Unit (1967) Original Source: Archives, Tata Institute of Fundamental Research

Olfactory creatures

Siddiqi returned to India where he was the head of the Molecular Biology Unit in the Tata Institute of Fundamental Research (TIFR), Bombay. He continued his work with Drosophila – their genetics and their neurophysiology. He began thinking about olfaction - or smell- in Drosophila – uncharted territory at the time. Fruit flies are extremely olfactory creatures and so it made sense to look at olfaction to understand their neurophysiology.

Obaid Siddiqi's notes on the designs for a fly maze (1991) Original Source: Archives, National Centre for Biological Sciences

Olfaction was a mainstay for Siddiqi and for TIFR's Molecular Biology Unit. This image shows Siddiqi's attempt (much later, in 1991) to improve upon a fly maze.

Which brings us back to that image of Veronica Rodrigues and her fruit fly maze.

Veronica Rodrigues' letter to Obaid Siddiqi about her interest in doing a PhD at TIFR Original Source: Archives, National Centre for Biological Sciences

In the mid-1970s, the Kenya-born Rodrigues applied to TIFR to do a PhD under Obaid Siddiqi thinking he still worked on bacteria, as shown in this letter. She then decided to research olfaction in the fly, even building her own instrument – the Y-maze shown beside her in the previous photo.

The difference between humans and flies

The fruit flies in Siddiqi’s lab helped steer understanding of olfaction. But around the same time, in the mid 1970s, larvae of fruit flies in a research lab in Germany unpeeled our knowledge of larvae cuticles, the outer protective covering of larvae. Biologists looked at mutant flies with strange looking cuticles (these mutants were also given fun names like “Hedgehog” and “Hairy-Barrel”) and studied the genes responsible for their appearance.

Drosophila and human chromosomes (creative art) (2018) by Anmol Venkatesh Original Source: Archives, National Centre for Biological Sciences

What they found was that similar genes exist in more complex organisms. This was a stepping stone to eventually discovering that humans share versions of many genes with Drosophila. According to a 2001 study , it’s a 70% match.

Connecting the places of Drosophila research from the narrative (2018) by Nithila M.K. Original Source: Courtesy of Nithila M.K.

But no one knew this when Drosophila first entered research. For Castle, they were an easier alternative to guinea pigs and mice. Morgan picked Drosophila because it was an organism whose genes had already been studied to some extent. Benzer says he chose Drosophila because it was convenient. Siddiqi picked up from Benzer’s suggestion and, along with Rodrigues, pioneered a new field in Drosophila research.

An excerpt from Seymour Benzer's paper "From the Gene to Behaviour" (1972) by Seymour Benzer (Accessed through the Caltech Library) Original Source: Benzer S. From the Gene to Behavior. JAMA. 1971;218(7):1015–1022.

From the Gene to Behaviour

As research progressed from the 1970s, the potential to understand humans better through the fly was no longer incidental, but rather a motive to study Drosophila further. The fly helped establish connections between genes and the behaviour resulting from them. Benzer puts this succinctly in a 1971 paper titled “From the Gene to Behaviour”

Jacques Monod (1971-03-11) by Farabola Original Source: Wikimedia Commons

Jacques Monod , a French biochemist, famously said that “anything found to be true of E. coli must also be true of elephants.” This implies that the simplest of model organisms can help us understand the most complex creatures. But is this always the case?

Model organisms and humans (2008) Original Source: Hunter, Philip. “The paradox of model organisms. The use of model organisms in research will continue despite their shortcomings” EMBO reports vol. 9,8 (2008): 717-20.

As Sanjay Sane, a former student at TIFR, and now a scientist at NCBS, says here, using model organisms comes with a limitation. Despite the tools and knowledge at your disposal, there is always the possibility that the organism you are studying is not suited to the question you are pursuing.

Answering questions

There's a reason we keep coming back to the Rodrigues image. It gives us many perspectives to think about the history of Drosophila research. Today, we look back at a scientist who contributed significantly to our understanding of olfaction. But in the late 70s, this was a picture of a young biology student entering the fast-growing world of research with a question that she tackles with the help of a fruit fly.

Drosophila as being more than a tool (creative art) (2018) by Anmol Venkatesh Original Source: Archives, National Centre for Biological Sciences

Drosophila is a model organism and a tool of understanding. But beyond the literal meaning in biology, it has also been a model in other ways. It connects stories. Stories of education, research, science and community. The fruit fly has propelled itself on an interlinking journey across many disciplines, countries, and people. It is the link between these stories that gives us new ways of seeing

This exhibit was a project of second year undergraduate students who interned at the Archives at NCBS: Nithila Madhu Kumar and Kailas Honasoge With contributions from Kushal Choudhary and Shalom Gauri Image Credits: Veronica Rodrigues observes the behaviour of Drosophila in the fly maze Courtesy of Department of Biological Sciences, Tata Institute of Fundamental Research Obaid Siddiqi in the TIFR Molecular Biology Unit Courtesy of Tata Institute of Fundamental Research Archives Seymour Benzer Courtesy of the Archives, California Institute of Technology Obaid Siddiqi and Seymour Benzer in Pasadena Courtesy of the Siddiqi Family Columbia University Fly Room with a bunch of ripe bananas Courtesy of the American Philosophical Society Model organisms and humans Courtesy of The European Molecular Biology Organization

The Indian Spice Trade: In Search for Knowledge and Riches

National centre for biological sciences, tata institute of fundamental research, india: the nexus of international trade in the first millennium, in search of knowledge and riches: communities in indian spice trade, europeans enter indian spice trade, portuguese and dutch records of indian medicine, british and the botanical wealth of india, visions of india in early modern europe.

Morgan used Drosophila as experimental material because They could be grown on simple synthetic medium in the laboratory. It has a short life span There was a clear differentiation of the sexes, the male and female flies are easily distinguishable. All of the above

Morgan worked with the tiny fruit flies, drosophila melanogaster. he found drosophila suitable because - they could be grown on simple synthetic medium in the laboratory. they complete their life cycle in about two weeks, and a single mating could produce a large number of progeny flies. there was a clear differentiation of the sexes, the male and female flies are easily distinguishable. so, the correct option is 'it has a short life span'..

Fruit flies were used as experimental organism by Morgan because

The correct option is b single mating produces a large number of progeny flies fruit fly (drosophila melanogaster ) is considered the “cinderella of genetics” as it was used as a model organism in numerous genetic experiments. this led to the exploration of various important concepts of genetics like linkage and recombination. the reason behind choosing it as an experimental organism is as follows:- they have a life cycle of about 40 to 50 days (or 6-7 weeks). female flies are larger than male flies and are easily distinguishable. flies have many types of hereditary variations that can be seen even with low power microscopes or sometimes even with the naked eye. single mating produces a large number of progeny flies..

Technology in scientific practice: how H. J. Muller used the fruit fly to investigate the X-ray machine

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• Published: 02 June 2023
• Volume 45 , article number  22 , ( 2023 )

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Since the practice turn, the role technologies play in the production of scientific knowledge has become a prominent topic in science studies. Much existing scholarship, however, either limits technology to merely mechanical instrumentation or uses the term for a wide variety of items. This article argues that technologies in scientific practice can be understood as a result of past scientific knowledge becoming sedimented in materials, like model organisms, synthetic reagents or mechanical instruments, through the routine use of these materials in subsequent research practice. The proposed theoretical interpretation of technology is examined through a case where a model organism— Drosophila melanogaster —acted as a technology for investigating a contested biological effect of a mechanical instrument: Hermann J. Muller’s experiments on X-ray mutagenicity in the 1920s. The article reconstructs how Muller employed two synthetic Drosophila stocks as tests for measuring X-rays’ capacity to cause genetic aberration. It argues that past scientific knowledge sedimented in the Drosophila stocks influenced Muller’s perception of X-ray-induced mutation. It further describes how Muller’s concept of X-ray mutagenicity sedimented through the adoption of X-ray machines as a ready-made resource for producing mutants by other geneticists, for instance George Beadle and Edward Tatum in their experiments on Neurospora crassa , despite ongoing disputes surrounding Muller’s conclusions. Technological sedimentation is proposed as a potential explanation why sedimentation and disputation may often coexist in the history of science.

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1 Introduction

Since at least Bachelard ( 1938 , 1951 ) and Heidegger ( 1977 ), it has been repeatedly asserted that science’s reliance on technology distinguishes it from other forms of knowledge. In recent decades, exploring the impact of technology on scientific work has become somewhat of a trademark among authors associated with the so-called practice turn. Notwithstanding their numerous rewarding insights, these accounts have based their notion of technology mostly on mechanical instruments. Even when the focus shifted to non-physical sciences, the archetypes of technology remained pieces of apparatus, like spectrometers, microscopes, lasers, ultracentrifuges, etc. (Hacking, 1983 , 1992 ; Collins, 1974 , 1985 ; Lynch, 1985 ; Galison, 1987 ; Lenoir, 1986 ; Baird, 2004 ; Gooding et al., 1989 ; Pickering, 1995 ) On the other hand, in attempts to capture a more extensive gamut of implements, the terms “technologies” and “tools” tend to cover a broad array of items. One influential example of a wider understanding of technology is Steven Shapin and Simon Schaffer’s tripartite scheme of material, social and literary technologies (Schaffer, 1988 , 1992 ; Shapin, 1984 ; Shapin & Schaffer,  2011[1985] ). Footnote 1 Treating rhetorical devices, pictures, organisation of space, discipline and training as technologies provides an innovative method for highlighting their role in the construction of scientific knowledge. However, the only characteristic that these strategies and objects have common, according to Shapin and Schaffer, is being means for producing facts and making these facts appear as objectively given, rather than manmade—a trait attributable to most elements of scientific practice. Since they essentially equate technology with manner of knowledge production, their interpretation makes it difficult to distinguish technology from other facets of research. Whereas Shapin and Schaffer identify an important common feature of technology—the creation of seemingly objective matters of fact—later comparable accounts tend to be vaguer and do not address at all what constitutes something as a technology in scientific practice. One STS-inspired volume, for instance, devoted to the role of tools in the life sciences, employs this notion as a metaphorical umbrella term encompassing everything from screwdrivers, saws, instruments and organisms to statistics, inscriptions, mathematics, concepts and even entire disciplines (Clarke & Fujimura, 1992 , especially the introduction and contributions of Griesemer, 1992 , and Holmes, 1992 ; see also Feest, 2010 ).

