“Chip Quinn once”: S. Benzer, “A Fly’s Eye View of Development,” lecture, Symposium on Molecular Biology of Development, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y, May 29, 1985.
“A worm is only a worm”: Denis Diderot, Rameau’s Nephew and Other Works, Jacques Barzun and Ralph H. Bowen, trans. (Indianapolis, Ind.: The Bobbs-Merrill Company, 1964), 119.
10 no talent for learning: Yadin Dudai, Yuh-Nung Jan, et al., “dunce, a Mutant of Drosophila Deficient in Learning,” Proceedings of the U.S. National Academy of Sciences 73 (1976): 1684–8.
11 “The body is but a watch”: Julien Offray de La Mettrie, Machine Man and Other Writings, Ann Thomson, trans. and ed. (Cambridge: Cambridge University Press, 1996), 31.
“The selfish gene”: Richard Dawkins, The Selfish Gene, 2d ed. (Oxford: Oxford University Press, 1989).
12 “A man is but what he knoweth”: Quoted in René Dubos, So Human an Animal (New York: Charles Scribner’s Sons, 1968), 111.
PART THREE: PICKETT’S CHARGE
1 “and thus beneath”: Conrad Aiken, “Time in the Rock, or Preludes to Definition,” Selected Poems (Cleveland, Ohio: Meridian Books, 1964), 148.
CHAPTER ELEVEN: THE DROSOPHILA ARMS
1 “The flies, poor things”: “The Invisible World,” in Primo Levi, Other People’s Trades (New York: Summit Books, 1989), 60.
In the scientific literature: Many of the classic studies of Drosophila courtship had been done by Aubrey Manning and colleagues at the University of Edinburgh. For a review, see Aubrey Manning, “Drosophila and the Evolution of Behaviour,” Viewpoints in Biology 4 (1964): 125–69.
So Kyriacou built a recording studio: My account of Kyriacou’s early work comes from interviews with Kyriacou, Hall, and colleagues, and from C. P. Kyriacou and Jeffrey C. Hall, “Circadian Rhythm Mutations in Drosophila melanogaster Affect Short-Term Fluctuations in the Male’s Courtship Song,” Proceedings of the U.S. National Academy of Sciences 77, no. 11 (1980): 6729–33.
2 “Triple phrases sound as to a drumbeat”: Garry Wills, Lincoln at Gettysburg: The Words That Remade America (New York: Simon & Schuster, 1992), 171–72.
3 “Mein Gott!”: The phage watcher was J. J. Bronfenbrenner. His surprise is described in Thomas F. Anderson, “Electron Microscopy of Phages,” in Cairns et al., Phage, 65.
4 a jumping gene called mariner: T. Oosumi, W. R. Belknap, and B. Gar-lick, “Mariner Transposons in Humans,” Nature 378 (1995): 672.
5 “A Valentine for NIH”: M. Delbrück, Trends in Biochemical Science (February 1980): xii; quoted in Fischer and Lipson, Thinking About Biology, 283.
CHAPTER TWELVE: CLONING AN INSTINCT
1 “No doubt the process”: Marcel Proust, Time Regained, vol. 3 of Remembrance of Things Past, C. K. Scott-Moncrieff and Terence Kilmartin, trans. (New York: Random House, 1982), 912.
the giant chromosomes: Their discovery had been a major step for geneticists. See, e.g., Theophilus S. Painter, “Salivary Chromosomes and the Attack on the Gene,” Journal of Heredity 25 (1934): 464–76.
2 raced their papers into print: William A. Zehring et al., “P-Element Transformation with period Locus DNA Restores Rhythmicity to Mutant, Arrhythmic Drosophila melanogaster,” Cell 39 (1984): 369–76; T. A. Bargiello, F. R. Jackson, and M. W. Young, “Restoration of Circadian Behavioural Rhythms by Gene Transfer in Drosophila,” Nature 312 (1984): 752–4.
3 jumped from one species to another: David A. Wheeler et al., “Molecular Transfer of a Species-Specific Behavior from Drosophila simulans to Drosophila melanogaster,” Science 251 (1991): 1082–5.
