by Jamie Metzl
33Darwin Life, https://www.darwinlife.com/. In August 2017, however, Zhang received a letter from the FDA telling him that his public offer to place the DNA of older women into the donor eggs of younger women “cannot legally be performed in the United States. Nor is exportation permitted.” See Ariana Eunjung Cha, “This Fertility Doctor Is Pushing the Boundaries of Human Reproduction, with Little Regulation.” Washington Post, May 14, 2018, accessed June 1, 2018, https://www.washingtonpost.com/national/health-science/this-fertility-doctor-is-pushing-the-boundaries-of-human-reproduction-with-little-regulation/2018/05/11/ea9105dc-1831–11e8–8b08–027a6ccb38eb_story.html?utm_term=.220a3ce466e2.
34Rob Stein, “Clinic Claims Success in Making Babies With 3 Parents’ DNA.” NPR, June 06, 2018, accessed June 7, 2018, https://www.npr.org/sections/health-shots/2018/06/06/615909572/inside-the-ukrainian-clinic-making-3-parent-babies-for-women-who-are-infertile.
35C. Sallevelt et al., “Preimplantation Genetic Diagnosis for Single Gene Disorders,” Journal of Medical Genetics 50 (2013): 125–132, http://jmg.bmj.com/content/50/2/125.long.
36Shoukhrat Mitalipov et al., “Limitations of Preimplantation Genetic Diagnosis for Mitochondrial DNA Diseases,” Cell Reports 7, no. 4 (2014): 935–37, doi:10.1016/j.celrep.2014.05.004.
37“Mitochondrial Replacement Therapy,” United Mitochondrial Disease Foundation, https://www.umdf.org/mitochondrial-replacement-therapy/.
38Rachel Kahn Best, “Disease Politics and Medical Research Funding,” American Sociological Review 77 (2012): 780–803, http://journals.sagepub.com/doi/10.1177/0003122412458509; Sara Reardon, “Lobbying Sways NIH Grants.” Nature 515 (November 2014): 19.
39David Cyranoski and Sara Reardon, “Chinese Scientists Genetically Modify Human Embryos,” Nature, April 22, 2015, https://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378.
40Ewen Callaway, “Second Chinese Team Reports Gene Editing in Human Embryos,” Nature, April 8, 2016, https://www.nature.com/news/second-chinese-team-reports-gene-editing-in-human-embryos-1.19718#/b2.
41Hong Ma et al., “Correction of a Pathogenic Gene Mutation in Human Embryos,” Nature 548 (2017): 413–419, https://www.nature.com/articles/nature23305.
42Pam Belluck, “In Breakthrough, Scientists Edit a Dangerous Mutation from Genes in Human Embryos,” New York Times, August 2, 2017, https://www.nytimes.com/2017/08/02/science/gene-editing-human-embryos.html.
CHAPTER 6
1Flannick et al., “Loss-of-Function Mutations in SLC30A8 Protect against Type 2 Diabetes,” Nature Genetics 46 (2014): 357–363, https://www.ncbi.nlm.nih.gov/pubmed/24584071.
2Rong Liu et al., “Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection,” Cell 86 (1996): 367–377, http://www.cell.com/abstract/S0092–8674(00)80110–5.
3Christopher P. Cannon et al., “Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes,” New England Journal of Medicine 372 (2015): 2387–2397, http://www.nejm.org/doi/full/10.1056/NEJMoa1410489.
4Yanfang Fu et al., “High-Frequency Off-Target Mutagenesis Induced by CRISPR-Cas Nucleases in Human Cells,” Nature Biotechnology 31 (2013): 822–826.
5David Cyranoski and Sara Reardon, “Chinese Scientists Genetically Modify Human Embryos,” Nature, April 22, 2015, https://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378.
6Emma Haapaniemi et al., “CRISPR–Cas9 Genome Editing Induces a P53-mediated DNA Damage Response.” Nature Medicine, 2018, doi:10.1038/s41591-018-0049-z.
