Drosophila embryos as transitional objects: The work of Donald Poulson and Christiane Nüsslein-Volhard

Historical Studies in the Physical and Biological Sciences

Volumn 26, Issue 2, 1996, Pages 312-345

  Fox Keller, Evelyn ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

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EID: 0042785482     PISSN: 08909997     EISSN: None     Source Type: Journal    
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References (96)

1. Walther Nernst, The goals of physical chemistry, 1896, in S.S. Schweber and Jed Z. Buchwald, "Epilogue," in Jed Z. Buchwald, ed., Scientific practice: Theories, and stories of doing physics (Chicago, 1995), 12.
2. Walther Nernst, The goals of physical chemistry, 1896, in S.S. Schweber and Jed Z. Buchwald, "Epilogue," in Jed Z. Buchwald, ed., Scientific practice: Theories, and stories of doing physics (Chicago, 1995), 12.
3. Walther Nernst, The goals of physical chemistry, 1896, in S.S. Schweber and Jed Z. Buchwald, "Epilogue," in Jed Z. Buchwald, ed., Scientific practice: Theories, and stories of doing physics (Chicago, 1995), 12.
4. S. Leigh Star and James R. Griesemer, "Institutional ecology, 'translations' and boundary objects: Amateurs and professionals in Berkeley's Museum of Vertebrate Zoology," Social studies of science, 19 (1988), 387-420, on 393.
5. Iiana Löwy, "The strength of loose concepts - Boundary concepts, federative experimental strategies and disciplinary growth: The case of immunology," History of science, 30 (1992), 371-396, on 391.
6. As this manuscript was undergoing its final revisions, the importance of the Drosophila embryo was formally acknowledged by the award of the Nobel Prize in Physiology and Medicine on 9 Oct 1995 to Christiane Nüsslein-Volhard, Eric Wieschaus, and Edward B. Lewis for their work on its early development.
7. D.W. Winnicott, Playing and reality (New York, 1971).
8. Robert Kohler, Lords of the fly (Chicago, 1994).
9. As Alice Bull points out, it meant that, by contrast to the many slides needed for a whole chick or frog embryo, several Drosophila embryos could be mounted on a single slide. Alice Bull to the author, 29 Aug 1995.
10. T.H. Morgan et al, The mechanism of Mendelian heredity (London, 1915), 220.
11. T.H. Morgan, The physical basis of heredity (Philadelphia, 1919), on 226.
12. Charles Zeleny, "Genetics and embryology," Science, 77 (1933), 177-181, on 181.
13. Ernst Hadorn, Letalfaktoren in ihrer Bedeutung für Erbpathologie und Genphysiologie der Entwicklung (1955); quote from English edn, Developmental genetics and lethal factors (London, 1961), xvii.
14. Ernst Hadorn, Letalfaktoren in ihrer Bedeutung für Erbpathologie und Genphysiologie der Entwicklung (1955); quote from English edn, Developmental genetics and lethal factors (London, 1961), xvii.
15. George W. Beadle and Edward L. Tatum, "Genetic control of biochemical reactions in neurospora," PNAS, 27 (1941), 499-506.
16. They neglect to mention, for example that one reason for the rapid disappearance of this belief was the decline of embryology as a discipline, and the demise of many of its most outspoken advocates.