4 “Jimmy Crack Corn”: The song was written by Bill Wood and sung by Robert Sinsheimer as part of an evening of homegrown theatricals entitled “I Am Curious, Max” at Caltech on November 22, 1969.
5 “All of you neurogeneticists”: J. C. Hall, “Pleiotropy of Behavioral Genes,” in R. J. Greenspan and C. P. Kyriacou, eds. Flexibility and Constraint in Behavioral Systems (New York: John Wiley & Sons, 1994), 15–27.
elegiacal essays: See, e.g., Gunther S. Stent, “That Was the Molecular Biology That Was,” Science 160 (1968): 390–5.
Stent had now reconsidered: Gunther S. Stent, “Strength and Weakness of the Genetic Approach to the Development of the Nervous System,” Annual Review of Neurosciences 4 (1981): 163–94.
“The method of nature”: Ralph Waldo Emerson, “The Method of Nature,” in Essays and Lectures, 119.
“sick at heart”: M. Delbrück, diary entry, July 29, 1972; quoted by Fischer and Lipson in Thinking About Biology, 251. They write, “This is one of the few emotional comments to appear in the diary, which he kept to the end of his life.”
6 commencement address: M. Delbrück, “The Arrow of Time—Beginning and End,” Caltech, June 9, 1978.
CHAPTER THIRTEEN: READING AN INSTINCT
1 “I am a book”: Delmore Schwartz, “I Am a Book I Neither Wrote Nor Read,” in Nancy Sullivan, ed., The Treasury of American Poetry (Garden City, N.Y.: Doubleday & Company, 1978), 548.
a little handbook: F. M. Cornford, Microcosmographia Academica: Being a Guide for the Young Academic Politician (Cambridge, England: Bowes & Bowes, 1908).
“the merest sketch”: Ibid., 3.
a lonely letter: S. Benzer to Max Delbrück, September 26, 1952, Caltech Archives.
2 One of its formative meetings: James Watson, “The Human Genome Initiative,” in Genetics and Society, Barry Holland and Charabambos Kyriacou, eds. (Reading, Mass.: Addison-Wesley Publishing Company, 1993), 15.
3 Entrepreneurs raced: For a sketch of the big science and big business of gene mapping at the close of the twentieth century, see Jon Cohen, “The Genomics Gamble,” Science 275 (1997): 767–72.
“I just sold one hundred thousand genes”: Ibid., 769.
“In genetics there is no mystery”: The molecular biologist is Daniel Cohen of the French biotechnology company Genset; quoted in Michael Balter, “… And a Recent Recruit,” Science 275 (1997): 773.
4 wrinkled or smooth: J. R. S. Fincham, “Mendel—Now Down to the Molecular Level,” Nature 343 (1990): 208–9.
tall or short: Stewart B. Rood et al., “Why Mendel’s Peas Came Up Short,” Science 277 (1997): 1611. Rood et al., “Gibberellins: A Phytohormonal Basis for Heterosis in Maize,” Science 241 (1988): 1216–18.
5 the complete sequence: Young’s lab reported a full sequence in March 1986; see F. R. Jackson, T. A. Bargiello, S.–H. Yun, et al., “Product of per Locus of Drosophila Shares Homology with Proteoglycans,” Nature 320 (1986): 185–8. Rosbash then published his first sequence, which was partial and focused on the Thr-Gly repeat region, in July 1986; see P. Reddy, A. C. Jacquier, N. Abovich, et al., “The period Clock Locus of D. melanogaster Codes for a Proteoglycan,” Cell 46 (1986): 53–61. One year later, Rosbash came out with a paper reporting the full-length sequence of period together with the per-zero and per-short mutations; see Qiang Yu et al., “Molecular Mapping of Point Mutations in the period Gene That Stop or Speed Up Biological Clocks in Drosophila melanogaster,” Proceedings of the U.S. National Academy of Sciences 84 (1987): 784–8. Both rival labs were wrong about the proteoglycan connection.