7Kosicki, Michael, Kärt Tomberg, and Allan Bradley. “Repair of Double-Strand Breaks Induced by CRISPR–Cas9 Leads to Large Deletions and Complex Rearrangements.” Nature Biotechnology 36 (July 16, 2018): 765–771. The share price of CRISPR-related companies regularly dip when major reports like this are released. CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics lost a collective $300 million in share value the day this report was released in July 2018.
8Emily Mullin, “CRISPR 2.0 Is Here, and It’s Way More Precise,” MIT Technology Review, October 25, 2017, https://www.technologyreview.com/s/609203/crispr-20-is-here-and-its-way-more-precise/.
9Mullin, “CRISPR 2.0 Is Here, and It’s Way More Precise.”
10Nicole M. Gaudelli et al., “Programmable Base Editing of A•T to G•C in Genomic DNA without DNA Cleavage,” Nature 551 (2017): 464–471, http://evolve.harvard.edu/138-ABE.pdf.
11Yanting Zeng et al., “Correction of the Marfan Syndrome Pathogenic FBN1 Mutation by Base Editing in Human Cells and Heterozygous Embryos,” Molecular Therapy, August 13, 2018. doi:10.1016/j.ymthe.2018.08.007.
12Michael Gapinske et al., “CRISPR-SKIP: Programmable Gene Splicing with Single Base Editors,” Genome Biology 19, no. 1 (2018). doi:10.1186/s13059-018-1482-5.
13Cassandra Willyard, “The Epigenome Editors: How Tools Such as CRISPR Offer New Details about Epigenetics,” Nature Medicine 23, no. 8 (2017): 900–03, doi:10.1038/nm0817–900; Ianis G. Matsoukas, “Commentary: RNA Editing with CRISPR-Cas13,” Frontiers in Genetics 9 (2018), doi:10.3389/fgene.2018.00134.
14Zhuchi Tu et al., “Promoting Cas9 Degradation Reduces Mosaic Mutations in Non-Human Primate Embryos,” Scientific Reports 7 (2017), https://www.nature.com/articles/srep42081; Michael Le Page, “Mosaic Problem Stands in the Way of Gene Editing Embryos,” New Scientist, March 15, 2017, https://www.newscientist.com/article/mg23331174–400-mosaic-problem-stands-in-the-way-of-gene-editing-embryos/; P. Singh, J. C. Schimenti, and E. Bolcun-Filas, “A Mouse Geneticist’s Practical Guide to CRISPR Applications,” Genetics 199 (2014): 1–15, http://www.genetics.org/content/199/1/1.full; Michael Le Page, “Male Infertility Cure Will Be Gateway to Editing Our Kids’ Genes,” New Scientist, June 23, 2016, https://www.newscientist.com/article/2094926-male-infertility-cure-will-be-gateway-to-editing-our-kids-genes/.
15Hong Ma et al., “Correction of a Pathogenic Gene Mutation in Human Embryos,” Nature 548 (2017): 413–419, https://www.nature.com/articles/nature23305.
16Dieter Egli et al., “Inter-homologue Repair in Fertilized Human Eggs?” BioRxiv (2017).
17Adikusuma, Fatwa, Sandra Piltz, Mark A. Corbett, Michelle Turvey, Shaun R. Mccoll, Karla J. Helbig, Michael R. Beard, James Hughes, Richard T. Pomerantz, and Paul Q. Thomas. “Large Deletions Induced by Cas9 Cleavage,” Nature 560, no. 7,717 (2018). doi:10.1038/s41586-018-0380-z; Dieter Egli, et al. “Inter-homologue Repair in Fertilized Human Eggs?” Nature 560 (2018); Fatwa Adikusuma et al., “Large Deletions Induced by Cas9 Cleavage,” Nature 560 (August 2018): E8–E9.
18Genome 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. 45.
