DNA, the secret of life j watson (knopf, 2004)

DNA THE S E C R E T OF LIFE J A M E S D W A T S O N WITH A N D R E W BERRY A L F R E D A K N O P F N E W YORK 2003 T H I S IS A B O R Z O I B O O K P U B L I S H E D BY A L F R E D A KNOPF Copyright © 2003 by DNA Show LLC All rights reserved under International and Pan-American Copyright Conventions Published in the United States by Alfred A Knopf, a division of Random House, Inc., New York, and simultaneously in Canada by Alfred A Knopf Canada, Limited, Toronto Distributed by Random House, Inc., New York www aaknopf com Knopf, Borzoi Books, and the colophon are registered trademarks of Random House, Inc Library of Congress Cataloging-in-Publication Data Watson, James D., 1928DNA: the secret of life /James D Watson, with Andrew Berry p cm Includes bibliographical references and index ISBN 0-375-41546-7 Genetics—Popular works DNA—Popular works I Berry, Andrew II Title QH437W387 2003 576.5—dc21 2002190725 Manufactured in the United States of America First Edition A U T H O R S ' NOTE D NA: The Secret of Life was conceived over dinner in 1999 Under discussion was how best to mark the fiftieth anniversary of the discovery the double helix Publisher Neil Patterson joined one of us, James D Watson, in dreaming up a multifaceted venture including this book, a television series, and additional more avowedly educational projects Neil's presence was no accident: he published JDW's first book, The Molecular Biology of the Gene, in 1965, and ever since has lurked genielike behind JDW's writing projects Doron Weber at the Alfred P Sloan Foundation then secured seed money to ensure that the idea would turn into something more concrete Andrew Berry was recruited in 2000 to hammer out a detailed outline for the TV series and has since become a regular commuter between his base in Cambridge, Massachusetts, and JDW's at Cold Spring Harbor Laboratory on the north coast of Long Island, close to New York City From the start, our goal was to go beyond merely recounting the events of the past fifty years DNA has moved from being an esoteric molecule only of interest to a handful of specialists to being the heart of a technology that is transforming many aspects of the way we all live With that transformation has come a host of difficult questions about its impact—practical, social, and ethical Taking the fiftieth anniversary as an opportunity to pause and take stock of where we are, we give an unabashedly personal view both of the history and of the issues Moreover, it is JDW's personal view and is accordingly written in the first-person singular The double helix was already ten years old when DNA was working its in utero magic on a fetal AB ix Authors' Note We have tried to write for a general audience, intending that someone with zero biological knowledge should be able to understand the book's every word Every technical term is explained when first introduced Should you need to refresh your memory about a term when you come across one of its later appearances, you can refer to the index, where such words are printed in bold to make locating them easy; a number also in bold will take you to the page on which the term is defined We have inevitably skimped on many of the technical details and recommend that readers interested in learning more go to DNAi.org, the Web site of the multimedia companion project, DNA Interactive, aimed at high-schoolers and entry-level college students Here you will find animations explaining basic processes and an extensive archive of interviews with the scientists involved In addition, the Further Reading section lists books relevant to each chapter Where possible we have avoided the technical literature, but the titles listed nevertheless provide a more in-depth exploration of particular topics than we supply We thank the many people who contributed generously to this project in one way or another in the acknowledgments at the back of the book Four individuals, however, deserve special mention George Andreou, our preternaturally patient editor at Knopf, wrote much more of this book—the good bits—than either of us would ever let on Kiryn Hasfinger, our superbly efficient assistant at Cold Spring Harbor Lab, cajoled, bullied, edited, researched, nit-picked, mediated, wrote—all in approximately equal measure The book simply would not have happened without her Jan Witkowski, also of Cold Spring Harbor Lab, did a marvelous job of pulling together chapters 10, 11, and 12 in record time and provided indispensable guidance throughout the project Maureen Berejka, J D W s assistant, rendered sterling service as usual in her capacity as the sole inhabitant of Planet Earth capable of interpreting J D W s handwriting James D Watson Cold Spring Harbor, New York Andrew Berry Cambridge, Massachusetts x I N T R O D U C T I O N THE S E C R E T OF LIFE A s was normal for a