The Gene

by Siddhartha Mukherjee

  “domineering, nagging and hostile mother”: Silvano Arieti and Eugene B. Brody, Adult Clinical Psychiatry (New York: Basic Books, 1974), 553.

  National Book Award for science: “1975: Interpretation of Schizophrenia by Silvano Arieti,” National Book Award Winners: 1950–2014, National Book Foundation, http://www.nationalbook.org/nbawinners_category.html#.vcnit7fxhom.

  In 2013, an enormous study identified: Menachem Fromer et al., “De novo mutations in schizophrenia implicate synaptic networks,” Nature 506, no. 7487 (2014): 179–84.

  108 genes (or rather genetic regions): Schizophrenia Working Group of the Psychiatric Genomics, Nature 511 (2014): 421–27.

  The strongest, and most: “Schizophrenia risk from complex variation of complement component 4,” Sekar et al. Nature 530, 177–183.

  “There are lots of”: Benjamin Neale, quoted in Simon Makin, “Massive study reveals schizophrenia’s genetic roots: The largest-ever genetic study of mental illness reveals a complex set of factors,” Scientific American, November 1, 2014.

  “We of the craft are all crazy”: Carey’s Library of Choice Literature, vol. 2 (Philadelphia: E. L. Carey & A. Hart, 1836), 458.

  In Touched with Fire, an authoritative: Kay Redfield Jamison, Touched with Fire (New York: Simon & Schuster, 1996).

  Hans Asperger, the psychologist who first: Tony Attwood, The Complete Guide to Asperger’s Syndrome (London: Jessica Kingsley, 2006).

  As Edvard Munch put it: Adrienne Sussman, “Mental illness and creativity: A neurological view of the ‘tortured artist,’ ” Stanford Journal of Neuroscience 1, no. 1 (2007): 21–24.

  illness as the “night-side of life”: Susan Sontag, Illness as Metaphor and AIDS and Its Metaphors (New York: Macmillan, 2001).

  Entitled “The Future of Genomic Medicine”: Details of the conference can be found in “The future of genomic medicine VI,” Scripps Translational Science Institute, http://www.slideshare.net/mdconferencefinder/the-future-of-genomic-medicine-vi-23895019; Eryne Brown, “Gene mutation didn’t slow down high school senior,” Los Angeles Times, July 5, 2015, http://www.latimes.com/local/california/la-me-lilly-grossman-update-20150702-story.html; and Konrad J. Karczewski, “The future of genomic medicine is here,” Genome Biology 14, no. 3 (2013): 304.

  Alexis and Noah Beery: “Genome maps solve medical mystery for California twins,” National Public Radio broadcast, June 16, 2011.

  Based on that genetic diagnosis: Matthew N. Bainbridge et al., “Whole-genome sequencing for optimized patient management,” Science Translational Medicine 3, no. 87 (2011): 87re3.

  That a mutation in the gene MECP2: Antonio M. Persico and Valerio Napolioni, “Autism genetics,” Behavioural Brain Research 251 (2013): 95–112; and Guillaume Huguet, Elodie Ey, and Thomas Bourgeron, “The genetic landscapes of autism spectrum disorders,” Annual Review of Genomics and Human Genetics 14 (2013): 191–213.

  the eventual effects of these gene-environment: Albert H. C. Wong, Irving I. Gottesman, and Arturas Petronis, “Phenotypic differences in genetically identical organisms: The epigenetic perspective,” Human Molecular Genetics 14, suppl. 1 (2005): R11–R18. Also see Nicholas J. Roberts et al., “The predictive capacity of personal genome sequencing,” Science Translational Medicine 4, no. 133 (2012): 133ra58.

  an article in Nature magazine announced: Alan H. Handyside et al., “Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification,” Nature 344, no. 6268 (1990): 768–70.

  As the political theorist Desmond King puts it: D. King, “The state of eugenics,” New Statesman & Society 25 (1995): 25–26.

  Take, for instance, a series of startlingly provocative: K. P. Lesch et al., “Association of anxiety-related traits with a polymorphism in the serotonergic transporter gene regulatory region,” Science 274 (1996): 1527–31.

  the short allele has been associated with: Douglas F. Levinson, “The genetics of depression: A review,” Biological Psychiatry 60, no. 2 (2006): 84–92.

  In 2010, a team of researchers launched: “Strong African American Families Program,” Blueprints for Healthy Youth Development, http://www.blueprintsprograms.com/evaluationAbstracts.php?pid=f76b2ea6b45eff3bc8e4399145cc17a0601f5c8d.

  Six hundred African-American families with early-adolescent: Gene H. Brody et al., “Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene × environment hypotheses tested via a randomized prevention design,” Child Development 80, no. 3 (2009): 645–61; and Gene H. Brody, Yi-fu Chen, and Steven R. H. Beach, “Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects,” Journal of Child Psychology and Psychiatry 54, no. 8 (2013): 863–71.

