Genomic Messages: How the Evolving Science of Genetics Affects Our Health, Families, and Future - George Annas, Sherman Elias (2015)
Chapter 1: The Coming Flood of Genomic Messages
sending of a message: James Gleick, The Information (New York: Pantheon Books, 2011), 296.
into different kinds of relationships: Hallam Stevens, Life Out of Sequence: A Data-Driven History of Bioinformatics (Chicago: University of Chicago Press, 2013), 8, 69.
on metaphors for DNA: Dorothy Nelkin and M. Susan Lindee, The DNA Mystique: The Gene as a Cultural Icon (Ann Arbor: University of Michigan, 2004); Ruth Hubbard and Elijah Wald, Exploding the Gene Myth (Boston: Beacon Press, 1993).
Borges’s Library of Babel: Jorge Luis Borges, Labyrinths (New York: New Directions, 1962), 51–58.
DNA is not linear: E. Pennisi, Inching toward the 3D genome, Nature 347: 10 (2015)
nonsense, synonym, and redundancy: Gleick, The Information, 1, 299.
regulate expression of distant genes: J. R. Ecker et al., “Forum: ENCODE Explained,” Nature 489 (2012): 52–55.
amount of data: E. Lander, quoted in G. Kolata, “Bits of Mystery DNA, Far from ‘Junk,’ Play Crucial Role,” New York Times, September 5, 2012, A1.
Lander commented that: quoted in G. Kolata, Projects Sheds Light on What Drives Genes, New York Times, February 19, 2015, A16.
despite the progress: editorial, Beyond the genome, Nature 518: 273 (2015).
known unknown: Donald Rumsfeld, Known and Unknown (New York: Sentinel, 2011), xiii–xiv.
$1,000,000 interpretation: T. Caulfield, J. Evans, A. McGuire, et al., “Reflections on the Cost of ‘Low-Cost’ Whole Genome Sequencing: Framing the Health Policy Debate,” PLoS Biol. 11 (November 2013): e1001699.
on MaddAddam trilogy: Margaret Atwood, Oryx and Crake (New York: Anchor Books, 2004); The Year of the Flood (New York: Nan A. Talese/Doubleday, 2009); MaddAddam (New York: Nan A. Talese/Doubleday, 2009).
private as your diary: G. J. Annas, “Privacy rules for DNA databanks,” JAMA 270 (1993): 2346-50.
to our aging selves: W. Safire, “Sleazy Senate Inquiry,” New York Times, October 25, 1993, 11A.
a life’s meaning: A. Jureic, “Life Writing in the Genomic Age,” Lancet 383 (2014): 776–77.
shaped by the past: Christine Kenneally, The Invisible History of the Human Race (New York: Viking, 2014), 312.
Genetic McCarthyism: R. C. Green and G. J. Annas, “The Genetic Privacy of Presidential Candidates,” New England Journal of Medicine 359 (2008): 2192–93.
mass-shooter gene: G. Kolata, “Seeking Answers in Genome of Gunman,” New York Times, December 24, 2012, D5.
“thinking slow”: Daniel Kahneman, Thinking, Fast and Slow (New York: Penguin), 2011.
on Angelina Jolie Pitt: A. Jolie, “My Medical Choice,” New York Times, May 14, 2013, A25.
you know about yourself: “23andMe TV Spot” (television commercial), www.ispot.tv/ad/7qoF/23-and-me.
on 23andMe and the FDA: G. J. Annas and S. Elias, “23andMe and the FDA,” New England Journal of Medicine 370 (2014): 985–88, and sources cited therein.
The Patient Will See You Now: Eric Topol, The Patient Will See You Now (New York: Basic Books), 2015.
The FDA is in continuing talks: A. Pollack, F.D.A. Reverses Course on 23andMe DNA Test in Move to Ease Restrictions, New York Times, February 19, 2015.
My mother’s ovarian cancer: Angelina Jolie Pitt, “Diary of a Surgery,” New York Times, March 24, 2015, A23; Pam Belluck, “Experts Back Actress in Choices for Cancer Prevention,” New York Times, March 25, 2015, A3.
on Sergey Brin: T. Goetz, “Sergey Brin’s Search for a Parkinson’s Cure,” Wired Magazine, June 22, 2010, www.wired.com/magazine/2010/06/ff_sergeys_search/all/.
disease in the world: “Parkinson’s Disease,” 23andMe, https://www.23andme.com/pd/.
Can you imagine?: C. Y. Johnson, “Scientist Hoping to Ease Interpretation of the DNA ‘Book of Life,’” Boston Globe, May 19, 2014. Green’s genome also revealed “a few million variations, 109,000 of which could initially be considered medically relevant.” Of those, 11,900 were identified by computational analysis to have an effect on a protein. Of these, 1,800 were common enough to warrant checking against data banks, after which 16 rare mutations (including the Treacher Collins variant) remained (as reported by David Cameron in Harvard Medicine).
mirrors four major characteristics: G. J. Annas, “Reframing the Debate on Healthcare Reform by Replacing our Metaphors,” New England Journal of Medicine 332 (1995): 744-7, 1995.
Chapter 2: Personalized (Genomic) Medicine
they are not arriving at the doorsteps of our patients: C. Lenfant, “Clinical Research to Clinical Practice—Lost in Translation?” New England Journal of Medicine 349 (2003): 868–74.
Reinventing American Health Care: Ezekiel Emanuel, Reinventing American Health Care (New York: Public Affairs, 2014), 1–9.
better individual treatment: National Academy of Sciences, Toward Precision Medicine: Building a Knowledge Network for Biomedical and a New Taxonomy of Disease (Washington, DC: 2011).
influence their health outcomes: M. H. Chin, “How to Achieve Health Equity,” New England Journal of Medicine 371 (2014): 2331–32.
family history information: S. Kaminer, “Sizing Up the Family Gene Pool,” New York Times, February 24, 2012, MM13.
My Family Health Portrait: “My Family Health Portrait: A Tool from the Surgeon General,” https://familyhistory.hhs.gov/FHH/html/index.html.
by about 20 percent: T. M. Frezzo, W. S. Rubinstein, D. Dunham, et al., “The Genetic Family History as a Risk Assessment Tool in Internal Medicine,” Genetic Medicine 5 (2003): 84–91.
predictions for cardiovascular disease: N. P. Paynter, D. I. Chasman, G. Pare, et al., “Association between a Literature-Based Genetic Risk Score and Cardiovascular Events in Women,” JAMA 303 (2010): 631–37.
gallstones, [or] hemochromatosis: A. Gutierrez, “Warning Letter Re: Personal Genome Service,” Food and Drug Administration, www.fda.gov/ICECI?EnforcementActions/WarningLetter/2013/ucm376296.htm.
manage what you can’t: Elias and Annas, “23andMe and the FDA.”
the FDA was correct: Elias and Annas, “23andMe and the FDA.”
on Jim Mathis poll: J. Schulte, C. S. Rothaus, J. N. Adler, et al., “Screening an Asymptomatic Person for Genetic Risk—Polling Results,” New England Journal of Medicine 370 (2014): 2442–43.
across the street: “Ancestry,” 23andMe, https://www.23andme.com/ancestry/.
family even mean?: A. Jacobs, “Are You My Cousin?” New York Times, February 2, 2014, SR1.
on Relman becoming a patient: A. Relman, “On Breaking One’s Neck,” New York Review of Books, February 6, 2014, 61.
on the Cheesecake Factory: A. Gawande, “Big Med,” New Yorker, August 13 and 20, 2012, 52–63.
anyone who needs care: A. Gawande, quoted in C. Nobel, “Attention Medical Shoppers: What Health Care Can Learn from Walmart and Amazon,” HBS Working Knowledge, http://hbswk.hbs.edu/item/6658.html.
ball bearing factory: G. J. Annas, “Reframing the Debate on Health Care Reform by Replacing Our Metaphors,” New England Journal of Medicine 332 (1995): 744–47.
surgeons adopt checklists: Atul Gawande, The Checklist Manifesto (New York: Picador), 2009.