Saturday morning, I got to work at Cambridge University's Cavendish Laboratory earlier than Franeis Crick on February 28, 1953 I had good reason for being up early I knew that we were close—though I had no idea just how close—to figuring out the structure of a then little-known molecule called deoxyribonucleic acid: DNA This was not any old molecule: DNA, as Crick and I appreciated, holds the very key to the nature of living things It stores the hereditary information that is passed on from one generation to the next, and it orchestrates the incredibly complex world of the cell Figuring out its 3-D structure—the molecule's architecture— would, we hoped, provide a glimpse of what Crick referred to only half-jokingly as "the secret of life." We already knew that DNA molecules consist of multiple copies of a single basic unit, the nucleotide, which comes in four forms: adenine (A), thymine (T), guanine (G), and cytosine (C) I had spent the previous afternoon making cardboard cutouts of these various components, and now, undisturbed on a quiet Saturday morning, I could shuffle around the pieces of the 3-D jigsaw puzzle How did they all fit together? Soon I realized that a simple pairing scheme worked exquisitely well: A fitted neatly with T, and G with C Was this it? Did the molecule consist of two chains linked together by A-T and G-C pairs? It was so simple, so elegant, that it almost had to be right But I had made mistakes in the past, and before I could get too excited, my pairing scheme would have to survive the scrutiny of Crick's critical eye It was an anxious wait xi Introduction But I need not have worried: Crick realized straightaway that my pairing idea implied a double-helix structure with the two molecular chains running in opposite directions Everything known about DNA and its properties—the facts we had been wrestling with as we tried to solve the problem—made sense in light of those gentle complementary twists Most important, the way the molecule was organized immediately suggested solutions to two of biology's oldest mysteries: how hereditary information is stored, and how it is replicated Despite this, Crick's brag in the Eagle, the pub where we habitually ate lunch, that we had indeed discovered that "secret of life," struck me as somewhat immodest, especially in England, where understatement is a way of life Crick, however, was right Our discovery put an end to a debate as old as the human species: Does life have some magical, mystical essence, or is it, like any chemical reaction carried out in a science class, the product of normal physical and chemical processes? Is there something divine at the heart of a cell that brings it to life? The double helix answered that question with a definitive No Charles Darwin's theory of evolution, which showed how all of life is interrelated, was a major advance in our understanding of the world in materialistic— physicochemical—terms The breakthroughs of biologists Theodor Schwann and Louis Pasteur during the second half of the nineteenth century were also an important step forward Rotting meat did not spontaneously yield maggots; rather, familiar biological agents and processes were responsible—in this case egg-laying flies The idea of spontaneous generation had been discredited Despite these advances, various forms of vitalism—the belief that physicochemical processes cannot explain life and its processes—lingered on Many biologists, reluctant to accept natural selection as the sole determinant of the fate of evolutionary lineages, invoked a poorly defined overseeing spiritual force to account for adaptation Physicists, accustomed to dealing with a simple, pared-down world—a few particles, a few forces—found the messy complexity of biology bewildering Maybe, they suggested, the processes at the heart of the cell, the ones governing the basics of life, go beyond the familiar laws of physics and chemistry That is why the double helix was so important It brought the Enlightenment's revolution in materialistic thinking into the cell The intellectual journey that had begun with Copernicus displacing humans from the center of the uni- xii Introduction verse and continued with Darwin's insistence that humans are merely modified monkeys had finally focused in on the very essence of life And there was nothing special about it The double helix is an elegant structure, but its message is downright prosaic: life is simply a matter of chemistry Crick and I were quick to grasp the intellectual significance of our discovery, but there was no way we could have foreseen the explosive impact of the double helix on science and society Contained in the molecule's graceful curves was the key to molecular biology, a new science whose progress over the subsequent fifty years has been astounding Not only has it yielded a stunning array of insights into fundamental biological processes, but