19Dennis Normile, “CRISPR Bombshell: Chinese Researcher Claims to Have Created Gene-Edited Twins,” Science, November 26, 2018, https://www.sciencemag.org/news/2018/11/crispr-bombshell-chinese-researcher-claims-have-created-gene-edited-twins.
20Jacob Gratten and Peter M. Visscher, “Genetic Pleiotropy in Complex Traits and Diseases: Implications for Genomic Medicine,” Genome Medicine 8 (2016), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4952057/.
21Evan A. Boyle et al., “An Expanded View of Complex Traits: From Polygenic to Omnigenic,” Cell 169 (2017): 1177–1186, http://www.cell.com/cell/fulltext/S0092–8674(17)30629–3.
22The omnigenic hypothesis remains controversial and has been hotly debated by scientists since the publication of the 2017 Boyle and Li article in Cell. See “The Omnigenic Model: Special Issue,” Journal of Psychiatry and Brain Science 2, no. 5 (2017). doi:10.20900/jpbs.20170014s1, http://jpbs.qingres.com/IssueList.aspx?yearsno=2017&volumeno=2&issueno=5 and Naomi Wray et al., “Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model,” Cell 173, no. 7 (June 14, 2018): 1573–1580, doi:10.1016/j.cell.2018.05.051.
23I hope you will visit the website of this incredible project: http://www.openworm.org/.
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24Lucy Black, “A Worm’s Mind in a Lego Body,” I Programmer, November 16, 2014, http://www.i-programmer.info/news/105-artificial-intelligence/7985-a-worms-mind-in-a-lego-body.html#.
25Human Cell Atlas, https://www.humancellatlas.org/.
26Ray Kurzweil, “The Law of Accelerating Returns,” Kurzweil Accelerating Intelligence, March 7, 2001, http://www.kurzweilai.net/the-law-of-accelerating-returns.
27Ray Kurzweil, The Singularity Is Near: When Humans Transcend Biology (London: Duckworth, 2016): 39. For a wonderful explanation, see also Tim Urban, “The Artificial Intelligence Revolution: The Road to Superintelligence,” Wait But Why, January 22, 2015, https://waitbutwhy.com/2015/01/artificial-intelligence-revolution-1.html.
28Homer, The Iliad, trans. Robert Fagles (Chicago: Penguin Books, 1951).
29Dante Aligheri, Divine Comedy, trans. Henry Wadsworth Longfellow (Project Gutenburg EBook, 1997): Canto 17.
30Catherine Easterbrook and Guy Maddern, “Porcine and Bovine Surgical Products: Jewish, Muslim, and Hindu Perspectives,” JAMA 143 (2008): 366–370, https://jamanetwork.com/journals/jamasurgery/fullarticle/599037.
31Simon Bramhall, “Presumed Consent for Organ Donation: A Case Against,” Annals of the Royal College of Surgeons of England 93 (2011): 270–272, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3363073/. Monty Python does a hilarious spoof of “live organ transplants” in its 1983 film, The Meaning of Life. https://www.youtube.com/watch?v=5ig9wr8517E.
32Policy changes, like shifting from an opt-out to an opt-in system for organ donation or allowing compensation to be provided to the families of donors, could help address this shortfall. “Organ Donation Statistics,” U.S. Department of Health and Human Services, https://www.organdonor.gov/statistics-stories/statistics.html.
33Bethany Pellegrino, “Immunosuppression,” Medscape, last modified January 4, 2016, https://emedicine.medscape.com/article/432316-overview#a2.
34Li Wei et al., “Inactivation of Porcine Endogenous Retrovirus in Pigs Using CRISPR-Cas9,” Science, September 22, 2017. http://science.sciencemag.org/content/357/6357/1303.
35Nicola Davis, “Breakthrough as Scientists Grow Sheep Embryos Containing Human Cells,” The Guardian, February 17, 2018, https://www.theguardian.com/science/2018/feb/17/breakthrough-as-scientists-grow-sheep-embryos-containing-human-cells.
36Registry of Standard Biological Parts, http://parts.igem.org/Main_Page.