17. Donald Poulson, "Chromosomal deficiencies and the embryonic development of Drosophila melanogaster," PNAS, 21:3 (1937), 133-137; The embryonic development of Drosophila melanogaster (Paris, 1937). Poulson's bibliography cites three earlier papers: Alfred Huettner, "The origin of the germ cells in Drosophila melanogaster," Journal of morphology, 39 (1923), 385-423; Alfred Huettner and Morris Rabinowitz, "Demonstration of the central body in the living cell," Science, 78 (1933), 367-8;
18. Donald Poulson, "Chromosomal deficiencies and the embryonic development of Drosophila melanogaster," PNAS, 21:3 (1937), 133-137; The embryonic development of Drosophila melanogaster (Paris, 1937). Poulson's bibliography cites three earlier papers: Alfred Huettner, "The origin of the germ cells in Drosophila melanogaster," Journal of morphology, 39 (1923), 385-423; Alfred Huettner and Morris Rabinowitz, "Demonstration of the central body in the living cell," Science, 78 (1933), 367-8;
19. Donald Poulson, "Chromosomal deficiencies and the embryonic development of Drosophila melanogaster," PNAS, 21:3 (1937), 133-137; The embryonic development of Drosophila melanogaster (Paris, 1937). Poulson's bibliography cites three earlier papers: Alfred Huettner, "The origin of the germ cells in Drosophila melanogaster," Journal of morphology, 39 (1923), 385-423; Alfred Huettner and Morris Rabinowitz, "Demonstration of the central body in the living cell," Science, 78 (1933), 367-8;
20. Donald Poulson, "Chromosomal deficiencies and the embryonic development of Drosophila melanogaster," PNAS, 21:3 (1937), 133-137; The embryonic development of Drosophila melanogaster (Paris, 1937). Poulson's bibliography cites three earlier papers: Alfred Huettner, "The origin of the germ cells in Drosophila melanogaster," Journal of morphology, 39 (1923), 385-423; Alfred Huettner and Morris Rabinowitz, "Demonstration of the central body in the living cell," Science, 78 (1933), 367-8;
21. and Ruth B. Howland and George P. Child, "Experimental studies on development in Drosophila melanogaster I: Removal of protoplasmic materials during late cleavage and early embryonic stages," Journal of experimental zoology, 70 (1935), 415-424. A longer paper published the same year, Ruth B. Howland and B.P. Sonnenblick, "Experimental studies on development in Drosophila melanogaster. II. Regulation in the early egg," Journal of experimental zoology, 73 (1936), 109-125, adds a fourth.
22. and Ruth B. Howland and George P. Child, "Experimental studies on development in Drosophila melanogaster I: Removal of protoplasmic materials during late cleavage and early embryonic stages," Journal of experimental zoology, 70 (1935), 415-424. A longer paper published the same year, Ruth B. Howland and B.P. Sonnenblick, "Experimental studies on development in Drosophila melanogaster. II. Regulation in the early egg," Journal of experimental zoology, 73 (1936), 109-125, adds a fourth.
23. Kohler (ref. 6), 244.
24. See, e.g., T.H. Morgan, The theory of the gene (New Haven, 1928), 25.
25. T.H. Morgan, Embryology and genetics (New York, 1934), 9-10.
26. Later, in 1950, Poulson explicitly attempted a linguistic and conceptual reformulation, arguing that the evidence from genetics itself demands a far more complex understanding of the causal relations between genes and effects than the one Morgan had assumed in 1928: "First, the efficacy of a gene depends. . .on the second allele in the gene pair; the gene action is influenced by other genes in the same or in other chromosomes, and eventually it is subject to factors originating in the inner environment of the organism itself or in the external environment." Likening the relation between genes and characters to Margeneau's analysis of the causal relations between lightning and thunder, he continued, "Only as partial aspects of the state of the atmosphere can they be connected by a chain of causal relations." See his unpublished ms., "Causal Explanations of Hereditary Processes" presented at the Symposium on Causality, 1948, on 7 (Poulson papers, Biology Dept., Yale Univ.).
27. Sheila Counce, "The analysis of insect embryogenesis," Annual review of entomology, 6 (1961), 295-312; Theodore Wright, "The genetics of embryogenesis in Drosophila," Advanced genetics, 15 (1970), 261-395. Counce had come to Poulson's lab as a research assistant after her Ph.D. with Waddington, and Wright was Poulson's Ph.D. student.
28. Sheila Counce, "The analysis of insect embryogenesis," Annual review of entomology, 6 (1961), 295-312; Theodore Wright, "The genetics of embryogenesis in Drosophila," Advanced genetics, 15 (1970), 261-395. Counce had come to Poulson's lab as a research assistant after her Ph.D. with Waddington, and Wright was Poulson's Ph.D. student.