avatar physician: R. Cook and E. Topol, “How Digital Medicine Will Soon Save Your Life,” Wall Street Journal, February 21, 2014.
place in the world: “Church Family History Records Lead to Groundbreaking Genetic Research,” Newsroom: The Church of Jesus Christ of Latter-Day Saints, July 18, 2008, http://www.mormonnewsroom.org/article/church-family-history-records-lead-to-groundbreaking-genetic-research.
more than thirty states: D. B. Kraybill, K. M. Johnson-Weiner, and S. M. Nolt, The Amish (Baltimore, MD: Johns Hopkins University Press, 2013), 4.
on genetic research among the Amish: V. A. McKusick, J. A. Hostetler, and J. A. Egeland, “Genetic Studies of the Amish,” Bulletin of Johns Hopkins Hospital 121C (1964): 1–4; M. S. Lindee, “Provenance and the Pedigree: Victor McKusick’s Fieldwork with the Old Order Amish,” in Alan Goodman, Deborah Health, Susan Lindee, eds., Genetic Nature/Culture (Berkeley: University of California Press, 2003), pp. 41–57.
on genetic research in Saudi Arabia: B. McKay and E. Knickmeyer, “Saudi Researchers Mount Genome-Sequencing Push,” Wall Street Journal, February 5, 2014, B8.
biases the judgment: Arthur Conan Doyle, A Study in Scarlet and the Sign of the Four (New York: Harper & Brothers, 1904), 28.
clinical expertise and patient values: D. L. Sackett, S. E. Straus, W. S. Richardson, and W. Rosenberg, Evidence-Based Medicine: How to Practice and Teach EBM (Edinburgh: Churchill Livingstone, 2000), 1.
on PSA screening: H. C. Cox, “Quality of Life Guidelines for PSA Screening,” New England Journal of Medicine 367 (2012): 669–71.
fruit and vegetable intake: M. Ruffin, D. Nease, A. Sen, et al., “Effect of Preventive Messages Tailored to Family History on Health Behaviors: The Family Healthware Impact Trial,” Annals of Family Medicine 9 (2011): 3–11.
and laboratory testing: D. McCormick, D. H. Bor, S. Woolhandler, et al., “Giving Office-Based Physicians Electronic Access to Patients’ Prior Imaging and Lab Results Did Not Deter Ordering of Tests,” Health Affairs 31 (2012): 488–96.
act on the information: D. B. Goldstein, “Growth of Genome Screening Needs Debate,” Nature 476 (2011): 27–28.
Chapter 3: Nature, Nurture, and the Microbiome
Abigail Zuger wrote that her own experience: A. Zuger, “Genes Tell Only Part of Story,” New York Times, February 17, 2015, D4.
that it is genetic: B. Marshall, quoted in M. Azad, “A Bold Experiment,” Nature 514 (2014): S6–7.
on 2012 Nobel Prize: N. Wade, “Cloning and Stem Cell Work Earns Nobel,” New York Times, October 9, 2012, A9.
human embryonic stem cells: Y. G. Chung, J. H. Eum, and J. E. Lee, “Human Somatic Cell Nuclear Transfer Using Adult Cells,” Cell Stem Cell 14 (2014): 777–80; M. Yamada, B. Johannesson, and I. Sagi, “Human Oocyte Reprogram Adult Somatic Nuclei of a Type 1 Diabetic to Diploid Pluripotent Stem Cell,” Nature 501 (2014): 533–36.
on Woo Suk Hwang: D. Cyranoski, “Cloning Comeback,” Nature 505 (2014): 468–71.
or an oak tree: Ian Wilmut, Keith Campbell, and Colin Tudge, The Second Creation: Dolly and the Age of Biological Control (Cambridge, MA: Harvard University Press, 2001).
on Mengele: Gerald L. Posner and John Ware, Mengele: The Complete Story (New York: Cooper Square Press, 2000), 29.
Francis Galton: F. Galton, “The History of Twins as a Criterion of the Relative Powers of Nature and Nurture,” Journal of the Anthropological Institute of Great Britain and Ireland 5 (1876): 391–406.
twin study: N. J. Roberts, J. T. Vogelstein, G. Parmigiani, et al., “The Predictive Capacity of Personal Genome Sequencing,” Science Translational Medicine 4 (2012): 133ra58.
prediction will remain probabilistic: David Altshuler, quoted in G. Kolata, “Capacity of Genome to Predict Is Limited,” New York Times, April 3, 2012, D5.
prevention of NTDs: “Spina Bifida and Anecephaly Before and After Folic Mandate—United States, 1995–1996 and 1999–2000,” Morbidity and Mortality Weekly Report 53 (2004): 362–65.
folate fortification of foods: J. L. Mills and C. Signore, “Neural Tube Defect Rates Before and After Food Fortification with Folic Acid,” Birth Defects Research: Part A, Clinical and Molecular Teratology 70 (2004): 844–45.
McDonaldization of society: George Ritzer, The McDonaldization of Society (London: Sage, 2013). See also T. Caulfield, “The Obesity Gene and the (Misplaced) Search for a Personalized Approach to Our Weight Gain Problems,” Wake Forest Journal of Law and Policy 5 (2015): 125–145.
two to nineteen years are obese: “Overweight and Obesity,” Centers for Disease Control and Prevention, http://www.cdc.gov/obesity/data/adult.html.
on diabetes statistics: “National Diabetes Statistics, 2011,” National Diabetes Information Clearinghouse, http://diabetes.niddk.nih.gov/dm/pubs/statistics/#fast.
on MODY: M. Shepherd, A. C. Sparkes, and A. T. Hattersley, “Genetic Testing in Maturity Onset Diabetes of the Young (MODY): A New Challenge for the Diabetic Clinic,” Practical Diabetes 18 (2001): 16–21.
on the Barker Hypothesis: K. Calkins and S. U. Devaskar, “Fetal Origins of Adult Disease,” Current Problems in Pediatric Adolescent Health Care 41 (2011): 158–76; D. J. Barker, P. D. Winter, C. Osmond, et al., “Fetal Nutrition and Cardiovascular Disease in Adult Life,” Lancet 341 (1993): 938–41.
hunger dominated all misery: T. J. Roseboom, J. H. P. van der Meulen, A. C. Ravelli, et al., “Effects of Prenatal Exposure to the Dutch Famine on Adult Disease Later in Life: An Overview,” Molecular and Cell Endocrinology 185 (2001): 93–98.
on diabetes in Pima Indian women: D. J. Pettitt and W. C. Knowler, “Diabetes and Obesity in the Pima Indians: A Cross Generational Vicious Cycle,” Obesity Weight Regulation 7 (1988): 61–65; D. Dabelea, R. L. Hanson, P. H. Bennett, et al., “Increased Prevalence of Type II Diabetes and Obesity in American Indian Children,” Diabetologia 41 (1998): 904–10.
slows growth in most organs: J. Deardorff, “Your Health Partly Wired in the Womb,” Chicago Tribune, November 13, 2011.
two to six pounds of bacteria: “NIH Human Microbiome Project Defines Normal Bacterial Makeup of the Body,” NIH News Release, June 13, 2013, http://www.nih.gov/news/health/jun2012/nhgri-13.htm.
on tooth decay: M. Specter, “Germs Are Us,” New Yorker¸ October 22, 2012, 32–39; R. Eckert, R. Sullivan, and W. Shi, “Targeted Antimicrobial Treatment to Re-establish a Healthy Microbial Flora for Long-Term Protection,” Advances in Dental Research 24 (2012): 94–97.
on the story of Alice: A. Khoruts, J. Dicksved, J. K. Jansson, et al., “Changes in the composition of Human Fecal Microbiome after Bacteriotherapy for Recurrent Clostridium difficile–Associated Diarrhea,” Journal of Clinical Gastroenterology 44 (2010): 354–60.
tablet form for consumption: I. Youngster, G. H. Russell, C. Pindar, et al., “Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection,” JAMA 312 (2014): 1772–78; M. B. Smith, C. Kelly, and E. J. Alm, “How to Regulate Faecal Transplants,” Nature 506 (2014): 290–91.
