I had swallowed open consent whole. I wondered if George might yet live to regret it … if he ever regretted anything.
“I’m still at the ‘pre-gret’ stage,” he told me in an email with a subject line that read “RE: gret.” “I suppose that dissecting the past can help with planning the future … so my regrets are for opportunities missed in the future despite warnings in the present. There are a vast number of alternative universes: perhaps in some my career goes better, but global warming goes worse.”18
As I sat in the audience in a chilly lecture hall in Boston and listened to him rhapsodize yet again about the $0 genome (and all of the other cheap “omes” headed our way), I was struck anew by his tirelessness and optimism. Only George could have had the audacity and the naïveté, the cojones and the guilelessness, to write an article in Scientific American in January 2006 called “Genomes for All.”19 It was a declaration that while we may have only the vaguest of clues as to what the genome means or what it does, like Roald Amundsen headed south, we were ready to find out for ourselves. Not because we have any illusions about genes as the secrets of our being.
But because we don’t.
Notes
A WORD ABOUT VERACITY
This book is true, it is nonfiction, which is to say that I didn’t make anything up or change any names. I made a good-faith effort to honestly and accurately portray people and events as I experienced them. Interviews were recorded digitally or are derived from detailed notes during and/or after conversations and meetings. I edited dialogue for clarity or grammar and in a few instances I spliced together statements from the same person that were made at different times. In rare cases (e.g., the James Sherley affair), I relied more heavily on secondary sources, be they journalistic or scholarly. Wherever possible, sources are end-noted and all web links were active at the time this book was being edited. Where first-person speculative statements and opinions are offered without attribution or quotation marks, they are mine and mine alone. Please don’t hassle the nice people at Duke University or HarperCollins on account of my mishegas.
EPIGRAPH
1. D. J. Kevles and L. E. Hood, The Code of Codes: Scientific and Social Issues in the Human Genome Project (Cambridge, Mass.: Harvard University Press, 1992).
2. J. W. v. Goethe and D. J. Enright, The Sayings of Goethe (London: Duckworth, 1996).
3. Seen in George Plimpton’s diary by James Scott Linville: http://themain point.blogspot.com/2009/02/more-on-plimpton.html.
CHAPTER 1: THE NUMERATOR
1. http://www.myspace.com/seacowrocks.
2. personalgenomes.org.
3. P. Dizikes, “Your DNA is a snitch,” Salon.com, February 17, 2009.
4. P. Szekely, “Railroad to pay $2.2 million in DNA test case illegally testing workers for genetic defects,” Reuters, May 8, 2002.
5. Norman-Bloodsaw v. Lawrence Berkeley Laboratory, Fed Report, 1998, 135, pp. 1260–76; S. French, “Genetic testing in the workplace: The employer’s coin toss,” Duke Law & Technology Review, September 5, 2002, p. E1.
6. S. Greenhouse and M. Barbaro, “Wal-Mart memo suggests ways to cut employee benefit costs,” New York Times, October 26, 2005.
7. K. Kaplan, “U.S. military practices genetic discrimination in denying benefits,” Los Angeles Times, August 18, 2007.
8. S. Baruch and K. Hudson, “Civilian and military genetics: Nondiscrimination policy in a post-GINA world,” American Journal of Human Genetics, 2008, 83(4): 435–44.
9. K. L. Hudson, M. K. Holohan, and F. S. Collins, “Keeping pace with the times—the genetic information nondiscrimination act of 2008,” New England Journal of Medicine, 2008, 358(25): 2661–63.
10. L. A. Cupples, L. A. Farrer, A. D. Sadovnick, N. Relkin, P. Whitehouse, and R. C. Green, “Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study,” Genetics in Medicine, 2004, 6(4): 192–96.
11. A. L. McGuire and M. A. Majumder, “Two cheers for GINA?” Genome Medicine, 2009, 1(1): 6; M. A. Rothstein, “Putting the Genetic Information Nondiscrimination Act in context,” Genetics in Medicine, 2008, 10(9): 655–56.
12. S. Reitz, “Connecticut woman alleges genetic discrimination at work,” AP, April 1, 2010.
13. R. N. Haricharan and K. E. Georgeson, “Hirschsprung disease,” Seminars in Pediatric Surgery, 2008, 17(4): 266–75.
14. A. J. Burns and V. Pachnis, “Development of the enteric nervous system: Bringing together cells, signals and genes,” Neurogastroenterology & Motility, 2009, 21(2): 100–2.
15. F. de Lorijn, G. E. Boeckxstaens, and M. A. Benninga, “Symptomatology, pathophysiology, diagnostic work-up, and treatment of Hirschsprung disease in infancy and childhood,” Current Gastroenterology Reports, 2007, 9(3): 245–53.