29. My interview with E.B. Lewis, 11 Jun 1992.
30. Conversation with Richard Lewontin, 19 Apr 1995.
31. Sturtevant supported Poulson as someone "very well grounded in Genetics," the kind "who is interested in real problems," and who is "also a damned decent likeable fellow as well." Writing to Demerec on his behalf in 1936, when Poulson was completing his Ph.D. dissertation, Sturtevant concluded that he and Dobzhansky regarded him as "good enough so that we should hate to see him land no job or one that would offer no opportunity for research." Perhaps not surprisingly, such a recommendation was not sufficient to win Poulson the NRC fellowship he had applied for that year. Sturtevant to Demerec, 24 Apr 1936, Demerec Papers 3/D 394, American Philosophical Society.
32. By the mid 1950s, Poulson had supervised nine Ph.D. dissertations. Although several of these students have had eminently respectable careers, only one (J.G. Gall) went on to a career in the major leagues.
33. Maternal effect mutations are those in which the maternal genotype can affect the phenotype of the offspring, irrespective of the genotype of the zygote. To distinguish these effects from cytoplasmic inheritance, it is necessary to follow the crosses through to the second generation.
34. Represented in a time-line, taken from Dunn, on which the moment of fertilization is explicitly marked as the origin. Curt Stern, "Gene action," in Benjamin Willier, Paul Weiss, and Viktor Hamburger eds., Analysis of development (Philadelphia, 1955), 151-169, on 156.
35. Hadorn, Developmental genetics and lethal factors, 1955 in German, and English trans. in 1961. Italics added; ibid., 105.
36. Hadorn, Developmental genetics and lethal factors, 1955 in German, and English trans. in 1961. Italics added; ibid., 105.
37. Michael Ashburner, "Epilogue" to The development of Drosophila melanogaster, ed. Alfonso Martinez Arias Bate (Plainview, NY, 1993), 1493-1506, on 1499.
38. A proper history of the rapprochement of genetics and embryology over the last twenty-five years - one that does justice to its technological, cognitive, and social dimensions -has yet to be wrilten. One aspect of this history is explored in E.F. Keller, "Genetics, embryology, and the discourse of gene action," Great ideas today (Chicago, 1994), 2-29; reprinted in Keller, Refiguring life: Metaphors of 20th-century biology (New York, 1995), 1-42.
39. A proper history of the rapprochement of genetics and embryology over the last twenty-five years - one that does justice to its technological, cognitive, and social dimensions - has yet to be wrilten. One aspect of this history is explored in E.F. Keller, "Genetics, embryology, and the discourse of gene action," Great ideas today (Chicago, 1994), 2-29; reprinted in Keller, Refiguring life: Metaphors of 20th-century biology (New York, 1995), 1-42.
40. Wright (ref. 19), 354-355.
41. Karl Illmensee, "Transplantation of embryonic nuclei into unfertilized eggs of Drosophila melanogaster," Nature, 219 (1968), 1268-69.
42. Madeleine Gans, Claudie Audit, and Michele Massen, "Isolation and characterization of sex-linked female-sterile mutants in Drosophila melanogaster," Genetics, 81 (1975), 683-704. Like Garen, Rice, and Gehring (see discussion below), Gans, too, thought her screen a failure when she failed to find genes encoding cytoplasmic determinants.
43. Alan Garen, "Looking for the homunculus in Drosophila," Genetics, 131:1 (1992), 5-7.
44. This distinction appears to depend on subsequent regulatory interactions that build on the pre-pattern laid down by the egg.
45. Alan Garen and Walter Gehring, "Repair of the lethal developmental defect in deep orange embryos of Drosophila by injection of normal egg cytoplasm," PNAS, 69:10 (1972), 2982-85. Two years later, Illmensee and Mahowald (another Poulson student) published a parallel study on pole-plasm transplantation: K. Illmensee, and A.P. Mahowald, "Transplantation of posterior polar plasma in Drosophila: Induction of germ cells at the anterior pole of the egg," PNAS, 71 (1974), 1016-1020.