evidence-based medical practice: C. P. Kelly, “Fecal Microbiota Transplantation: An Old Therapy Comes to Age,” New England Journal of Medicine 385 (2013): 474–75.
fecal transplants or other means: E. Yong, “There Is No ‘Healthy’ Microbiome,” New York Times, November 2, 2014, 4.
born by cesarean delivery: J. A. Martin, B. E. Hamilton, M. J. K. Osterman, et al., “Births: Final Data for 2012,” National Vital Statistics Reports, December 30, 2013, 2.
on exposure to Staphylococcus via cesarean delivery: M. G. Dominguez-Bello, E. K. Costello, M. Contreras, et al., “Delivery Mode Shapes the Acquisition and Structure of the Initial Microbiota Across Multiple Body Habitats in Newborns,” Proceedings of the National Academy of Science USA 107 (2010): 11971–75.
on the hygiene hypothesis: G. A. W. Rook, “99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian Medicine and the ‘Hygiene’ or ‘Old Friends’ Hypothesis,” Clinical and Experimental Immunology 160 (2010): 70–79.
condition is 20 percent: S. C. Fitzgibbons, Y. Ching, and D. Yu, “Mortality of Necrotizing Enterocolitis Expressed by Birth Weight Categories,” Journal of Pediatric Surgery 44 (2009): 1072–75.
on probiotics preventing NEC: G. Deshpande, S. Rao, S. Patole, et al., “Updated Meta-analysis of Probiotics for Preventing Necrotizing Enterocolitis in Preterm Infants,” Pediatrics 125 (2010): 921–30; K. Ganquli and W. A. Walker, “Probiotics in the Prevention of Necrotizing Enterocolitis,” Journal of Clinical Gastroenterology 45 (2011): S133–38.
the child is eighteen years old: M. Sharland and the SACAR Pediatric Subgroup, “The Use of Antibacterials in Children: A Report of the Special Advisory Committee on Antimicrobial Resistance (SACAR) Pediatric Subgroup,” Journal of Antimicrobial Chemotherapy 60 suppl. (2007): i15–26.
on H. pylori: Y. Chen and M. J. Blaser, “Inverse Associations of Heliobacter pylori with Asthma and Allergy,” Archives of Internal Medicine 167 (2007): 821–27; M. Blaser, “Antibiotic Overuse: Stop the Killing of Beneficial Bacteria,” Nature 476 (2011): 393–94.
steady, unassertive, and passive: M. Usser, “Causes of Peptic Ulcers: A Selective Epidemiological Review,” Journal of Chronic Diseases 20 (1967): 435–56.
all those endoscopies go?: “Barry J. Marshall,” NNDB: Tracking the Entire World, http://www.nndb.com/people/899/000136491/.
on earwax transplant: Specter, “Germs Are Us.”
microbial wildlife managers: Julie Segre, quoted in C. Zimmer, “Tending the Body’s Microbial Garden,” New York Times, June 18, 2012; see also W. P. Hanage, “Microbiome Science Needs a Healthy Dose of Skepticism,” Nature 512 (2014): 247–48.
dialogue with their surroundings: Wilmut, Campbell, and Tudge, The Second Creation, 276.
Chapter 4: Pharmacogenomics
measure of triumph: Elie Wiesel, quoted in George J. Annas and Michael A. Grodin, The Nazi Doctors and the Nuremberg Code (New York: Oxford University Press, 1992), ix.
on Henrietta Lacks: Rebecca Skloot, The Immortal Life of Henrietta Lacks (New York: Random House, 2011).
get some more blood: Skloot, The Immortal Life of Henrietta Lacks, 190.
testify to our common humanity: Dorothy Roberts, Fatal Invention (New York: New Press, 2011), 258.
delayed diagnosis and treatment: B. R. Hunt, S. Whitman, and M. S. Hurlbert, “Increasing Black:White Disparities in Breast Cancer Mortality in the 50 Largest Cities in the United States,” Cancer Epidemiology 38 (2014): 118–23.
for all our citizens: Bill Clinton, “Presidential Apology,” White House Office of the Press Secretary, May, 16, 1997.
in medical history: James Jones, Bad Blood: The Tuskegee Syphilis Experiment (New York: Simon & Schuster, 1993), 91.
cannot be undone: H. Shaw, quoted in “Ceremony in Recognition of Survivors of the Study at Tuskegee, White House, East Room, May 16, 1997,” Tuskegee University YouTube Channel, http://www.youtube.com/watch?v=l1A-YP24QwA.
genetically conditioned drug reactions: A. G. Motulsky, “Drug Reactions, Enzymes, and Biochemical Genetics,” Journal of American Medical Association 165 (1957): 837.
and colonized the world: George J. Annas, Worst Case Bioethics: Death, Disaster and Public Health (New York: Oxford University Press, 2010), 254.
believe we killed it: E. Bonilla-Silva, quoted in Roberts, Fatal Invention, (New York: The New Press, 2011), back cover.
on BiDil: Jonathan Kahn, Race in a Bottle: The Story of BiDil (New York: Columbia University Press, 2013), 2, 6.
race in drug marketing: Kahn, Race in a Bottle, 89, 109.
Iraq or Afghanistan: Nicolas Wade, A Troublesome Inheritance: Genes, Race and Human History (New York: Penguin, 2014), 127.
American and Afghan societies: H. A. Orr, “Stretch Genes,” New York Review of Books, June 5, 2014, 61.
on Serena Williams: Serena Williams, quoted in M. Lauer, “Serena Williams Taking Recovery ‘One Day at a Time,’” Today Show, March 9, 2011, http://www.nbcnews.com/id/21134540/vp/41986568#41986568.
on Secretary Hillary Clinton: H. Cooper and D. Grady, “Doctors Expect Clinton to Recover Fully from Blood Clot near Brain,” New York Times, December 31, 2012.
medicines Americans depend upon: A. C. von Eschenbach, “FDA Approves Updated Warfarin (Coumadin) Prescribing Information,” New Genetic Information May Help Providers Improve Initial Dosing Estimates of the Anticoagulant for Individual Patients, FDA News Release, August 16, 2007.
first month of therapy: S. E. Kimmel, B. French, and S. E. Kasner, “A Pharmacogenetic Versus a Clinical Algorithm for Warfarin Dosing,” New England Journal of Medicine 369 (2013): 2283–93.
on ultrarapid metabolizers: M. Pirmohamed, “Pharmacogenetics: Past, Present, and Future,” Drug Discovery Today 16 (2011): 853–54; G. Koren, J. Cairns, A. Gaedigk, et al., “Pharmacogenetics of Morphine Poisoning in a Breastfed Neonate of a Codeine-Prescribed Mother,” Lancet 368 (2006): 704.
on TPMT gene: H. L. McLeod and C. Siva, “The Thiopurine S-methyltransferase Gene Locus—Implications for Clinical Pharmacogenomics,” Pharmacogenomics 3 (2002): 89–98; N. K. DeBoer, A. A. van Bodegraven, P. de Graaf, et al., “Paradoxical Elevated Thiopurine S-methyltransferase Activity During Azathioprine Therapy: Potential Influence of Red Blood Cell Age,” Therapeutic Drug Monitoring 30 (2008): 390–93.
almanac-makers and the doctors: Michel de Montaigne, The Complete Essays of Montaigne, trans. Donald Frame (Stanford, CA: Stanford University Press, 1958), 846–47; quoted in Stephen Greenblatt, The Swerve (New York: Norton, 2011), p. 244.
