Hacking Darwin

by Jamie Metzl

  10Rachel D. Melamed et al., “Genetic Similarity between Cancers and Comorbid Mendelian Diseases Identifies Candidate Driver Genes,” Nature Communications, no. 1 (2015), doi:10.1038/ncomms8033.

  11See Lidewij Henneman et al., “Responsible Implementation of Expanded Carrier Screening,” European Journal of Human Genetics 24, no. 6 (June 2016): e1–e12. Published online 2016 Mar 16. doi: 10.1038/ejhg.2015.271; and Nancy C. Rose, “Expanded Carrier Screening: Too Much of a Good Thing?” Prenatal Diagnosis 35, no. 10 (2015): 936–37, doi:10.1002/pd.4638.

  12Heather Mason Kiefer, “Gallup Brain: The Birth of In Vitro Fertilization,” Gallup News, August 5, 2003, http://news.gallup.com/poll/8983/gallup-brain-birth-vitro-fertilization.aspx.

  13Kiefer, “Gallup Brain.”

  14John M. Haas, “Begotten Not Made: A Catholic View of Reproductive Technology,” United States Conference of Catholic Bishops, 1998, http://www.usccb.org/issues-and-action/human-life-and-dignity/reproductive-technology/begotten-not-made-a-catholic-view-of-reproductive-technology.cfm.

  15Jason Pontin, “Science Is Getting Us Closer to the End of Infertility,” Wired, March 27, 2018, https://www.wired.com/story/reverse-infertility/.

  16G. Edwards and R. L. Gardner, “Sexing of Live Rabbit Blastocysts,” Nature 214 (1967): 576–77, https://www.nature.com/articles/214576a0.

  17Genome Editing and Human Reproduction. Report. July 17, 2018, Nuffield Council on Bioethics. http://nuffieldbioethics.org/wp-content/uploads/Genome-editing-and-human-reproduction-FINAL-website.pdf, p. 10.

  18Henry T. Greely, The End of Sex and the Future of Human Reproduction (Cambridge: Harvard University Press, 2016): 114, 331.

  19The mathematics are a bit more complicated than this preliminary calculation suggests because PGT is more accurate with some categories of genetic disorders than others. Recessive conditions where both parents are heterozygous for the particular disorder, for example, would be statistically easier to identify than a dominant condition where one parent is a heterozygous carrier and the other is a noncarrier.

  20Petula Dvorak, “Parents Who Refuse to Vaccinate Their Children Are Putting Others at Risk,” Washington Post, January 26, 2015, https://www.washingtonpost.com/local/parents-who-refuse-to-vaccinate-their-children-are-putting-others-at-risk/2015/01/26/9c538266-a5aa-11e4-a06b-9df2002b86a0_story.html?utm_term=.3b17e2cf1ccf.

  21“Vaccines Do Not Cause Autism,” Centers for Disease Control, last modified November 23, 2015, https://www.cdc.gov/vaccinesafety/concerns/autism.html.

  22Laura Entis, “Donald Trump Has Long Linked Autism to Vaccines. He Isn’t Stopping Now That He’s President,” Fortune, February 16, 2017, http://fortune.com/2017/02/16/donald-trump-autism-vaccines/.

  23Cary Funk, Brian Kennedy, and Meg Hefferon, “Public Opinion about Childhood Vaccines for Measles, Mumps, and Rubella,” Pew Research Center, February 2, 2017, http://www.pewinternet.org/2017/02/02/public-opinion-about-childhood-vaccines-for-measles-mumps-and-rubella/.

  24Norbert Gleicher and Raoul Orvieto, “Is the Hypothesis of Preimplantation Genetic Screening (PGS) Still Supportable? A Review,” Journal of Ovarian Research 10 (2017), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368937/. A major review of 455 publications on genetic screening, published in March 2017, asserted there was a higher than appreciated rate of false positives when screening early-stage human embryos for genetic abnormalities, because both cells with these mutations were spread unevenly across the embryos and because doctors didn’t fully appreciate the ability of the embryos to self-correct.