37The Free Genes Project, https://biobricks.org/freegenes/.
38Onkar Sumant, “Synthetic Biology Market by Products (DNA Synthesis, Oligonucleotide Synthesis, Synthetic DNA, Synthetic Genes, Synthetic Cells, XNA) and Technology (Genome Engineering, Microfluidics Technologies, DNA Synthesis & Sequencing Technologies): Global Opportunity Analysis and Industry Forecast, 2013–2020,” March 2014, https://www.alliedmarketresearch.com/synthetic-biology-market; “The Global Synthetic Biology Market Is Projected to Grow at a CAGR of 19.9%,” PR Newswire, January 5, 2018, https://www.prnewswire.com/news-releases/the-global-synthetic-biology-market-is-projected-to-grow-at-a-cagr-of-199–300578132.html.
39Steven Cerier, “Synthetic Biology’s ‘Promise and Potential’ Capture Investor Attention.” Genetic Literacy Project, May 8, 2018, accessed May 8, 2018, https://geneticliteracyproject.org/2018/05/08/synthetic-biologys-promise-potential-investor-attention/?mc_cid=9b36f13d19&mc_eid=6d7f502b6d.
40Robert F. Service, “Synthetic Microbe Lives with Fewer Than 500 Genes,” Science, December 9, 2017, accessed May 8, 2018, http://www.sciencemag.org/news/2016/03/synthetic-microbe-lives-fewer-500-genes.
41David Ewing Duncan, “Is the World Ready for Synthetic People?” Neo.Life, April 5, 2018, accessed April 22, 2018, https://medium.com/neodotlife/q-a-with-drew-endy-bde0950fd038. See also George M. Church and Edward Regis, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves (New York: Basic Books, 2014): 53.
42Importantly, the HGP-write scientists stressed the ethical consideration of this initiative. Jef D. Boeke et al., “The Genome Project-Write,” Science 353 no. 6295 (July 8, 2016): 126–127, http://science.sciencemag.org/content/353/6295/126.
43David Ewing Duncan, “The Next Best Version of Me: How to Live Forever,” Wired, March 27, 2018, https://www.wired.com/story/live-forever-synthetic-human-genome/.
44The Mason Lab, http://www.masonlab.net/.
CHAPTER 7
1David Ferry, Gilgamesh: A New Rendering in English Verse (New York: Farrar, Straus, and Giroux, 1992): 56–57.
2Eric Grundhauser, “The True Story of Dr. Voronoff’s Plan to Use Monkey Testicles to Make Us Immortal,” Atlas Obscura, October 13, 2015, https://www.atlasobscura.com/articles/the-true-story-of-dr-voronoffs-plan-to-use-monkey-testicles-to-make-us-immortal.
3Renee Stepler, “World’s Centenarian Population Projected to Grow Eightfold by 2050,” Pew Research Center, April 21, 2016, http://www.pewresearch.org/fact-tank/2016/04/21/worlds-centenarian-population-projected-to-grow-eightfold-by-2050/.
4“Living to 120 and Beyond: Americans’ Views on Aging, Medical Advances and Radical Life Extension,” Pew Research Center, August 6, 2013, http://www.pewforum.org/2013/08/06/living-to-120-and-beyond-americans-views-on-aging-medical-advances-and-radical-life-extension/.
5Xian Xia et al., “Molecular and Phenotypic Biomarkers of Aging,” F1000 Research 6 (2017), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473407/.
6Carola Weidner, “Aging of Blood Can Be Tracked by DNA Methylation Changes at Just Three CpG Sites,” Genome Biology 15 (2014), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053864/pdf/gb-2014-15-2-r24.pdf. Interestingly, the p53 gene has also been shown to play an important cancer-fighting role in elephants. See Carl Zimmer, “The ‘Zombie Gene’ That May Protect Elephants from Cancer,” New York Times, August 14, 2018, https://www.nytimes.com/2018/08/14/science/the-zombie-gene-that-may-protect-elephants-from-cancer.html.