G6PD deficiency in black prisoners: R. S. Hockwald and C. B. Clayman, “Toxicity of Primaquine in Negroes,” JAMA 149 (1952): 1568; M. D. Cappellini and G. Fiorelli, “Glucose 06-phosphate Dehydrogenase Deficiency,” Lancet 371 (2008): 64–74.
well-controlled studies: “Companies Pitching Genetically Customized Nutritional Supplements Will Drop Misleading Disease Claims,” Federal Trade Commission, January 7, 2014.
opportunities for personalized medicine: S. C. Sim and M. Ingelman-Sundberg, “Pharmacogenomic Biomarkers: New Tools in Current and Future Drug Therapy,” Trends in Pharmacological Sciences 32 (2011): 72.
deaths annually in the United States: E. Hood, “Pharmacogenomics: The Promise of Personalized Medicine,” Environmental Health Perspectives 111 (2003): A581; J. Lazarou, B. H. Pomeranz, and P. N. Corey, “Incidence of Adverse Drug Reactions in Hospitalized Patients: A Meta-Analysis of Prospective Studies,” JAMA 279 (1998): 1200–1205.
on Kalydeco: B. Werth, “Cure for some could cost us all,” The Boston Globe, March 23, 2014.
contain pharmacogenomics information: M. A. Hamburg and F. S. Collins, “The Path to Personalized Medicine,” New England Journal of Medicine 363 (2010): 302.
on clopidogrel poor metabolizers: K. L. Hudson, “Genomics, Health Care, and Society,” New England Journal of Medicine 365 (2011): 1037.
on variants affecting clopidogrel response: R. C. Green, H. L. Rehm, and I. S. Kohane, “Challenges in the Clinical Use of Genome Sequencing,” in Geoffrey S. Gisburg and Huntington F. Ward, eds., Genomics and Personalized Medicine (New York: Academic Press, 2013), 112–13.
advances in technology alone: J. Sills, ed., “Personalize Medicine: Temper Expectations,” in D. W. Nebert and G. Zhang, “Letters,” Science 337 (2012): 910.
well-designed randomized clinical trials: S. E. Nissen, “Pharmacogenomics and Clopidogrel: Irrational Exuberance?” JAMA 306 (2011): 2727–28.
Chapter 5: Reprogenomics
untested, unregulated treatments: Debora L. Spar, The Baby Business (Boston: Harvard Business School, 2006), xiii.
outside the reach of restrictive laws: T. Audi and A. Chang, “Assembling the Global Baby,” Wall Street Journal, December 10, 2010, C1.
David Sigal and Brad Hoylman: A. Hartocollis, “And Surrogacy Makes 3,” New York Times, February 20, 2014, E1.
on the case of Baby M: George J. Annas, Standard of Care (New York: Oxford University Press, 1993), 61–70.
traditional beginnings of a family: S. K. Livio, “Christie Vetoes Bill That Would Have Eased Tough Rules for Gestational Surrogates,” Star-Ledger, Newark, NJ, August 8, 2012.
possibility of substitution disappears: Spar, The Baby Business, 2, 4.
Edwards Nobel Prize: G. Vogel and M. Enserink, “Honor for Test Tube Bay Pioneer,” Science, October 8, 2010, 158–59.
on “Social Policy Considerations in Noncoital Reproduction”: S. Elias and G. J. Annas, “Social Policy Considerations in Noncoital Reproduction,” JAMA 225 (1986): 62–68.
by simply being: “1978: Louise Brown,” People, March 5, 1984 82.
and criminal sanctions: P. J. Williams, “Womb Wars,” Nation, February 24, 2014, 10.
California: G. J. Annas, “Using Genes to Define Motherhood: The California Solution,” New England Journal of Medicine 326 (1992): 417–20.
on Canada’s prohibition of sale of gametes and surrogacy: G. J. Annas, “Assisted Reproduction: Canada’s Supreme Court and the ‘Global Baby,’” New England Journal of Medicine 365 (2011): 459–63, and sources cited therein. See also Michele Bratcher Goodwin, ed., Baby Markets: Money and the New Politics of Creating Families (New York: Cambridge University Press, 2010).
It was uninheritable! But now?: Carl Djerassi, An Immaculate Misconception (London: Imperial College Press, 2000).
usefulness of egg freezing: J. Johnston and M. Zoll, “Is Freezing Your Eggs Dangerous? A Primer,” New Republic, November 1, 2014, www.newrepublic.com/article/120077/dangers-and-realities-egg-freezing.
on Barbara Bailey: S. S. Wang, “Genetic Tests for People Who’d Rather Not Know,” Wall Street Journal, October 14, 2014, D3.
annually with a mitochondrial disease: A. M. Schaefer, R. W. Taylor, and D. M. Turnbull, “The Epidemiology of Mitochondrial Disorders—Past, Present and Future,” BBA: Bioenergetics 1659 (2004): 115–20.
on three-parent baby: M. Tachibana, M. Sparman, H. Sritanaudomchai, et al., “Mitochondrial Gene Replacement and Embryonic Stem Cells,” Nature 461 (2009): 367–72.
gives the green light to tinker: M. Le Page, Crossing the germ line—facing genetics’ great taboo, New Scientist, February 6, 2015 (available at www.newscxientist.com/article/dn26927-crossing-the-germ-line-facing-genetics-greatest-taboo)
“Can bioethics in the United States rise above politics?”: G. J. Annas and S. Elias, “Politics, Morals and Embryos,” Nature 431 (2004): 19–20.
on ARTs statistics: S. Sunderam, D. M. Kissin, S. B. Crawford, et al., “Assisted Reproductive Technology Surveillance—United States 2011,” Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report 63, November 21, 2014, 1–28.
Cecil Jacobson: A. Stone, “Va. Doctor Guilty in Fertility Fraud,” USA Today, March 5, 1992, 1A; R. F. Howe, “Fertility Doctors’ Ex-patients see Con Man, Saint,” Washington Post, January 31, 1992, B1.
for athletic ability: Ricardo Asch, quoted in D. Sawyer, Prime Time Live, November 16, 1995.
on Jamie Grifo: A. Caplan, “Ethics and Octuplets: Society Is Responsible,” Philly.com, February 6, 2009.
on Michael Kamrava: R. Lin, “Michael Kamrava’s Medical License Revoked,” Los Angeles Times, June 1, 2011, http://documents.latimes.com/michael-kamrava-disciplinary-decision/.
a single healthy baby: R. T. Scott and N. R. Treff, “Assessing the Reproductive Competence of Individual Embryos: A Proposal for the Validation of New ‘-Omics’ Technologies,” Fertility and Sterility 94 (2010): 791–94.
has around 6.7 billion relatives: A. Chakravarti, “Being Human: Kinship: Race Relations,” Nature 457 (2009): 380–81.
Chapter 6: Genomic Messages from Fetuses
fast in the past: Jay Katz, The Silent World of Doctor and Patient (New York: Free Press, 1984), 202.
a critically important option: “ACMG Releases Statement on Access to Reproductive Options after Prenatal Diagnosis,” ACMG, July 19, 2013, https://www.acmg.net/docs/Reproductive_Rights_News_Release.pdf.
on North Dakota law: See generally J. S. King, “Political and Fetal Diagnostics Collide,” Nature 491 (2012): 33–34.
boundaries of Roe v. Wade: J. MacPherson, “North Dakota Abortion Ban Signed by Governor Jack Dalrymple,” Associated Press, March 26, 2013.
life or health: Roe v. Wade, 410 U.S. 113 (1973) 165.
terminate their pregnancy: J. L. Natoli, D. L. Ackerman, S. McDermott, et al., “Parental Diagnosis of Down Syndrome: A Systematic Review of Termination Rates,” Prenatal Diagnosis 32 (2012): 142–53.
IOM clinical guidelines: Lori Andrews, Jane Fullarton, Neil Holtzman, and Arno Motulsky, eds., Assessing Genetic Risks: Implications for Health and Social Policy (Washington, DC: National Academy Press, 1994), 7–8, 35.
selection abortion: Paul Billings, quoted in Designing Genetic Information Policy: The Need for an Independent Policy Review of the Ethical, Legal, and Social Implications of the Human Genome Project, Sixteenth Report (Washington, DC: U.S. Government Printing Office, 1992), 30.
rates of prenatal screening and diagnosis: “Births and Natality,” Centers for Disease Control and Prevention, http://www.cdc.gov/nchs/fastats/births.htm.