6 “We used to think”: J. Watson, quoted in Leon Jaroff, “The Gene Hunt,” Time 133, no. 12 (March 20, 1989): 62–7.
CHAPTER FOURTEEN: SINGED WINGS
1 “Philosophy is really Homesickness”: Pollen and Fragments: Selected Poetry and Prose of Novalis, Arthur Versluis, trans. (Grand Rapids, MI: Phanes Press, 1989), 56. Quoted in Richard Holmes, “Paradise in a Dream,” The New York Review of Books (July 17, 1997): 4–6.
his famous book: E. O. Wilson, Sociobiology: The New Synthesis (Cambridge, Mass.: Harvard University Press, 1975).
“Wilson, you’re all wet”: Wilson, Naturalist, 349.
2 he was depressed: Fischer and Lipson, Thinking About Biology; 274.
3 six-page, single-spaced letter: Jerry Hirsch, “Benzer’s ‘Learning’ Claim,” September 14, 1979.
Hirsch’s man
ifesto: J. Hirsch, “Behavior Genetics and Individuality Understood,” Science 142 (1963): 1436–42.
4 “The pursuit is repeated”: The struggles of sticklebacks were studied by Niko Tinbergen. Lorenz describes them in King Solomon’s Ring, 45. Though Benzer dropped the debate with Hirsch, rebuttals came from his students and, later, from their students; see Tim Tully, “Measuring Learning in Individual Flies Is Not Necessary to Study the Effects of Single-Gene Mutations in Drosophila: A Reply to Holliday and Hirsch,” Behavior Genetics 16, no. 4 (1986): 449–55.
The clash between Hirsch and Benzer was not only a clash of egos but also of traditions, and Tully came to feel that both are valuable. See Tim Tully, “Discovery of Genes Involved with Learning and Memory: An Experimental Synthesis of Hirschian and Benzerian Perspectives,” Proceedings of the U.S. National Academy of Sciences 93 (1996): 13460–67.
5 a neurocrystal: Benzer coined the term; see Donald F. Ready, Thomas E. Hanson, and Seymour Benzer, “Development of the Drosophila Retina, A Neurocrystalline Lattice,” Developmental Biology 53 (1976): 217–40. For a well-illustrated overview, see Peter A. Lawrence, The Making of a Fly: The Genetics of Animal Design (Oxford: Blackwell Scientific Publications, 1992), 180–94.
sevenless: William A. Harris, William S. Stark, and John A. Walker, “Genetic Dissection of the Photoreceptor System in the Compound Eye of Drosophila melanogaster,” Journal of Physiology 256 (1976): 415–39. The discovery of sevenless opened an entire field: it is still used as a model of the way cells communicate in the growing embryo.
6 monoclonal antibodies: Shinobu C. Fujita et al., “Monoclonal Antibodies Against the Drosophila Nervous System,” Proceedings of the U.S. National Academy of Sciences 79 (1982): 7929–33.
a marriage of true minds: Carol A. Miller and Seymour Benzer, “Monoclonal Antibody Cross-Reactions Between Drosophila and Human Brain,” Proceedings of the U.S. National Academy of Sciences 80 (1983): 7641–5.
7 “Herbes gladly cure”: Quoted in Barkan, Nature’s Work of Art, 1.
8 “that we were looking”: Cohen, “The Genomics Gamble,” 769.
CHAPTER FIFTEEN: THE LORD’S MASTERPIECE
1 “The Gods are here”: Heraclitus, quoted in M. Delbrück, “Aristotle-totle-totle,” in J. Monod and E. Borek, eds. Of Microbes and Life (New York: Columbia University Press, 1971), 52.
Kyriacou knew that repetitions: My description of this work is based on interviews with Kyriacou and colleagues, and on their papers, including: M. A. Castiglione-Morelli et al., “Conformational Study of the Thr-Gly Repeat in the Drosophila Clock Protein, PERIOD,” Proceedings of the Royal Society of London B 260 (1995): 155–63; C. P. Kyriacou et al., “Evolution and Population Biology of the period Gene,” Seminars in Cell and Developmental Biology 7 (1996): 803–10; and Lesley Sawyer et al., “Natural Variation in a Drosophila Clock Gene and Temperature Compensation,” Science 278 (1997): 2117–20.
