Hacking Darwin

by Jamie Metzl

  13Patrick F. McKay et al., “The Effects of Demographic Variables and Stereotype Threat on Black/White Differences in Cognitive Ability Test Performance,” Journal of Business and Psychology 18 (2003): 1–14, https://link.springer.com/article/10.1023/A:1025062703113. See also Daphne Martschenko, “The IQ Test Wars: Why Screening for Intelligence Is Still So Controversial,” The Conversation, October 10, 2017, accessed June 26, 2018, https://theconversation.com/the-iq-test-wars-why-screening-for-intelligence-is-still-so-controversial-81428.

  14Richard J. Herrnstein and Charles A. Murray, The Bell Curve: Intelligence and Class Structure in American Life (New York: Free Press, 1997). This book was first published in 1994.

  15Bob Herbert, “In America; Throwing a Curve,” New York Times, October 26, 1994, accessed June 26, 2018. https://www.nytimes.com/1994/10/26/opinion/in-america-throwing-a-curve.html.

  16Stephen Jay Gould, “Curveball,” New Yorker, November 28, 1994, http://www.dartmouth.edu/~chance/course/topics/curveball.html. For a thoughtful, strong critique of The Bell Curve see also Siddhartha Mukherjee, The Gene: An Intimate History (London: Vintage, 2017), 343.

  17For a compilation of some of these critiques, see Steve Fraser, The Bell Curve Wars: Race, Intelligence, and the Future of America (New York: BasicBooks, 1998). See also Eric Siegel, “The Real Problem with Charles Murray and ‘The Bell Curve,’” Scientific American Blog Network, April 12, 2017, accessed June 17, 2018. https://blogs.scientificamerican.com/voices/the-real-problem-with-charles-murray-and-the-bell-curve/.

  18Reprinted in Linda S. Gottfredson, “Mainstream Science on Intelligence: An Editorial with 52 Signatories, History, and Bibliography,” Intelligence 24, no. 1 (1997): 13–23, doi:10.1016/s0160–2896(97)90011–8. The American Psychological Association also created a special task force to assess the findings of the book that arrived at similar results.

  19Bouchard et al., “Sources of Human Psychological Differences.”

  20Plomin and I. J. Deary, “Genetics and Intelligence Differences: Five Special Findings,” Molecular Psychiatry 20 (2014): 98–108, https://www.nature.com/articles/mp2014105.pdf.

  21Thomas J. Bouchard, “The Wilson Effect: The Increase in Heritability of IQ with Age,” Twin Research and Human Genetics 16, no. 5 (2013): 923–30, doi:10.1017/thg.2013.54. Because IQ is a relative term, genetics would need to be a more important factor in IQ as we age relative to other people as they age. Another study suggested that adult IQ is 80 percent heritable. Valerie S. Knopik et al., Behavioral Genetics, 7th ed. (Worth Publishers, 2016); Susan Bouregy, Elena L. Grigorenko, and Stephen R. Latham, Genetics, Ethics and Education (Cambridge: Cambridge University Press, 2017).

  22Eric Turkheimer et al., “Socioeconomic Status Modifies Heritability of IQ in Young Children,” Psychological Science 14 (2003): 623–628.

  23Mutations and variants are essentially the same thing, but we tend to call them mutations when they are disease-related and often rarer, and we call them variants when they impact nondisease traits and are more common. Some researchers have recently begun using the term pathogenic variant instead of mutation to make this point. Because the line between disorders and traits is so squishy, these terms are largely interchangeable.

  24D. Hill et al., “A Combined Analysis of Genetically Correlated Traits Identifies 187 Loci and a Role for Neurogenesis and Myelination in Intelligence,” Molecular Psychiatry (2018): doi:10.1038/s41380-017-0001-5, https://www.nature.com/articles/s41380-017-0001-5; D. Zabaneh et al., “A Genome-Wide Association Study for Extremely High Intelligence,” Molecular Psychiatry 23 (July 4, 2017): 1226–1232, https://www.nature.com/articles/mp2017121; Gail Davies et al., “Ninety-Nine Independent Genetic Loci Influencing General Cognitive Function Include Genes Associated with Brain Health and Structure,” BioRxiv (2017), https://www.biorxiv.org/content/biorxiv/early/2017/08/18/176511.full.pdf; Robert Plomin and Sophie von Stumm, “The New Genetics of Intelligence,” Nature Reviews Genetics 19 (January 8, 2018): 148–159, doi:10.1038/nrg.2017.104, https://www.nature.com/articles/nrg.2017.104. The number will likely exceed two hundred by the time this book is published.