  Writing in the New York Times in 2014: Jay Belsky, “The downside of resilience,” New York Times, November 28, 2014.

  “a technology of abnormal individuals”: Michel Foucault, Abnormal: Lectures at the Collège de France, 1974–1975, vol. 2 (New York: Macmillan, 2007).

  Genetic Therapies: Post-Human

  There is in biology at the moment: “Biology’s Big Bang,” Economist, June 14, 2007.

  a journalist visited James Watson at: Lyon and Gorner, Altered Fates, 537.

  Jesse Gelsinger’s “biotech death”: Stolberg, “Biotech death of Jesse Gelsinger,” 136–40.

  In 2014, a landmark study: Amit C. Nathwani et al., “Long-term safety and efficacy of factor IX gene therapy in hemophilia B,” New England Journal of Medicine 371, no. 21 (2014): 1994–2004.

  In 1998, soon after Thomson’s paper: James A. Thomson et al., “Embryonic stem cell lines derived from human blastocysts,” Science 282, no. 5391 (1998): 1145–47.

  President George W. Bush sharply restricted: Dorothy C. Wertz, “Embryo and stem cell research in the United States: History and politics,” Gene Therapy 9, no. 11 (2002): 674–78.

  Doudna and Charpentier published their data: Martin Jinek et al., “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity,” Science 337, no. 6096 (2012): 816–21.

  this technique has exploded: Key contributors to the use of CRISPR/Cas9 in human cells include Feng Zhang (MIT) and George Church (Harvard). See, for instance, L. Cong et al., “Multiplex genome engineering using CRISPR/Cas systems,” Science 339, no. 6121 (2013): 819–23; and F. A. Ran, “Genome engineering using the CRISPR-Cas9 system,” Nature Protocols 11 (2013): 2281–308.

  In the winter of 2014, a team: Walfred W. C. Tang et al., “A unique gene regulatory network resets the human germline epigenome for development,” Cell 161, no. 6 (2015): 1453–67; and “In a first, Weizmann Institute and Cambridge University scientists create human primordial germ cells,” Weizmann Institute of Science, December 24, 2014, http://www.newswise.com/articles/in-a-first-weizmann-institute-and-cambridge-university-scientists-create-human-primordial-germ-cells.

  Jennifer Doudna and David Baltimore: B. D. Baltimore et al., “A prudent path forward for genomic engineering and germline gene modification,” Science 348, no. 6230 (2015): 36–38; and Cormac Sheridan, “CRISPR germline editing reverberates through biotech industry,” Nature Biotechnology 33, no. 5 (2015): 431–32.

  “It is very clear that people will try”: Nicholas Wade, “Scientists seek ban on method of editing the human genome,” New York Times, March 19, 2015.

  “This reality means”: Francis Collins, Letter to the author, October 2015.

  In the spring of 2015, a laboratory: David Cyranoski and Sara Reardon, “Chinese scientists genetically modify human embryos,” Nature (April 22, 2015).

  The highest-ranking scientific journals: Chris Gyngell and Julian Savulescu, “The moral imperative to research editing embryos: The need to modify nature and science,” Oxford University, April 23, 2015, Blog.Practicalethics.Ox.Ac.Uk/2015/04/the-Moral-Imperative-to-Research-Editing-Embryos-the-Need-to-Modify-Nature-and-Science/.

  the results were eventually published in: Puping Liang et al., “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes,” P
rotein & Cell 6, no. 5 (2015): 1–10.

  “planning to decrease the number of off-target”: Cyranoski and Reardon, “Chinese scientists genetically modify human embryos.”

  “I don’t think China wants”: Didi Kristen Tatlow, “A scientific ethical divide between China and West,” New York Times, June 29, 2015.

  Epilogue: Bheda, Abheda

  “No sane biologist believes”: Paul Berg, author interview, 1993.

  “very few human genes”: David Botstein, letter to the author, October 2015.

  In an influential review published in 2011: Eric Turkheimer, “Still missing,” Research in Human Development 8, nos. 3–4 (2011): 227–41.

  “Perhaps,” as one observer complained: Peter Conrad, “A mirage of genes,” Sociology of Health & Illness 21, no. 2 (1999): 228–41.

  “Imagine you are a soldier returning from war”: Richard A. Friedman, “The feel-good gene,” New York Times, March 6, 2015.

  “[Nature] may, after all, be entirely approachable”: Morgan, Physical Basis of Heredity, 15.

