by Jamie Metzl
22Antonio Regalado, “Google’s Long, Strange, Life Span Trip,” MIT Technology Review, December 15, 2016, https://www.technologyreview.com/s/603087/googles-long-strange-life-span-trip/.
23Karl A. Rodriguez et al., “Determinants of Rodent Longevity in the Chaperone-protein Degradation Network,” Cell Stress and Chaperones 21, no. 3 (2016): 453–66. doi:10.1007/s12192-016-0672-x.
24Jorge Azpurua et al., “Naked Mole-Rat Has Increased Translational Fidelity Compared with the Mouse, as well as a Unique 28S Ribosomal RNA Cleavage,” Proceedings of the National Academy of Sciences of the United States of America 110 (2013): 17350–17355, http://www.pnas.org/content/110/43/17350.
25Joseph Stromberg, “Why Do Naked Mole Rats Live So Long?” Smithsonian.com, September 30, 2013, https://www.smithsonianmag.com/science-nature/why-do-naked-mole-rats-live-so-long-230258/.
26Ungvari et al., “Extreme Longevity Is Associated with Increased Resistance to Oxidative Stress in Arctica islandica, the Longest-Living Non-Colonial Animal,” The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 66A(2011): 741–750, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143345/.
27Piraino et al., “Reversing the Life Cycle: Medusae Transforming into Polyps and Cell Transdifferentiation in Turritopsis nutricula (Cnidaria, Hydrozoa),” The Biological Bulletin 190 (1996): 302–312, https://www.jstor.org/stable/1543022?seq=1#page_scan_tab_contents.
28For a fantastic review of how scientists are studying various long-lived simple organisms, see: Ronald S. Petralia, Mark P. Mattson, and Pamela J. Yao, “Aging and Longevity in the Simplest Animals and the Quest for Immortality,” Ageing Research Reviews 16 (2014): 66–82, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133289/.
29The mutation of a single gene called Daf-2 helped the roundworms live twice as long as their compatriots without the mutation. A mutation on the Daf-16 gene had the opposite effect. It is important to note, however, that the life span extending mutations also had significant side effects including decreased fertility, smaller size, and sometimes a higher chance of dying in utero. Cynthia J. Kenyon, “The Genetics of Ageing,” Nature 464 (2010): 504–512, https://www.nature.com/articles/nature08980; Masaharu Uno and Eisuke Nishida, “Life Span-Regulating Genes in C. elegans,” Aging and Mechanisms of Disease 2 (2016); “Caenorhabditis Elegans,” AnAge: The Animal Ageing and Longevity Database, http://genomics.senescence.info/species/entry.php?species=Caenorhabditis_Elegans; David Michaelson et al., “Insulin Signaling Promotes Germline Proliferation in C. Elegans.” Development, February 15, 2010, accessed May 12, 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827619/.
30Elizabeth H. Blackburn and Elissa Epel, The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer (London: Orion Spring, 2018). See also my conversation with Nobel laureate and telomere pioneer Elizabeth Blackburn (and Harvard geneticist George Church) at the 2017 Google Zeitgeist conference, Zeitgeistminds, “Unlocking the Code of Life,” YouTube, October 24, 2017, accessed May 25, 2018, https://www.youtube.com/watch?v=srX79RA-HPQ&feature=youtu.be.
31Wei et al., “Fasting-Mimicking Diet and Markers/Risk Factors for Aging, Diabetes, Cancer, and Cardiovascular Disease,” Science Translational Medicine 9 (2017), http://stm.sciencemag.org/content/9/377/eaai8700.short.
32Steven C. Moore et al., “Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis,” PLoS Medicine 9 (2012), http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001335.
33Michael S. Bonkowski and David A. Sinclair, “Slowing Ageing by Design: The Rise of NAD and Sirtuin-Activating Compounds,” Nature Reviews Molecular Cell Biology 17 (2016): 679–690, https://www.nature.com/articles/nrm.2016.93; Abhirup Das et al., “Impairment of an Endothelial NAD-H 2 S Signaling Network Is a Reversible Cause of Vascular Aging,” Cell 173 (2018): 74–89.
34M. Evans et al., “Metformin and Reduced Risk of Cancer in Diabetic Patients,” BMJ 330 (2005): 1304–1305, https://www.ncbi.nlm.nih.gov/pubmed/15849206.