  25Julian Quinones and Arijeta Lajka, “‘What Kind of Society Do You Want to Live In?’: Inside the Country Where Down Syndrome Is Disappearing,” CBS News, August 15, 2017, https://www.cbsnews.com/news/down-syndrome-iceland/.

  26Susannah Maxwell, Carol Bower, and Peter O’Leary, “Impact of Prenatal Screening and Diagnostic Testing on Trends in Down Syndrome Births and Terminations in Western Australia 1980 to 2013,” Prenatal Diagnosis 35 (2015): 1324–1330; Manya Koetse, “The Last Downer: China and the End of Down Syndrome,” What’s On Weibo, May 2, 2016, https://www.whatsonweibo.com/china-end-syndrome/; Polina Bachlakova, “Why Are 95% of Danish Women Aborting Babies with Severe Developmental Disabilities?” VICE News, April 24, 2015, https://www.vice.com/da/article/ex9daw/why-are-95-of-danish-women-aborting-babies-with-severe-developmental-disabilities-020; Myrthe Jacobs et al., “Pregnancy Outcome Following Prenatal Diagnosis of Chromosomal Anomaly: A Record Linkage Study of 26,261 Pregnancies,” Plos One 11 (2016).

  27Yuval Levin, “Public Opinion and the Embryo Debates,” The New Atlantis 20 (2008): 47–62, https://www.thenewatlantis.com/publications/public-opinion-and-the-embryo-debates.

  28Jaime L. Natoli et al., “Prenatal Diagnosis of Down Syndrome: A Systematic Review of Termination Rates (1995–2011),” Prenatal Diagnosis 32 (2012): 142–153, http://onlinelibrary.wiley.com/doi/10.1002/pd.2910/abstract;jsessionid=48749E1687B81B0E20AD95934451778E.f01t03.

  29Henry T. Greely, The End of Sex and the Future of Human Reproduction (Cambridge: Harvard University Press, 2016).

  30Kees van Gool et al., “Understanding the Costs of Care for Cystic Fibrosis: An Analysis by Age and Health State,” Value in Health 16 (2013): 345–355, https://www.sciencedirect.com/science/article/pii/S1098301512042684. A 2010 study was far more aggressive in its estimates of the cost savings that would come from using PGT to prevent cystic fibrosis. Claiming that the average additional cost of care for a person with CF was $63,127 for an average life expectancy of thirty-seven years, the authors estimate the cumulative savings over thirty-seven years as $33.3 billion, a far larger number than mine. Additionally, according to the authors, “a total of 618,714 cumulative years of patients suffering because of CF and thousands of abortions could be prevented.” These higher estimates strengthen the cost-benefit case for universal embryo screening. I. Tur-Kaspa et al., “PGT for All Cystic Fibrosis Carrier Couples: Novel Strategy for Preventive Medicine and Cost Analysis.” Reproductive BioMedicine Online 21, no. 2 (2010): 186–95. doi:10.1016/j.rbmo.2010.04.031.

  31Victoria Divino et al., “The Direct Medical Costs of Huntington’s Disease by Stage: A Retrospective Commercial and Medicaid Claims Data Analysis,” Journal of Medical Economics 16 (2013): 1043–1050, https://www.researchgate.net/publication/241690299_The_Direct_Medical_Costs_of_Huntington’s_Disease_by_Stage_A_Retrospective_Commercial_and_Medicaid_Claims_Data_Analysis.

  32Using CDC estimates, David Sable calculates that 150,000 affected children are born annually, of which 30,000 are congenital. See David Sable, “Why the Future of Precision Medicine Runs through the IVF Lab.” Forbes, April 22, 2018. https://bit.ly/2FF2NaS.

  33“Findings Suggest Increased Number of IVF Cycles Can Be Beneficial,” The JAMA Network, December 22, 2015, https://media.jamanetwork.com/news-item/findings-suggest-increased-number-of-ivf-cycles-can-be-beneficial/.