In contrast, I argue for a notion of research technology both broader and narrower than these approaches, which goes beyond equating technology with mechanical artefacts, while aiming to specify its unique nature among other elements of scientific knowledge production. I propose that technology in research practice can be considered as an outcome of past scientific knowledge becoming sedimented in materials that are employed routinely in new investigations of puzzling phenomena. The term sedimentation is borrowed from Husserl, who used it to describe the process of established scientific concepts transforming into passively received thought. Through sedimentation, concepts that were once actively examined and contested become taken for granted. As will be shown, sedimentation occurs when concepts are shared through a perceptible medium, though Husserl mostly limits himself to language (Husserl, 1970b ; Merleau-Ponty, 2002 ). Expanding on his remarks, I argue that technologies result from scientific knowledge becoming sedimented in particular material shapes which can be used to physically interact with investigated phenomena. Following this definition, instruments represent merely one kind of technology alongside standard laboratory organisms, synthetic reagents and other materials with which scientists may probe their research objects. These particular types of technologies can be distinguished from one another according to the different knowledge sedimented in them and their unique physical properties which allow distinct ways of manipulating research phenomena.

The article develops this interpretation of technology by examining a historical episode in which an organism—the fruit fly ( Drosophila melanogaster )—served as a technology for investigating a poorly understood biological effect of a mechanically produced physical phenomenon—the mutagenic effects of X-rays—in Herman J. Muller’s experiments in the 1920s. Until 1915 Muller was one of the leading workers in Thomas Hunt Morgan’s famous Fly Room at Columbia University where Drosophila was first developed into a technology for genetic analysis. After leaving Columbia, Muller began to use specimens of fly mutants to determine the effect of temperature and radiation on the frequency of mutation. In the most successful of these experiments, for which he received the Nobel Prize in 1946, Muller relied on specific Drosophila strains as tests for measuring the mutagenicity of Roentgen radiation.

In Sect.  2 , I outline the general features of technological sedimentation and compare my view to other authors who have similarly suggested that technologies can be regarded as reified scientific thought. Section  3 recounts how Drosophila mutants were constructed into technologies for genetic research, focusing especially on the particular concepts of the gene and mutation that sedimented in the flies and impacted Muller’s later X-ray experiments. Section  4 details how Muller exploited two synthetically designed fly stocks to measure the mutagenic effects of X-rays. I argue that due to the genetic knowledge sedimented in the fly stocks, the Drosophila technologies influenced how Muller framed and perceived the problem of X-ray mutagenicity. Furthermore, I show that Muller attempted to abstract from the results he obtained with the flies a much more general conclusion, alleging that X-ray-induced mutations resembled naturally occurring mutations. By considering the claims Muller made after performing his experiments, I demonstrate how technologies may generate underdetermination. In Sect.  5 , I contend that Muller’s concept of X-ray mutagenicity sedimented by virtue of other geneticists adopting the X-ray machine as a ready-made resource for inducing mutation in various organisms. In parallel, some researchers still scrutinized Muller’s interpretation of X-ray mutagenicity. It follows that technological sedimentation does not presume a complete resolution of disputes, but can rather help explain why users of the X-ray machine took Muller’s concept of X-ray mutagenicity for granted despite new findings raising potential doubts against Muller’s initial claims.

2 Technological sedimentation

Treating technologies as stores of reified past scientific knowledge finds support in remarks made by several previous writers (e.g., Heidegger, 1977 ; Fleck, 1986 [1947]; Wise, 1993 ). Two authors in particular offer more elaborate accounts which inform my position: Hans-Jörg Rheinberger and Bruno Latour.

In his historical analyses of post-war research on protein synthesis, Rheinberger ( 1992a , 1992b , 1995 , 1997 ) introduced a distinction between technological and epistemic things. With the latter he denotes material entities that constitute the object of inquiry in a given experimental system. Epistemic things represent a difference, a surprising result, at which practitioners direct their experiments without yet having a clear idea with what exactly they are working. Once understood and established, epistemic things transform into technologies, which for Rheinberger comprise instruments, organisms, reagents, kits and other materials that form the stable basis of an experimental system. One example are radioactive amino acids, employed as tracer molecules for investigating biosynthetic pathways. Technological objects thus “embody the heavy load of knowledge taken for granted at a particular time” (Rheinberger, 1997 ). Having become settled as “reified theorems”, they are handled routinely and usually outside the line of research in which they initially emerged as epistemic things. What constitutes an epistemic or technological thing at any given time depends on its application in a particular research setting. No object is categorised eternally or in itself. Rheinberger’s analytical framework is attractive, in my opinion, precisely because it captures this fluid interplay between science and technology in experimental practice, instead of reducing it to a distinction between basic and applied research or science versus engineering. However, Rheinberger does not focus on the technological side, but is rather concentrated on scientific activity as a “generator of surprises” ( 1997 ). Although he lays the groundwork for a theory of technology, he pays less attention to the transformation of research objects into devices than to how experimental research transcends its stable technological conditions by creatively tinkering with unanticipated phenomena.

Latour paints a cognate picture of technology in his earlier individual work ( 1987 ) and collaboration with Woolgar ( 1986 ). Like Rheinberger he is inspired by Bachelard and regards pieces of apparatus as reified theory. Also related is Latour’s point that skills, procedures, instruments and documents embody the end-results of controversies in a given field. Once arguments are resolved, knowledge produced within a discipline is packaged into black boxes , devices that may be rallied outside their initial setting, in other laboratories, where they function as a foundation for future research (Latour, 1987 ). Footnote 2 The mass-spectrometer, say, embodies conceptual contents of physics. In sum, the technological equipment of each laboratory “represents the reification of knowledge established in another field” (Latour & Woolgar, 1986 ). While Latour and Woolgar’s account of black boxes is to an extent compatible with my view, I have several issues with their approach to technology. First, most of their examples are mechanical instruments, like the mass-spectrometer or centrifuge. Second, when they move beyond black boxes of physics, they tend to group together an unselective bundle of items, which among other things also include routinized technical procedures, such as bioassays or chromatography (Latour & Woolgar, 1986 ). In my opinion these are better understood as techniques , i.e., sequences of standardised practical operations, which are distinct from reified, material technology (although the two depend on one another, as I explain in the continuation of the paper). Finally, aside from the alternating mechano-centrism and vagueness, Latour and Woolgar overhastily adopt the practitioners’ perspective that literary output is the raison d’être of laboratory activity. This tendency is reflected in the notion of inscription devices , according to which the essential common characteristic of technologies is that they produce inscriptions—figures, diagrams, graphs—which are directly published in scientific texts and used as arguments in disputes (Latour & Woolgar, 1986 ). In other words, what supposedly justifies equating diverse phenomena like statistics, programming languages, machines and technical skill as devices is their production of documents that can be mobilised to resolve controversies and create facts (Latour, 1987 ; Latour & Woolgar, 1986 ). Material technology and technical practices are thus subordinated to writing and visual imagery, regarded as the main goals of laboratory work. Footnote 3 This version of Latour has been relatively widely emulated in science studies, not least by Rheinberger who also attaches primary importance to the “signifiers of science” or what he calls “graphematic traces”—charts, micrographs, ultracentrifugal patterns, etc. (Rheinberger, 1992b , 1995 , 1997 ).

Neither Rheinberger nor Latour devote much attention to how past scientific results actually become reified in technologies. Both mostly limit themselves to observing that the transformation of successful, undisputed scientific knowledge into technologies is a constantly occurring process, and instead focus on how technologies shape research phenomena into “bundles of inscriptions”, to borrow Rheinberger’s ( 1997 ) Latourian expression. My aim is to reinterpret this reification of past scientific knowledge as a process of sedimentation, which I believe to be constitutive of technologies in scientific practice, and analyse how the circumstance that technologies are results of sedimentation affects subsequent research performed with them.

Husserl ( 1970b ) introduced the term sedimentation in his Origin of Geometry (written 1936, published 1939) to describe a socio-historical process through which scientific concepts turn from an object of investigation and debate into taken for granted, ready-made concepts that scientists apply routinely. Sedimentation implies a passive adoption of past concepts as acquired tradition, without consciously reflecting on the origins of their meaning. This is why Husserl also designates it as “traditionalization” of scientific knowledge. Sedimented concepts are employed unthinkingly, without retracing the activities that had initially given rise to them. The history of “the whole toilsome work of achieving” these concepts is hence forgotten and “takes on the character of a mere pathway to a goal” (Husserl, 1970a ). In science, Husserl explains, some sedimentation is unavoidable as it allows each worker to focus on their part of the building, without having to run “through the whole chain of groundings back to the original premises” ( 1970b ). New results are attained based on past acquisitions and in turn become working materials for other findings. Scientific thought is thus continuously realised through sediments of forgotten former activity, which provide a foundation for producing new knowledge (Merleau-Ponty, 2002 ). Moreover, sedimentation is not only imperative for the progression of thought, but represents for Husserl the manner in which concepts may be shared beyond the level of the individual subject as ideas held in common—as “social knowledge” or “general intellect”, one might say, even though Husserl and his interpreters would avoid those terms (Buckley, 1992 ; Merleau-Ponty, 2002 ).