16. J. Kessmann, “Hirschsprung’s disease: Diagnosis and management,” American Family Physician, 2006, 74(8): 1319–22.
17. Localizing major disease susceptibility genes to a chromosomal neighborhood was still a big deal in the early 1990s. Today, thanks in large part to the Human Genome Project, most of that work has been done. If we want to learn about a gene involved in disease, we usually just have to turn on our computers and read. M. Angrist, E. Kauffman, S. A. Slaugenhaupt, et al., “A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10,” Nature Genetics, 1993, 4(4): 351–56; S. Lyonnet, A. Bolino, A. Pelet, et al., “A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10,” Nature Genetics, 1993, 4(4): 346–50.
18. J. Amiel, E. Sproat-Emison, M. Garcia-Barcelo, et al., “Hirschsprung disease, associated syndromes and genetics: A review,” Journal of Medical Genetics, 2008, 45(1): 1–14.
19. M. Angrist, S. Bolk, B. Thiel, et al., “Mutation analysis of the ret receptor tyrosine kinase in Hirschsprung disease,” Human Molecular Genetics, 1995, 4(5): 821–30.
CHAPTER 2: “HIS OWN DRUM”
1. Interview with John Halamka, July 18, 2007.
2. Interview with John Halamka, October 26, 2006.
3. http://geekdoctor.blogspot.com/2008/01/engineering-eye-for-average-guy_16.html.
4. Interview with John Halamka, July 18, 2007.
5. Interview with John Halamka, October 26, 2006.
6. Ibid.
7. From the Personal Genome Project Consent Form, 10th Draft, July 27, 2006.
8. C. R. Scriver, “After the genome—the phenome?” Journal of Inherited Metabolic Disease, 2004, 27(3): 305–17.
9. http://www.bccresearch.com/report/BIO045A.html.
10. E. Pettersson, J. Lundeberg, and A. Ahmadian, “Generations of sequencing technologies,” Genomics, 2009, 93(2): 105–11.
11. Interviews with George Church, February 9 and March 13, 2007.
12. http://www.personalgenomes.org/public/Lhtml.
13. Interview with George Church, February 2, 2009.
14. http://nobelprize.org/nobel_prizes/medicine/laureates/2007/index.html.
15. http://www.genome.duke.edu/press/genomelife/archives/issue09/GL_Aug04.pdf.
16. Interview with George Church, August 11, 2008.
17. J. Kirshenbaum, “Top hat, white tie and bare toes,” Sports Illustrated, January 4, 1971.
18. http://www.waterskihalloffame.com/docs/Bios/Stew%20McDonald.htm.
19. Interview with George Church, October 20, 2008.
20. Interview with Ting Wu, July 17, 2007.
21. Interview with George Church, October 25, 2006.
22. G. M. Church, J. L. Sussman, and S. H. Kim, “Secondary structural complementarity between DNA and proteins,” Proceedings of the National Academy of Sciences, 1977, 74(4): 1458- 62.
23. Interviews with Walter Gilbert, January 16 and 23, 2007.
24. A. M. Maxam and W. Gilbert, “A new method for sequencing DNA,” Proceedings of the National Academy of Sciences, 1977, 74(2): 560–64.
25. G. B. Kolata, “The 1980 Nobel Prize in chemistry,” Science, 1980, 210(4472): 887–89.
; 26. Interview with Ting Wu, July 17, 2007.
27. Ibid.
28. Interview with George Church, October 25, 2006.
29. http://thepersonalgenome.com/2007/08/nom-de-ome-a-pseudonym-for-your-genome/.
30. Interview with George Church, October 25, 2006.
31. D. Kennedy, “Not wicked, perhaps, but tacky,” Science, 2002, 297(5585): 1237.
32. S. Levy, G. Sutton, P. C. Ng, et al., “The diploid genome sequence of an individual human,” PLoS Biology, 2007, 5(10): e254.
33. http://www.genomeweb.com/2003-genome-technology-all-stars.
34. R. D. Mitra, J. Shendure, J. Olejnik, O. Edyta Krzymanska, and G. M. Church, “Fluorescent in situ sequencing on polymerase colonies,” Analytical Biochemistry, 2003, 320(1): 55–65.
35. http://www.genomeweb.com/sequencing/danaher-ship-first-church-labpolonator-week-presenting-instrument-agbt.
36. Interviews with George Church, February 9 and March 13, 2007.
37. Interview with George Church, October 26, 2006.
38. http://arep.med.harvard.edu/PGP/Anon.htm.