46. Alan Garen and Walter Gehring, "Repair of the lethal developmental defect in deep orange embryos of Drosophila by injection of normal egg cytoplasm," PNAS, 69:10 (1972), 2982-85. Two years later, Illmensee and Mahowald (another Poulson student) published a parallel study on pole-plasm transplantation: K. Illmensee, and A.P. Mahowald, "Transplantation of posterior polar plasma in Drosophila: Induction of germ cells at the anterior pole of the egg," PNAS, 71 (1974), 1016-1020.
47. Walter J. Gehring, "The Homeobox in perspective," Trends in biochemical sciences, 17 (1992), 277-280.
48. Ashburner (ref. 27), 1503.
49. Between the late 1960s and the early 1990s, the annual number of papers listed in Medline under the subject of Drosophila embryology rose from close to zero (0.2) to 13.5; listed under Drosophila developmental genetics, the annual number of papers rose from 9.0 to 213.5.
50. Ashburner (ref. 27), 1500.
51. Keller, Refiguring life (ref. 28).
52. With such a spatial and temporal map, the category of "maternal effect" mutants presented a special problem for geneticists, a problem that is clearly illustrated by the decade's long uncertainty (and debate) over their proper nomenclature (reviewed in E.F. Keller, "History of Developmental Biology Lecture Notes," International History of Science Summer School, Berkeley, Ca, 1992 [unpublished]).
53. Cited in Klaus Sander, "The role of genes in ontogenesis -evolving concepts from 1883 to 1983 as perceived by an insect embryologist," in T.J. Horder, J.A. Witkowski, and C.C. Wylie, ed., History of embryology (Cambridge, 1986), 363-395.
54. See also Scott Gilbert, et al., "The importance of feminist critique for contemporary cell biology," Hypatia, 3:1 (1988), 61-76, and Scott Gilbert, "Cellular politics: Just, Goldschmidt, and the attempts to reconcile embryology and genetics," in R. Rainger et al., eds., The American development of biology (Philadelphia, 1988), 311-346.
55. See also Scott Gilbert, et al., "The importance of feminist critique for contemporary cell biology," Hypatia, 3:1 (1988), 61-76, and Scott Gilbert, "Cellular politics: Just, Goldschmidt, and the attempts to reconcile embryology and genetics," in R. Rainger et al., eds., The American development of biology (Philadelphia, 1988), 311-346.
56. This argument is further developed in Keller, Refiguring life (ref. 28). See also Scott Gilbert, "Induction and the origin of developmental genetics," in Scott Gilbert, ed., A conceptual history of modern embryology (Baltimore, 1991), 181-206, on 200.
57. This argument is further developed in Keller, Refiguring life (ref. 28). See also Scott Gilbert, "Induction and the origin of developmental genetics," in Scott Gilbert, ed., A conceptual history of modern embryology (Baltimore, 1991), 181-206, on 200.
58. I am grateful to Professor Nüsslein-Volhard for her generosity during my visit to Tübingen in July, 1994, both in opening her files to me and in answering my questions. Much of what follows is based on the information and materials I gathered during that visit.
59. All unattributed quotations are taken from interviews I conducted with Nüsslein-Volhard in July, 1994.
60. Christiane Nüsslein-Volhard, "Antrittsrede," 14 Jul 1990, in Akademie der Wissenschaften, Heidelberg.
61. Schaller had also been to the U.S: he spent two years (1961-1962) with Gobind Khorana at the University of Wisconsin, Madison.
62. From a saturation screen for E. coli mutants defective in DNA replication, Bonhoeffer located a mutant defective in the enzyme that (as he, Schaller, and Tom Kornberg were eventually able to show) was - unlike the enzyme that Arthur Kornberg had earlier identified-actually required for replication (see, e.g., M. Goulian and P. Hanawalt, eds., DNA synthesis and its regulation (Menlo Park, 1975).