35A. Bannister et al., “Can People with Type 2 Diabetes Live Longer Than Those Without? A Comparison of Mortality in People Initiated with Metformin or Sulphonylurea Monotherapy and Matched, Non-Diabetic Controls,” Diabetes, Obesity and Metabolism 16 (2014): 1165–1173, http://onlinelibrary.wiley.com/doi/10.1111/dom.12354/full.
36P. Ng et al., “Long-Term Metformin Usage and Cognitive Function among Older Adults with Diabetes,” Journal of Alzheimer’s Disease 41 (2014): 61–68, https://www.ncbi.nlm.nih.gov/pubmed/24577463; V. N. Anisimov, “Metformin for Cancer and Aging Prevention: Is It a Time to Make the Long Story Short?” Oncotarget. November 24, 2015, accessed April 28, 2018, https://www.ncbi.nlm.nih.gov/pubmed/26583576. Other studies have shown a lesser positive impact of metformin.
37Alejandro Martin-Montalvo, “Metformin Improves Healthspan and Life Span in Mice,” Nature Communications 4 (2013), https://www.nature.com/articles/ncomms3192.
38Jing Li, Sang Gyun Kim, and John Blenis, “Rapamycin: One Drug, Many Effects,” Cell Metabolism 19 (2014): 373–379, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972801/.
39Simon C. Johnson, Peter S. Rabinovitch, and Matt Kaeberlein, “MTOR Is a Key Modulator of Ageing and Age-Related Disease,” Nature 493 (2013): 338–345, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687363/.
40Dog Aging Project, accessed June 18, 2018, http://dogagingproject.com/. Silvan R. Urfer et al., “A Randomized Controlled Trial to Establish Effects of Short-Term Rapamycin Treatment in 24 Middle-Aged Companion Dogs,” GeroScience39, no. 2 (2017): 117–27. doi:10.1007/s11357-017-9972-z; Matt Kaeberlein, Kate E. Creevy, and Daniel E. L. Promislow, “The Dog Aging Project: Translational Geroscience in Companion Animals,” Mammalian Genome 27, no. 7–8 (2016): 279–88, doi:10.1007/s00335-016-9638-7.
41Simon C. Johnson, Peter S. Rabinovitch, and Matt Kaeberlein, “MTOR Is a Key Modulator of Ageing and Age-Related Disease,” Nature 493 (2013): 338–345, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687363/.
42Simon C. Johnson and Matt Kaeberlein, “Rapamycin in Aging and Disease: Maximizing Efficacy While Minimizing Side Effects,” Oncotarget 7 (2016): 44876–44878, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216691/; V. N. Anisimov, “Metformin for Cancer and Aging Prevention: Is It a Time to Make the Long Story Short?” Oncotarget November 24, 2015, accessed April 28, 2018, https://www.ncbi.nlm.nih.gov/pubmed/26583576.
43A series of recent mouse studies point in the direction of how this type of cocktail might work. In one, metformin increased the life span of mice by 7 percent overall, but mice fed both metformin and rapamycin together were the longest-lived mice studied. Female mice fed a daily dose of rapamycin alone lived 18 to 21 percent longer than nondrugged mice, but female mice fed rapamycin and metformin together lived 23 percent longer. Males lived 10 to 13 percent longer with rapamycin alone but 23 percent longer with both. L. J. Wei, D. Y. Lin, and L. Weissfeld, “Regression Analysis of Multivariate Incomplete Failure Time Data by Modeling Marginal Distributions,” Journal of the American Statistical Association 84 (1989): 1065, http://dlin.web.unc.edu/files/2013/04/WeiLinWeissfeld89.pdf.
44Abel Soto-Gamez and Marco Demaria, “Therapeutic Interventions for Aging: The Case of Cellular Senescence,” Drug Discovery Today 22 (2017): 786–795, http://www.sciencedirect.com/science/article/pii/S135964461730017X.
45Eva Latorre et al., “Mitochondria-Targeted Hydrogen Sulfide Attenuates Endothelial Senescence by Selective Induction of Splicing Factors HNRNPD and SRSF2,” Aging, August 19, 2018. doi:10.18632/aging.101500.
