The Gene

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The Gene Page 67

by Siddhartha Mukherjee


  “I feel like I have the brain of a man”: Ibid.

  In 2005, a team of researchers at Columbia University: Heino F. L. Meyer-Bahlburg, “Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation,” Archives of Sexual Behavior 34, no. 4 (2005): 423–38.

  “Is it really the case that all”: Otto Weininger, Sex and Character: An Investigation of Fundamental Principles (Bloomington: Indiana University Press, 2005), 2.

  these animals might be anatomically female: Carey Reed, “Brain ‘gender’ more flexible than once believed, study finds,” PBS NewsHour, April 5, 2015, http://www.pbs.org/newshour/rundown/brain-gender-flexible-believed-study-finds/. Also see Bridget M. Nugent et al., “Brain feminization requires active repression of masculinization via DNA methylation,” Nature Neuroscience 18 (2015): 690–97.

  The Last Mile

  Like sleeping dogs, unknown twins: Wright, Born That Way, 27.

  “It is the consensus of many contemporary”: Sándor Lorand and Michael Balint, ed., Perversions: Psychodynamics and Therapy (New York: Random House, 1956; repr., London: Ortolan Press, 1965), 75.

  “The homosexual’s real enemy”: Bernard J. Oliver Jr., Sexual Deviation in American Society (New Haven, CT: New College and University Press, 1967), 146.

  “close-binding and [sexually] intimate”: Irving Bieber, Homosexuality: A Psychoanalytic Study (Lanham, MD: Jason Aronson, 1962), 52.

  “a homosexual is a person”: Jack Drescher, Ariel Shidlo, and Michael Schroeder, Sexual Conversion Therapy: Ethical, Clinical and Research Perspectives (Boca Raton, FL: CRC Press, 2002), 33.

  “homosexuality is more of a choice”: “The 1992 campaign: The vice president; Quayle contends homosexuality is a matter of choice, not biology,” New York Times, September 14, 1992, http://www.nytimes.com/1992/09/14/us/1992-campaign-vice-president-quayle-contends-homosexuality-matter-choice-not.html.

  In July 1993, the discovery of the: David Miller, “Introducing the ‘gay gene’: Media and scientific representations,” Public Understanding of Science 4, no. 3 (1995): 269–84, http://www.academia.edu/3172354/Introducing_the_Gay_Gene_Media_and_Scientific_Representations.

  “What do we say of the woman”: C. Sarler, “Moral majority gets its genes all in a twist,” People, July 1993, 27.

  The second book, Richard Lewontin’s: Richard C. Lewontin, Steven P. R. Rose, and Leon J. Kamin, Not in Our Genes: Biology, Ideology, and Human Nature (New York: Pantheon Books, 1984).

  “There is no acceptable evidence that”: Ibid., 261.

  In the 1980s, a professor of psychology: J. Michael Bailey and Richard C. Pillard, “A genetic study of male sexual orientation,” Archives of General Psychiatry 48, no. 12 (1991): 1089–96.

  The brothers, who looked virtually identical: Frederick L. Whitam, Milton Diamond, and James Martin, “Homosexual orientation in twins: A report on 61 pairs and three triplet sets,” Archives of Sexual Behavior 22, no. 3 (1993): 187–206.

  Protocol #92-C-0078 was launched: Dean Hamer, Science of Desire: The Gay Gene and the Biology of Behavior (New York: Simon & Schuster, 2011), 40.

  “gay Roots project”: Ibid., 91–104.

  “There were TV cameramen lined up”: “The ‘gay gene’ debate,” Frontline, PBS, http://www.pbs.org/wgbh/pages/frontline/shows/assault/genetics/.

  “science could be used to eradicate it”: Richard Horton, “Is homosexuality inherited?” Frontline, PBS, http://www.pbs.org/wgbh/pages/frontline/shows/assault/genetics/nyreview.html.

  “does identify a chromosomal region”: Timothy F. Murphy, Gay Science: The Ethics of Sexual Orientation Research (New York: Columbia University Press, 1997), 144.

  Hamer was attacked left and right: M. Philip, “A review of Xq28 and the effect on homosexuality,” Interdisciplinary Journal of Health Science 1 (2010): 44–48.

  Since Hamer’s 1993 paper in Science: Dean H. Hamer et al., “A linkage between DNA markers on the X chromosome and male sexual orientation,” Science 261, no. 5119 (1993): 321–27.

  In 2005, in perhaps the largest study: Brian S. Mustanski et al., “A genomewide scan of male sexual orientation,” Human Genetics 116, no. 4 (2005): 272–78.

  In 2015, in yet another detailed analysis of 409: A. R. Sanders et al., “Genome-wide scan demonstrates significant linkage for male sexual orientation,” Psychological Medicine 45, no. 7 (2015): 1379–88.