it is now having an ever more profound impact on medicine, on agriculture, and on the law DNA is no longer a matter of interest only to white-coated scientists in obscure university laboratories; it affects us all By the mid-sixties, we had worked out the basic mechanics of the cell, and we knew how, via the "genetic code," the four-letter alphabet of DNA sequence is translated into the twenty-letter alphabet of the proteins The next explosive spurt in the new science's growth came in the 1970s with the introduction of techniques for manipulating DNA and reading its sequence of base pairs We were no longer condemned to watch nature from the sidelines but could actually tinker with the DNA of living organisms, and we could actually read life's basic script Extraordinary new scientific vistas opened up: we would at last come to grips with genetic diseases from cystic fibrosis to cancer; we would revolutionize criminal justice through genetic fingerprinting methods; we would profoundly revise ideas about human origins—about who we are and where we came from—by using DNA-bascd approaches to prehistory; and we would improve agriculturally important species with an effectiveness we had previously only dreamed of But the climax of the first fifty years of the DNA revolution came on Monday, June 26, 2000, with the announcement by U.S president Bill Clinton of the completion of the rough draft sequence of the human genome: "Today, we are learning the language in which God created life With this profound new knowledge, humankind is on the verge of gaining immense, new power to heal." The genome project was a coming-of-age for molecular biology: it had become "big science," with big money and big results Not only was it an extraordinary xiii Introduction technological achievement—the amount of information mined from the human complement of twenty-three pairs of chromosomes is staggering—but it was also a landmark in terms of our idea of what it is to be human It is our DNA that distinguishes us from all other species, and that makes us the creative, conscious, dominant, destructive creatures that we arc And here, in its entirety, was that set of DNA—the human instruction book DNA has come a long way from that Saturday morning in Cambridge However, it is also clear that the science of molecular biology—what DNA can for us—still has a long way to go Cancer still has to be cured; effective gene therapies for genetic diseases still have to be developed; genetic engineering still has to realize its phenomenal potential for improving our food But all these things will come The first fifty years of the DNA revolution witnessed a great deal of remarkable scientific progress as well as the initial application of that progress to human problems The future will see many more scientific advances, but increasingly the focus will be on DNA's ever greater impact on the way we live C H A P T E R ONE BEGINNINGS OF GENETICS: FROM M E N D E L TO HITLER M y mother, Bonnie Jean, believed in genes She was proud of her father's Scottish origins, and saw in him the traditional Scottish virtues of honesty, hard work, and thriftiness She, too, possessed these qualities and felt that they must have been passed down to her from him His tragic early death meant that her only nongenetic legacy was a set of tiny little girl's kilts he had ordered for her from Glasgow Perhaps therefore it is not surprising that she valued her father's biological legacy over his material one Growing up, I had endless arguments with Mother about the relative roles played by nature and nurture in shaping us By choosing nurture over nature, I was effectively subscribing to the belief that I could make myself into whatever I wanted to be I did not want to accept that my genes mattered that much, preferring to attribute my Watson grandmother's extreme fatness to her having overeaten If her shape was the product of her genes, then I too might have a hefty future However, even as a teenager, I would not have disputed the evident basics of inheritance, that like begets like My arguments with my mother concerned complex characteristics like aspects of personality, not the simple attributes that, even as an obstinate adolescent, I could see were passed down over the generations, resulting in "family likeness." My nose is my mother's and now belongs to my son Duncan Sometimes characteristics come and go within a few generations, but sometimes they persist over many One of the most famous examples of a long-lived trait is known as the "Hapsburg Lip." This distinctive elongation of the jaw and DNA At age eleven, with my sister Elizabeth and my father, James droopiness to the lower lip—which made the Hapsburg rulers of Europe such a nightmare assignment for generations of court portrait painters—was passed down intact over at least twenty-three generations The Hapsburgs added to