2 “Attempting to study”: Lawrence, Making of a Fly, 180.
“A defense from heat”: Ecclesiasticus 34: 10.
Blind Watchmaker: Richard Dawkins, The Blind Watchmaker (New York: W. W. Norton & Company, 1987).
3 evolved in a hot climate: For a popular article about human sleep and our need for more of it, see Verlyn Klinkenborn, “Awakening to Sleep,” New York Times Magazine (January 5, 1997): 26.
Siwicki harvested: K. Siwicki et al., “Antibodies to the period Gene Product of Drosophila Reveal Diverse Tissue Distribution and Rhythmic Changes in the Visual System,” Neuron 1 (1988): 141–50.
4 Hardin: Paul E. Hardin, Jeffrey C. Hall, and Michael Rosbash, “Feedback of the Drosophila period Gene Product on Circadian Cycling of Its Messenger RNA Levels,” Nature 343 (1990): 536–40.
found a new mutant: Amita Sehgal et al., “Loss of Circadian Behavioral Rhythms and per RNA Oscillations in the Drosophila Mutant timeless,” Science 263 (1994): 1603–6; Leslie B. Vosshall et al., “Block in Nuclear Localization of period Protein by a Second Clock Mutation, timeless,” Science 263 (1994): 1606–9.
managed to clone the gene: Michael P. Myers et al., “Positional Cloning and Sequence Analysis of the Drosophila Clock Gene, timeless,” Science 270 (1995): 805–8.
5 found a mouse with something wrong: M. H. Vitaterna et al., “Mutagenesis and Mapping of a Mouse Gene, Clock, Essential for Circadian Behavior,” Science 264 (1994): 719–25.
cloned Clock: Marina P. Antoch et al., “Functional Identification of the Mouse Circadian Clock Gene by Transgenic BAC Rescue,” Cell 89 (1997): 655–67.
6 dClock: For reviews of the explosion of research and synthesis that followed, see Ueli Schibler, “New Cogwheels in the Clockworks,” Nature 393 (1998): 620–1; and Steven M. Reppert, “A Clockwork Explosion!,” Neuron 21 (1998): 1–4.
7 a molecular biologist in Switzerland: Schibler, “New Cogwheels.”
8 many more that intermesh: Jeffrey M. Friedman, “The Alphabet of Weight Control,” Nature 385 (1997): 119–20.
A normal Huntington gene: Xiao-Jiang Li et al., “A Huntington-associated Protein Enriched in Brain with Implications for Pathology,” Nature 378 (1995): 398–402; Yvon Trottier et al., “Polyglutamine Expansion as a Pathological Epitope in Huntington’s Disease and Four Dominant Cerebellar Ataxias,” Nature 378 (1995): 403–6.
9 “I mean it to stand”: Anthony Burgess, A Clockwork Orange (New York: W. W. Norton & Company, 1987 [1962]), preface.
“The question is”: Ibid., 83.
10 “What does God want?”: Ibid., 95.
11 fruitless was mapped: Donald A. Gailey and Jeffrey C. Hall, “Behavior and Cytogenetics of fruitless in Drosophila melanogaster: Different Courtship Defects Caused by Separate, Closely Linked Lesions,” Genetics 121 (1989): 773–85.
great generality: Lisa C. Ryner et al., “Control of Male Sexual Behavior and Sexual Orientation in Drosophila by the fruitless Gene,” Cell 87 (1996): 1079–89. For reviews of the story as it unfolded, see Jean Marx, “Tracing How the Sexes Develop,” Science 269 (1995): 1822–24; and Paul Burgoyne, “Fruit(less) Flies Provide a Clue,” Nature 381 (1996): 740–1.
12 “Behold, we put”: Epistle of James, 3.
Huxley warned: Julian Huxley, foreword, King Solomon’s Ring, ix.