  34Said M. Yildiz and M. Mahmud Khan, “Opportunities for Reproductive Tourism: Cost and Quality Advantages of Turkey in the Provision of In-Vitro Fertilization (IVF) Services,” BMC Health Services Research 16 (2016): 378, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982316/.

  35Ido Efrati, “Israel Remains an IVF Paradise as Number of Treatments Rises 11% in 2016,” Haaretz, May 11, 2017, https://www.haaretz.com/israel-news/.premium-israel-remains-as-ivf-paradise-as-number-of-treatments-rises-1.5470164.

  36David Sable, “The Seven Trends That Define the Future of IVF,” Forbes, February 28, 2015, https://www.forbes.com/sites/davidsable/2015/02/28/the-seven-trends-that-define-the-future-of-ivf/#67c863c8494b.

  37Claire Cain Miller, “Freezing Eggs as Part of Employee Benefits: Some Women See Darker Message,” New York Times, October 14, 2014, https://www.nytimes.com/2014/10/15/upshot/egg-freezing-as-a-work-benefit-some-women-see-darker-message.html.

  38Charlotte Alter, “Sheryl Sandberg Explains Why Facebook Covers Egg-Freezing,” Time, April 25, 2015, http://time.com/3835233/sheryl-sandberg-explains-why-facebook-covers-egg-freezing/.

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sp; 39The FertilityIQ Family Builder Workplace Index: 2017–2018, https://www.fertilityiq.com/fertilityiq-data-and-notes/fertilityiq-best-companies-to-work-for-family-builder-workplace-index-2017–2018.

  40I recognize that the widespread adoption of preimplantation embryo screening to date has been less than might have been predicted. This is likely because the procedure is in its early stage of development, expensive, and not covered by insurance in many jurisdictions, and because medical and social norms are still evolving. It may be that some jurisdictions adopt PGT at different rates, but it is my contention that adoption rates will increase over time everywhere, with the biggest jumps in places like China.

  CHAPTER 2

  1For more on “multi-omics” systems biology, see Yehudit Hasin, Marcus Seldin, and Aldons Lusism, “Multi-Omics Approaches to Disease.” Genome Biology, May 5, 2017, accessed June 26, 2018, https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1215-1, and Marc Santolini et al., “A Personalized, Multiomics Approach Identifies Genes Involved in Cardiac Hypertrophy and Heart Failure.” NPJ Systems Biology and Applications 4, no. 1 (2018), doi:10.1038/s41540-018-0046-3.

  2Erika Check Hayden, “Human Genome at Ten: Life Is Complicated,” Nature 464 (2010): 664–667, https://www.nature.com/news/2010/100331/full/464664a.html.

  3Hayden, “Human Genome at Ten.”

  4Holley, Peter, “Elon Musk’s Nightmarish Warning: AI Could Become ‘An Immortal Dictator from Which We Would Never Escape,’” Washington Post, April 6, 2018, https://www.washingtonpost.com/news/innovations/wp/2018/04/06/elon-musks-nightmarish-warning-ai-could-become-an-immortal-dictator-from-which-we-would-never-escape/?noredirect=on&utm_term=.b662dac58897.

  5“How Much Data Does the World Generate Every Minute?” IFL Science, http://www.iflscience.com/technology/how-much-data-does-the-world-generate-every-minute/.

  6Deep Genomics, https://www.deepgenomics.com/.

  7Sara Castellanos, “Quantum Computing May Speed Drug Discovery, Biogen Test Suggests,” Wall Street Journal, June 13, 2017, https://blogs.wsj.com/cio/2017/06/13/quantum-computing-may-speed-drug-discovery-biogen-test-suggests/.

  8“The World’s Most Valuable Resource Is No Longer Oil, but Data,” The Economist, May 6, 2017, https://www.economist.com/news/leaders/21721656-data-economy-demands-new-approach-antitrust-rules-worlds-most-valuable-resource.