95 percent of all fetuses with Down syndrome: F. D. Malone, J. A. Canick, and R. H. Ball, “First-Trimester or Second Trimester Screening, or Both, for Down’s Syndrome,” New England Journal of Medicine 353 (2010): 2001–11.
on NIPS: M. M. Gil, R. Akolekar, M. S. Quezada, et al., “Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis,” Fetal Diagnosis and Therapy 35 (2014): 156–73.
on the MAStudy: R. J. Wapner, C. L. Martin, B. Levy, et al., “Chromosomal Microarray Versus Karyotyping for Prenatal Diagnosis,” New England Journal of Medicine 367 (2012): 2175–84.
on MAStudy interviews: B. A. Bernhardt, D. Soucier, K. Hanson, et al., “Women’s Experiences Receiving Abnormal Prenatal Chromosomal Microarray Testing Results,” Genetics in Medicine 15 (2013): 139–45.
on negative capability: Katz, The Silent World of Doctor and Patient, 202–5.
wood chipper: Titus Brown, quoted in V. Marx, “The Genome Jigsaw,” Nature Reprints, Tech. Features, November 2014, S39.
for general obstetric patients: “ACOG Committee Opinion No. 545, Noninvasive Prenatal Testing for Fetal Aneuploidy,” Obstetrics and Gynecology 120 (2012): 1532–34.
More recent data: L. S. Chitty, “Use of Cell-Free DNA to Screen for Down’s Syndrome,” New England Journal of Medicine, DOI: 1-.1056/NEJMe1502441 (April 1, 2015); M. E. Norton et al., “Cell-Free DNA Analysis for Noninvasive Examination of Trisomy,” New England Journal of Medicine, DOI: 1056/NEJMoa1407349 (April 1, 2015).
reliable enough to make a diagnosis: B. Daley, “Prenatal Tests Often Oversold, Imprecise,” Boston Globe, December 14, 2014, A1.
3,600 genes: E. S. Lander, “Cutting the Gordian Helix: Regulating Genomic Testing in the Era of Precision Medicine,” New England Journal of Medicine 372 (2015): 1185–86.
warrant carrying to term: E. Shuster, “Microarray Genetic Screening: A Prenatal Roadblock for Life?” Lancet 369 (2007): 526–29.
gene police: Georges Canguilhem, The Normal and the Pathological (New York: Zone Books, 1989), 280–81.
on generic genetic consent: S. Elias and G. J. Annas, “Generic Consent for Genetic Screening,” New England Journal of Medicine 330 (1994): 1611–13.
prenatal screening companies: J. Mozersky, M. Mennuti, Cell-free fetal DNA testing: who is driving implementation? Genetics in Medicine 15 (2013) 433-4; and DNA Blood Test Gives Women a New Option for prenatal screening, NPR, January 28, 2015.
Chapter 7: Genomic Messages from Newborns and Children
the sick and the well: F. Scott Fitzgerald, The Great Gatsby (New York: Charles Scribner’s Sons, 1925), 131.
their consent obtained: ACMG Board of Directors, “Points to Consider in the Clinical Application of Genomic Sequencing,” Genetics in Medicine 14 (2012): 759–61; Committee on Genetics, “Molecular Genetic Testing in Pediatric Practice: A Subject Review,” Pediatrics 106 (2000): 1494–97.
withdrawal of life support: C. J. Saunders, N. A. Miller, S. E. Soden, et al., “Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units,” Science Translational Medicine 4 (2012): 154ra135.
single-gene genetic disorder: Y. Yang, D. M. Muzny, and J. G. Reid, “Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders,” New England Journal of Medicine 369 (2013): 1502–11.
5 percent of children: Y. Yang, D. M. Muzny, F. Xia, et al., “Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing,” JAMA 312 (2014): 1870–79; H. Lee, J. L. Deignan, and N. Dorrani, “Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders,” JAMA 312 (2014): 1880–87.
applied more universally: J. S. Berg, “Genome-Scale Sequencing in Clinical Care,” JAMA 312 (2014): 1865–67.
on Retta Beery: Presidential Commission for the Study of Bioethical Issues, Privacy and Progress in Whole Genome Sequencing (October 2012), 14.
on Nicholas Volker: E. A. Worthey, A. N. Mayer, G. E. Syverson, et al., “Making a Definitive Diagnosis: Successful Clinical Application of Whole Exome Sequencing in a Child with Intractable Inflammatory Bowel Disease,” Genetics in Medicine 13 (2011): 255–61.
child’s clinical outcome: K. A. Johansen Taber, B. D. Dickinson, and M. Wilson, “The Promise and Challenges of Next-Generation Genome Sequencing for Clinical Care,” JAMA Internal Medicine 174 (2014): 275–80.
genetic advantage lies: “What Is ACTN3 Sports Genet?” Atlas Sports Genetics (2009), http://www.atlasgene.com/.
on ACTN3: A. G. William and H. Wacherhage, “Genetic Testing in Athletes,” Medicine and Sports Science 54 (2009): 174–86; N. Yang, D. G. MacArthur, and J. P. Gulbin, “ACTN3 Genotype Is Associated with Human Elite Athletic Performance,” American Journal of Human Genetics 73 (2003): 627–31.
race the other kids: David Epstein, The Sports Gene (New York: Current, 2013), 157.
on ACMG recommendations: Robert C. Green, Jonathan S. Berg, et al., ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing (American College of Medical Genetics and Genomics, 2013); ACMG Board of Directors, “ACMG Policy Statement: Updated Recommendations Regarding Analysis and Reporting of Secondary Findings in Clinical Genome-Scale Sequencing,” Genetics in Medicine, November 13, 2014.
respect for their rights: S. M. Wolf, G. J. Annas, and S. Elias, “Patient Autonomy and Incidental Findings in Clinical Genomics,” Science 340 (2013): 1049–50.
nothing about their DNA: H. Gilbert Welch, Lisa Schwartz, and Steven Woloshin, Overdiagnosed (Boston: Beacon Press, 2011), 134–35.
complexity of clinical care: W. G. Feero, “Clinical Application of Whole-Genome Sequencing: Proceed with Care,” JAMA 311 (2014): 1017–19.
Life expectancy, 33 years: Gattaca (Columbia Pictures, 1997).
genetic and endocrine disorders: Centers for Disease Control and Prevention, “Ten Great Public Health Achievements—United States, 2001–2010,” Morbidity and Mortality Weekly Report (MMWR), May 20, 2011, http://www.cdc.gov/mmwr/preview/mmwrthml/mm6019a5.htm.
for very rare conditions: Stefan Timmermans and Mara Buchbinder, Saving Babies? The Consequences of Newborn Genetic Screening (Chicago: University of Chicago Press, 2013), 233.
for all babies everywhere: D. B. Paul, “Appendix 5: The History of Newborn Phenylketonuria,” in Neil Holtzman and M. S. Watson, eds., Screening in the US, Promoting Safe and Effective Genetic Testing in the United States: Final Report of the Task Force on Genetic Testing (September 1997), http://biotech.law.lsu.edu/research/fed/tfgt/appendix5.htm.
lost to follow-up: S. A. Berry, C. Brown, M. Grant, et al., “Newborn Screening 50 Years Later: Access Issues Faced by Adults with PKU,” Genetics in Medicine 15 (2013): 591–99.
on neonatal screening survey results: R. Faden, A. J. Chwalow, N. A. Holtzman, et al., “A Survey to Evaluate Parental Consent as Public Policy for Neonatal Screening,” American Journal of Public Health 72 (1982): 1347–52.