39. http://ncvhs.hhs.gov/980128tr.htm.
40. A. Motluk, “Anonymous sperm donor traced on Internet,” New Scientist, November 3, 2005.
41. Z. Lin, R. B. Altman, and A. B. Owen, “Confidentiality in genome research,” Science, 2006, 313(5786): 441–42.
42. N. Homer, S. Szelinger, M. Redman, et al., “Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays,” PLoS Genetics, 2008, 4(8): e1000167.
43. http://grants.nih.gov/grants/gwas/data_sharing_policy_modifications_20080828.pdf.
44. Interview with George Church, June 6, 2007.
45. Interview with George Church, October 27, 2006.
46. http://arep.med.harvard.edu/gmc/diet.html.
47. Interview with George Church, August 11, 2008.
48. Interview with Isaac Kohane, October 26, 2006.
49. http://www.1000genomes.org/page.php.
50. Interview with George Church, October 26, 2006.
51. A. Regalado, “Entrepreneur puts himself up for study in genetic ‘tell-all,'” Wall Street Journal, October 18, 2006.
52. http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/.
53. P. Sherwell, “DNA father James Watson’s ‘holy grail’ request,” Telegraph .co.uk, May 10, 2009.
54. Interview with James Watson, May 11, 2007.
55. H. Nugent, “Black people ‘less intelligent,’ scientist claims,” Times of London online, October 17, 2007.
56. J. Crace, “Double helix trouble,” Guardian.co.uk, October 16, 2007.
57. Interview with George Church, February 9, 2007.
58. Interview with Terry Bard, November 8, 2006.
59. Ibid.
60. Ibid.
61. Anonymous, February 22, 2007.
62. Email correspondence between Jeff Schloss and George Church, May 6, 2006.
63. T. A. Manolio and F. S. Collins, “The HapMap and genome-wide association studies in diagnosis and therapy,” Annual Review of Medicine, 2009, 60: 443–56.
64. http://www.hapmap.org/downloads/elsi/consent/Consent_Form_Template.doc.
65. Personal Genome Project Informed Consent Form, 10th draft, July 27, 2006.
66. S. Olson, “Who’s your daddy?” Atlantic, July/August 2007.
67. G. J. Annas, L. H. Glantz, and P. A. Roche, “Drafting the genetic privacy act: Science, policy, and practical considerations,” Journal of Law, Medicine & Ethics, 1995, 23(4): 360–66.
68. Interview with Winnie Roche and George Annas, October 26, 2006.
69. R. C. Green and G. J. Annas, “The genetic privacy of presidential candidates,” New England Journal of Medicine, 2008, 359(21): 2192–93.
70. http://arep.med.harvard.edu/gmc/.
71. http://arep.med.harvard.edu/gmc/pers.html.
72. Interview with Ting Wu, July 17, 2007.
73. Interview with George Church, October 25, 2006.
74. Ibid.
75. http://www.dw-world.de/dw/article/0,,4201588,00.html.
76. Interview with Margret Hoehe, October 10 and 11, 2008.
CHAPTER 3: “WHY SHOULD WE MAKE THEM GO OUT ON THE DANCE FLOOR?”
1. E. Phillips and S. Mallal, “Successful translation of pharmacogenetics into the clinic: The Abacavir example,” Molecular Diagnosis & Therapy, 2009, 13(1): 1–9.
2. J. Lazarou, B. H. Pomeranz, and P. N. Corey, “Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies,” JAMA, 1998, 279(15): 1200–5.
3. C. Elliott, “Guinea-pigging: Healthy human subjects for drug-safety trials are in demand. But is it a living?” New Yorker, January 7, 2008, p. 36.
4. S. D. Warren and L. D. Brandeis, “The right to privacy,” Harvard Law Review, 1890, 4(5).
5. R. Rao, “Genes and spleens: Property, contract, or privacy rights in the human body?” Journal of Law, Medicine & Ethics, 2007, 35(3): 371–82.
6. Interview with William Catalona, June 9, 2008.
7. www.circare.org/lex/03cv01065_pltfposthearingreply.pdf.
8. J. R. Minkel, “Uninformed consent,” Scientific American, 2006, 295(4): 22, 24.
9. Interview with William Catalona, June 9, 2008.
10. http://vlex.com/vid/catalona-mcgurk-wilard-parron-missios-37825718.
11. T. Herrmann, “8th circuit rules Washington University has ownership of medical research,” Kansas City (Missouri) Daily Record, June 21, 2007.