  One gene that sits: Elizabeth M. Wilson, “Androgen receptor molecular biology and potential targets in prostate cancer,” Therapeutic Advances in Urology 2, no. 3 (2010): 105–17.

  In 1971, in a book titled: Macfarlane Burnet, Genes, Dreams and Realities (Dordrecht: Springer Science & Business Media, 1971), 170.

  “An environmentalist view”: Nancy L. Segal, Born Together—Reared Apart: The Landmark Minnesota Twin Study (Cambridge: Harvard University Press, 2012), 4.

  “random access memory onto which”: Wright, Born That Way, viii.

  “Whatever back-porch wisdom”: Ibid., vii.

  Minnesota Study of Twins: Thomas J. Bouchard et al., “Sources of human psychological differences: The Minnesota study of twins reared apart,” Science 250, no. 4978 (1990): 223–28.

  “Empathy, altruism, sense of equity”: Richard P. Ebstein et al., “Genetics of human social behavior,” Neuron 65, no. 6 (2010): 831–44.

  “A surprisingly high genetic component”: Wright, Born That Way, 52.

  Daphne Goodship and Barbara Herbert: Ibid., 63–67.

  “Both drove Chevrolets”: Ibid., 28.

  Two other women, also separated at birth: Ibid., 74.

  oxford shirts with epaulets: Ibid., 70.

  to describe the odd habit: squidging: Ibid., 65.

  “door-knobs, needles and fishhooks”: Ibid., 80.

  The most extreme novelty seekers, he discovered: Richard P. Ebstein et al., “Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking,” Nature Genetics 12, no. 1 (1996): 78–80.

  Perhaps the subtle drive caused by: Luke J. Matthews and Paul M. Butler, “Novelty-seeking DRD4 polymorphisms are associated with human migration distance out-of-Africa after controlling for neutral population gene structure,” American Journal of Physical Anthropology 145, no. 3 (2011): 382–89.

  “How nice it would be”: Lewis Carroll, Alice in Wonderland (New York: W. W. Norton, 2013).

  Forty-three studies, performed: Eric Turkheimer, “Three laws of behavior genetics and what they mean,” Current Directions in Psychological Science 9, no. 5 (2000): 160–64; and E. Turkheimer and M. C. Waldron, “Nonshared environment: A theoretical, methodological, and quantitative review,” Psychological Bulletin 126 (2000): 78–108.

  “unsystematic, idiosyncratic, serendipitous events”: Robert Plomin and Denise Daniels, “Why are children in the same family so different from one another?” Behavioral and Brain Sciences 10, no. 1 (1987): 1–16.

  “a devil, a born devil”: William Shakespeare, The Tempest, act 4, scene 1.

  The Hunger Winter

  Identical twins have exactly the same: Nessa Carey, The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance (New York: Columbia University Press, 2012), 5.

  Genes have had a glorious run in the 20th century: Evelyn Fox Keller, quoted in Margaret Lock and Vinh-Kim Nguyen, An Anthropology of Biomedicine (Hoboken, NJ: John Wiley & Sons, 2010).

  When a songbird encounters a new: Erich D. Jarvis et al., “For whom the bird sings: Context-dependent gene expression,” Neuron 21, no. 4 (1998): 775–88.

  This question bothered Conrad Waddington: Conrad Hal Waddington, The Strategy of the Genes: A Discussion of Some Aspects of Theoretical Biology (London: Allen & Unwin, 1957), ix, 262.

  “only [consists of] a stomach”: Max Hastings, Armageddon: The Battle for Germany, 1944–1945 (New York: Alfred A. Knopf, 2004), 414.

  In the 1980s, however: Bastiaan T. Heijmans et al., “Persi
stent epigenetic differences associated with prenatal exposure to famine in humans,” Proceedings of the National Academy of Sciences 105, no. 44 (2008): 17046–49.

  “aptitude for doing things on a small scale”: John Gurdon, “Nuclear reprogramming in eggs,” Nature Medicine 15, no. 10 (2009): 1141–44.

  In 1961, Gurdon began to test: J. B. Gurdon and H. R. Woodland, “The cytoplasmic control of nuclear activity in animal development,” Biological Reviews 43, no. 2 (1968): 233–67.

  It would lead, famously, to the cloning of Dolly: “Sir John B. Gurdon—facts,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/gurdon-facts.html.

  the only other “observed case”: John Maynard Smith, interview in the Web of Stories. www.webofstories.com/play/john.maynard.smith/78.

  Lyon found: in one cell: The Japanese scientist Susumu Ohno had hypothesized about X inactivation before the phenomenon was discovered.

  simple organisms, such as yeast: K. Raghunathan et al., “Epigenetic inheritance uncoupled from sequence-specific recruitment,” Science 348 (April 3, 2015): 6230.