We think not: R. R. Faden, N. A. Holtzman, and A. J. Chwalow, “Parental Rights, Child Welfare, and Public Health: The Case of PKU Screening,” American Journal of Public Health 72 (1982): 1396–1400.
genetic well-being: G. J. Annas, “Mandatory PKU Screening: The Other Side of the Looking Glass,” American Journal of Public Health 72 (1982): 1401–3.
thirty-one primary conditions: American College of Medical Genetics, “Newborn Screening: Towards a Uniform Screening Panel and System,” Genetics in Medicine 8 (2006): S12–S252; “Recommended Uniform Screening Panel of the Secretary’s Advisory Committee on Heritable Disorders in Newborns,” US Department of Health and Human Services, http://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommendedpanel/index.html.
on false-positive statistics: A. Schulze, M. Lindner, D. Kohlmuller, et al., “Expanded Newborn Screening for Inborn Errors of Metabolism by Electrospray Ionization-Tandem Mass Spectrometry: Results, Outcome and Implications,” Pediatrics 111 (2003): 1399–1406; C. Kwon and P. M. Farrell, “The Magnitude and Challenge of False-Positive Newborn Screening Test Results,” Archives of Pediatric and Adolescent Medicine 154 (2000): 714–18. And see Appendix B.
on impact of false positives on families: J. L. Schmidt, K. Castellanos-Brown, S. Childress, et al., “The Impact of False-Positive Newborn Screening Results on Families: A Qualitative Study,” Genetics in Medicine 14 (2012): 76–80.
content is inconsistent: A. R. Kemper, K. E. Fant, and S. J. Clark, “Informing Parents About Newborn Screening,” Public Health Nursing 22 (2005): 332–38.
and this makes sense: Committee on Genetics, “Committee Opinion Number 481,” American College of Obstetricians and Gynecologists, March 2011.
approach to genetic screening: President’s Council on Bioethics, The Changing Moral Focus of Newborn Screening (December 2008), 51.
more harm than good: Karen Rothenberg and Lynn Bush, The Drama of DNA: Narrative Genomics (New York: Oxford University Press, 2014), 54.
all of medicine is genomic medicine. Robert C. Green, quoted in A. D. Marcus, “Scientists Will Study Genome Sequencing of Newborns,” Wall Street Journal, December 30, 2014, D1.
ethics and science right: “Sequenced from the Start,” Nature 501 (2013): 135; see also B. M. Knoppers, K. Senecal, P. Borry, and D. Avard, “Whole-Genome Sequencing in Newborn Screening Programs,” Science Translational Medicine 6 (2014): 229.
Chapter 8: Cancer Genomics
kingdom of the sick: Susan Sontag, Illness as Metaphor and AIDS and Its Metaphors (New York: Macmillan, 1979), 3.
difficult time of transition: L. Gravitz, “Therapy: This Time It’s Personal,” Nature 509 (2014): S52–S54.
but the body count: Sontag, Illness as Metaphor and AIDS and Its Metaphors, 65.
on cancer statistics: “Cancer Facts & Figures 2013,” American Cancer Society, http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2013/.
majority of variation in cancers . . . due to “bad luck”: C. Tomasetti, B. Vogelstein, “Variation in cancer risk among tissues can be explained by the number of stem cell divisions,” Science, 347 (2015) 78-80. Also, J. Couzin-Frankel, “The bad luck of cancer,” Science, 347 (2015) 12-13, and editorial, “Cancer: mixed messages, common purpose,” Lancet, 385 (2015) 201.
on the hypothetical Joan: American Society of Clinical Oncology, Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research (November 2011).
on the hallmarks of cancer: D. Hanahan and R. A. Weinberg, “The Hallmarks of Cancer,” Cell 100 (2000): 57–70; D. Hanahan and R. A. Weinberg, “Hallmarks of Cancer: The Next Generation,” Cell 144 (2011): 646–74.
feeling like death: Christopher Hitchens, Mortality (Toronto: McClelland & Stewart, 2012).
fundamental understanding of cancer: B. Vogelstein, N. Papadopoulos, and V. E. Velculescu, “Cancer Genome Landscapes,” Science 339 (2013): 1546–58.
Cancer Genome Atlas: The Cancer Genome Atlas Research Network et al., “The Cancer Genome Atlas Pan-Cancer Analysis Project,” Nature Genetics 45 (2013): 1113–20, and H. Ledford, End of cancer atlas prompts rethink, Nature 517 (2015) 128-9.
FDA approves olaparib: FDA Press Release, “FDA Approves Lynparza to Treat Advanced Ovarian Cancer,” December 19, 2014, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm
talented enough to do it: K. Schulman, “President Obama on the Passing of Steve Jobs,” White House Blog, October 5, 2011, http://www.whitehouse.gov/blog/2011/10/05/president-obama-passing-steve-jobs-he-changed-way-each-us-sees-world..
to die of it: Walter Isaacson, Steve Jobs (New York: Simon & Schuster, 2011).
5 percent of all new cancers: D. Holmes, “The Cancer That Rises with the Sun,” Nature Outlook: Melanoma 515 (2014): S110–11.
well under one year: D. B. Johnson and J. A. Sosman, “Update on the Targeted Therapy of Melanoma,” Current Treatment Options in Oncology 14 (2013): 280–92.
on BRAF gene: H. Curtin, J. Fridlyand, T. Kageshita, et al., “Distinct Sets of Genetic Alterations in Melanoma,” New England Journal of Medicine 353 (2005): 2135–47; C. Wellbrock, M. Karasarides, and R. Marais, “The RAF Proteins Take Center Stage,” Nature Reviews: Molecular Cell Biology 5 (2004): 875–85.
substantial percentage of patients: K. S. M. Smalley and V. K. Sondak, “Melanoma—an Unlikely Poster Child for Personalized Cancer Therapy,” New England Journal of Medicine 363 (2010): 876–78.
squamous cell carcinomas: F. Su, A. Viros, C. Milagre, et al., “RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors,” New England Journal of Medicine 366 (2012): 207–15.
helps fight drug resistance: K. T. Flaherty, J. R. Infante, A. Daud, et al., “Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations,” New England Journal of Medicine 367 (2012): 1694–1703.
on Coley’s toxin: Editorial, “The Failure of the Erysipelas Toxins,” JAMA 24 (1894): 919.
therapy with immunotherapy: Gravitz, “Therapy: This Time It’s Personal.”
not be detected on scans: O. Hamid, C. Robert, A. Daud, et al., “Safety and Tumor Responses with Lambrolizumab (anti-PD-1) in Melanoma,” New England Journal of Medicine 369 (2013): 134–44.
substantial proportion of patients: J. D. Wolchok, H. Kluger, M. K. Callahan, et al., “Nivolumab Plus Ipilimumab in Advanced Melanoma,” New England Journal of Medicine 369 (2013): 122–33.
to the next level: J. L. Riley, “Combination Checkpoint Blockade—Taking Melanoma Immunotherapy to the Next Level,” New England Journal of Medicine 369 (2013): 187–89.
on Steinman: L. Gravitz, “A Fight for Life That United a Field,” Nature 478 (2011): 163–64.
approach to breast cancer prevention: M. S. Ong and K. D. Mandl, “National Expenditure for False-Positive Mammograms and Breast Cancer Overdiagnoses Estimated at $4 Billion a Year,” Health Affairs 34 (2015): 576–583.
on BRCA statistics: “ACOG: ACOG Practice Bulletin No. 103, April 2009 (Reaffirmed 2011). “Hereditary Breast and Ovarian Cancer Syndrome,” Gynecologic Oncology 113 (2009): 6–11. Note: Other ranges and statistics outside of the ranges in this source have been published, but the ACOG numbers represent the most up-to-date research.
designated 617delT: C. M. Phelan, E. Kwan, E. Jack, et al., “A Low Frequency of Non-founder BRCA1 Mutations in Ashkenazi Jewish Breast-Ovarian Cancer Families,” Human Mutation 20 (2002): 352–57.
1–2 percent, respectively: Y. C. Tai, S. Domcheck, G. Parmigiani, et al., “Breast Cancer Risk Among Male BRCA1 and BRCA2 Mutation Carriers,” Journal of the National Cancer Institute 99 (2007): 1811–14.
risk of prostate cancer: S. M. Edwards, Z. Kote-Jarai, J. Meitz, et al., “Two Percent of Men with Early-Onset Prostate Cancer Harbor Germline Mutations in the BRCA2 Gene,” American Journal of Human Genetics 72 (2003): 1–12.