their genetic woes by intermarrying Arranging marriages between different branches of the Hapsburg clan and often among close relatives may have made political sense as a way of building alliances and ensuring dynastic succession, but it was anything but astute in genetic terms Inbreeding of this kind can result in genetic disease, as the Hapsburgs found out to their cost Charles II, the last of the Hapsburg monarchs in Spain, not only boasted a prize-worthy example of the family lip—he could not even chew his own food—but was also a complete invalid, and incapable, despite two marriages, of producing children Genetic disease has long stalked humanity In some cases, such as Charles II's, it has had a direct impact on history Retrospective diagnosis has suggested that George III, the English king whose principal claim to fame is to have lost the American colonies in the Revolutionary War, suffered from an inherited disease, porphyria, which causes periodic bouts of madness Some historians— mainly British ones—have argued that it was the distraction caused by George's illness that permitted the Americans' against-the-odds military success While DNA moral intuition long ago shaped by natural selection promoting social cohesion in groups of our ancestors The rift between tradition and secularism first opened by the Enlightenment has, in more or less its present form, dictated biology's place in society since the Victorian period There are those who will continue to believe humans are creations of God, whose will we must serve, while others will continue to embrace the empirical evidence indicating that humans are the product of many millions of generations of evolutionary change John Scopes, the Tennessee high school teacher famously convicted in 1925 of teaching evolution, continues to be symbolically retried in the twenty-first century; religious fundamentalists, having their say in designing public school curricula, continue to demand that a religious story be taught as a serious alternative to Darwinism With its direct contradiction of religious accounts of creation, evolution represents science's most direct incursion into the religious domain and accordingly provokes the acute defensiveness that characterizes creationism It could be that as genetic knowledge grows in centuries to come, with ever more individuals coming to understand themselves as products of random throws of the genetic dice—chance mixtures of their parents' genes and a few equally accidental mutations—a new gnosis in fact much more ancient than today's religions will come to be sanctified Our DNA, the instruction book of human creation, may well come to rival religious scripture as the keeper of the truth I may not be religious, but I still see much in scripture that is profoundly true In the first letter to the Corinthians, for example, Paul writes: Though I speak with the tongues of men and of angels, but have not love, I have become sounding brass or a clanging cymbal And though I have the gift of prophecy, and understand all mysteries and all knowledge, and though I have all faith, so that I could remove mountains, but have not love, I am nothing Paul has in my judgment proclaimed rightly the essence of our humanity Love, that impulse which promotes our caring for one another, is what has permitted our survival and success on the planet It is this impulse that I believe will safeguard our future as we venture into uncharted genetic territory So fun- 404 Our Genes and Our Future damental is it to human nature that I am sure that the capacity to love is inscribed in our DNA—a secular Paul would say that love is the greatest gift of our genes to humanity And if someday those particular genes too could be enhanced by our science, to defeat petty hatreds and violence, in what sense would our humanity be diminished? In addition to laying out a misleadingly dismal vision of our future within the film itself, the creators of Gattaca concocted a promotional tag line aimed at the deepest prejudices against genetic knowledge: "There is no gene for the human spirit." It remains a dangerous blind spot in our society that so many wish this were so If the truth revealed by DNA could be accepted without fear, we should not despair for those who follow us 405 N O T E S INTRODUCTION: THE SECRET OF LIFE xiii "Today, we are"- White House Press Release, available at: http://www.ornI.gov/hgmis/ project/clinton html CHAPTER I: B E G I N N I N G S OF G E N E T I C S "Hair, nails, veins": Anaxagoras as cited in F Vogel and A G Motulsky, Human Genetics (Berlin, N.Y.: Springer, 1996), p 11 "very difficult for me": Mendel as cited in R Marantz Henig, A Monk and 'Two Peas (London: Weidenfeld & Nicolson, 2000), pp 117-18 15 "The elephant is": Charles Darwin, The Origin of Species (New York: Penguin, 1985),p 117 "I profess to be": Francis Galton, Narrative of an Explorer