Sedimentation thus occurs when knowledge is shared and becomes a thing in communal use. But to be made accessible to others and shareable, thought must be embodied in a perceptible medium. In Origin, Husserl mentions merely linguistic modes of expression—speech and especially writing. In this article, however, I would like to highlight a particular mode of sedimentation that occurs when scientific thought sediments in instruments, organisms, reagents, kits and other materials used in scientific practice, by virtue of which these materials come to act as technologies in scientific research. Footnote 4 As outcomes of this distinct form of sedimentation, technologies possess a dual quality: (1) a concrete, physical existence as a material thing, and (2) an abstract quality as a sedimentation of mental products of past scientific work. Both the physical and the conceptual quality are significant. The material form of technology allows concepts, sedimented in it, to be brought upon nature. Whereas linguistic or visual forms lack the appropriate shape to physically interact with phenomena emerging in scientific practice, technologies reintroduce past sedimented concepts into current research in a material form that can be used to manipulate new objects of investigation. Muller’s flies, for instance, yielded results about X-ray mutagenicity that were published in journals, newspapers, textbooks, presented at conferences and, eventually, taught in schools. But his concept of X-ray mutagenicity could not be applied as a mutant-producing technology in other laboratories had it not sedimented in the X-ray machine, which became a routinely used material in subsequent genetic experiments. On the other hand, because technologies are freighted with conceptual sediments, interventions with them are not neutral. They impose upon new objects a set of what I call technological parameters . These parameters are certain select characteristics that technologies isolate in the investigated phenomenon, which serve as handholds that researchers use to manipulate and understand the phenomenon. The particular characteristics by means of which scientists initially grasp unexpected phenomena therefore depend on the particular technologies with which they handle them. Footnote 5

Although my analysis of technological sedimentation is inspired by Husserl’s term, I will depart from his interpretation in several interrelated aspects. First, I agree with Husserl that the object of sedimentation are concepts and the accompanying propositions which fix their meaning and relation to other concepts. What sediments are thus not full-fledged theories, but rather more circumscribed abstract descriptions of a phenomenon, property, process or reaction, like X-ray mutagenicity, crossing-over, gene-enzyme relationship, etc. However, Husserl overlooked that the sedimentation of these abstractions occurs through their practical use. When we read an article or listen to a lecture about the gene, for instance, we do not merely receive a concept but also concrete examples of how this term should be applied in written or oral utterances. By experiencing socially situated instances of communication, we spontaneously also learn conventions of using received concepts; to the extent that most scientists and lay-people can adopt the term gene in their own everyday use without necessarily meditating on the precise meaning ascribed to the word. Similarly, past scientific concepts associated with research materials like the fruit fly or X-ray tube become sedimented knowledge for practitioners as they use these materials in concrete experimental situations. The more they work with these materials, the more practical situations they experience, the more routine becomes the use of these technologies and the more taken for granted, familiar and inconspicuous become the conceptual abstractions sedimented in them. Much like one does not need to know precisely what a gene is to form meaningful utterances with the word, merely be conversant with the rules of using it in a sentence, it suffices for a biologist to be capable of operating an X-ray tube (or recognising when to have someone operate it) to conduct experiments on genetic mutation, without scrutinizing the established scientific knowledge about X-rays.

Second, the practical nature of sedimentation is why I propose technologies be distinguished from techniques —sequences of practical operations for working with technologies in experimental situations (cf. Jordan & Lynch, 1992 ; Latour, 1994 ; Rapp, 1981 ). Whereas the concepts sedimented in technology usually represent explicit, theoretical knowledge, techniques comprise manual and perceptual skills that presuppose rehearsal and bodily discipline. The two types of knowledge are obviously mutually dependent: practical expertise can often be theoretically codified and operating a technology inevitably demands an appropriate assortment of skills (Collins, 1990 ; MacKenzie, 1996 ). But sedimentation can occur precisely because the concepts sedimented in technologies and the techniques for using them may exist and develop separately. One can master the use of a technology while taking for granted the concepts sedimented in it. Within each historical site of scientific production, we can thus identify a particular combination of technologies and techniques that drive them. When concepts sediment in new materials that are adopted in research, these new technologies typically bring about a reorganisation of the labour process and development of different techniques.

The practical nature of sedimentation is also closely related to my third point: both a medium and its use by a community of people are necessary for sedimentation to happen. Husserl mostly emphasises that sedimentation occurs by virtue of concepts becoming embodied in perceptible media. But it is just as important that these media are used by other people than their original creators. If no one adopts an expression introduced in an article, if scientists do not apply a material in their research practice, no sedimentation takes place. Sedimentation therefore presumes a community for which the sedimented concepts come to represent a shared tradition. At the same time, Husserl is right in emphasising that the form in which concepts are shared is not a neutral means of transmission. Footnote 6 Because concepts are sedimented in a material like the fruit fly or the X-ray machine, scientists may use them in their practice without actively examining the concepts sedimented in these technologies. The medium enables techniques and sedimented knowledge to exist and evolve separately. Practitioners may master using a material in concrete situations without reflecting on how “they”, as a community of people who deploy this material as a ready-made thing, have come to know what this material is or how it works. By adopting the medium in this matter-of-factly manner, however, users also more-or-less tacitly accept the conceptual abstractions sedimented in it. The medium therefore facilitates the undeliberated way of receiving past scientific concepts, which is characteristic of sedimentation.

Finally, I distance myself from Husserl’s view of sedimentation as a unidirectional process, a “continuous synthesis in which all acquisitions maintain their validity” ( 1970b ; see also Hacking, 2010 ). Just as schematic, albeit less teleological, is Latour and Rheinberger’s shared belief that the transformation of facts into technologies only happens after these facts become undisputed (Latour, 1987 ; Latour & Woolgar, 1986 ; Rheinberger, 1997 ). As I will demonstrate in Sect.  5 , sedimentation usually unfolds in parallel with ongoing disputes, even in textbook success stories like Muller’s. Technological sedimentation is not inhibited by ongoing controversy, but can rather help explain ambivalent cases in history of science where a community of researchers adopts a technology despite other scientists questioning the knowledge sedimented in it.

3 Technologizing Drosophila

Before looking at Muller’s experiments on mutation frequency, it is imperative to recount how Drosophila first came to function as a genetic technology in Thomas Hunt Morgan’s laboratory at Columbia University. It is a well-known story how Morgan spotted the white-eyed fly mutant in 1910 and proceeded to recruit Calvin Bridges, Alfred Sturtevant and Muller, three students at Columbia, to work in his “Fly Room” (Sturtevant, 2001 [1965]; Allen, 1975 , 1978 ; Carlson, 1971 , 1974 ; Kohler, 1993 , 1994 ; Waters, 2004 , 2008 ). The group of drosophilists epitomised in this elite quadruplet collaborated until 1915 when Muller left Columbia. The aim of this section is not to tell the story of the Fly Room anew, but to retrace some of the concepts sedimented in the fly stocks that prompted Muller to approach X-ray mutagenicity differently than contemporary scientists working with other organisms. In particular, I contend that the Morgan group’s tendency to treat fly mutants as embodiments of gene mutations led Muller to restrict the possible genetic effects of X-rays that were being studied to changes in individual genes.

When Drosophila first entered the laboratory, its chromosomes were filled with pre-existing mutations that randomly expressed themselves and flouted theoretical predictions. Since Morgan’s group worked in an era before synthetic or even molecular biology, the only available technique for modifying hereditary material were selective breeding procedures (Rheinberger & Gaudillière, 2004 ). By executing complex crosses, they were able to break down the genetic melange that had accumulated in the flies over their evolutionary history and obtain purified stocks. Through artificial selection and inbreeding, they gradually sequestered a collection of “good mutants” whose particular traits enabled them to serve as reagents for analysing particular hereditary processes (Carlson, 1974 ; Kohler, 1994 ; Waters, 2008 ). These useful aberrations could then be further combined into synthetically designed compound stocks, which amalgamated several known mutations.

As opposed to frog muscle tissue in physiology (Holmes, 1993 ) or algae in photosynthesis research (Zallen, 1993 ), Drosophila was not just a more convenient experimental organism, through which investigated phenomena would reveal themselves more plainly. Its pragmatic properties, like its short reproduction rate, were merely one side of the story. What made Drosophila special was that each examined strain was a potential genetic device, which could be brought to bear upon future abnormalities. Already purified and clarified fly specimens were no longer mere research objects, but primarily acted as technologies for studying inheritance in other mutants (which might be transformed into still new devices). Every “discovered” abnormality could be employed to determine the basic genetic characteristics of aberrations that appeared later. Thus, each stock was, successively, a surprising phenomenon and a technology. As the repository of stocks grew, it provided an ever more refined and multi-purpose toolkit for testing diverse genetic phenomena.

The three fundamental, interrelated concepts that sedimented through this work in all the flies, binding them together as specimens of the same technology, were linkage, crossing-over and the “factor” or gene as the basic unit of heredity. The general prediction, connecting these concepts, was that the closer two linked factors or genes are on the same chromosome, the lower the frequency of crossover events between them. Reduced to this parameter of recombination rate, all genes could be placed in a common virtual space: the linkage map (Fig.  1 ; Allen, 1978 ; Falk, 2004 ; Kohler, 1994 ). Fly specimens exhibiting new mutations could be crossed with existing ones to estimate their relative place on a chromosome . Previously mapped mutations hence served as marker genes or “identifying factors”, as they were also called at the time (e.g., Muller, 1928a ). For instance, when a bar-eyed mutant was observed in 1913, it was first mated with the wild-type to establish that it was dominant and linked to the X chromosome (the wild-type here denoting the standard non-mutant laboratory strain, not an actually wild fly). It was then crossed with two already studied mutations located on the X chromosome to calculate its relative position. After its basic genetic properties were defined, the bar-eyed mutant was stored as potentially “valuable for linkage experiments” (Tice, 1914 ). This type of investigative approach, which started with an observation of a potentially interesting new phenotype and ideally resulted in obtaining a stable stock for future experiments, characterised the work of Morgan’s group (Waters, 2004 ).