7Masayuki Kimura et al., “Telomere Length and Mortality: A Study of Leukocytes in Elderly Danish Twins,” American Journal of Epidemiology 167 (2008): 799–806, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631778/.
8F. Huber et al., “Walking Speed as an Aging Biomarker in Baboons (Papio Hamadryas).” Journal of Medical Primatology, U.S. National Library of Medicine (December 2015), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802968/.
9Weiyang Chen et al., “Three-Dimensional Human Facial Morphologies as Robust Aging Markers,” Cell Research 25, no. 5 (May 2015): 574–587, accessed April 28, 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423077/.
10A group of revisionist anthropologists recently made the case that grandmothers in particular play a more important evolutionary role than previously imagined. Matthew H. Chan, Kristen Hawkes, and Peter S. Kim. “Modelling the Evolution of Traits in a Two-Sex Population, with an Application to Grandmothering,” Bulletin of Mathematical Biology 79, no. 9 (2017): 2132–148, doi:10.1007/s11538-017-0323-0.
11Julie A. Mattison et al., “Caloric Restriction Improves Health and Survival of Rhesus Monkeys,” Nature Communications 8 (2017), https://www.nature.com/articles/ncomms14063. Although at first it looked like one of the studies showed that CR worked in extending the life and health of the monkeys and the other did not, a later review of the data confirmed that both studies shared the same result.
12Leanne M. Redman et al., “Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging,” Cell Metabolism 27 (2018): 1–11.
13These chronic diseases account for over 90 percent of all deaths in the United States. Khadija Ismail et al., “Compression of Morbidity Is Observed Across Cohorts with Exceptional Longevity,” Journal of the American Geriatrics Society 64 (2016): 1583–1591, https://www.ncbi.nlm.nih.gov/pubmed/27377170.
14“Wellderly Study Suggests Link Between Genes That Protect against Cognitive Decline and Overall Healthy Aging,” The Scripps Research Institute, April 21, 2016, https://www.scripps.edu/news/press/2016/20160421wellderly.html; Galina A. E
rikson et al., “Whole-Genome Sequencing of a Healthy Aging Cohort,” Cell 165 (2016): 1002–1011, http://www.cell.com/cell/fulltext/S0092–8674(16)30278–1.
15Freudenberg-Hua et al., “Disease Variants in Genomes of 44 Centenarians,” Molecular Genetics and Genomic Medicine 2 (2014): 438–450, https://www.ncbi.nlm.nih.gov/pubmed/25333069.
16Clyde B. Schechter et al., “Cholesteryl Ester Transfer Protein (CETP) Genotype and Reduced CETP Levels Associated with Decreased Prevalence of Hypertension,” Mayo Clinic Proceedings 85 (2010): 522–526, https://www.ncbi.nlm.nih.gov/pubmed/20511482.
17Nir Barzilai and Ilan Gabriely, “Genetic Studies Reveal the Role of the Endocrine and Metabolic Systems in Aging,” The Journal of Clinical Endocrinology & Metabolism 95 (2010): 4493–4500, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050096/.
18Galina A. Erikson et al., “Whole-Genome Sequencing of a Healthy Aging Cohort,” Cell 165 (2016): 1002–1011, http://www.cell.com/cell/fulltext/S0092–8674(16)30278–1.
19Luke C. Pilling et al., “Human Longevity: 25 Genetic Loci Associated in 389,166 UK Biobank Participants,” Aging 9 (2017): 2504–2520, http://www.aging-us.com/article/101334/text#fulltext.
20Dan Buettner, The Blue Zones: Lessons for Living Longer from the People Who’ve Lived the Longest (National Geographic Books, 2009): vii.
21R. Speakman, “Body Size, Energy Metabolism and Life Span,” Journal of Experimental Biology 208 (2005): 1717–1730, https://www.ncbi.nlm.nih.gov/pubmed/15855403.