in Tropical South Africa (London: Ward Lock, 1889), pp - "a devil": William Shakespeare, The Tempest (IV:i: 188-9) "I have no patience": Francis Galton, Hereditary Genius (London: MacMillan, 1892), p 12 "It is easy": ibid., p "there is now no": George Bernard Shaw as cited in Diane B Paul, Controlling Human Heredity (Atlantic Highlands, N.J.: Humanities Press, 1995), p 75 22 "The Wyandotte is": ibid., p 66 24 "family with mechanical": C B Davenport, Heredity in Relation to Eugenics (New York: 19 19 19 20 Henry Holt, 1911), p 56 25 "broad-shouldered, dark hair": ibid., p 245 26 "More children": Margaret Sanger as quoted in D M Kennedy, Birth Control in America (New Haven: Yale University Press, 1970), p 115 27 "criminals, idiots": Harry Sharp as cited in E A Carlson, The Unfit (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2001), p 218 27 "It is better": Oliver Wendell Holmes as cited in ibid., p 255 28 "Under existing": Madison Grant, The Passing of the Great Race (New York: Scribner, 1916), p 49 29 "America must": Calvin Coolidge as cited in D Kevles, In the Name of Eugenics (Cambridge, Mass.: Harvard University Press, 1995), p 97 29 "the farseeing": Harry Laughlin as cited in S Kuhl, The Nazi Connection (New York: Oxford University Press, 1994), p 88 407 Notes 31 31 31 "must declare": Adolf Hitler's Mein Kampf as cited in Paul, p 86 "those who": Adolf Hitler, Mein Kampf, trans Ralph Manheim (Boston: Houghton Mifflin Company, 1971), p 404 "law for": Benno Mullcr-Hill, Murderous Science (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1998), p 35 31 "extra-marital": ibid 32 "simply the meddlesome": Alfred Russel Wallace as cited in A Berry, Infinite tropics (NewYork: Verso, 2002), p 214 32 "orthodox eugcnicists": Raymond Pearl as cited in D Miklos and E A Carlson, "Engineering American Society: The Lesson of Eugenics," Nature Genetics (2000): - CHAPTER 2: THE D O U B L E H E L I X 36 "Inheritance insures": Friedrich Miescher as cited in Franklin Portugal and Jack Cohen, A Century of DNA (Cambridge, Mass.: MIT Press, 1977), p 107 46 "stupid, bigoted": Rosalind Franklin as cited in Brenda Maddox, Rosalind Franklin (NewYork: HarperCollins, 2002), p 82 55 "Nobody told me": Linus Pauling, interview, as cited at http://wwAv.achievemcnt.org/ autodoc/page/pauOint-1 59 "The most beautiful experiment": John Cairns as quoted in Horace Judson, The Eighth Day of Creation (New York: Simon & Schuster, 1979), p 188 CHAPTER 3: 71 READING THE CODE "That's when I saw": Sydney Brenner, My Life in Science (London: BiolMed Central, 2001), p 26 74 "We're the only two": Francis Crick as quoted in Horace Judson, The Eighth Day of Creation (New York: Simon & Schuster, 1979), p 485 81 "Without giving me": Francois Jacob as quoted in ibid., p 385 CHAPTER 4: PLAYING GOD 88 "rivaled the importance": Jeremy Rifkin as quoted by Randall Rothenberg in "Robert A Swanson: Chief Genetic Officer," Esquire, December 1984 91 "from corned beef to": Stanley Cohen, http://vvwAv.accessexcellenee.org/ABAVlYV/cohen/ 95 "She made": Paul Berg as quoted at http://www.ascb.org/profiles/9610.html 96 "scientists throughout": Paul Berg et al, "Potential Biohazards of Recombinant DNA Molecules," letter to Science 185 (1974): 303 96 "until the potential": ibid 97 "our concern": ibid 97 "the molecular biologists had clearly reached": Michael Rogers, "The Pandoras Box Congress," Rolling Stone 189 (1975): - 408 Notes 100 "I felt": Leon Heppcl as quoted in James 1) Watson and J Tooze, The DNA Story (San Francisco: W H Freeman and Co., 1981), p 204 102 "In his cranberry": Arthur Lubow as cited in ibid., p 121 102 "In today's": Alfred Vellucci as cited in ibid., p 206 104 "Compared to": Watson as cited in James D Watson, A Passion for DNA (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2001), p 73 108 "You get a nice medal": Fred Sanger as quoted by Anjana Ahuja, "The Double Nobel Laureate W h o Began the Book of Life," The Times (London), January 2000 CHAPTER 5: DNA, DOLLARS, AND DRUGS 113 "to become": Herb Boyer as quoted in Stephen Hall, Invisible Frontiers (New York: Oxford University Press, 2002), p 65 121 "a live human-made": Diamond vs Chakrabarty et al as cited in Nicholas Wade, "Court Says Lab-Made Life Can Be Patented," Science 208 (1980): 1445 132 "I'll make it an issue": Jeremy Rifkin as cited in Daniel Charles, Lords of the Harvest (Cambridge, Mass.: Perseus, 2001), p 94 CHAPTER 6: TEMPEST IN A CEREAL BOX 35 "If man": http://www.nrdc.org/health/pesticides/hcarson.asp 138 "operating outside": Mary-Dell Chilton et al as cited in Daniel Charles, Lords of the Harvest (Cambridge, Mass.: Perseus, 2001), p 16 138 "loved the smell": Rob Horsch as quoted in ibid., p 150 "Put a molecular": Bob Meyer as quoted in ibid., p 132 153 "I naively": Roger Beachy, Daphne Preuss, and Dean Dellapenna, "The Genomic Revolution: EverythingYou Wanted to Know About Plant