  9Stephen 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.

  10Michael D. Lemonick, “The Iceland Experiment,” Time, February 12, 2006, http://content.time.com/time/printout/0,8816,1158968,00.html#.

  11“Harnessing the Power of Genomics through Global Collaborations and Scientific Innovation,” AstraZeneca, January 12, 2018, accessed August 5, 2018, https://www.astrazeneca.com/media-centre/articles/2017/harnessing-the-power-of-genomics-through-global-collaborations-and-scientific-innovation-12012018.html.

  12“The 1,000 Genomes Project,” Genomics England, https://www.genomicsengland.co.uk/the-100000-genomes-project/.

  13All of Us, National Institutes of Health, https://allofus.nih.gov/; Gina Kolata, “The Struggle to Build a Massive ‘Biobank’ of Patient Data,” New York Times, March 19, 2018, https://www.nytimes.com/2018/03/19/health/nih-biobank-genes.html; Megan Molteni, “The NIH Launches Its Ambitious Million-Person Genetic Survey,” Wired, May 5, 2018, accessed June 1, 2018, https://www.wired.com/story/all-of-us-launches/.

  14As of 2018, around 600,000 veterans had been sequenced. “Million Veteran Program (MVP),” Office of Research and Development, U.S. Department of Veterans Affairs, https://www.research.va.gov/mvp/.

  15Luna DNA, accessed June 17, 2018, https://www.lunadna.com/. Nebula Genomics also uses blockchain technology to help consumers understand how their genetic information is being used and benefit from commercial activity surrounding that information. “Nebula Genomics,” accessed August 27, 2018, https://www.nebulagenomics.io/.

  16Founded in 2005, the Personal Genome Project is an international coalition of genome projects using an open-source, volunteer strategy to bring together vast pools of genetic data matched with medical and other life records. As of March 2018, partners in the United States, Canada, United Kingdom, Austria, and China have together pooled data on a mere 522 genomes, according to Madeleine Price Ball, cofounder of the Open Humans Project, which runs the Personal Genomes Project.

  17David Cyranoski, “China’s Bid to Be a DNA Superpower,” Nature 534 (2016): 462–463, http://www.nature.com/news/china-s-bid-to-be-a-dna-superpower-1.20121.

  18China’s Jiangsu province, to give one example, is partnering with the National Health and Family Planning Commission to sequence the genes of one million human subjects and create the largest sequencing platform and biomedical big data analysis center in Asia. Chinese companies BGI Shenzhen and WuXi NextCode, an offshoot of Iceland’s deCODE, are also building massive genomic databases. See Dou Shicong, “Jiangsu Government Unveils Plans to Sequence Genes of 1 Million Subjects,” Yicai Global, October 30, 2017, https://www.yicaiglobal.com/news/jiangsu-government-unveils-plans-sequence-genes-1-million-subjects; “Jiangsu Officially Launches Million Population Genome Sequencing Project,” China News, October 29, 2017, http://www.chinanews.com/gn/2017/10–29/8362987.shtml; Preetika Rana, “Made-to-Order Medicine: China, U.S. Race to Decode Your Genes,” Wall Street Journal, September 20, 2017, https://www.wsj.com/articles/china-rushes-to-surpass-u-s-in-decoding-citizens-genes-1505899806; David Cyranoski, “China Embraces Precision Medicine on a Massive Scale,” Nature News, January 6, 2016, https://www.nature.com/news/china-embraces-precision-medicine-on-a-massive-scale-1.19108.

  19Bertil Schmidt and Andreas Hildebrandt, “Next-Generation Sequencing: Big Data Meets High Performance Computing,” Drug Discovery Today 22 (2017): 712–717.

  20Valeria D’Argenio, “The High-Throughput Analyses Era: Are We Ready for the Data Struggle?” High-Throughput 7 (2018): 8.