CHAPTER SIXTEEN: PAVLOV’S HAT
1 “If knowledge isn’t self-knowledge”: Tom Stoppard, Arcadia (London: Faber and Faber, 1993), 61.
found more slow learners: For a review, see E. O. Aceves-Piña et al., “Learning and Memory in Drosophila, Studied with Mutants,” Cold Spring Harbor Symposium in Quantitative Biology 48 (1983): 831–40.
“essentially the same”: R. J. Greenspan, “Flies, Genes, Learning and Memory,” Neuron 15 (1995): 747.
2 “we will need”: Ronald Booker and William G. Quinn, “Conditioning of Leg Position in Normal and Mutant Drosophila,” Proceedings of the U.S. National Academy of Sciences 78, no. 6 (1981): 3940–4.
When Tully was a boy: Tully tells the story in John B. Connolly and Tim Tully, “You Must Remember This,” The Sciences (May-June 1996): 37–42.
3 discern varieties of stupidity: Tim Tully and William G. Quinn, “Classical Conditioning and Retention in Normal and Mutant Drosophila melanogaster,” Journal of Comparative Physiology 157 (1985): 263–77.
stuck a microelectrode: For a review, see Eric Kandel, “Nerve Cells and Behavior,” Scientific American 223 (1970): 57–70.
4 molecules that compose the message: Reviewed in E. R. Kandel, “Small Systems of Neurons,” Scientific American 241 (1979): 67–76.
5 remarkable genetic engineering projects: For background, see T. Tully et al., “Genetic Dissection of Consolidated Memory in Drosophila,” Cell 79 (1994): 35–47. For a review, see David A. Frank and Michael E. Green-berg, “CREB: A Mediator of Long-Term Memory from Mollusks to Mammals,” Cell 79 (1994): 5–8. The experiment itself is reported in two papers: J. C. P. Yin et al., “Induction of a Dominant Negative CREB Transgene Specifically Blocks Long-Term Memory in Drosophila,” Cell 79 (1994): 49–58; and J. C. P.
Yin et al., “CREB as a Memory Modulator: Induced Expression of a dCREB2 Activator Isoform Enhances Long-Term Memory in Drosophila,” Cell 81 (1995): 107–15. As Greenspan writes in “Flies, Genes, Learning and Memory,” “The rest is history.”
“For flies in the wild”: Ibid., 747.
6 The mouse genome: Lee M. Silver, Mouse Genetics: Concepts and Applications (New York: Oxford University Press, 1995).
Silva tested a strain: The mice were deficient in long-term memory when they were deficient for CREB; see Roussoudan Bourtchuladze et al., “Deficient Long-Term Memory in Mice with a Targeted Mutation of the cAMP-responsive Element-binding Protein,” Cell 79 (1994): 59–68. Note that Silvas group was able to engineer a mouse with an extra-bad memory but not a mouse with an extra-good memory. Kandel and his group: Cristina M. Alberini et al., “A Molecular Switch for the Consolidation of Long-Term Memory: cAMP-inducible Gene Expression,” Annals of the New York Academy of Sciences 758 (1995): 261–86.
7 “We have nothing against universities”: James Barron, “Letters from Serial Bomber Sent Before Blast,” New York Times (April 26, 1995): A1.
8 Just as Pavlov’s work: Pavlovian conditioning remains Russia’s only serious contribution to the study of behavior, partly because “Mendelo-Morganism” was crushed there early on; see James L. Gould, “Review of Russian Contributions to Invertebrate Behavior, Edited by Charles I. Abramson, Zhanna P. Shuranova, and Yuri M. Burmistrov,” American Scientist 85 (November–December 1997): 572–4.
CHAPTER SEVENTEEN: ROUGH MOUNTAIN
1 “Felicity is”: Thomas Hobbes, Leviathan, 1651; quoted in David Denby, Great Books (New York: Simon & Schuster, 1996), 208.
2 “Darwin’s theory”: Quoted in Walter Gratzer, “Per Ardua ad Stockholm: Review of I Wish I’d Made You Angry Earlier: Essays on Science, Scientists, and Humanity, by Max Perutz,” Nature 393 (1998): 640–1.
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