63. Alfred Kühn, Vorlesungen über Entwicklungsphysiologie (Berlin, 1955).
64. Wright (ref. 19).
65. L.N. Chan and Walter Gehring, "Determination of blastoderm cells in Drosophila melanogaster," PNAS, 68:9 (1991), 2217-21.
66. Alan Garen and Walter Gehring, "Repair of the lethal developmental defect in deep orange embryos of Drosophila by injection of normal egg cytoplasm," PNAS, 69:10 (1972), 2982-85.
67. Alice Bull, "An embryonic lethal with reversed polarity in Drosophila melanogaster," 11th International Congress of Genetics, Proceedings, 1 (1963), 10-11; Bull, "Bicaudal, a genetic factor which affects the polarity of the embryo in Drosophila melanogaster," Journal of experimental zoology, 161 (1965), 221-242.
68. Alice Bull, "An embryonic lethal with reversed polarity in Drosophila melanogaster," 11th International Congress of Genetics, Proceedings, 1 (1963), 10-11; Bull, "Bicaudal, a genetic factor which affects the polarity of the embryo in Drosophila melanogaster," Journal of experimental zoology, 161 (1965), 221-242.
69. Christiane Nüsslein-Volhard, "A rapid method for screening eggs from single Drosophila females," Drosophila Information Service, 52 (1977), 166.
70. Isolating such mutants requires considerably more than manual dexterity and clever technique: it requires the ability to recognize the potential importance of a variation. This, of course, requires a conception of what one is looking for and visual sensitivity to signs of interest. For her particular visual acumen, Nüsslein-Volhard credits the artistic temperament she claims runs in her family.
71. John Kendrew to Nüsslein-Volhard, 9 Nov 1976 (NVP).
72. Sander's world was not the one from which she desired recognition. She saw it as a backwater, mired in a tradition of "not getting anywhere."
73. Wright to Nüsslein-Volhard, 9 Apr 1980 (NVP).
74. Nüsslein-Volhard and Eric Wieschaus, "Mutations affecting segment number and polarity," Nature, 287 (30 Oct 1980), 798-801. Both Wieshaus and Nüsslein-Volhard intended their screen for segmentation genes (genes called into action after fertilization) as a way station for the more difficult screen they planned for the genes involved in laying down the earliest body plan of the Drosophila embryo (i.e., for maternal effect mutants).
75. Further results from that same screen were not published until 1984 (see C. Nüsslein-Volhard, E. Wieschaus and H. Kluding, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster 1: Zygotic loci on the second chromosome," Wilhelm Roux's archives of developmental biology, 193 (1984), 267-282; Gerd Jürgens et al., "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster II: Zygotic loci on the third chromosome." ibid., 283-295; and Wieschaus, Nüsslein-Volhard, and Jürgens, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster III: Zygotic loci on the X-chromosome and fourth chromosome," ibid., 296-308.
76. Further results from that same screen were not published until 1984 (see C. Nüsslein-Volhard, E. Wieschaus and H. Kluding, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster 1: Zygotic loci on the second chromosome," Wilhelm Roux's archives of developmental biology, 193 (1984), 267-282; Gerd Jürgens et al., "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster II: Zygotic loci on the third chromosome." ibid., 283-295; and Wieschaus, Nüsslein-Volhard, and Jürgens, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster III: Zygotic loci on the X-chromosome and fourth chromosome," ibid., 296-308.
77. Further results from that same screen were not published until 1984 (see C. Nüsslein-Volhard, E. Wieschaus and H. Kluding, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster 1: Zygotic loci on the second chromosome," Wilhelm Roux's archives of developmental biology, 193 (1984), 267-282; Gerd Jürgens et al., "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster II: Zygotic loci on the third chromosome." ibid., 283-295; and Wieschaus, Nüsslein-Volhard, and Jürgens, "Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster III: Zygotic loci on the X-chromosome and fourth chromosome," ibid., 296-308.