Linkage maps (redrawn from Tice, 1914 ). The maps depict the relative loci of white-eye ( w ), vermilion-eye ( v ) and bar-eye ( Br ) mutations on the X chromosome. Crossing-over is indicated by “X” between the lines, which depict homologous chromosomes

Through years of repeated experimental work with the flies, the factor or gene came to be regarded within Morgan’s group as a hypothetical location on the chromosome that influenced outwardly perceptible characteristics of the organism. As members of the group worked with the flies, treating them as embodiments of different mutant factors or genes, they began to take the concept of the gene for granted. Many of their articles, especially later ones, use the terms “factor” and “gene” synonymously without explaining their meaning (Muller, 1916 , 1918 ; Muller & Altenburg, 1919 ; Sturtevant, 1917 ; Tice, 1914 ). Footnote 7 Individual factors and fly cultures were completely conflated in signifiers like “white-eye”, “barred”, etc., which were concomitantly used to denote a mutant gene and the purified stock that supposedly personified this gene. Although referring to a merely hypothetical entity, the concept of the gene consequently became as obviously real and manipulatable as the flies in which it had sedimented. A similar transformation happened with the corresponding concept of mutation. Through repeated use of the flies, the members of Morgan’s group came to assume that the perceived changes were predominantly due to gene mutations, not other forms of genetic aberration. Each fly stock was regarded as a ready-made embodiment of one or several “mutant factors” or “mutant genes” (Muller, 1916 ; Sturtevant, 1917 ). The linkage map is essentially a visual representation of this sedimented assumption, correlating points on individual chromosomes to stocks of mutant flies. Thus, as the concept of the gene sedimented in the flies, mutation also tended to be limited to changes in hypothetical segments of the chromosome. In the next section, it will be shown that this sedimented concept of mutation as gene mutation crucially affected how Muller framed X-ray-induced mutation as a research object. Footnote 8

As I emphasised, sedimentation takes place through the practical use of materials in experimental situations. Making Drosophila mutants work as a technology therefore demanded the development of complex experimental techniques, as Waters ( 2004 , 2008 ) has argued. When Drosophila had first entered the laboratory, it was considered a convenient practice material for students (Kohler, 1993 ). By the late 1910s, when the fly had turned into a sensitive genetic technology, commanding the several hundred existing stocks required an intricate know-how, from performing the breeding procedures (test-cross, two-point and three-point backcross, etc.) to preparing the food, maintaining a relatively constant temperature, etherizing, sorting and examining the flies, etc. Muller dismissed data from an experiment in 1918, which did not conform to his expectations, because it was carried out by students. The “labor of so many inexperienced persons”, as Muller ( 1928a ) called it, so productively exploited in the early years, no longer sufficed.

Because genetic knowledge was sedimented in specimens of flies, it was possible to physically inflict it on other strains, either to produce synthetic stocks or to test new baffling mutations. Undoubtedly, the bar-eye and other mutations were presented in journals, textbooks and lectures. But without the vials of actively reproducing mutants as a material substrate, concepts distilled from the flies could not be employed in future research to extract additional knowledge. Making concepts operational crucially depends on an appropriate vehicle, which allows the intellectual products of past science to physically interact with other research objects. This material aspect is why I insist on distinguishing technology proper from what Shapin and Schaffer call literary technology, as well as Latour’s inscriptions. The most prominent inscription in Morgan’s lab was the aforementioned linkage map. Its purpose was to classify mutant genes, to order and compare data gleaned from years of crosses. However, without the flies the map would be like a treasure or a museum: a collection of well-organised valuable antiquities that lack the appropriate material form to twist nature into yielding new value. In order for past, sedimented knowledge to be mobilised in drawing out other unknown phenomena, it had to be invested in up-to-date fly mutants with the appropriate genetic traits for pinning down fresh research objects. As new concepts sedimented in the flies, they modified the material shape of the technology. The design of the stocks was constantly refurbished to reflect the current state of genetic expertise, meaning that some of the older Drosophila mutants had to be discarded to free up space for cutting edge models of fly technology (Kohler, 1993 ).

Overall, though, the total amount of mutant commodities grew. In 1914 over a hundred strains were maintained at Columbia. Ten years later that number had more than tripled (Kohler, 1994 ). Practitioners recognised the paramount importance of their fly technology and created exchange networks for sharing specimens. Researchers visited distant Drosophila laboratories to obtain samples of state-of-the-art stocks or sent letters of requests to their colleagues (Fig.  2 ). Drosophilists also carried cultures of mutants with them as their prized possessions. Muller was perhaps the most extreme example of this Drosophila pilgrimage, migrating his fly fortune between the East Coast of the US and Texas, eventually shipping it all the way to the up-and-coming genetics facilities in the USSR. On 16 September 1933, when he took up a position at the Institute of Genetics in Leningrad, he brought with him “10,000 glass vials and 1,000 bottles” of Drosophila cultures (Carlson, 1981 ). In September 1937, while preparing for his departure from the Soviet Union, Muller made “subcultures of some 250 Drosophila stocks” before leaving for Paris (Schwartz, 2008 ). His expeditions give us an approximate geography of the Atlanticist research tradition that developed around Drosophila material culture. What defined and linked this tradition and its members was precisely a received, held in common, sedimented knowledge, bound with the stocks of fly mutants. And, vice versa, this knowledge acquired the status of a tradition as practicing drosophilists traded materials and expertise . Fruit flies only existed as technologies within this particular community, as embodiments of its traditionalized knowledge. If a mutant from a Drosophila laboratory had escaped into an adjacent physics department, it would have been regarded as an insignificant pest. At the same time, geographically dispersed researchers were tied into a community of drosophilists because they organised their practice around the fly and tacitly accepted it as an embodiment of common genetic knowledge. The process of sedimentation thus explains the intertwined meanings of research tradition , denoting both a habitual, common mode of acting and thinking whose historical origins are forgotten, as well as a community within which this received knowledge circulates and is recognised as shared culture. Footnote 9

A letter from Asa Orrin Weese, professor of zoology at the University of Oklahoma, to H. J. Muller, asking for a bottle of eyeless Drosophila (1926). The body of the letter reads: “Dear Dr Muller! Do you have a stock of “eyeless” Drosophila? If so could you send me a bottle? I have a student who wants to work on the embryology of this mutant, which is not in our stock at present. We shall be indebted to you if you can comply with this request.” Courtesy Helen Muller and Lilly Library, Indiana University, Bloomington, Indiana. I sincerely thank Helen Muller for identifying the sender

4 Making X-ray mutagenicity fly

In 1915 Muller packed his fly cultures and left for Houston to take up a tenure at the recently established Rice Institute. He was joined there by Edgar Altenburg, his co-worker in the Fly Room. The geographical displacement came with a shift in research orientation. Within Morgan’s group the objective had been to identify the rare, spontaneously arising mutants and exploit them to decipher “normal” hereditary processes. The nature of mutations themselves, why they occurred and the various physical or chemical agents that potentially caused them remained elusive. After his departure from Columbia, these questions increasingly occupied Muller’s work. Individually and in collaboration with Altenburg, Muller used special Drosophila stocks as handles for approaching the problem of mutation. In doing so, he reduced X-ray-induced genetic change to a select set of parameters, which turned X-ray mutagenicity into a malleable object of investigation.

The main issue with experimenting on genetic variation was the diversity of circumstances that could influence it. It consequently seemed troublesome, if not impossible, to isolate the impact of a single agent. Aside from the plethora of substances to be tested, there existed a variety of possible genetic effects. These could range from gene or chromosomal mutation to other phenomena connected with inheritance—substances could alter chromosome reassortment or crossover frequency, cause non-disjunction, etc. Moreover, different criteria could be chosen as to which mutants should be counted (visible, lethal, recessive, dominant, sex-linked, autosome-linked). With “visibles”, i.e., mutations that affect outwardly noticeable properties, the observer’s perception may quickly compromise the count, considering that merely a few mutants would usually appear during experiments. Furthermore, it was questionable at which developmental stage mutagens acted, how they influenced viability and how to determine whether they arose in the experiment itself; all of which could distort the data. Finally, given the extremely low rate at which mutation occurred, it was hard to discern statistically significant effects from error. If Muller’s ( 1928a ) count is to be trusted, the community of drosophilists found barely 400 mutants among approximately 20 million flies inspected between 1910 and 1926, a 1:50.000 ratio. Thus, even in experiments with thousands of specimens, a significant mutagenic effect of an agent would reflect itself in a minor difference of one or several mutants between the treated and control series, a divergence that could easily be criticised as artefactual noise.

When Muller turned to mutation studies, several attempts had already been made to “speed up” natural mutation by treating organisms with all kinds of substances. Soon after the discovery of X-rays in 1895, their influence on hereditary mechanisms was examined in multiple species, including frogs, higher plants and protozoa (Koernicke, 1904 –1905; Bardeen, 1907 ). In 1907 Morgan and his student Fernandus Payne tried to provoke mutations in flies by subjecting them to heat, cold, centrifuging, X-rays, ultraviolet light, low pressure and other agents (Allen, 1975 ; Carlson, 1981 ). Morgan also assayed the effects of radium, acids, bases, salts, sugars and alcohol (Allen, 1975 ; Kohler, 1993 ). Daniel MacDougal, Charles Gager and Albert Blakeslee all tested radium in their respective experiments on plant genetics (Campos, 2015 ). By the summer of 1917, Morgan’s former student Harold Plough had surveyed the effects of both temperature and radium on the frequency of crossing-over in Drosophila (Plough, 1917 , 1921 , 1924 ). After Muller had started his first mutagenicity experiments, but before he moved to radiation, the radiologist James Mavor ( 1923 ) reported an influence of X-rays on crossover frequency and non-disjunction in Drosophila .

Muller therefore did not come up with the idea of artificially inducing genetic change nor with X-rays as the means of choice. His tactic was rather to reframe the mutation problem in a manner that allowed him to discredit past research as necessarily inconclusive, as Luis Campos ( 2015 ) has noted. Contrary to Campos, however, I do not believe that Muller's reassessment of mutation was primarily a theoretical choice fuelled by his metaphysical beliefs. It was largely influenced by the concepts sedimented in the flies through years of laboratory work. Between 1918 and 1920 Muller managed to compound some of the existing Drosophila stocks into “special genetic devices”, as he called them ( 1928a ). The known hereditary properties of these strains allowed them to function as reliable detectors for particular types of mutation, which Muller adopted as parameters for measuring X-ray mutagenicity. In the remainder of this section, I describe how the fly technologies influenced Muller’s perception of X-ray-induced mutation. I will limit myself to his two most prominent devices: the ClB and the “sex-linked identifying genes” (SLIG) stocks (Muller, 1928a ). Footnote 10

The SLIG is an improved version of the sex-ratio test, which Altenburg adopted in his earliest 1918–1919 experiments on mutation rate (Muller & Altenburg, 1919 ). Footnote 11 The sex-ratio test is employed for detecting X-linked recessive lethal mutations. It consists of crossing two normal-type flies. All sons inherit their only X chromosome from their mother. One maternal X is transferred to half of the sons, the other to the rest. A new lethal mutation that appears on one of the mother’s chromosomes therefore kills half of the sons. The daughters obtain another mutation-free X from their father which prevents the recessive lethal from expressing itself. Thus, if a recessive X-linked lethal appears in a culture, it is revealed by a 2:1 sex-ratio, instead of the regular 1:1 proportion. When Muller and Altenburg met in the summer of 1919 at Woods Hole to repeat Altenburg’s earlier experiment, they did not cross wild-types but instead utilised a stock that Muller had refined for a similar experiment with his students in 1918. The females in this stock were heterozygous, containing three marker genes spread across their two Xs. The males carried matching recessive traits on their only X (Fig.  3 ). Each half of their sons would exhibit different characteristics, depending on which maternal X chromosome they inherited. Consequently, it was not merely possible to detect the presence of a lethal, but also determine on which maternal chromosome it arose by examining the markers in the surviving sons. The daughters carrying their mother’s lethal could also be distinguished more efficiently from their non-mutant sisters and reused in the next round of breeding (Muller & Altenburg, 1919 ; Muller, 1928a ).