Genetic Engineering but Were Afraid to Ask," Bulletin of the American Academy of Arts and Sciences, Spring 2002, p 31 155 "After BSE": Friends of the Earth press release as cited in Charles, p 214 156 "this kind": Charles, Prince of Wales, "The Seeds of Disaster," Daily telegraph (London), June 1998 161 "Where genetically": E O Wilson, The Future of Life (New York: Knopf, 2002), p 163 CHAPTER 7: THE H U M A N G E N O M E 167 "put Santa Cruz": Robert Sinsheimer as quoted in Robert Cook-Deegan, The Gene Wars (New York: W W Norton & Co., 1994), p 79 167 168 168 169 71 "DOE's program": David Botstein as cited in ibid., p 98 "the National Bureau": James Wyngaarden as quoted in ibid., p 39 "It means": David Botstein as quoted in ibid., p 111 "an incomparable": Walter Gilbert as cited in ibid., p 88 "from the very start": James Wyngaarden as cjuoted in ibid., p 142 409 Notes 174 "The revelation": Kary B Mullis, "The Unusual Origin of the Polymerase Chain Reaction," Scientific American 262 (April 1990): - 174 "Mullis had": Frank McCormick as quoted in Nicholas Wade, "After the Eureka, a Nobelist Drops Out," New York Times, 15 September 1998 182 "If somebody": William Haseltine as quoted in Paul Jacobs and Peter G Gosselin, "Experts Fret Over Effect of Gene Patents on Research," Los Angeles Times, 28 February 2000 82 "We'd be entitled": William Haseltine as quoted in ibid 84 "I was": Francis Collins as quoted in interview, Christianity Today, October 0 185 "little more": John Sulston and Georgina Ferry, The Common 'Thread (London: Bantam Press), p 123 185 "After we'd invested": Bridget Ogilvie as quoted in ibid., p 125 188 "Fix it": President Clinton as quoted in Kevin Davies, Cracking the Code (New York: The Free Press, 2001), p 238 188 "I'd love": Rhoda Lander as quoted in Aaron Zitner, "The DNA Detective," Boston Globe Sunday Magazine, 10 October 1999 188 "an isolated": Eric Lander as quoted in ibid 188 "I pretty much": Eric Lander as quoted in ibid 191 "Today, we are": White House Press Release, available at: http://www.ornl.gov/hgmis/ project/clintonl html CHAPTER 8: 195 READING GENOMES "seeing the surface": Mark Patterson as cited in Kevin Davies, Cracking the Code (New York: The Free Press, 2001), p 194 206 "Really trust": Barbara McClintock as paraphrased by Elizabeth Blackburn at http://www.cshl.edu/cgi-bin/ubb/library/ultimatebb.cgi?ubb=get_topic;f=l;t=00001 212 "had felt like an outcast": Claire Fraser as quoted in Ricki Lewis, "Exploring the Very Depths of Life," Rennselaer Magazine, March 2001 212 "Well, young lady": Claire Fraser as quoted in ibid 212 "We went to": Claire Fraser as quoted in ibid 221 "a new kind": http://cmgm.stanford.edu/bioehem/brown.html 221 "We're toddlers": Pat Brown as quoted in Dan Cray, "Gene Detective," Time 58 (20 August 2001): - 221 "It was like thinking": Pat Brown as quoted in ibid 225 "Because embryos are beautiful": Eric Wieschaus as quoted in Ethan Bier, The Coiled Spring (Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory Press, 2000), p 64 CHAPTER 9: OUT OF AFRICA 231 "It was like": Ralf Schmitz as quoted in Steve Olson, Mapping Human History (Boston: Houghton Mifflin, 2002), p 80 232 "I can't": Matthias Krings as quoted in Patricia Kahn and Ann Gibbons, "DNA from an extinct human," Science 277 (1997): 176-78 410 Notes 232 "That's when": Matthias Krings as quoted in ibid 235 "If everyone": Allan Wilson as quoted by Mary-Claire King at http://www.chemheritage.org/ EducationalServices/pharm/chemo/readings/king.htm 240 "It turned out": Luigi Luca Cavalli-Sforza as quoted in Olson, p 164 249 "If we": Charles Darwin, The Origin of Species (New York, Penguin, 1985), p 406 CHAPTER 10: GENETIC FINGERPRINTING 261 "having a white woman": Brooke A Masters, "For Trucker, the High Road to DNA Victory," Washington Post, Saturday, December 2001, p B01 262 "unwelcome precedent": the Director of the Virginia Department of Criminal Justice as quoted at http://www.innocenceproject.org/case/display_profile.php?id=99 263 "profile provides": Alec Jeffreys, Victoria Wilson, and Swee Lay Thein, "Hypervariable 'minisatellite' regions in human DNA," Nature 314 (1985): - 263 "In theory": Alec Jeffreys as quoted at http://www.dist.gov.au/events/ausprize/ap98/jeffreys html 266 "must be sufficiently": Fryevs United States, 293 F.2d 1013, at 104 268 "The implementation": Eric Lander, "Population genetic considerations in the forensic use of DNA typing," in Jack Ballantyne, et al., DNA Technology and Forensic Science (Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1989), p 153 269 "mountain of evidence": Johnnie Cochran as quoted at http://simpson.walraven.org/sep27 htm] 272 "Where is": Barry Schcck as quoted at http://simpson.walraven.org/aprl html 275 "State of Wisconsin": Geraldine Sealey, "DNA Profile Charged in Rape," http://abcnews go.com/sections/us/DailyNews/dna991007.html 275 "unknown