46P. Baar et al., “Target Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging,” Cell 169 (2017): 132–147, https://www.ncbi.nlm.nih.gov/pubmed/28340339.
47Alejandro Ocampo, “In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming,” Cell 167 (2016): 1719–1733, http://www.cell.com/cell/fulltext/S0092–8674(16)31664–6.
48“Turning Back Time: Salk S
cientists Reverse Signs of Aging,” The Salk Institute, December 15, 2016, https://www.salk.edu/news-release/turning-back-time-salk-scientists-reverse-signs-aging/.
49M. Conboy, “Rejuvenation of Aged Progenitor Cells by Exposure to a Young Systemic Environment,” Nature 433 (2005): 760–764, https://www.ncbi.nlm.nih.gov/pubmed/15716955.
50Jocelyn Kaiser, “Young Blood Renews Old Mice,” Science, May 4, 2014, http://www.sciencemag.org/news/2014/05/young-blood-renews-old-mice.
51“Longevity Industry Landscape Overview 2017,” Geroscience, Policy, and Economics, p. 7, https://daks2k3a4ib2z.cloudfront.net/581ba14cc9b0d76c5dcededf/5a0e1db85db6530001540224_Infographic%20Summary%20Longevity%20Industry%20Report.pdf.
52P. Goldman et al., “Substantial Health And Economic Returns from Delayed Aging May Warrant A New Focus for Medical Research,” Health Affairs 32 (2013): 1698–1705, http://sjayolshansky.com/sjo/Longevity_Dividend_Initative_files/Health%20Affairs%202013%20LDI%20Final.pdf.
CHAPTER 8
1Andrew Hammond et al., “A CRISPR-Cas9 Gene Drive System Targeting Female Reproduction in the Malaria Mosquito Vector Anopheles gambiae,” Nature Biotechnology 34 (2016): 78–83, https://www.nature.com/articles/nbt.3439. For a good description of gene drives, see “FAQs: Gene Drives,” Wyss Institute, Harvard University, accessed May 12, 2018, https://wyss.harvard.edu/staticfiles/newsroom/pressreleases/Gene drives FAQ FINAL.pdf.
2Peter, Paul and Mary, vocalists, “I Know an Old Lady,” by Rose Bonne and Alan Mills, 1952, released 1993, track 7 on Peter, Paul & Mommy, Too, http://www.peterpaulandmary.com/music/17–07.htm.
3Human Dignity and Bioethics: Essays Commissioned by the President’s Council on Bioethics (Washington, DC: March 2008): 329, https://bioethicsarchive.georgetown.edu/pcbe/reports/human_dignity/.
4Michael J. Sandel, “The Case Against Perfection,” The Atlantic, April 2014, https://www.theatlantic.com/magazine/archive/2004/04/the-case-against-perfection/302927/.
5Excerpt from letter 49. TO J.D. HOOKER. July 13th, 1856, More Letters of Charles Darwin, Volume I, https://charles-darwin.classic-literature.co.uk/more-letters-of-charles-darwin-volume-i/ebook-page-57.asp.
6Marcy Darnovsky, “A Slippery Slope to Human Germline Modification,” Nature 499, no. 7457 (July 9, 2013): 127, http://www.nature.com/news/a-slippery-slope-to-human-germline-modification-1.13358.
7César Palacios-González, John Harris, and Giuseppe Testa, “Multiplex Parenting: IVG and the Generations to Come,” Journal of Medical Ethics 40 (March 7, 2014): 752–758, http://jme.bmj.com/content/early/2014/03/07/medethics-2013–101810.
8Siddhartha Mukherjee, The Gene: An Intimate History. New York: Simon and Schuster, 2016, pp. 275–276.
9Julian Savulescu and Guy Kahane, “The Moral Obligation to Create Children with the Best Chance of the Best Life,” Bioethics 23, no. 5 (2009): 274–290, https://www.ncbi.nlm.nih.gov/pubmed/19076124.
10Nick Bostrom and Toby Ord, “How to Avoid Status Quo Bias in Bioethics: The Case for Human Enhancement,” 2004, https://nickbostrom.com/ethics/statusquo.doc.
11Carl Zimmer, She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity (New York: Dutton, 2018).