Sex-linked identifying genes test for detecting lethals (based on descriptions in Muller & Altenburg, 1919 ; Muller, 1928a ). The “x” marks the new recessive lethal mutation. One F 1 male is killed by the mutation arising on the X chromosome inherited from his mother. Lower case letters represent recessive alleles, upper case dominant ones. The marker genes are: eosin eye (w e ), vermilion eye (v), forked bristles (f)

Muller adopted a similar test system in his first X-ray experiment seven years later. This time, however, he screened both males and females. Additionally, he switched the markers: homozygous scute-vermilion-forked ( scvf ) females instead of W e VF/w e vf , and bobbed bristled ( bb ) males in lieu of w e vf . Because the males were marked differently, one could easily detect mutations appearing on the male X chromosome. The flies were divided between the control and treated series. The treated males were further split into four groups, each exposed to a different duration of radiation. Treated females were segregated into two groups, receiving two distinct spans of radiation. Muller’s colleague, radiologist Dalton Richardson, first irradiated the flies. The X-rayed flies were then mated to virgin, untreated flies of the opposite sex. Mutations in maternal Xs were revealed by roughly the same test as described above. Screening for new lethals in the paternal bb X required an extra step (Fig.  4 ). In the first generation, all sons would normally survive, inheriting one of their mother’s mutation-free scvf Xs. The daughters received one maternal X and their father’s bb X, containing the recessive lethal that had been potentially induced by radiation. In the second generation, these daughters were mated to their scvf brothers. If a lethal had generated in the father’s X, it killed all bb grandsons, sparing only the male progeny carrying scvf characters. If, on the contrary, the scvf males were missing, the mutation was attributed to the untreated maternal X chromosome. In this way, Muller could simultaneously compare the frequency of X-ray-induced mutation with the rate of spontaneous mutation in the control group (Muller, 1927 , 1928b ; Carlson, 1981 ).

Test in Muller’s first X-ray experiment (autumn 1926) for screening recessive X-linked lethals in irradiated male gametes (based on Muller, 1928b ). The scheme represents the scenario where mutation appears in the treated male flies. The “x” marks the recessive lethal mutation arising in the P 1 sperm. This mutation expresses itself in the death of the F 2 bb male. The markers are all recessive: scute bristles (sc), vermilion eye (v), forked bristles (f), bobbed bristles (bb)

The second genetic device was the ClB stock. As opposed to the SLIG, it was not synthetically designed from existing strains, but emerged as a fortuitous accident in 1920. Muller, Altenburg and their flies met again at Woods Hole (Carlson, 1981 ; Schwartz, 2008 ). Muller was synthetising “an elaborate X-chromosome stock” in preparation for a much larger experiment than those conducted between 1918 and 1919 (Muller, 1928a ). His ambitious design planned to compound more than a dozen markers, including the dominant bar-eye mutation. He failed, but in one of the last cultures he noticed a complete absence of bar-eyed male offspring. According to Altenburg, Muller instantly realised what had happened, exclaiming: “This is what I can use for lethals! It’s got a lethal in it and it suppresses crossing-over.” (cited in Carlson, 1981 ; Schwartz, 2008 ) Muller deduced that a mutant condition had cropped up on the female X chromosome, which concomitantly suppressed crossing-over and acted as a recessive lethal. Since it was composed of mutations previously encountered and explained in Morgan’s lab, it is not surprising that Muller immediately understood its “unexampled technical advantages” for detecting X-linked lethals (Muller, 1928a ). Crossover suppression had been first encountered in a fly found in 1913 and analysed in detail by both Sturtevant and Muller (Muller, 1916 ; Sturtevant, 1917 ). The bar-eye mutant had already been explained and turned into a standard strain by 1914 (Tice, 1914 ). The new composite stock was labelled ClB ( C for crossover suppression, l for lethal, B for bar-eye). It consisted of females who carried the ClB combination on one X chromosome, meaning that half of their sons would ordinarily die. If a new lethal emerged on the other X, it would kill the rest of the male progeny (Fig.  5 ). Appearance of an X-linked lethal was therefore reflected in a 1:0 sex-ratio, an even more absolute yardstick than the SLIG stock. Vials could be examined with the naked eye or lens without etherising the flies, thus minimising the risk of killing or sterilising them. Due to different markers, the daughters inheriting the ClB mutation could be effortlessly segregated from their sisters. The absence of crossing-over also kept the ratios of offspring more constant. Furthermore, because only one type of males could survive, the females did not have to be kept virgin, “a procedure that otherwise occupie[d] perhaps a third of the working time” (Muller, 1928a ). Thanks to its beneficial traits, the ClB mutagenicity test is still regarded as Muller’s lasting technological contribution to genetics. A non-lethal variation of it remains in use today as a standard stock named “Muller-5” or “Basc” (Crow, 1987 ; Graf et al., 1992 ; “M5 technique”,  2006 ).

ClB test for screening recessive X-linked lethals in irradiated male gametes, used in Muller’s second X-ray experiment (based on Muller, 1928b ). The ClB X chromosome also contained some other markers (sc, sm, v and t) which are omitted for sake of clarity, in accordance with Muller’s own notation. The “x” marks the recessive lethal mutation arising in the irradiated P 1 father’s gametes. One class of males is killed by the ClB lethal, the other by the new X-ray-induced mutation on the paternal sy  X. The marker on the sole male P 1 X is small eye (sy). The markers on the second female P 1 X are: scute bristles (sc), vermilion eye (v), forked bristles (f), bobbed bristles (bb). Lower case letters represent recessive alleles, upper case dominant ones

Muller’s two mutagenicity tests demonstrate how technologies impact the investigation of new phenomena. The SLIG and ClB stocks were material embodiments of sedimented concepts. The marker genes in these fly stocks, like bar-eye, all represented ready-made “mutant genes”, acquired from past Drosophila research. The concepts of crossover suppression, sex-linkage, zygosity and the gene had also become sedimented knowledge through repeated practical use of mutant stocks within Morgan’s group. Due to the particular concepts sedimented in them, the stocks imposed a set of parameters bringing out certain features of X-ray mutagenicity, while excluding other circumstances from consideration. As I indicated above, contemporary researchers suspected that X-rays affected hereditary material in various ways. Muller’s stocks reduced these manifold genetic effects to just four parameters: (1) recessive, (2) lethal, (3) X-linked and (4) gene mutation. All other types of abnormalities were eliminated from the count. Muller ( 1928b ) explicitly acknowledged that his tests were incapable of detecting autosomal lethals. Occurrences in the Y chromosome were also neglected. Recessive (autosomal) visible mutations similarly evaded detection and became apparent only after several generations of crossings. Even if they were perceived, visibles not situated on the X chromosome were hard to identify, since no marker genes were inserted in the stocks’ autosomes. Despite not pursuing them systematically, Muller ( 1928b ) took note of visibles that emerged, but did not add them to the final tallies which were compared in order to determine the frequency of X-ray-induced mutation in relation to the spontaneous mutation rate. Thus, the Drosophila technologies limited the diverse mutagenic effects that X-rays might provoke to a purified object consisting of merely four select parameters. They framed X-ray-induced mutation as a precisely defined type of change occurring in individual locations of the X chromosome. By excluding other abnormalities, the tests allowed Muller to detect and measure X-ray mutagenicity as variation in these parameters. The technological parameters therefore functioned as handholds, restricting a convoluted natural property to a simplified object, with which one could experiment in a controlled manner. Gripping nature by these parameters, Muller could disentangle a clear-cut influence of X-rays on the rate of mutation.