  25Suzanne Sniekers et al., “Genome-Wide Association Meta-analysis of 78,308 Individuals Identifies New Loci and Genes Influencing Human Intelligence,” Nature Genetics 49 (2017): 1107–1112.

  26Already, researchers are moving from the bottom-up model of inferring general intelligence from identifying single-gene mutations to a more top-down approach, based on the big-data analytics of patterns identified in all of these mutations. See Plomin and Stumm, “The New Genetics of Intelligence.”

  27Yan Zhang et al., “Estimation of Complex Effect-Size Distributions Using Summary-Level Statistics from Genome-wide Association Studies across 32 Complex Traits and Implications for the Future,” BioRxiv (2017), https://www.biorxiv.org/content/biorxiv/early/2017/08/11/175406.full.pdf; Stephen Hsu, “Genomic Prediction of Complex Traits,” lecture, The Paul G. Allen Frontiers Group, January 19, 2018, http://infoproc.blogspot.com/2018/01/allen-institute-meeting-on-genetics-of.html; “Heritability,” SNPedia, last modified March 13, 2018, https://www.snpedia.com/index.php/Heritability. A preliminary list of select diseases and human body conditions estimated to be on average 50 percent or more genetic on SNPedia.com, a genetics wiki that brings together scientific research from around the world, includes: abdominal aortic aneurysm, acne, age-related macular degeneration, alcoholism, Alzheimer’s disease, androgenic alopecia, anorexia, attention deficit hyperactivity disorder, beard thickness, bipolar disorder, bone mineral density, celiac disease, chronic obstructive pulmonary disease, Crohn’s disease, Dupuytren’s disease, eczema, epilepsy, eye color, freckle counts, Graves’ disease, hair color, hair curliness, height, kidney stones, lupus, menarche, monobrow, polycystic ovary syndrome, psoriasis, rheumatoid arthritis, schizophrenia, sexual orientation, stuttering, thyroid cancer, Tourette’s syndrome, type 1 diabetes, and varicose veins. The full list will eventually include many tens of thousands of diseases and traits.

  28Bouchard et al., “Sources of Human Psychological Differences.”

  29Min-Tzu Lo et al., “Genome-Wide Analyses for Personality Traits Identify Six Genomic Loci and Show Correlations with Psychiatric Disorders,” Nature Genetics 49 (2017): 152–156, https://www.nature.com/articles/ng.3736.

  CHAPTER 4

  1“Masturbatorium,” Wiktionary, last modified June 7, 2017, https://en.wiktionary.org/wiki/masturbatorium.

  2“Odontophilia,” Urban Dictionary, accessed June 26, 2018, https://www.urbandictionary.com/define.php?term=Odontophilia.

  3Japan has both the highest percentage of IVF births and the lowest success rate among industrialized countries. This is in part because the women receiving IVF tend to be older than their counterparts in other countries and because the IVF industry in Japan has inconsistent standards. See “A Corked Tube: No Country Resorts to IVF More Than Japan—or Has Less Success,” The Economist, May 26, 2018, https://www.economist.com/asia/2018/05/26/no-country-resorts-to-ivf-more-than-japan-or-has-less-success.

  4Gary J. Gates, “In U.S., More Adults Identifying as LGBT,” Gallup, January 11, 2017, http://news.gallup.com/poll/201731/lgbt-identification-rises.aspx. Measures of the exact size of the U.S. and global LGBTQIAP populations are inherently imperfect and do not account for the gender and sexual orientation fluidity, particularly common among younger generations. See: Katy Steinmetz, “Inside the Efforts to Finally Identify the Size of the Nation’s LGBT Population,” Time, May 18, 2016, http://time.com/lgbt-stats/.