male": Case Number 00F06871, The People of the State of California vs John Doe, Aug , 0 276 "DNA appears": Judge Tani G Cantil-Sakauye, Case Number 00F06871, The People of the State of California vs Paul Robinson, Motion to Dismiss, reporter's transcript, p 136, Feb 23,2001 281 "My son": Jean Blassie as quoted in Pat McKenna, "Unknown, No More," http://www.af mil/news/airman/0998/unknown.htm 289 "The D N A evidence": Lord Woolf, Case Number 199902010 S2, "Regina and James Hanratty," Judgment, May 10, 2002, paragraph 1 289 291 "In hindsight": "DNA testing also proves guilt," editorial, St Petersburg Times, 30 May 2002 "DNA testing": Barry Scheck et al., Actual Innocence (New York: Doubleday, 2000), p xv CHAPTER II: GENE 294 HUNTING "Fifty-fifty": Milton Wexler as quoted in Alice Wexler, Mapping Fate (New York: Random House, 1995), p 43 294 "Over 50 years": George Huntington as cited in Charles Stevenson "A Biography of George Huntington, M.D.," Bulletin of the Institute of the History of Medicine (1934) 4JJ Notes 295 "gradually increase": ibid 295 "As the disease": ibid 295 "When either": ibid 296 "without theater": Americo Negrette as quoted in Robert Cook-Deegan, The Gene Wars (New York: W W Norton & Co., 1994), p 235 298 "tends to think": ibid., p 37 302 "We would never": Ray White as quoted in Leslie Roberts, "Flap arises over genetic map," Science 239 (1987): - 309 "We own": Orrie Friedman as quoted in Richard Saltus, "Biotech Firms compete in Genetic Diagnosis," Science 234 (1986): 1318-20 318 "committing": Rural Advancement Foundation International, at http://www.rafi.org/article asp?newsid=207 319 "the creation": Althing (Icelandic Parliament), "Law on a Health Sector Database," at http://www.mannvernd.is/english/laws/law.HSD.html CHAPTER 12: DEFYING DISEASE 327 "So marked": John Langdon Down as quoted in Elaine Johansen Mange and Arthur P Mange, Basic Human Genetics (Sunderland, Mass.: Sinauer Associates, 1999), p 267 331 "ear-piercing": Kathleen McAulitfe, "The Hardest Choice," at http://blueprint.bluecrossmn com/topic/hardestchoice 343 "Some people": Debbie Stevenson, "The Mystery Disease No One Tests For," Redbook, July 2002: 137 346 "biological Holocaust": Daniel Pollen, Hannahs Heirs (New York: Oxford University Press, 1993), p 14 354 "informed consent": U.S Department of Health and Human Services Press Release "New Initiatives to Protect Participants in Gene Therapy Trials," March 2000 Available at http://www.fda.gov/bbs/topics/NEWS/NEW00717.html C H A P T E R : W H O W E ARE 362 "Whatever person": Penal Laws as cited at http://www.law.umn.edu/irishlaw/education.html 362 "They might as well": Arthur Young as cited in Julie Henigan, "For Want of Education: The Origins of the Hedge Schoolmaster Songs," Ulster Folklife 40 (1994): - 362 "Still crouching": John O'Hagan as cited at http://www.in2it.co.Uk/history/2.htrnl 366 "barefoot professor": Vitaly Fyodorovich as cited in David Joravsky, The Lysenko Affair (Cambridge, Mass.: Harvard University Press, 1970), p 189 366 "Turkic peasant": Vitaly Fyodorovich as cited in Valery N Soyfer, Lysenko and the Tragedy of Soviet Science (New Brunswick, N.J.: Rutgers University Press, 1994), p 11 366 "He didn't": Vitaly Fyodorovich as cited in ibid., p 11 367 "In order": Trofim Lysenko as cited in Joravsky, p 1 370 "hard core": ibid., p 226 370 "It deals": K Iu Kostriukova as cited in ibid., p 247 412 Notes 370 "In our": Trofim Lysenko as cited in ibid., p 210 373 "Give me": John B Watson, Behaviorism (New York: W W Norton & Co., 1924), p 104 378 "On multiple": Thomas J Bouchard et al., "Sources of Human Psychological Differences: The Minnesota Study of Twins Beared Apart," Science 250 (1990): 2 - 389 "In no field": Neil Risch and David Botstein, "A Manic Depressive History," Nature Genetics 12 (1996): - CODA 395 "The event": Percy Bysshe Shelley, introduction to Mary Wollstonecraft Shelley, Frankenstein (New York: Oxford University Press, 1969), p 13 402 "Ethical Implications": James D Watson in Frankfurter Allgemeine Zeitung, September 26, 2000 402 "following the logic": Jorg Dietrich Hoppe as cited in Benno Muller-Hill, "Speaking Out in Favor of the Right to Choose" Frankfurter Allgemeine Zeitung, December 5, 2000 403 "value and sense": Johannes Rau as cited in ibid 403 "Ethics of Horror": Dietmar Mieth in Frankfurter Allgemeine Zeitung as cited in ibid 404 "Though I speak": Corinthians 13: 1-2 413 F U R T H E R R E A D I N G CHAPTER I: BEGINNINGS OF GENETICS Carlson, Elof Axel The Unfit: A History of a Bad Idea Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2002 Discussion of eugenics beginning in biblical times and ending with contemporary clinical genetics Gillham, Nicholas Wright A Life of Sir Francis Galton: From African Exploration to the Birth of Eugenics New York: Oxford University Press, 2001 Engaging recent study of an extraordinary but neglected