  Acknowledgments

  “distorted version of our normal selves”: H.Varmus, Nobel lecture, 1989. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1989/varmus-lecture.html. For the paper describing the existence of endogenous proto-oncogenes in cells see D. Stehelin et al., “DNA related to the transforming genes of avian sarcoma viruses is present in normal DNA,” Nature 260, no. 5547 (1976): 170–73. Also see Harold Varmus to Dominique Stehelin, February 3, 1976, Harold Varmus Papers, National Library of Medicine Archives.

  Selected Bibliography

  Arendt, Hannah. Eichmann in Jerusalem: A Report on the Banality of Evil. New York: Viking, 1963.

  Aristotle. Generation of Animals. Leiden: Brill Archive, 1943.

  Aristotle, and D. M. Balme, ed. History of Animals. Cambridge: Harvard University Press, 1991.

  Aristotle, and Jonathan Barnes, ed. The Complete Works of Aristotle. Revised Oxford Translation. Princeton, NJ: Princeton University Press, 1984.

  Berg, Paul, and Maxine Singer. Dealing with Genes: The Language of Heredity. Mill Valley, CA: University Science Books, 1992.

  ———. George Beadle, An Uncommon Farmer: The Emergence of Genetics in the 20th Century. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2003.

  Bliss, Catherine. Race Decoded: The Genomic Fight for Social Justice. Palo Alto, CA: Stanford University Press, 2012.

  Browne, E. J. Charles Darwin: A Biography. New York: Alfred A. Knopf, 1995.

  Cairns, John, Gunther Siegmund Stent, and James D. Watson, eds. Phage and the Origins of Molecular Biology. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1968.

  Carey, Nessa. The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance. New York: Columbia University Press, 2012.

  Chesterton, G. K. Eugenics and Other Evils. London: Cassell, 1922.

  Cobb, Matthew. Generation: The Seventeenth-Century Scientists Who Unraveled the Secrets of Sex, Life, and Growth. New York: Bloomsbury Publishing, 2006.

  Cook-Deegan, Robert M. The Gene Wars: Science, Politics, and the Human Genome. New York: W. W. Norton, 1994.

  Crick, Francis. What Mad Pursuit: A Personal View of Scientific Discovery. New York: Basic Books, 1988.

  Crotty, Shane. Ahead of the Curve: David Baltimore’s Life in Science. Berkeley: University of California Press, 2001.

  Darwin, Charles. On the Origin of Species by Means of Natural Selection. London: Murray, 1859.

  Darwin, Charles, and Francis Darwin, ed. The Autobiography of Charles Darwin. Amherst, NY: Prometheus Books, 2000.

  Dawkins, Richard. The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe without Design. New York: W. W. Norton, 1986.

  ———. The Selfish Gene. Oxford: Oxford University Press, 1989.

  Desmond, Adrian, and James Moore. Darwin. New York: Warner Books, 1991.

  De Vries, Hugo. The Mutation Theory. Vol. 1. Chicago: Open Court, 1909.

  Dobzhansky, Theodosius. Genetics and the Origin of Species. New York: Columbia University Press, 1937.

  ———. Heredity and the Nature of Man. New York: New American Library, 1966.

  Edelson, Edward. Gregor Mendel, and the Roots of Genetics. New York: Oxford University Press, 1999.

  Feinstein, Adam. A History of Autism: Conversations with the Pioneers. West Sussex: Wiley-Blackwell, 2010.

  Flynn, James. Intelligence and Human Progress: The Story of What Was Hidden in Our Genes. Oxford: Elsevier, 2013.

  Fox Keller, Evelyn. The Century of the Gene. Cambridge: Harvard University Press, 2009.

  Fredrickson, Donald S. The Recombinant DNA Controversy: A Memoir: Science, Politics, and the Public Interest 1974–1981. Washington, DC: American Society for Microbiology Press, 2001.

  Friedberg, Errol C. A Biography of Paul Berg: The Recombinant DNA Controversy Revisited. Singapore: World Scientific Publishing, 2014.

  Gardner, Howard E. Frames of Mind: The Theory of Multiple Intelligences. New York: Basic Books, 2011.

  ———. Intelligence Reframed: Multiple Intelligences for the 21st Century. New York: Perseus Books Group, 2000.

  Glimm, Adele. Gene Hunter: The Story of Neuropsychologist Nancy Wexler. New York: Franklin Watts, 2005.

  Hamer, Dean. Science of Desire: The Gay Gene and the Biology of Behavior. New York: Simon & Schuster, 2011

  Happe, Kelly E. The Material Gene: Gender, Race, and Heredity after the Human Genome Project. New York: NYU Press, 2013.

  Harper, Peter S. A Short History of Medical Genetics. Oxford: Oxford University Press, 2008.

  Hausmann, Rudolf. To Grasp the Essence of Life: A History of Molecular Biology. Berlin: Springer Science & Business Media, 2013.