Having used the two fly stocks to reframe X-ray mutagenicity into an object consisting of the indicated four parameters, Muller could criticise the results of competing scientists who belonged to research traditions constituted around other organisms-technologies. First, Muller limited the diverse genetic aberrations, which could hypothetically be examined, to mutations in individual genes (Campos, 2015 ; Muller, 1928a ). While Campos ( 2015 ) has already emphasised this point, he underestimates the extent to which Muller’s approach stemmed from the technologies he relied on. As I showed in the previous section, Morgan’s group came to assume that most fly strains were embodiments of one or several mutant genes. Given the Drosophila technology Muller was using, he was inclined to perceive the genetic changes happening in the stocks as gene mutations. The influence of the distinctive concept of mutation, sedimented in the fly, becomes particularly evident if we compare Muller’s view to geneticists radiating plant organisms. Blakeslee and Gager ( 1927 ), testing the influence of X-rays in Jimsonweed, distinguished between “chromosome and gene mutations”. Lewis Stadler ( 1928a , 1928b ), working with maize and barley, spoke of the “genetic effects of X-rays”, which he understood to also encompass the influence of X-rays on the frequency of crossing over and chromosome deficiency. Past concepts, sedimented in the Drosophila mutants that Muller adopted in his practice, therefore compelled him to reduce the effects of X-rays to gene mutation. Second, Muller contested other researchers’ decision to choose visible mutants as indices of mutation, claiming that visibles represented only a small fraction of all mutation and that their determination was too dependent on each observer (Carlson, 1981 ; Muller, 1928a , 1928b , 1929 ). Indeed, there were several borderline cases where even trained drosophilists had trouble distinguishing mere variation, like an awkwardly folded wing, from a genuine mutation (Kohler, 1993 ). It is not without relevance that Altenburg suffered from severe myopia, Sturtevant was colour-blind and Muller was practically incapable of seeing on his right eye (Carlson, 1981 ). Recessive lethals had not been picked before because they were much harder to detect (Muller, 1928a ). They could remain hidden for several generations and even when they were eventually expressed, they simply resulted in part of the offspring missing from the vials. Muller’s technologies, however, allowed him to spot this invisible absence, both due to their physical properties and the sedimented knowledge which limited possible interpretations of the genetic changes arising in the stocks. Third, Muller criticised the qualitative, fragmentary nature of previous observation, arguing that mutation should instead be investigated quantitatively, as a rate (Muller, 1928b ). According to Muller’s new standards of proof, none of the existing experiments operated with a large enough sample to produce “meaningful” data (Muller, 1927 , 1928a ). Judging past experiments against these evidential standards, Muller concluded that they indicated nothing more than the fact that “mutations cannot be produced en masse ” by the tested agents (Muller, 1928a ; also Muller, 1927 , 1928b ). Again, Muller could impose such an exacting criterion of what constituted sufficient quantitative data because the material properties of the fly stocks allowed him to maintain a much larger number of irradiated individuals than competing experimenters working on mammals or higher plants. The absence of crossovers in the ClB stock also increased the proportion of flies that “gave evidence” (Muller, 1928a ), enabling him to maintain smaller cultures. Muller could consequently keep the flies in vials, instead of milk bottles, further optimizing the use of available laboratory space and increasing the number of specimens that could be included in an experiment. Aside from the known material properties of the fly technologies, Muller could quantify the mutagenic effect of X-rays because of the parameters imposed by his technologies, which reduced potential genetic effects to a well-defined type of mutation that was less equivocal and consequently easier to count.

The technological parameters were thus indispensable for isolating a mutagenic effect of X-rays from among the complex of naturally occurring aberrations. Yet Muller relied on these parameters in order to derive a concept of X-ray mutagenicity that would extend beyond the constraints of his technologies. Although the restrictive technological parameters were needed to make the effect of X-rays conspicuous to scientific cognition and subjectable to quantitative measurement, Muller's underlying claim was that his selection of parameters was representative of all types of X-ray-induced mutation; that recessive-lethal-x-linked-gene mutation can stand for X-ray mutagenicity in general; and that, consequently, his particular choice of technology did not matter. His aim was to establish a conceptual description of nature as nature presumably is, independently of these technological interventions ever taking place. In fact, the further that Muller’s concept of X-ray mutagenicity could extend beyond the technological parameters, which had been imperative for arriving at his concept, and the more his technologies could be disregarded, the more far-reaching his discovery would become.

An obvious gap lay between the technological parameters and the concept that Muller aspired to abstract from them. The two tests allowed him to measure that X-linked recessive lethal mutation arose with a 0.083% frequency in the control group, as compared with 7.96% in the series exposed to 24 minutes of radiation and 12.15% in flies given 48 minutes of treatment (Muller, 1928b ). The conceptualisation of this result could range from a strict interpretation—“X-rays heighten the rate of X-linked recessive lethal genes in Drosophila gametes”—, to the more general—“X-rays are mutagens”—, to the most unqualified abstraction, endorsed by Muller ( 1929 ) himself: “[M]utations in general bear all the earmarks of the X-ray mutations […] even if not all of them have actually been produced by radiation.”

A leap therefore occurred in the transition from X-ray-induced mutation as a puzzling natural phenomenon, to the technological parameters imposed by using the flies, to Muller’s concept of X-ray mutagenicity. The choice of technology depended on the studied natural phenomenon—the technology had to be at first glance physically, as well as conceptually, suitable for holding onto certain material properties of the investigated object. To measure X-ray-induced mutation, Muller had to use a living being with specific genetic attributes (physical quality), which were comprehended through the sedimented concepts of past research (conceptual quality). Irradiating his 1915 monograph or an uncharted or different organism, in which the same pieces of knowledge had not sedimented, would not work. However, technological parameters are underdetermined by nature. In Muller’s experiments, the parameters isolated only a particular mutagenic effect of X-rays. The traits of the two Drosophila stocks made them capable of detecting merely certain types of mutation. This reduction of natural events to a few select parameters is to an extent discretionary, because there is no necessary reason in nature itself for the scientific object to be framed exclusively in this manner. Now if the aim was to stubbornly stick to these parameters, their underdetermination would not have significant consequences. Yet, as in Muller’s case, the claim typically being made is that the technological parameters can be forgotten because they are representative of the natural phenomenon in general, even if technological interventions had not restricted it to these parameters. The problem of underdetermination comes into play when this leap occurs, from a technologically parametrized object to an abstract description of nature as nature supposedly is, regardless of the technologies used. Subsequent experiments may always call the assumption of the parameters’ representativity into question by furnishing new information. It might be revealed, for instance, that radiation has an incomparably strong effect on Drosophila, that X-rays can produce only some types of mutation or that the flies were killed by other X-ray-related causes than gene mutation. In Sect.  5 , we will see that some of these objections were indeed raised and later proven against Muller's initial findings.

Muller put substantial effort into generalising the interpretation of his results beyond the technological parameters which had made them feasible. He repeatedly asserted in his articles and presentations that the parameters singled out by his testing devices can be taken as representative of artificially induced mutation in general. First, he maintained that lethals were an appropriate parameter because they did not differ “in their essential nature” from other types of mutation (Muller, 1928a ). Lethals, he claimed, may therefore be “considered as random samples of ‘ordinary’ gene mutations, so far as the loci involved, and the mechanism […] of the mutations are concerned” (Muller, 1928b ). Second, he guaranteed that while most detected X-ray-induced mutations were sex-linked there was “ample proof that mutations were occurring similarly throughout the chromatin” (Muller, 1927 ). Third, he held that his choice of Drosophila did not affect his results (Muller, 1929 ). In this respect, he profited from the contemporary popularity of radiation genetics and the findings of other groups working on a similar problem with different organisms (Stadler, 1928a , 1928b ; Blakeslee & Gager, 1927 ; Whiting, 1928 ; Goodspeed & Olson, 1927 ; Goodspeed, 1929 ). As others have remarked (Carlson, 1981 ; Crow & Abrahamson, 1997 ), Muller attempted to secure priority for his discovery by publishing a four-page article without much data or descriptions of his experimental designs and methods (Muller, 1927 ). This manoeuvre initially provoked suspicion among other scientists, but he succeeded in appeasing most critiques by presenting a more substantiated paper two months later at the International Congress of Genetics (Muller, 1928b ). It also helped that Muller’s closest rivals, especially Stadler ( 1928a ), accepted his priority. Consequently, Muller could turn these competitors into confirmations. Fourth and most importantly, Muller alleged that artificially induced X-ray mutations were of the same kind as natural, spontaneous mutations. His principal argument was that many of the visible mutants, noticed in his experiments, were similar to those described during the past sixteen years of Drosophila research. Thus, rather amusingly, he relied on a class of mutants that was excluded from his parameters to fend off critics. To substantiate his claim of similarity between the natural and artificial, Muller ( 1928b ) performed separate tests to determine that X-ray-induced visibles were allelomorphic to previously observed natural mutants (i.e., that their mutant genes lay on the same locus in the chromosome). Additional crosses were executed to check whether artificial mutants’ hereditary behaviour replicated that of their natural counterparts (Muller, 1928b , 1929 ). On a more metaphysical level, Muller suggested that X-rays were similar to evolution itself, by alluding that electrons, like evolution, strike the cells at random. Having made these extrapolations, Muller ( 1927 ) declared: “The changes produced by X-rays are of just the same kind as the ‘gene mutations’ which are obtained […] without such treatment, and which we believe furnish the building blocks of evolution.” Accordingly, the title of his 1927 article, in which he first announced his conclusions, was simply entitled Artificial Transmutation of the Gene .

The arguments Muller employed to generalise and entrench his concept of X-ray mutagenicity beyond the parameters of his fly technologies can be called strategies of sedimentation : rhetoric devices, visual representations, metaphors, arguments of priority, etc., that aim to persuade other scientists to assume the newly proposed conceptual abstraction as a legitimate description of nature in their own practice. The more successful these strategies are, the larger the community of scientists among which this new knowledge sediments. Muller managed to gain broad support for his interpretation of X-ray mutagenicity, leading to what Campos ( 2015 p. 226) has appropriately described as the “near-excision of decades of earlier work from the historical record”. This is precisely the result of sedimentation. Instead of being treated as an object of decades-long research, X-ray mutagenicity turned into a received ahistorical truth, on which new research could be based. As Muller’s concept sedimented, the distinction between what he had done with the flies and the interpretation he abstracted from his results, became blurred. Even recent historiographical studies, examining Muller’s experiments in detail, tend to be persuaded by Muller’s strategies of sedimentation. Footnote 12 Schwartz ( 2008 pp. 240–241), for instance, simply adopts Muller’s voice as his own: “Man had for the first time willfully manipulated the genetic material.” Whereas Carlson ( 1981 p. 150) surmises that the abundant data, clever design of stocks and planned steps by themselves “dispelled the doubts and created a sensation”.

5 Sedimentation and disputation

Though achieving remarkably wide acceptance, Muller’s results did not dispel all doubt. The sedimentation of Muller's concept of X-ray mutagenicity did not preclude the persistence of research that addressed open questions in Muller’s experiments. The purpose of this section is to explore why some practitioners could take Muller’s concept for granted while it was being questioned by other contemporary researchers—how can sedimentation and disputation co-exist? I believe this seemingly contradictory situation can be explained at least in part by the fact that the sedimentation of Muller's interpretation of X-ray mutagenicity hinged not mainly on discourse or explicit resolution of controversy, but mostly transpired tacitly through the dissemination and use of a commonly available instrument—the X-ray tube. The existence of ready-made X-ray tubes allowed practitioners to immediately adopt these machines in their everyday work to produce mutants, without necessarily paying attention to debates about the implications of Muller’s understanding of X-ray mutagenicity. As the tube came to be used routinely by a community of geneticists, Muller’s concept of X-rays as artificial transmuters of genes would sediment, irrespective of new findings made by scientists in other areas of research, including Muller himself, who continued to study X-ray mutagenicity. Technological sedimentation can therefore help explain why Muller’s concept of X-ray mutagenicity could remain taken for granted despite being questioned and corrected by subsequent research. Footnote 13

Muller himself tried to encourage the sedimentation of his interpretation of X-ray mutagenicity by proposing to other workers in classical genetics to employ the Roentgen machine to create a “series of artificial races for use in the study of genetic […] phenomena” (Muller, 1927 ). He offered the “readily-obtainable X-ray” as a “handle” for producing and studying mutation (Muller, 1929 ). Muller presented the X-ray machine as a technology which could give rise to a new research tradition that he called the “physiology of mutation-production” ( 1929 ). The tube was therefore deployed to attract members to a potential scientific community, bound together by its acceptance of the X-ray as a standard technology for producing mutants and, implicitly, Muller’s concept of X-ray mutagenicity as sedimented knowledge.