  21“White House Precision Medicine Initiative,” National Archives and Records Administration, https://obamawhitehouse.archives.gov/node/333101. The Precision Medicine Initiative later morphed into the Cancer Moonshot and All of Us initiatives. William Lane and his colleagues released an important study in 2018 showing how whole genome sequencing could do a far more precise job blood typing for transfusions than the traditional blood-typing model, potentially saving many lives. Robert Flower, Eileen Roulis, and Catherine Hyland, “Whole-Genome Sequencing Algorithm for Blood-Group Typing,” The Lancet Haematology 5, no. 6 (2018): doi:10.1016/s2352–3026(18)30064–4.

  22Ellie Kincaid, “Geisinger Says DNA Sequencing as Preventative Care Is Ready for the Clinic,” Forbes, May 9, 2018, accessed May 12, 2018, https://www.forbes.com/sites/elliekincaid/2018/05/07/geisinger-says-dna-sequencing-as-preventative-care-is-ready-for-the-clinic/#60fc3ba34d63.

  23Robert Green et al., “Whole-Genome Sequencing in Primary Care,” Annals of Internal Medicine 167, no. 3 (2017): doi:10.7326/p17–9040.

  24Amit V. Khera et al., “Genome-Wide Polygenic Scores for Common Diseases Identify Individuals with Risk Equivalent to Monogenic Mutations,” Nature Genetics 50 (August 13, 2018): doi:10.1038/s41588-018-0183-z.

  25“About Genomic Prediction,” Genomic Prediction, accessed August 5, 2018, https://genomicprediction.com/about/.

  CHAPTER 3

  1Bouchard et al., “Sources of Human Psychological Differences: The Minnesota Study of Twins Reared Apart,” Science 250 (1990): 223–228, https://www.ncbi.nlm.nih.gov/pubmed/2218526.

  2Bouchard et al., “Sources of Human Psychological Differences.”

  3J. Polderman et al., “Meta-Analysis of the Heritability of Human Traits Based on Fifty Years of Twin Studies,” Nature Genetics 47 (2015): 702–709, https://www.ncbi.nlm.nih.gov/pubmed/25985137.

  4Daniel Schwekendiek, “Determinants of Well-Being in North Korea: Evidence from the Post-Famine Period,” Economics & Human Biology 6 (2008): 446–454. The
malnourishment of a pregnant mother can lead to lower cognitive function, shorter stature, immune deficiencies, shorter life spans, and many other problems. Caroline H. D. Fall, “Fetal Malnutrition and Long-Term Outcomes,” in Maternal and Child Nutrition: The First 1,000 Days, 74th Nestlé Nutrition Institute Workshop Series (2013): 11–25, doi:10.1159/000348384.

  5Chao-Qiang Lai, “How Much of Human Height Is Genetic and How Much Is Due to Nutrition?” Scientific American, December 11, 2006, https://www.scientificamerican.com/article/how-much-of-human-height/.

  6Louis Lello et al., “Accurate Genomic Prediction of Human Height,” BioRxiv (2017), https://www.biorxiv.org/content/early/2017/10/07/190124.

  7Lello et al.; 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.

  8Ian J. Deary, “Intelligence,” Current Biology 23 (2013): R673–R676, http://www.cell.com/current-biology/fulltext/S0960–9822(13)00844–0; Yan 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.”

  9Yan Zhang et al., “Estimation of Complex Effect-Size Distribution.”

  10Deary, “Intelligence.”

  11Charles Spearman, “‘General Intelligence,’ Objectively Determined and Measured,” American Journal of Psychology 15, no. 2 (1904): 201–93, http://dx.doi.org/10.2307/1412107.

  12Brian Resnick, “IQ, Explained in 9 Charts,” Vox, October 10, 2017, https://www.vox.com/2016/5/24/11723182/iq-test-intelligence. Robert Plomin and Sophie Von Stumm, “The New Genetics of Intelligence,” Nature Reviews Genetics 19, no. 3 (2018): 148–59, doi:10.1038/nrg.2017.104.