  Henig, Robin Marantz. The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics. Boston: Houghton Mifflin, 2000.

  Herring, Mark Youngblood. Genetic Engineering. Westport, CT: Greenwood, 2006.

  Herrnstein, Richard, and Charles Murray. The Bell Curve. New York: Simon & Schuster, 1994.

  Herschel, John F. W. A Preliminary Discourse on the Study of Natural Philosophy. A Facsim. of the 1830 Ed. New York: Johnson Reprint, 1966.

  Hodge, Russ. The Future of Genetics: Beyond the Human Genome Project. New York: Facts on File, 2010.

  Hughes, Sally Smith. Genentech: The Beginnings of Biotech. Chicago: University of Chicago Press, 2011.

  Jamison, Kay Redfield. Touched with Fire. New York: Simon & Schuster, 1996.

  Judson, Horace Freeland. The Eighth Day of Creation. New York: Simon & Schuster, 1979.

  ———. The Search for Solutions. New York: Holt, Rinehart, and Winston, 1980.

  Kevles, Daniel J. In the Name of Eugenics: Genetics and the Uses of Human Heredity. New York: Alfred A. Knopf, 1985.

  Kornberg, Arthur. For the Love of Enzymes: The Odyssey of a Biochemist. Cambridge: Harvard University Press, 1991.

  ———. The Golden Helix: Inside Biotech Ventures. Sausalito, CA: University Science Books, 2002.

  Kornberg, Arthur, Adam Alaniz, and Roberto Kolter. Germ Stories. Sausalito, CA: University Science Books, 2007.

  Kornberg, Arthur, and Tania A. Baker. DNA Replication. San Francisco: W. H. Freeman, 1980.

  Krimsky, Sheldon. Genetic Alchemy: The Social History of the Recombinant DNA Controversy. Cambridge: MIT Press, 1982.

  ———. Race and the Genetic Revolution: Science, Myth, and Culture. New York: Columbia University Press, 2011.

  Kush, Joseph C., ed. Intelligence Quotient: Testing, Role of Genetics and the Environment and Social Outcomes. New York: Nova Science, 2013.

  Larson, Edward John. Evolution: The Remarkable History of a Scientific Theory. Vol. 17. New York: Random House Digital, 2004.

  Lombardo, Paul A. Three Generations, No Imbeciles: Eugenics, the Supreme Court, and Buck v. Bell. Baltimore: Johns Hopkins University Press, 2008.

  Lyell, Charles. Principles of Geo
logy: Or, The Modern Changes of the Earth and Its Inhabitants Considered as Illustrative of Geology. New York: D. Appleton & Company, 1872.

  Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York: W. W. Norton, 1996.

  Maddox, Brenda. Rosalind Franklin: The Dark Lady of DNA. UK: HarperCollins, 2002.

  McCabe, Linda L., and Edward R. B. McCabe. DNA: Promise and Peril. Berkeley: University of California Press, 2008.

  McElheny, Victor K. Drawing the Map of Life: Inside the Human Genome Project. New York: Basic Books, 2012.

  ———. Watson and DNA: Making a Scientific Revolution. Cambridge: Perseus, 2003.

  Mendel, Gregor, Alain F. Corcos, and Floyd V. Monaghan, eds. Gregor Mendel’s Experiments on Plant Hybrids: A Guided Study. New Brunswick, NJ: Rutgers University Press, 1993.

  Morange, Michel. A History of Molecular Biology. Trans. Matthew Cobb. Cambridge: Harvard University Press, 1998.

  Morgan, Thomas Hunt. The Mechanism of Mendelian Heredity. New York: Holt, 1915.

  ———. The Physical Basis of Heredity. Philadelphia: J. B. Lippincott, 1919.

  Müller-Wille, Staffan, and Hans-Jörg Rheinberger. A Cultural History of Heredity. Chicago: University of Chicago Press, 2012.

  Olby, Robert C. The Path to the Double Helix: The Discovery of DNA. New York: Dover Publications, 1994.

  Paley, William. The Works of William Paley. Philadelphia: J. J. Woodward, 1836.

  Patterson, Paul H. The Origins of Schizophrenia. New York: Columbia University Press, 2013.

  Portugal, Franklin H., and Jack S. Cohen. A Century of DNA: A History of the Discovery of the Structure and Function of the Genetic Substance. Cambridge: MIT Press, 1977.

  Posner, Gerald L., and John Ware. Mengele: The Complete Story. New York: McGraw-Hill, 1986.

  Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters. New York: HarperCollins, 1999.

  Sambrook, Joseph, Edward F. Fritsch, and Tom Maniatis. Molecular Cloning. Vol. 2. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1989.

  Sayre, Anne. Rosalind Franklin and DNA. New York: W. W. Norton, 2000.