  5Elizabeth Cohen, “Researchers Isolate Human Stem Cells in the Lab,” CNN Interactive, November 5, 1998, http://www.cnn.com/HEALTH/9811/05/stem.cell.discovery/.

  6Jessica Reaves, “The Great Debate over Stem Cell Research,” Time, July 11, 2001, http://content.time.com/time/nation/article/0,8599,167245,00.html.

  7Hayashi, “Offspring from Oocytes Derived from In Vitro Primordial Germ Cell-Like Cells in Mice,” Science 16 (2012): 971–975, https://www.ncbi.nlm.nih.gov/pubmed/23042
295. Interestingly, Hayashi is also leading efforts to use induced stem-cell technology to save the endangered white rhino from extinction.

  8David Cyranoski, “Rudimentary Egg and Sperm Cells Made from Stem Cells,” Nature, December 24, 2014, https://www.nature.com/news/rudimentary-egg-and-sperm-cells-made-from-stem-cells-1.16636.

  9Naoko Irie, Shinseog Kim, and M. Azim Surani, “Human Germline Development from Pluripotent Stem Cells In Vitro,” Journal of Mammalian Ova Research 33 (2016): 79–87; Naoko Irie and M. Azim Surani, “Efficient Induction and Isolation of Human Primordial Germ Cell-like Cells from Competent Human Pluripotent Stem Cells” in Germline Stem Cells, ed. Steven X. Hou and Shree Ram Singh, in Methods in Molecular Biology 1463 (2016): 217–226. Caution is also in order here. One of the four Yamanaka “master genes”—myc—is among the most aggressive catalysts of cancer.

  10CIA World Factbook, Central Intelligence Agency, accessed May 21, 2018. https://www.cia.gov/library/publications/the-world-factbook/fields/2256.html.

  11Carl Shulman and Nick Bostrom, “Embryo Selection for Cognitive Enhancement: Curiosity or Game-Changer?” Global Policy 5 (2014): 85–92, https://nickbostrom.com/papers/embryo.pdf.

  12Stephen Hsu, “Super-Intelligent Humans Are Coming,” Nautilus, October 16, 2014, http://nautil.us/issue/18/genius/super_intelligent-humans-are-coming.

  CHAPTER 5

  1“Method of the Year 2011,” Nature Methods 9 (2012): 1, https://www.nature.com/articles/nmeth.1852.

  2Eric S. Lander, “The Heroes of CRISPR,” Cell 164 (2016): 18–28.

  3See “CRISPR Off-Targets: A Reassessment,” Nature News, March 30, 2018, accessed May 8, 2018, https://www.nature.com/articles/nmeth.4664.

  4“SHERLOCK, DETECTR, CAMERA: Three New CRISPR Technologies.,” AACC, accessed May 8, 2018, https://www.aacc.org/publications/cln/cln-stat/2018/march/15/sherlock-detectr-camera-three-new-crispr-technologies.

  5Pratiksha I. Thakore et al., “Editing the Epigenome: Technologies for Programmable Transcription and Epigenetic Modulation,” Nature Methods 13 (2016): 127–137, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922638/.

  6David Cano-Rodriguez and Marianne G. Rots, “Epigenetic Editing: On the Verge of Reprogramming Gene Expression at Will,” Current Genetic Medicine Reports 4 (2016): 170–179, https://link.springer.com/article/10.1007/s40142-016-0104-3; Heidi Ledford, “CRISPR: Gene Editing Is Just the Beginning,” Nature 531 (2016): 156–159, https://www.nature.com/news/crispr-gene-editing-is-just-the-beginning-1.19510.

  7Emily Waltz, “Gene-Edited CRISPR Mushroom Escapes U.S. Regulation,” Nature 532 (2016): 293, https://www.nature.com/news/gene-edited-crispr-mushroom-escapes-us-regulation-1.19754.