  In his remarkable story “Funes the Memorious”: Jorge Luis Borges, Labyrinths, trans. James E. Irby (New York: New Directions, 1962), 59–66.

  One of the four genes used by Yamanaka: K. Takahashi and S. Yamanaka, “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell 126, no. 4 (2006): 663–76. Also see M. Nakagawa et al., “Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts,” Nature Biotechnology 26, no. 1 (2008): 101–6.

  “It sometimes seems as if curbing entropy”: James Gleick, The Information: A History, a Theory, a Flood (New York: Pantheon Books, 2011).

  At Harvard, a soft-spoken biochemist: Itay Budin and Jack W. Szostak, “Expanding roles for diverse physical phenomena during the origin of life,” Annual Review of Biophysics 39 (2010): 245–63; and Alonso Ricardo and Jack W. Szostak, “Origin of life on Earth,” Scientific American 301, no. 3 (2009): 54–61.

  followed the work of Stanley Miller: The original experiments were performed by Miller in conjunction with Harold Urey at the University of Chicago; John Sutherland, in Manchester, also performed key experiments.

  Subsequent variations of the Miller experiment: Ricardo and Szostak, “Origin of life on Earth,” 54–61.

  Szostak has demonstrated that such micelles: Jack W. Szostak, David P. Bartel, and P. Luigi Luisi, “Synthesizing life,” Nature 409, no. 6818 (2001): 387–90. Also see Martin M. Hanczyc, Shelly M. Fujikawa, and Jack W. Szostak, “Experimental models of primitive cellular compartments: Encapsulation, growth, and division,” Science 302, no. 5645 (2003): 618–22.

  “It is relatively easy to see how”: Ricardo and Szostak, “Origin of life on Earth,” 54–61.

  PART SIX: POST-GENOME

  Those who promise us paradise on earth: Elias G. Carayannis and Ali Pirzadeh, The Knowledge of Culture and the Culture of Knowledge: Implications for Theory, Policy and Practice (London: Palgrave Macmillan, 2013), 90.

  It’s only we humans: Tom Stoppard, The Coast of Utopia (New York: Grove Press, 2007), “Act Two, August 1852.”

  The Future of the Future

  Probably no DNA science is at once: Gina Smith, The Genomics Age: How DNA Technology Is Transforming the Way We Live and Who We Are (New York: AMACOM, 2004).

  Clear the air!: Thomas Stearns Eliot, Murder in the Cathedral (Boston: Houghton Mifflin Harcourt, 2014).

  In 1974, barely three years after: Rudolf Jaenisch and Beatrice Mintz, “Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA,” Proceedings of the National Academy of Sciences 71, no. 4 (1974): 1250–54.

  biologists stumbled on a critical discovery: M. J. Evans and M. H. Kaufman, “Establishment in culture of pluripotential cells from mouse embryos,” Nature 292 (1981): 154–56.

  “Nobody seems to be interested in my cells”: M. Capecchi, “The first transgenic mice: An interview with Mario Capecchi. Interview by Kristin Kain,” Disease Models & Mechanisms 1, no. 4–5 (2008): 197.

  With ES cells, however, scientists: See for instance M. R. Capecchi, “High efficiency transformation by direct microinjection of DNA into cultured mammalian cells,” Cell 22 (1980): 479–88; and K. R. Thomas and M. R. Capecchi, “Site-directed mutagenesis by gene targeting in mouse embryo–derived stem cells,” Cell 51 (1987): 503–12.

  You could choose to change the insulin gene: O. Smithies et al., “Insertion of DNA sequences into the human chromosomal-globin locus by homologous re-combination,” Nature 317 (1985): 230–34.

  The “watchmaker” of evolution, as Richard Dawkins: Richard Dawkins, The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe without Design (W. W. Norton, 1986).

  They are the savants of the rodent world: Kiyohito Murai et al., “Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model,” Proceedings of the National Academy of Sciences 111, no. 25 (2014): 9115–20.

  “It may be the field’s dirty little secret”: Karen Hopkin, “Ready, reset, go,” The Scientist, March 11, 2011, http://www.the-scientist.com/?articles.view/articleNo/30726/title/Ready--Reset--Go/.

  In 1988, a two-year-old girl: Details of the story of Ashanti DeSilva are from W. French Anderson, “The best of times, the worst of times,” Science 288, no. 5466 (2000): 627; Lyon and Gorner, Altered Fates; and Nelson A. Wivel and W. French Anderson, “24: Human gene therapy: Public policy and regulatory issues,” Cold Spring Harbor Monograph Archive 36 (1999): 671–89.

  “Mommy, you shouldn’t have had”: Lyon and Gorner, Altered Fates, 107.