National Cancer Institute’s recommendations: “BRCA1 and BRCA2: Cancer Risk and Genetic Testing,” National Cancer Institute, http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA
on women of Ashkenazi background: R. Caryn Rabin, “Study of Jewish Women Shows Link to Cancer Without Family History,” New York Times, September 2, 2014, A15; and B. Daly, O. Olopade, Race, Ethnicity, and the Diagnosis of Breast Cancer, JAMA 313 (2015) 141-2.
her own experiences: Jennifer Couzin-Frankel, “Unknown Significance,” Science 346 (2014): 1167–70.
on VUS: T. S. Frank, A. M. Deffenbaugh, J. E. Reid, et al., “Clinical Characteristics of Individuals with Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals,” Journal of Clinical Oncology 20 (2002): 1480–90; J. N. Weitzel, V. Lagos, K. R. Blazer, et al., “Prevalence of BRCA Mutations and Founder Effect in High-Risk Hispanic Families,” Cancer Epidemiology, Biomarkers & Prevention 14 (2005): 1666–71; R. Nada, L. P. Shumm, S. Cummings, et al., “Genetic Testing in an Ethnically Diverse Cohort of High-Risk Women: A Comparative Analysis of BRCA1 and BRCA2 Mutations in American Families of European and African Ancestry,” JAMA 294 (2005): 1925–33.
95 percent or higher: Meijers-Heijboer, H., van Geel, B., van Putten, W.L., et al., “Breast Cancer after Prophylactic Bilateral Mastectomy in Women with BRCA1 or BRCA2 Mutations,” New England Journal of Medicine 345 (2001): 159–64; L. C. Hartmann, T. A. Sellers, D. J. Schaid, et al., “Efficacy of Bilateral Prophylactic Mastectomy in BRCA1 and BRCA2 Gene Mutation Carriers,” Journal of the National Cancer Institute 93 (2001): 1633–37.
40–70 percent: N. D. Kauff, J. M. Satagopan, M. E. Robson, et al., “Risk Reducing Salpingo-Oophorectomy in Women with a BRCA1 or BRCA2 Mutation,” New England Journal of Medicine 346 (2002): 1609–15; N. D. Kauff, S. M. Domcheck, T.M. Friebel, et al., “Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1 and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter Prospective Study,” Journal of Clinical Oncology 26 (2008): 1331–37; J. L. Kramer, I. A. Velazquez, B. E. Chen, et al., “Prophylactic Oophorectomy Reduces Breast Cancer Penetrance During Prospective, Long-Term Follow-Up of BRCA1 Mutation Carriers,” Journal of Clinical Oncology 23 (2005): 8629–35.
90 percent or higher: T. R. Rebbeck, N. D. Kauff, and S. M. Domcheck, “Meta-Analysis of Risk Reduction Estimates Associated with Risk-Reducing Salpingo-Oophorectomy in BRCA1 or BRCA2 Mutation Carriers,” Journal of the National Cancer Institute 101 (2009): 80–87.
on the story of Emily: N. Tung, “Management of Women with BRCA Mutations: A 41-Year Old Woman with a BRCA Mutation and Recent History of Breast Cancer,” JAMA 305 (2011): 2211–20.
As Frances Visco: F. Visco, “Can We Beat Cancer at Its Own Game?” New York Times, April 4, 2015, A16. See also M. A. Sekeres, “Trying to Fool Cancer,” New York Times, March 29, 2015, SR7.
and therapeutic intervention: Siddhartha Mukherjee, The Emperor of All Maladies (New York: Scribner, 2010), 458. See also Cancer: The Emperor of all Maladies, PBS video, 2015, http://video.pbs.org/program/story-cancer-emperor-all-maladies/.
Chapter 9: Genomic Privacy and DNA Data Banks
specific patterns and relationships: Hallam Stevens, Life Out of Sequence (Chicago: University of Chicago Press, 2013), 204.
special issue on “The End of Privacy”: Science, 347 (2015) 455.
patient privacy is built into our efforts from Day l: quoted in R. Pear, U.S. to Collect Genetic Data to Hone Care, New York Times, January 31, 2015, A11.
be preserved: George J. Annas and Sherman Elias, Gene Mapping: Using Law and Ethics as Guides (New York: Oxford University Press, 1992), 272.
on Alonzo King: Maryland v. King, 569 U.S. 1962 (2013).
The Blooding: Joseph Wambaugh, The Blooding (New York: Bantam Books, 1989).
crime and terrorism: G. J. Annas, “Protecting Privacy and the Public: Limits on Police Use of Bioidentifiers in Europe,” New England Journal of Medicine 361 (2009): 196–201, and sources cited therein.
right to be forgotten: Google Inc. v Agencia Española de Protección de Datos, Mario Costeja Gonzalez, ECLI:EU:C:2014: 317
Privacy is Theft: Dave Eggers, The Circle (New York: Random House, 2013).
Riley v. California: Riley v. California, 573 U.S. (2014).
these people’s authority: Alexandr Solzhenitsyn, The Cancer Ward (London: Random House, 2003), 208–9.
ways to barcode them: Editorial, “Watching Big Brother,” Nature 456 (2008): 675–76.
bodies and disease: Stevens, Life Out of Sequence, 8, 204.
via the Iceland legislature: J. R. Gulcher and K. Stefansson, “The Icelandic Healthcare Data Base and Informed Consent,” New England Journal of Medicine 342 (2000): 1827–30; G. J. Annas, “Rules for Research on Human Genetic Variation—Lessons from Iceland,” New England Journal of Medicine 342 (2000): 1830–33.
Nature Genetics: D. F. Gudbjartsson et al., “Large-Scale Whole-Genome Sequencing of the Icelandic Population,” Nature Genetics doi:10.1038/ng.3247, March 25, 2015.
At the push of a button: C. Zimmer, “Snapshot of Icelanders’ DNA Reveals Gene Mutations Tied to Disease,” New York Times, March 26, 2015, A6.
traced to specific individuals: Guomundsdottir v. Iceland, Icelandic Supreme Court, No. 151/2003, discussed in G. J. Annas, “Family Privacy and Death: Antigone, War, and Medical Research,” New England Journal of Medicine (2005); 501–5.
It just doesn’t matter: Quoted in M. Specter, “The Gene Factory,” New Yorker, January 6, 2014, 40.
even after death: “An Afternoon at UK Biobank,” Lancet 373 (2009): 1146.
to share their genome: George Church, quoted in “Welcome to My Genome,” Economist, September 6, 2014, 21.
Genetic Privacy Act: G. J. Annas, L. H. Glantz, and P. A. Roche, “The Genetic Privacy Act and Commentary,” February 28, 1995 (Sherman was the scientific adviser during the drafting process).
differing privacy protections: Editorial, “Ethical Overkill,” Nature 516 (2014): 143–44.
respected and cherished: Editorial, “Careless Data,” Nature 507 (2014): 7.
plague Big Data: M. J. Khoury and J. P. A. Ioannidis, “Big Data Meets Public Health,” Science 346 (2014): 1054.
several days: D. Butler, “When Google Got Flu Wrong,” Nature 494 (2013): 155–56.
factors than the Google model: NAHAM Government Relations, “Google Flu Trends Will Not Replace the CDC Flu Model,” National Association of Healthcare Access Management, http://nahamnews.blogspot.com/2013/01/google-flu-trends-will-not-replace-cdc.html.
even the best data tools: A. O’Leary, “In New Tools to Combat Epidemics, the Key Is Context,” New York Times, June 20, 2013, F2.
on John Moore’s case: George J. Annas, Standard of Care (New York: Oxford University Press, 1993), 167–77; Moore v. Regents of the University of California, 793 P.2d 479, 271 Cal. Rptr. 146 (1990).
cripple medical research: Greenberg v. Miami Children’s Research Institute, 264 F. Supp. 2d 1064 (S.D. Fla. 2003).
tissue to the researchers: Washington University v. Catalona, 490 F.3d 667 (8th Cir. 2007). On new tissue rules, see generally L. Glantz, P. Roche, and G. J. Annas, “Rules for Donations to Tissue Banks: What Next?” New England Journal of Medicine 358 (2008): 298–303.
workable consent process: Presidential Commission for the Study of Bioethical Issues, Privacy and Progress in Whole Genome Sequencing (October 2012), 5, 79, 91.
participates in research: Jeri Lacks-Whye, quoted in E. Callaway, “Deal Done over HeLa Cell Line,” Nature 500 (2013): 132–33.
capacity for degrading oil: Diamond v. Chakrabarty, 447 US 303 (1980).