  8Because neither the “Arctic apple” nor the nonbrowning mushrooms have foreign DNA in them, they are technically not GMOs as traditionally defined. On March 28, 2018, U.S. Secretary of Agriculture Sonny Perdue announced that gene-edited plants where no foreign DNA had been introduced would not be regulated as GMOs by the USDA. This is causing consternation among many GMO advocates concerned about any genetic alteration of the food supply. In November 2018, a coalition of thirteen countries, including the United States, Canada, and Brazil, announced at a World Trade Organization meeting in Geneva that they would support policies that enable genome editing in agriculture. Amy Maxmen, “Genetically Modified Apple Reaches U.S. Stores, but Will Consumers Bite?” Nature 551 (2017): 149–150, https://www.nature.com/news/genetically-modified-apple-reaches-us-stores-but-will-consumers-bite-1.22969. See also: “Secretary Perdue Issues USDA Statement on Plant Breeding Innovation.” USDA, March 28, 2018, accessed June 1, 2018, https://www.usda.gov/media/press-releases/2018/03/28/secretary-perdue-issues-usda-statement-plant-breeding-innovation and Emily Waltz, “CRISPR Crops—Exempt from GMO Regulations—Reaching U.S. Market in Record Time,” Genetic Literacy Project, January 15, 2018, https://geneticliteracyproject.org/2018/01/15/crispr-crops-exempt-gmo-regulations-reaching-us-market-record-time/. The European Court of Justice came to a similar conclusion in an opinion released in 2018: “Opinion of Advocate General Bobek delivered on 18 January 2018(1),” Case C-528/16, accessed June 6, 2018, http://curia.europa.eu/juris/document/document.jsf?text=&docid=198532&pageIndex=0&doclang=EN&mode=req&dir=&occ=first&part=1&cid=779174. This EU decision was then overturned by Europe’s highest court, which ruled in July 2018 that crops altered by gene-editing techniques like CRISPR, even when no foreign DNA was added, would be regulated with the same stringency as GMOs. “Organisms Obtained by Mutagenesis Are GMOs and Are, in Principle, Subject to the Obligations Laid Down by the GMO Directive,” Court of Justice of the European Union, press release no. 111/18, Luxembourg, July 25, 2018, Judgment in Case C-528/16, https://curia.europa.eu/jcms/upload/docs/application/pdf/2018–07/cp180111en.pdf.

  9Vitamin A has been genetically engineered into maize, cassava, and sweet potatoes; iron into beans and pearl millet; and zinc into rice and wheat. See Heather Ohly and Nicola Lowe, “Scientists Are Breeding Super-Nutritious Crops to Help Solve Global Hunger,” The Conversation, June 1, 2018, accessed June 3, 2018, https://theconversation.com/scientists-are-breeding-super-nutritious-crops-to-help-solve-global-hunger-89815.

  10Bill Gates, “Gene Editing for Good,” Foreign Affairs (May/June 2018), accessed May 3, 2018, https://www.foreignaffairs.com/articles/2018-04-10/gene-editing-good.

  11Tom Whipple, “Bill Gates Pumps Millions into Quest for a Supercow,” The Times, January 26, 2018, https://www.thetimes.co.uk/article/bill-gates-pumps-millions-into-quest-for-a-supercow-7swc6dntw.

  12Sara Reardon, “Welcome to the CRISPR Zoo,” Nature 531 (2016): 160–163, https://www.nature.com/news/welcome-to-the-crispr-zoo-1.19537. BGI Shenzhen announced in 2017 it was dropping its micropig program, likely because the press attention it was getting detracted from the company’s initial public offering.

  13For a fun description of this process, see Ben Mezrich, Woolly: The True Story of the Quest to Revive One of History’s Most Iconic Extinct Creatures (New York: Simon & Schuster, 2018); and also, George Church and Ed Regis, Regenesis (New York: Basic Books, 2014): 10–11.

  14Barbara Sibbald, “Death But One Unintended Consequence of Gene-Therapy Trial,” Canadian Medical Association Journal 164 (2001): 1612, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/; Osagie K. Obasogie, “Ten Years Later: Jesse Gelsinger’s Death and Human Subjects Protection,” The Hastings Center, October 22, 2009, https://www.thehastingscenter.org/ten-years-later-jesse-gelsingers-death-and-human-subjects-protection/.

  15Roland W. Herzog, Ou Cao, and Arun Srivastava, “Two Decades of Clinical Gene Therapy—Success Is Finally Mounting,” Discovery Medicine 9 (2010): 105–11, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586794/.