12Rebecca Bennett, “When Intuition Is Not Enough. Why the Principle of Procreative Beneficence Must Work Much Harder to Justify Its Eugenic Vision,” Bioethics 28 (July 10, 2013): 447–455, http://onlinelibrary.wiley.com/doi/10.1111/bioe.12044/full; Biplab Kumar Halder, “Can the Principle of Procreative Beneficence Justify the Non-Medical Use of Preimplantation Genetic Diagnosis?” Center for the Study of Ethics in Society Papers, Paper 103 (2016), http://scholarworks.wmich.edu/cgi/viewcontent.cgi?article=1101&context=ethics_papers.
13“The Laws of the Twelve Tables,” c. 450 B.C.E., https://facultystaff.richmond.edu/~wstevens/FYStexts/twelvetables.pdf.
14Francis Galton, Inquiries into the Human Faculty and Its Development (Macmillan, 1883): 24.
15The Eugenics Review 1, no. 1 (April 1909). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990364/?page=1. The journal ceased publication only in 1968.
16George F. Will, “The Liberals Who Loved Eugenics,” Washington Post, March 8, 2017, https://www.washingtonpost.com/opinions/the-liberals-who-loved-eugenics/2017/03/08/0cc5e9a0-0362-11e7-b9fa-ed727b644a0b_story.html?utm_term=.5758cd0c98e3.
17Henry Fairfield Osborn, Collected Papers (1877): Volume 4, p. 2. https://books.google.com/books?id=hHMuAAAAIAAJ&pg=PT32&lpg=PT32&dq=%22Negro+fails+in+government,+he+may+become+a+fine+agriculturist%22&source=bl&ots=OK7jUtTCeT&sig=cavOSWARMqiT550HwpTpopV9XXU&hl=en&sa=X&ved=2ahUKEwiMmc2PgOHcAhWO2FMKHWvFAVEQ6AEwAHoECAcQAQ#v=onepage&q=%22Negro%20fails%20in%20government%2C%20he%20may%20become%20a%20fine%20agriculturist%22&f=false.
18Steven A. Farber, “U.S. Scientists’ Role in the Eugenics Movement (1907–1939): A Contemporary Biologist’s Perspective,” Zebrafish 5, no. 4 (December 2008): 243–245, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757926/.
19For a list of materials on the particularly egregious case of Puerto Rico, see “Sterilization of Puerto Rican Women: A Selected, Partially Annotated Bibliography (Louis de Malave, 1999)” Special Collections, March 23, 2018, accessed June 26, 2018, https://www.library.wisc.edu/gwslibrarian/publications/bibliographies/sterilization/.
20Paul A. Lombardo, “Three Generations, No Imbeciles: New Light on Buck v. Bell,” NYU Law Review 80 (1985): 30–62, https://pdfs.semanticscholar.org/784b/f1b7cfbbc84b6966f4c3b0f3d554726d551e.pdf.
21Adolph Hitler, Mein Kampf (1925): 222–223, trans. Ralph Manheim (Boston: Houghton Mifflin Company, 1999). http://www.sjsu.edu/people/mary.pickering/courses/His146/s1/MeinKampfpartone0001.pdf.
22Charles J. Epstein, “Is Modern Genetics the New Eugenics?” Genetics in Medicine 5 (2003): 469–475, https://www.nature.com/articles/gim2003376.
23Michael J. Sandel, “The Case against Perfection,” The Atlantic, April 2004, https://www.theatlantic.com/magazine/archive/2004/04/the-case-against-perfection/302927/.
24Arthur Kaplan, “What Should the Rules Be?” Time, January 14, 2001, http://content.time.com/time/magazine/article/0,9171,95244,00.html.
25Richard Dawkins, The Genetic Revolution and Human Rights, ed. Justine Burley (Oxford: Oxford University Press, 1999): v–xviii; cited in Charles J. Epstein, “Is Modern Genetics the New Eugenics?” Nature, November 1, 2003, accessed May 10, 2018, https://www.nature.com/articles/gim2003376.
26Diane B. Paul, The Politics of Heredity: Essays on Eugenics, Biomedicine, and the Nature-Nurture Debate (New York: State University of NY Press, 1998) p. 97; cited in Charles J. Epstein, “Is Modern Genetics the New Eugenics?” Nature, November 1, 2003, accessed May 10, 2018, https://www.nature.com/articles/gim2003376.