Too bad: Michael Crichton, “Patenting Life,” New York Times, February 13, 2007, A23.
on patentable breast cancer genes: Association for Molecular Pathology, et al. v Myriad Genetics, Inc., 132 S. Ct. 1794 (2012).
sharing their data: Presidential Commission for the Study of Bioethical Issues, Privacy and Progress in Whole Genome Sequencing, 3.
can be identifiable: F. H. Cate, “The Big Data Debate,” Science 346 (2014): 818.
Chapter 10: Genomics Future
of course, science fiction: Craig Venter, Life at the Speed of Light: From the Double Helix to the Dawn of the Digital Age (New York: Viking, 2013), 160.
the century of biology: F. Dyson, “Our Biotech Future,” New York Review of Books, July 19, 2007, 54.
perfectly adjusted to their environment: Margaret Atwood, Oryx and Crake (New York: Anchor Books, 2004), 305.
end by killing themselves: Margaret Atwood, MaddAddam (New York: Doubleday, 2009), 291.
obtained from fresh DNA: Venter, Life at the Speed of Light, 87.
Gone but not Forgotten: K. Higgins, “Damien Hirst Unveils Gilded Woolly Mammoth Skeleton with ‘Gone but Not Forgotten,’” Greenlabel.com, http://green-label.com/art/damien-hirst-gilded-woolly-mammoth-skeleton-gone-but-not-forgotten/.
become a political force and their facial morphology and laws can change: “Interview with George Church: Can Neanderthals Be Brought Back from the Dead?” Der Spiegel, January 14, 2013, http://www.spiegel.de/international/zeitgeist/george-church-explains-how-dna-will-be-construction-material-of-the-future-a-877634.html.
and is widely used: George Church and Ed Regis, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves (New York: Basic Books, 2012), 148.
cloned cave baby: A. Hall and F. Macrae, “Wanted: ‘Adventurous Woman’ to Give Birth to Neanderthal Man—Harvard Professor Seeks Mother for Cloned Cave Baby,” Daily Mail, January 20, 2013, http://www.dailymail.co.uk/news/article-2265402/Adventurous-human-woman-wanted-birth-Neanderthal-man-Harvard-professor.html.
has never been so apt: J. Naish, “Neanderthal Man, DNA Experiments and the Shadow of Dr. Frankenstein,” Daily Mail, January 21, 2013, http://www.dailymail.co.uk/sciencetech/article-2266108/Neanderthal-man-DNA-experiments-shadow-Dr-Frankenstein.html.
the history of science: Michael Crichton, Jurassic Park (New York: Knopf, 1990), x.
Science writer Barry Werth: Barry Werth, The Billion Dollar Molecule (New York: Simon and Schuster) 1994, 189.
ethical arbitrage: R. M. Isasi and G. J. Annas, “Arbitrage, Bioethics, and Cloning: The ABCs of Gestating a United Nations Cloning Convention”, Case Western Reserve Journal of International Law 35 (2003): 397–414.
ending life on earth: Kurt Vonnegut, Cat’s Cradle (New York: Random House, 2010), 39.
genetic genocide: George J. Annas, “Genism, Racism and the Prospect of Genetic Genocide,” in Jérôme Bindé, ed., The Future of Values: 21st Century Talks (New York: Berghahn, 2004), 284.
are like as a species: Francis Fukuyama, Our Posthuman Future (New York: Macmillan, 2002), 128.
based on becoming immortal: J. Lanier, Who Owns the Future? (New York: Simon & Schuster, 2013), 326.
megawizard in futurist circles: J. Maslin, “Fightin Words Against Big Data,” New York Times, May 6, 2013, C1.
on “Can Google Solve Death?”: H. McCracken and L. Grossman, “Google vs. Death,” Time, September 30, 2013, 24–30.
This baby could live to be 142: Time cover, Special Health Double Issue, February 23-March 2, 2015.
on Baseline Study: A. Barr, “Google’s New Moonshot Project: The Human Body,” Wall Street Journal, July 27, 2014.
Kepler space observatory: Venter, Life at the Speed of Light, 187.
long line of human advances: Dan Brown, Inferno (New York: Knopf, 2013).
the Singularity: Ray Kurzweil, The Singularity is Near (New York, Viking) 2007, 7.
will trump technology: J. Enriquez and S. Gullans, Homo Evolutis: Please Meet the Next Human Species (New York: Ted Conferences, 2011).
risky and nontherapeutic: E. Lanphier et al., “Don’t edit the human germ line,” Nature 519 (2015): 410.
We are humans: Quoted in D. Cyrandski, “Embryo editing divides scientists,” Nature 519 (2015): 272.
need for open discussion: D. Baltimore et al., “A prudent path forward for genomic engineering and germline gene modification,” Science 348 (2015): 36–38.
needs to improve: T. Frieden, quoted in “CDC Press Conference on Laboratory Quality and Safety after Recent Lab Incidents,” Center for Disease Control, July 11, 2014, ttp://www.cdc.gov/media/releases/2014/t0711-lab-safety.html.
no such thing as perfect systems: Thomas Inglesby quoted in J. Cohen, “Alarm over Biosafety Blunders,” Science 345 (2014): 247–48.
as an acceptable threshold: Martin Rees, Our Final Hour (New York: Basic Books, 2003), 127.
on McConnell: T. McConnell, “Genetic Enhancement, Human Nature, and Rights,” Journal of Medical Philosophy 35 (2010): 415–28.
on Eric Juengst: E.T. Juengst, “Group Identity and Human Diversity: Keeping Biology Straight from Culture,” Human Genetics 63 (1998): 673-677.
size of the primal tribe: Atwood, Oryx and Crake, 343.
not possible in theory: Atwood, MaddAddam, 393.
science slightly over the edge: Ed Regis, Great Mambo Chicken and the Transhuman Condition (New York: Addison-Wesley, 1990).
genome of the Universe: Church and Regis, Regenesis, 25–26, 237–39.
and omnipresent: Frank Tipler, The Physics of Christianity (New York: Doubleday, 2007).
Appendix B: Limitations of Screening Tests
benefit from screening: S.D. Saini, F. van Hees, S. Vijan, “Smarter screening for cancer,” JAMA 312 (2014): 2211–12.
is about 0.01 percent: Omni Whole-Genome DNA Analysis BeadChips, San Diego: Illumina Inc. (2013).
10 times to 30 times: Estimating Sequencing Coverage, San Diego: Illumina Inc. (2011).
of their interesting SNPs: L. Pachter, “Multiple testing an issue for 23andMe,” Bits of DNA, November 30, 2013.
coverage depth (less than 5 times): D. Shigemizu, A. Fujimoto, S. Akiyama, et al., “A practical method to detect SNVs and indels from whole genome and exome sequencing data,” Nature Scientific Reports 3 (2013): 2161.
from 450 to 11: H., Ledford, “Lists of Cancer Mutations Awash with False Positives,” Nature News, June 17, 2013; M.S. Lawrence, P. Stojanov, P. Polak, et al., “Mutational Heterogeneity in Cancer and the Search for New Cancer-associated Genes,” Nature 499 (2013): 214–218.
six were consistently replicated: J.N. Hirschhorn, K. Lohmueller, E. Byrne, et al., “A Comprehensive Review of Genetic Association Studies,” Genetics in Medicine 4 (2002): 45–61.
cell free tumor DNA: C. Curtin, “At ACMG, Presenters Discuss False-positive, False-negative NIPT Results,” GenomeWeb News, March 25, 2013.
direct applicability to genomics: Nate Silver, The Signal and the Noise (New York: Penguin, 2012).
all at high risk of disease: H. Gilbert Welch, Lisa Schwartz, and Steven Woloshin, Overdiagnosed (Boston: Beacon Press, 2011), 135.