Many geneticists followed Muller’s proposal and adopted X-rays as “aids in experimental breeding” (Muller, 1928b ). When Morgan’s group moved from Columbia to Caltech in 1928, it gained access to the powerful X-ray tubes designed by Charles Lauritsen in the adjacent nuclear physics department (Beadle, 1974 ; Carlson, 1981 ; Holbrow, 2003 ). Other genetics laboratories invested in their own X-ray equipment (Campos, 2015 ; Kohler, 1994 ). In this regard, a central factor contributing to the rapid sedimentation of Muller’s concept of X-ray mutagenicity was the commercial availability of Roentgen machines in the US. The machine that Muller borrowed for his 1926–27 X-ray experiments from the radiologist at the University of Texas was a “Snook” hydrogen tube, a catalogue model sold by the Victor X-ray Corporation. By late 1927, Muller’s laboratory had acquired its own tube, which was “of the same make” (Patterson & Muller, 1930 ; Fig.  6 , 7 ). No further innovation was therefore necessary to craft a suitable frame in which Muller’s concept could travel to other scientific workstations and sediment. Some practitioners nevertheless modified the construction of the X-ray machine to enhance its gene-transmuting functions. One such custom-designed model was built in the 1930s at Stanford University by physicist Harry Clark and zoologist Morden Brown, experimenting on protozoa. Their apparatus had the same voltage as Muller’s but came with a modified metal construction, giving improved control over the intensity and constancy of the doses. It also added a more efficient cooling system, which was intended to minimise the potential impact of temperature on mutation (Taylor et al., 1933 ). Hence, in some cases, the sedimentation of Muller’s concept was reflected in a modification of the material shape of the X-ray machine. The second important circumstance, which facilitated the sedimentation of Muller’s concept of X-ray mutagenicity, was that a community of radiologists had already spread across US universities, supplying necessary know-how for operating X-ray machines. Their presence is recorded in numerous genetics articles, which acknowledge the help of local radiologists and physicists with conducting the experiments (Muller, 1927 ; Sax, 1938 ; Stadler, 1928a ; Weinstein, 1928 ).

Muller’s graduate student, Clarence Paul “Pete” Oliver, working the X-ray machine at the University of Texas in 1927. Courtesy Helen Muller and Lilly Library, Indiana University, Bloomington, Indiana

Victor catalogue description of the “Snook” hydrogen tube (Victor Corporation’s 1919 catalogue, pages 3–4, Medical Museion Collection, courtesy of Medical Museion, University of Copenhagen)

Muller’s concept was often assumed as a taken for granted basis for new experiments simply by virtue of X-ray tubes becoming used in everyday genetic research practice. A community of scientists developed, who applied the X-ray machine routinely, without thinking about how Muller had initially arrived at his interpretation of X-ray mutagenicity and without engaging in debates about X-ray mutagenicity that ensued in the next two decades. By 1940, the geneticist James Neel, studying Drosophila , wondered in a letter to his supervisor Curt Stern whether practitioners “ever thought of the gene as anything except a something that you push around with X-rays” (cited in Campos, 2015 ). Years of repeatedly using the X-ray machine to manipulate the hereditary material of various organisms thus made Muller’s conclusion that X-rays transmuted genes as obvious and habitual to the researchers who worked with the tube as the machine itself. If one questioned how they could know for certain that they were indeed manipulating genes, they would probably reply in Ian Hacking’s ( 1983 ) fashion: “So far as I'm concerned, if you can spray them then they are real.” Footnote 14

Within this new research tradition, for which Muller’s interpretation of X-ray mutagenicity represented sedimented knowledge, the Roentgen machine transformed from something researchers worked on to something they worked with . New experiments were designed, relying on the X-ray machine as a ready-made resource for producing mutation, without having to maintain the ClB and SLIG stocks or reproduce the crosses Muller had performed with the mutant flies. The technologies and techniques required to first arrive at Muller’s interpretation of X-ray mutagenicity were thus retroactively bracketed as unremarkable steps toward achieving a general description of a natural phenomenon. Inasmuch as it came to be applied routinely, together with the machine in which it had sedimented, Muller’s concept of X-ray mutagenicity hence became what Husserl ( 1970a ) called discovery-concealment : a novel conception of nature that conceals the historical process leading to its creation, insofar as it sediments as a presumed basis for subsequent research.

As with any technology, the particular concept of X-ray mutagenicity, which had sedimented in the tube, influenced how scientists perceived new scientific objects that they manipulated with the X-ray machine. Consider one experiment where X-rays acted as a ready-made technology: George Beadle and Edward Tatum’s research on physiological genetics, conducted at Stanford University. With the Roentgen tube modified by Clark and Brown, Beadle and Tatum irradiated a different organism, the red bread mold ( Neurospora crassa ), to show that specific genes control specific biochemical reactions (Beadle & Tatum, 1945 ). The gist of their experiment was to generate mutations in Neurospora and then verify which metabolic processes the offspring could still perform by placing the irradiated strains on chemically defined media, consisting of known nutrients. The minimal medium contained a combination of substances on which a strain could survive only if it was capable of executing all biochemical reactions occurring in “healthy” Neurospora . Supplements were subsequently added to the minimal culture one by one to identify the precise substance the mutants needed to survive. It would thereby be possible to determine the individual stages of metabolic processes inhibited by each mutation (Beadle & Tatum, 1941 ; Creager, 2004 ; Kay, 1989 ; Kohler, 1991 ). In the experimental run, which provided decisive evidence for their one gene-one enzyme hypothesis, Beadle and Tatum employed the X-ray tube as a technology for spawning mutations. The machine imposed on their research object a technological parameter that was fundamental for their claim. As they acknowledged themselves, their entire experiment was “based on the assumption that X-ray treatment will induce mutations in genes concerned with the control of known specific chemical reactions” (Beadle & Tatum, 1941 , emphasis added). In other words, they took for granted Muller’s conclusion that X-rays primarily modified genes , not other aspects of inheritance. Intriguingly, they declared this assumption as an anonymised statement of natural fact, without even quoting Muller or justifying it any further. Beadle and Tatum thus applied the concept of X-rays as transmuters of genes routinely, along with the Roentgen machine. Due to the concept of X-ray mutagenicity sedimented in the X-ray tube, the manifold genetic factors that might participate in the regulation of metabolism were reduced to genes alone. The “one gene” side of the one gene-one enzyme hypothesis was presumed established by sheer virtue of using the X-ray tube.

Strikingly, Beadle and Tatum made this assumption despite new findings running against Muller’s initial belief that X-rays caused only gene mutation. Indeed, Muller would personally revisit his earlier view of X-rays as artificial transmuters of genes. Through cytological analysis of Drosophila mutants’ chromosomes, he observed that X-rays provoked not merely gene or “point” mutations, but also translocations of entire chromosomal segments (Muller & Painter, 1929 ; Muller, 1928c ; Schwartz, 2008 ; Stadler, 1932 ). Another major issue was Muller’s conviction that X-ray-induced mutation was representative of all spontaneously arising mutation, a position he would defend repeatedly ( 1928b , 1954 ). Some researchers challenged his perspective, especially Lewis Stadler, experimenting with plants. Stadler ( 1932 ) insisted that X-rays can only cause types of mutation stemming from chromosomal breakage—deletions, chromosomal interchange, loss—but are incapable of generating new genes. Anticipating such objections, Muller conducted additional experiments in which he tried using X-rays to reverse known spontaneous mutations back to the normal-type. Together with two co-workers in Texas, he managed to reverse some mutants, like the forked bristles and bar-eye Drosophila . He presented this as proof that X-rays can also induce “progressive” forms of change, not just “break-down processes” (Hanson, 1928 ; Muller, 1928b , 1929 ; Patterson & Muller, 1930 ). However, since he failed with many other mutants, it remained possible that the successfully reversed mutants might have been duplications. Footnote 15 The effect of X-rays could therefore still be interpreted as a deletion of duplicated sequences, rather than an authentic creation of genes. In the absence of methods for analysing the chemical nature of the induced changes, it remained an experimentally undecided dilemma whether X-ray-induced mutations were representative of all mutation and, consequently, precisely what kind of abnormalities were actually being engendered with X-ray technology in other fields.

Although Stadler had been right from the perspective of today’s knowledge, his rebuttals did not prevent the X-ray tube from becoming a genetic technology. Beadle and Tatum still assumed it as a device for incising individual genes despite results indicating that X-ray-induced mutation might not be limited to the level of the gene and that X-rays possibly provoked merely destructive chromosomal changes. In their articles no reference is given to these new findings of radiation genetics and it is probable that they were not aware of them at all. While it is true that Stadler merely raised doubts against Muller’s interpretation of X-ray mutagenicity, without conclusively proving it wrong, his findings potentially affected the foundational assumption of Beadle and Tatum’s work: that X-rays manipulated individual genes. The case therefore shows how taken for granted past knowledge can become through repeated practical and collective use of a material, i.e., through technological sedimentation.