27Jon Entine, “Let’s (Cautiously) Celebrate the ‘New Eugenics,’” Huffington Post, October 30, 2014, https://www.huffingtonpost.com/jon-entine/lets-cautiously-celebrate_b_6070462.html.
28Nicholas Agar, Liberal Eugenics: In Defense of Human Enhancement (Oxford: Blackwell, 2004): vi, 5. Nicholas Agar, “Liberal Eugenics,” Public Affairs Quarterly 12 (1998): 137–155.
29Adam Cohen, “Is There Such a Thing as Good Eugenics?” Los Angeles Times, March 17, 2017, http://www.latimes.com/opinion/op-ed/la-oe-cohen-good-eugenics-20170317-story.html.
30Stephen Whyte, Benno Torgler, and Keith L. Harrison, “What Women Want in Their Sperm Donor: A Study of More Than 1000 Women’s Sperm Donor Selections,” Economics & Human Biology 23 (2016): 1–9, https://www.ncbi.nlm.nih.gov/pubmed/27359087.
31Shana Lebowitz, “Science Says Being Tall Could Make You Richer and More Successful—Here’s Why,” Business Insider, September 9, 2015, http://www.businessinsider.com/tall-people-are-richer-and-successful-2015–9; Roger Highfield, “Symmetrical Human Faces Are More Beautiful,” The Telegraph, June 5, 2008, http://www.telegraph.co.uk/news/science/science-news/3343640/Symmetrical-human-faces-are-more-beautiful.html.
32R. Sanders et al., “Genome-wide Scan Demonstrates Significant Linkage for Male Sexual Orientation,” Psychological Medicine 45 (2014): 1379�
�1388; Siddhartha Mukherjee, The Gene: An Intimate History (London: Vintage, 2017): 373–379.
33Nicholas G. Crawford et al., “Loci Associated with Skin Pigmentation Identified in African Populations,” Science Magazine 17 (2017), https://www.ncbi.nlm.nih.gov/pubmed/29025994.
34Kenta Watanabe et al., “CRISPR/Cas9-Mediated Mutagenesis of the Dihydroflavonol-4-reductase-B (DFR-B) Locus in the Japanese Morning Glory Ipomoea (Pharbitis) Nil,” Scientific Reports 7 (August 30, 2017), http://bio-engineering.ir/wp-content/uploads/2017/10/s41598-017-10715-1.pdf.
35“Study Finds Autistics Better at Problem-Solving,” EurekAlert!, June 16, 2009, https://www.eurekalert.org/pub_releases/2009–06/uom-sfa061609.php.
36Neel Burton, “Bipolar Disorder and Creativity,” Psychology Today, March 9, 2012, https://www.psychologytoday.com/blog/hide-and-seek/201203/bipolar-disorder-and-creativity.
37Elizabeth Theusch, Analabha Basu, and Jane Gitschier, “Genome-wide Study of Families with Absolute Pitch Reveals Linkage to 8q24.21 and Locus Heterogeneity,” The American Journal of Human Genetics 85 (2009): 112–119.
38“Central African Republic,” World Food Programme, accessed June 2, 2018, http://www1.wfp.org/countries/central-african-republic; Caroline H. D. Fall, “Fetal Malnutrition and Long-Term Outcomes,” in Maternal and Child Nutrition: The First 1,000 Days, Nestlé Nutrition Institute Workshop Series, 74 (2013): 11–25, doi:10.1159/000348384.
39Friedrich Wilhelm Nietzsche, Thus Spoke Zarathustra (Chicago: H. Regnery, 1957): 3.
40Paul Weindling, “Julian Huxley and the Continuity of Eugenics in Twentieth-century Britain,” Journal of Modern European History, November 1, 2012, accessed May 10, 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366572/.
41Tobiasz Mazan, Transcend the Flesh: Transhumanism Debate (2015): 8, https://www.researchgate.net/publication/279189548_Transcend_the_Flesh_Transhumanism_debate.
42Doug Baily et al., “Transhumanist Declaration,” drafted in 1998 and adopted by Humanity+ in 2009, http://humanityplus.org/philosophy/transhumanist-declaration/.