78. She was the first woman named as Director of a Max Planck Institute for biological research and remains the only woman Director of a Max Planck Institute for scientific research. Margot Becke, long since retired, had preceded her in chemistry, and at the time of Nüsslein-Volhard's appointment, another woman held a Directorship in Sociology. Over the last two years, three other women have been named as Max Planck Institute Directors, all for research in the social sciences.
79. Ruth Lehmann came in the middle of her graduate studies and stayed on as a post-doc; Jürgens, Stewart, and Anderson came as post-docs.
80. Awarded on 9 Oct 1995 (see ref. 4).
81. Nüsslein-Volhard to the author, 4 Oct 1992.
82. Sheila Counce, conversation with the author, January 1995.
83. In his letter of invitation to the 1980 Gordon Conference on Regulatory Mechanisms, Ira Herskowitz wrote, "we don't know which of you to invite" (Herskowitz to Nüsslein-Volhard and Wieschaus, 6 May 1980 (NVP)).
84. Of course, the work of Anderson and Lehmann also contributed significantly to Nüsslein-Volhard's success. It could be said thai all three were beneficiaries of an opportunity created by the much larger political and cultural transformation wrought by the contemporary women's movement. That transformation was responsible for the existence of a pool of talented young women scientists in the early 1980s, just beginning their careers and on the lookout for professional niches. It was also responsible for the existence of positions of responsibility in American universities when they were ready to move on.
85. Personal communication. For her own part, Nüsslein-Volhard takes some pride in the way she runs her lab: "I am not afraid of admitting a distinct and perhaps more 'motherly' style. .toward a more friendly, understanding, helpful, and familiar atmosphere in the lab." Nüsslein-Volhard to the author, 6 Oct 1995.
86. This does not reveal a contradiction in Nüsslein-Volhard's personality or behavior so much as it does a tension that has inhered in the goals of feminism throughout this century (see, e.g., Nancy Cott, The grounding of modern feminism (New Haven, 1987)).
87. In 1994, the proportion of women in her lab had dropped to only one out of ten, but this year, a new batch of women graduate students has raised the proportion significantly.
88. Reading through her correspondence, I was impressed by the support extended to her in the early years by a number of women colleagues. But when I asked her about this, she dismissed the suggestion of a certain "comraderie of women," recalling only the strain on her friendships with men caused by the jealousy of their girlfriends.
89. In contrast to Alice Bull's heavy teaching load, Nüsslein-Volhard has no formal teaching obligations.
90. Christiane Nüsslein-Volhard, "Genetic analysis of pattern-formation in the embryo of Drosophila melanogaster. Characterization of the maternal effect mutant bicaudal," Wilhelm Roux's archives of developmental biology, 183 (1977), 249-268.
91. Wright to Nüsslein-Volhard, 20 Sept 1977 (NVP).
92. Bull to Nüsslein-Volhard, 4 Dec 1977 (NVP).
93. In D.M. Glover and B.D. Harris, eds., Genes and embryos (Oxford, 1989), 1-37.
94. Conversation with K. Anderson, 28 Jul 1992. Elsewhere, I elaborate the reasons I believe this is not a likely consideration for most women in contemporary developmental biology ("Developmental biology as a feminist cause?," Osiris, in press.) In brief, I argued that women biologists may have historically gravitated (or were relegated) to the study of development either because of the cultural equation between women and reproduction or simply because of the lower status of that field; the prominence of women in the field today has far more to do with the temporal coincidence of the increased number of women in biology and the resurgence of development as a promising arena for research.
95. Lynn Manseau and Trudi Schüpbach, "The egg came first, Of course!," Trends in genetics, 5:12 (1989), 400-405.
96. At least not publicly. In private, however, Nüsslein-Volhard also speculates that there may be a special attraction for women in the subject of development and embryos. But to Nüsslein-Volhard as to virtually all the women developmental biologists I have spoken with, the more significant attraction to women by far comes from the presence of so many other women in the field, and from the sensation this brings of being a "wild-type" (the genetics terms for "normal"), Nüsslein-Volhard to the author, 9 Oct 1995.