Conversely, it also demonstrates that the sedimentation of Muller’s conclusions did not forestall controversy in other scientific fields where radiation mutagenicity was still actively explored. A separate tradition of researchers, like Stadler and—to a lesser extent—Muller in his later work, did not fully accept Muller’s initial interpretation of X-rays as artificial transmuters of genes and proceeded to explore the genetic effects of X-rays as an object of research, rather than use the tube as a ready-made technology for producing mutants. Among these scientists, Muller’s concept of X-ray mutagenicity did not sediment. X-ray mutagenicity hence existed in parallel as a sedimented concept and object of research, depending on the given research tradition. Scientists acting within separate traditions in the same period may therefore consider the same material thing in opposite ways: as a technology and as an object of inquiry.

6 Conclusion

The aim of the article has been to offer a new understanding of technology in scientific research by viewing it as the outcome of a particular mode of sedimentation of scientific thought. This technological sedimentation can be defined as the socialisation and routinisation of past scientific knowledge through the practical use of materials for manipulating investigated phenomena in experimental situations by a community of researchers. Every element of the definition is equally important for technological sedimentation to occur and consequently for an object to act as a technology in scientific research. First, past knowledge associated with the material . An example of such received knowledge in Muller’s 1926–27 experiments was that the fly stocks embodied mutant genes, as well as the knowledge about the genetic properties of the ClB and SLIG stocks. For Beadle, Tatum and numerous other geneticists who employed the X-ray machine, the most relevant piece of past knowledge was Muller’s interpretation that X-rays caused gene mutations, not other forms of genetic aberration, and that these genic changes mirrored naturally occurring mutation. Second, routine collective practical use . Technological sedimentation occurs when a number of practitioners adopt a machine, model organism or other equipment in their everyday work. As they use an organism or device in concrete experimental situations, practitioners come to accept and apply the concepts associated with this material as routinely as the material itself. Third, an appropriate medium . Technological sedimentation is unique due to the physical shape of its medium, which can be employed and shared differently than linguistic forms or visual representations. On the one hand, the particular material properties of technologies allow scientists to use them to physically manipulate new investigated phenomena. On the other hand, practitioners often encounter a standardised research material, like the X-ray tube, as a piece of mundane equipment in their workplace—as a thing that is already there, available for use. To work with it, they merely have to learn how to operate it, without delving into the history or ongoing debates outside their research tradition about what this material precisely does or how this knowledge had been gained. The material medium of technologies hence allows researchers to easily use them without deliberating on the concepts sedimented in them.

Due to sedimentation, interventions with technologies are not neutral. Past scientific knowledge sedimented in technologies affects how scientists perceive new phenomena which they manipulate with them. Because of the concepts sedimented in them, technologies restrict intricate natural phenomena to a set of isolated features or, as I called them, technological parameters . Past genetic knowledge sedimented in Muller’s fruit flies, for instance, prompted him to reduce the manifold genetic effects of X-rays to a research object defined by four parameters: recessive X-linked lethal gene mutation. In turn, Muller’s concept of X-ray mutagenicity, sedimented in the X-ray machine, led Beadle and Tatum to limit possible factors that may regulate metabolism to genes. In each of these cases, the knowledge sedimented in the chosen technology brought out certain select aspects of the studied natural phenomenon and thus confined it to a pliable research object.

I proposed that certain other elements involved in the production and spread of scientific knowledge, like images, diagrams, popular science media, rhetoric used in reporting experiments, etc., may be seen as strategies of sedimentation . These strategies serve to secure the assent of other scientists to new scientific results and thus establish a community within which newly produced knowledge may sediment. Footnote 16 The detailed descriptions of experiments, tables of data and visual representations of crosses that Muller presented at the fifth International Congress of Genetics ( 1928b ), along with the textbooks and newspaper articles proclaiming his discovery of artificial gene transmutation are examples of “literary” strategies, aimed at persuading other scientists, students and the general public to accept Muller’s claim that X-rays can transform genes. Furthermore, at least three “social” strategies can be recognised in Muller’s case, which precipitate technological sedimentation: (1) standardisation of materials; (2) metrology, reflected in the relatively established units for measuring doses of Roentgen radiation; (3) heuristics, training and discipline which codify and homogenize the techniques required to properly use a technology. Together, these strategies allow scientists located in spatially distant research facilities to assume that they are working with materials sufficiently similar, in a manner comparable enough to not cause meaningful discrepancies between their results. Standardisation, metrology and training therefore allow a piece of equipment to travel more inconspicuously and extend the community of scientists that can use it, thus accelerating the process of technological sedimentation. The X-ray machine was, for instance, such a powerful medium for the sedimentation of Muller’s concept of X-ray mutagenicity because of the commercial accessibility of catalogue models of X-ray machines as well as the widespread employment and cooperation of trained radiologists in genetic experiments with X-ray tubes in the US in the late 1920s. Footnote 17

Although in Muller’s example these strategies managed to largely overcome arguments mobilised against his broad interpretation of X-ray mutagenicity, the case also shows that sedimentation does not imply universal acceptance, even in instances of highest scientific success. Concepts usually sediment among a bounded community of scientists while remaining objects of research and dispute for others. Sedimentation is local , transpiring within particular research traditions, and provisional , contingent on new findings, reshaped alliances and scientific communities. One major reason for the provisional character of sedimentation is the underdetermination of technological parameters. Future investigation may always cast doubt on the selection of parameters through which technologies had framed research objects, or on the extrapolations scientists have made from these parameters in constructing more general conceptual abstractions. In Muller’s case, the questionable parameter was reducing the genetic effects of X-rays to gene mutation, whereas his most controversial generalisation was that X-ray-induced mutation is equivalent to naturally occurring mutation. Sedimentation therefore shapes revisable traditions. The concepts layered in technologies are not akin to Lakatos’ ( 1978 ) irrefutable hard cores; they are susceptible to being re-evaluated, altered and sometimes supplanted altogether.

Their account was for instance adopted by Kohler ( 1994 ) in his study of the fruit fly as a technology in classical genetics.

Despite shifts in Latour’s position, he retains this observation in his later discussions about technical objects ( 1994 , 1999 ).

See Shapin ( 1988 ), Hacking ( 1992 ) and Baird ( 2004 ) for consonant criticisms of Latour’s fixation on literary production.

The extension of sedimentation to material culture finds support in Husserl’s Crisis of European Sciences (Husserl, 1970a ), where he briefly hints that sedimentation can also occur in cultural artefacts ( Kulturobjekte ), like tongs and drills. Steinle ( 2010 ) advocates a similar understanding of sedimentation.

Technological parameters are further discussed in Sect.  4 . Galison ( 1987 p. 251) introduces a related notion, technological presuppositions , to highlight that “machines are not neutral”, but does not develop it further.

Cf. Latour ( 1994 ) who similarly stresses that technologies are not neutral intermediaries. Technical mediation is rather a translation, which shifts the meaning of past science congealed in technologies.

The only exception I found is the 1915 collective monograph (Morgan et al., 1915 p. 3, p. 208). Even here the term factor is defined only passingly, as a “something” that affects the organism’s observable characters.

My interpretation merely describes a predominant tendency among the Morgan group. It does not imply that they were unaware of other genetic aberrations than gene mutations or that they did not study them in certain experiments (e.g., Bridges’ 1913 article on non-disjunction).

In this respect, sedimentation expands not only on Ludwik Fleck’s points about the mutual relationship between thought collective and thought style , but also on the role of tradition in what sociologists of scientific knowledge call meaning finitism (Fleck, 1986 [1947]; Barnes et al., 1996 ). See also Latour’s ( 1999 ) remark that concepts, i.e. the contents of science, are what holds collectives together and, in turn, acquire scientific status by reason of belonging to these associations.

Muller also used a strain with balanced lethals inserted on the second chromosome for some of his temperature experiments, but abandoned it in the X-ray runs (Muller, 1928a , 1928b ), and an attached-X culture of females in his third X-ray experiment, which mostly served to verify results from the first two series (Muller, 1928b ). The argument I make about ClB and SLIG applies to these stocks as well.

Some secondary sources conflate the SLIG and sex-ratio tests (e.g., Carlson, 1981 ). To avoid ambiguity, I stick to Muller’s own expression, although it deviates from standard terminology in genetics.

A valuable exception is Campos ( 2015 ).

Whenever Muller’s concept/interpretation of X-ray mutagenicity is mentioned in the article, this refers to his interpretation of X-rays as artificial transmuters of genes, as described in Sect.  4 , not to the qualifications he made in his later work. It was this initial, broad interpretation that sedimented in the X-ray machine through its adoption by other geneticists.

In his famous proposal that manipulability can be taken as a criterion for the existence of scientific entities, Hacking overlooks that the mere possibility of manipulating something does not determine how that something should be perceived (Arabatzis, 2006 ). What made it obvious to geneticists that the something they were manipulating was a gene, was not manipulation itself, but Muller’s concept of X-ray mutagenicity sedimented in the X-ray machine. This loss of distinction between a technology’s physical interaction with the observed phenomenon and scientists’ interpretation of what the technology is doing, is a result of successful technological sedimentation.

And most likely were, at least according to current research (Ishimaru et al., 1995 ; Wolfner & Miller, 2016 ).

Strategies of sedimentation largely overlap with what Shapin and Schaffer ( 2011 [ 1985 ]) refer to as social and literary technologies. To an extent this is in accordance with Shapin and Schaffer’s own interpretation since they sometimes refer to technologies as “strategies for knowledge-production” ( 2011 [ 1985 ] p. 104, also pp. 76–77).

The list of strategies in the paragraph is not meant to be exhaustive. More could be said, for instance, about calibration (Collins, 1985 ) as a social strategy of sedimentation.

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Acknowledgements

I thank Hasok Chang, Staffan Müller-Wille, Aiden Woodcock and Olin Moctezuma-Burns for their many helpful comments on drafts of this paper. I am also grateful to Alastair Wright for helping me track down the images of the Victor catalogue and the Copenhagen Medicinsk Museion for letting me reproduce them, as well as to Helen Muller and Lilly Library, University of Indiana, for allowing me to use materials from the Muller collection. Finally, sincere thanks to the reviewers for their suggestions and corrections.

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Komel, S. Technology in scientific practice: how H. J. Muller used the fruit fly to investigate the X-ray machine. HPLS 45 , 22 (2023). https://doi.org/10.1007/s40656-023-00572-9

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Received : 27 October 2021

Accepted : 19 March 2023

Published : 02 June 2023

DOI : https://doi.org/10.1007/s40656-023-00572-9

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