12. J. Ritter, “Who owns your body,” Chicago Sun-Times, September 17, 2007.
13. Interview with William Catalona, June 9, 2008.
14. Ibid.
15. Email from William Catalona, October 22, 2009.
16. Interview with Hank Greely, December 6, 2007.
17. Interview with Amy McGuire, June 15, 2007.
18. Interview with Hank Greely, December 6, 2007.
19. http://grants.nih.gov/grants/gwas/town_hall_mtg/index.htm.
20. H. Skaletsky, T. Kuroda-Kawaguchi, P. J. Minx, et al., “The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes,” Nature, 2003, 423(6942): 825–37.
21. T. Francis, “Medical dilemma: Spread of records stirs patient fears of privacy erosion,” Wall Street Journal, December 26, 2006.
22. Email from George Church, January 4, 2007.
23. Interview with George Church, February 9, 2007.
24. Email from George Church, March 1, 2007.
25. E. Check, “Celebrity genomes alarm researchers,” Nature, 2007, 447(7143): 358–59.
26. D. M. Pressel, “Nuremberg and Tuskegee: Lessons for contemporary American medicine,” Journal of the National Medical Association, 2003, 95(12): 1216–25.
27. D. Micklos and E. Carlson, “Engineering American society: The lesson of eugenics,” Nature Reviews Genetics, 2000, 1(2): 153–58.
28. C. Hunt-Grubbe, “The elementary DNA of Dr Watson,” Sunday Times (of London), October 14, 2007.
29. J. D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (London: Weidenfeld & Nicolson, 1968).
30. http://nobelprize.org/nobel_prizes/medicine/laureates/1962/.
31. J. Kim, J. M. Basak, and D. M. Holtzman, “The role of apolipoprotein E in Alzheimer’s disease,” Neuron, 2009, 63(3): 287–303.
32. J. D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA, 1st ed. (New York: Atheneum, 1968).
33. "An intellectual entente,” Harvard Magazine, September 10, 2009.
34. S. Connor, “James Watson, Nobel Prize winner: Welcome to the Watson wonderland,” Independent (U.K.), February 3, 2003.
35. J. D. Watson, Recombinant DNA: Genes and Genomes: A Short Course, 3rd ed. (New York: W. H. Freeman and Cold Spring Harbor Laboratory Press, 2007).
36. D. A. Wheeler, M. Srinivasan, M. Egholm, et al., “The complete genome of an individual by
massively parallel DNA sequencing,” Nature, 2008, 452(7189): 872–76.
37. E. Singer, “The $2 million genome,” Technology Review, June 1, 2007.
38. K. Davies, “Project Jim: Watson’s genome goes public,” Bio-IT World, June 13, 2007.
39. Interview with Michael Egholm, May 9, 2007.
40. Interview with Amy McGuire, May 9, 2007.
41. http://biologos.org/news-events/francis-collins-talks-biologos-with-christianity-today/.
42. http://biologos.org/about.
43. http://meetings.cshl.edu/ … /2007%20Past%20Programs/Genome%20 Program.pdf.
44. N. Mekel-Bobrov, S. L. Gilbert, P. D. Evans, et al., “Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens,” Science, 2005, 309(5741): 1720–22.
45. Interview with James Watson, May 11, 2007.
46. Interview with George Church, February 9, 2007.
47. Interview with James Watson, May 11, 2007.
48. Ibid.
49. Remarks by James Watson to Biology of Genomes Meeting, Cold Spring Harbor Laboratory, May 11, 2007.
50. Interview with Ting Wu, July 17, 2007.
51. Interview with George Church, April 2, 2007.
52. http://thepersonalgenome.com/category/genetics-profession/.
53. Interview with George Church, June 6, 2007.
54. S. M. Wolf, F. P. Lawrenz, C. A. Nelson, et al., “Managing incidental findings in human subjects research: Analysis and recommendations,” Journal of Law, Medicine & Ethics, 2008, 36(2): 219–48, 211.
55. J. Murphy, J. Scott, D. Kaufman, G. Geller, L. LeRoy, and K. Hudson, “Public expectations for return of results from large-cohort genetic research,” American Journal of Bioethics, 2008, 8(11): 36–43.
56. Interview with George Church, October 25, 2006.
57. Ibid.
58. Interview with George Church, February 9, 2007.
59. Interview with Marie Wu, July 17, 2007
60. http://www.thepersonalgenome.com.
61. www.genome.duke.edu/press/genomelife/ … /GL_MarApr07.pdf.
CHAPTER 4: “BUT WHEN IS IT MATURE?”
1. Interview with Matt Crenson, December 5, 2007
2. http://spittoon.23andme.com/2008/02/22/23andmore-paternal-ancestry-free-demo-accounts-and-an-expanded-gene-journal/.
Here Is a Human Being Page 32