  16Herzog, Cao, and Srivastava, “Two Decades of Clinical Gene Therapy.”

  17Calvin J. Stephens et al., “Targeted In Vivo Knock-in of Human Alpha-1-antitrypsin CDNA Using Adenoviral Delivery of CRISPR/Cas9,” Gene Therapy 25, no. 2 (2018): 139–56. doi:10.1038/s41434-018-0003-1.

  18Francis S. Collins and Scott Gottlieb, “The Next Phase of Human Gene-Therapy Oversight,” New England Journal of Medicine (August 15, 2018): doi:10.1056/nejmp1810628.

  19H-Y Xue et al., “In Vivo Gene Therapy Potentials of CRISPR-Cas9,” Gene Therapy 23 (2016): 557–559, https://www.nature.com/articles/gt201625.

  20Lukas Villiger et al., “Treatment of a Metabolic Liver Disease by in Vivo Genome Base Editing in Adult Mice,” Nature Medicine 24, no. 10 (October 2018): 1519–525, doi:10.1038/s41591-018-0209-1.

  21Collins and Gottlieb, “The Next Phase of Human Gene-Therapy Oversight.”

  22Megan Molteni, “Biology Will Be the Next Great Computing Platform,” Wired, May 3, 2018, accessed May 4, 2018, https://www.wired.com/story/biology-will-be-the-next-great-computing-platform/.

  23Gerald Schwank et al., “Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients,” Cell Stem Cell 13 (2013): 653–658, http://www.cell.com/cell-stem-cell/fulltext/S1934�
�5909(13)00493–1.

  24Hao Yin et al., “Genome Editing with Cas9 in Adult Mice Corrects a Disease Mutation and Phenotype,” Nature Biotechnology 32 (2014): doi:10.1038/nbt.2884; Yanjiao Shao et al., “Cas9-Nickase–Mediated Genome Editing Corrects Hereditary Tyrosinemia in Rats,” Journal of Biological Chemistry 293, no. 18 (2018): 6883–892. doi:10.1074/jbc.ra117.000347.

  25Puping Liang et al., “CRISPR/Cas9-Mediated Gene Editing in Human Tripronuclear Zygotes,” Protein & Cell 6 (2015): 363–372, http://www.ncbi.nlm.nih.gov/pubmed/25894090.

  26Rafal Kaminski, “Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing,” Scientific Reports 6 (2016).

  27Hong Ma, “Correction of a Pathogenic Gene Mutation in Human Embryos,” Nature 548 (2017): 413–419.

  28Chengzu Long et al., “Correction of Diverse Muscular Dystrophy Mutations in Human Engineered Heart Muscle by Single-Site Genome Editing,” Science Advances 4 (2018), http://advances.sciencemag.org/content/4/1/eaap9004.

  29Alice Park, “Food and Drug Administration Approves a New Way to Use Gene Therapy,” Time, December 20, 2017, accessed June 17, 2018. http://time.com/5073751/gene-therapy-visual-impairment/.

  30Serena H. Chen et al., “A Limited Survey-Based Uncontrolled Follow-Up Study of Children Born after Ooplasmic Transplantation in a Single Centre.” Reproductive BioMedicine Online 33, no. 6 (2016): 737–44, doi:10.1016/j.rbmo.2016.10.003.

  31Rosa J. Castro, “Mitochondrial Replacement Therapy: The UK and U.S. Regulatory Landscapes,” Journal of Law and the Biosciences 3 (2016): 726–35, https://academic.oup.com/jlb/article/3/3/726/2566730.

  32Although information about the UK mitochondrial transfer embryos is being withheld from the public until the babies are born, the 2019 date is both a logical inference based on when the treatments began to be administered in 2018 and on private correspondence with parties directly involved in this process. Because the final edits of Hacking Darwin were submitted in November 2018, it was not possible to include the exact birth date of the first UK mitochondrial transfer baby in this edition of the book. Ian Sample, “UK Doctors Select First Women to Have ‘Three-Person Babies,’” The Guardian, February 1, 2018, https://www.theguardian.com/science/2018/feb/01/permission-given-to-create-britains-first-three-person-babies. Singapore is also considering whether to authorize clinical trials of mitochondrial transfer.