  The Bubble Boy, as David was called: “David Phillip Vetter (1971–1984),” American Experience, PBS, http://www.pbs.org/wgbh/amex/bubble/peopleevents/p_vetter.html.

  Richard Mulligan, a virologist and geneticist: Luigi Naldini et al., “In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector,” Science 272, no. 5259 (1996): 263–67.

  led by William French Anderson and Michael Blaese: “Hope for gene therapy,” Scientific American Frontiers, PBS, http://www.pbs.org/saf/1202/features/genetherapy.htm.

  In the early 1980s, Anderson and Blaese: W. French Anderson et al., “Gene transfer and expression in nonhuman primates using retroviral vectors,” Cold Spring Harbor Symposia on Quantitative Biology 51 (1986): 1073–81.

  “Nobody knows what may happen”: Lyon and Gorner, Altered Fates, 124.

  Perhaps predictably, the RAC rejected the protocol outright: Lisa Yount, Modern Genetics: Engineering Life (New York: Infobase Publishing, 2006), 70.

  “A cosmic moment has come and gone”: Lyon and Gorner, Altered Fates, 239.

  “Jesus Christ himself could walk by”: Ibid., 240.

  “It’s not a big improvement”: Ibid., 268.

  At four, he had joyfully eaten: Barbara Sibbald, “Death but one unintended consequence of gene-therapy trial,” Canadian Medical Association Journal 164, no. 11 (2001): 1612.

  In 1993, when Gelsinger was: For details of the Jesse Gelsinger story see Evelyn B. Kelly, Gene Therapy (Westport, CT: Greenwood Press, 2007); Lyon and Gorner, Altered Fates; and Sally Lehrman, “Virus treatment questioned after gene therapy death,” Nature 401, no. 6753 (1999): 517–18.

  By noon, the procedure was done: James M. Wilson, “Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency,” Molecular Genetics and Metabolism 96, no. 4 (2009): 151–57.

  “How could such a beautiful thing”: Paul Gelsinger, author interview, November 2014 and April 2015.

  That Wilson had a financial stake in: Robin Fretwell Wilson, “Death of Jesse Gelsinger: New evidence of the influence of money and prestige in human research,” American Journal of Law and Medicine 36 (2010): 295.

  In January 2000, when the FDA inspected: Sibbald, “Death but one unintended consequence,” 1612.r />
  “The entire field of gene therapy”: Carl Zimmer, “Gene therapy emerges from disgrace to be the next big thing, again,” Wired, August 13, 2013.

  “Gene therapy is not yet therapy”: Sheryl Gay Stolberg, “The biotech death of Jesse Gelsinger,” New York Times, November 27, 1999, http://www.nytimes.com/1999/11/28/magazine/the-biotech-death-of-jesse-gelsinger.html.

  “cautionary tale of scientific overreach”: Zimmer, “Gene therapy emerges.”

  Genetic Diagnosis: “Previvors”

  All that man is: W. B. Yeats, The Collected Poems of W. B. Yeats, ed. Richard Finneran (New York: Simon & Schuster, 1996), “Byzantium,” 248.

  The anti-determinists want to say: Jim Kozubek, “The birth of ‘transhumans,’ ” Providence (RI) Journal, September 29, 2013.

  “Genetic tests,” as Eric Topol: Eric Topol, author interview, 2013.

  Between 1978 and 1988, King added: Mary-Claire King, “Using pedigrees in the hunt for BRCA1,” DNA Learning Center, https://www.dnalc.org/view/15126-Using-pedigress-in-the-hunt-for-BRCA1-Mary-Claire-King.html.

  she had pinpointed it to a region: Jeff M. Hall et al., “Linkage of early-onset familial breast cancer to chromosome 17q21,” Science 250, no. 4988 (1990): 1684–89.

  “Being comfortable with uncertainty”: Jane Gitschier, “Evidence is evidence: An interview with Mary-Claire King,” PLOS, September 26, 2013.

  In 1998, Myriad was granted: E. Richard Gold and Julia Carbone, “Myriad Genetics: In the eye of the policy storm,” Genetics in Medicine 12 (2010): S39–S70.

  “Some of these women [with BRCA1 mutations]”: Masha Gessen, Blood Matters: From BRCA1 to Designer Babies, How the World and I Found Ourselves in the Future of the Gene (Boston: Houghton Mifflin Harcourt, 2009), 8.

  In 1908, the Swiss German psychiatrist: Eugen Bleuler and Carl Gustav Jung, “Komplexe und Krankheitsursachen bei Dementia praecox,” Zentralblatt für Nervenheilkunde und Psychiatrie 31 (1908): 220–27.

  In the 1970s, studies demonstrated: Susan Folstein and Michael Rutte, “Infantile autism: A genetic study of 21 twin pairs,” Journal of Child Psychology and Psychiatry 18, no. 4 (1977): 297–321.

 

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