figure Jacob, Francois The Logic of Life: A History of Heredity Princeton: Princeton University Press, 1993 Reflections by one of the founders of molecular genetics Kevles, Daniel J In the Name of Eugenics: Genetics and the Uses of Human Heredity New York: Alfred A Knopf, 1985 Scholarly but readable account of eugenics Kohler, Robert E Lords of the Fly: Drosophila Genetics and the Experimental Life Chicago: University of Chicago Press, 1994 Chronicle of the early days of fruit fly genetics Kuhl, Stefan The Nazi Connection: Eugenics, American Racism, and German National Socialism New York: Oxford University Press, 1994 Mayr, Ernst This Is Biology: The Science of the Living World Cambridge, Mass.: Harvard University Press, 1997 Fine overview from a biologist who has just celebrated the seventy-fifth anniversary of earning his Ph.D Muller-Hill, Benno Murderous Science: Elimination by Scientific Selection of Jews, Gypsies, and Others in Germany, 1933—1945 Translated by Todliche Wissenschaft New York: Oxford University Press, 1988 Reveals how German scientists and physicians were implicated in Nazi policies and how they resumed their academic positions after the war Olby, Robert C Origins of Mendelism Chicago: University of Chicago Press, 1985 Orel, Vitezslav Gregor Mendel: The First Geneticist New York: Oxford University Press, 1996 The most complete biography to date Paul, Diane B Controlling Human Heredity, 1865 to the Present Atlantic Highlands, N.J.: Humanities Press, 1995 A succinct history of eugenics CHAPTER 2: THE DOUBLE HELIX Crick, Francis H C What Mad Pursuit: A Personal View of Scientific Discovery New York: Basic Books, 1988 415 Further Reading Hager, Thomas Force of Nature: The Life of Linus Pauling New York: Simon & Schuster, 1995 An excellent biography of a scientific giant Holmes, Frederic Lawrence Meselson, Stahl, and the Replication of DNA: A History of "The Most Beautiful Experiment in Biology." New Haven: Yale University Press, 2001 McCarty, Maclyn The Transforming Principle: Discovering That Genes are Made of DNA New York: W W Norton & Co., 1995 Account of the experiments that showed DNA to be the hereditary material by one of the three scientists who carried them out Maddox, Brenda Rosalind Franklin: The Dark Lady of DNA New York: HarperCollins, 2002 Thorough biography that casts new light on Franklin Olby, Robert The Path to the Double Helix: The Discovery of DNA Foreword by Francis Crick Dover Publishers, 1994 Scholarly historical perspective Watson, James D The Double Helix: A Personal Account of the Discovery of the Structure of DNA New York: Atheneum Press, 1968 CHAPTER 3: READING THE CODE Brenner, Sydney My Life in Science London: BioMed Central Limited, 2001 A rare combination: illuminating and funny Hunt, Tim, Steve Prentis, and John Tooze, ed DNA Makes RNA Makes Protein New York: Elsevier Biomedical Press, 1983 Collection of essays summarizing the state of molecular genetics in 1980 Jacob, Francois The Statue Within: An Autobiography Translated by Franklin Philip Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1995 Lucid and beautifully written Judson, Horace Freeland The Eighth Day of Creation: Makers of the Revolution in Biology Expanded edition Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1996 Classic study on the origins of molecular biology Monod, Jacques Chance and Necessity: An Essay on the Natural Philosophy of Modern Biology Translated by Austryn Wainhouse New York: Alfred A Knopf, 1971 Philosophical musings by a key figure in molecular genetics Watson, James D Genes, Girls, and Gamow New York: Alfred A Knopf, 2001 Sequel to The Double Helix CHAPTER 4: PLAYING GOD Fredrickson, Donald S The Recombinant DNA Controversy: A Memoir: Science, Politics, and the Public Interest 1974-1981 Washington, D C : American Society for Microbiology Press, 2001 Account of turbulent times in biomedical research by the then-director of the National Institutes of Health Krimsky, Sheldon Genetic Alchemy: The Social History of the Recombinant DNA Controversy Cambridge, Mass.: MIT Press, 1982 A critic's perspective Rogers, Michael Biohazard New York: Alfred A Knopf, 1977 Expansion of Rogers's insightful account in Rolling Stone of the Asilomar meeting 416 Further Reading Watson, James D A Passion for DNA: Genes, Genomes, and Society Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2000 Collection of essays drawn from newspapers, magazines, talks, and Cold Spring Harbor Laboratory reports Watson, James D., Michael Gilman, Jan Witkowski, and Mark Zoller Recombinant DNA New York: Scientific American Books, distributed by W H Freeman, 1992 Now out of date but still a sound introduction to the basic science underlying genetic engineering Watson, James D., and John Tooze The DNA Stars': A Documentary History of Gene Cloning San Francisco: W H Freeman and Co., 1981 The recombinant DNA debate recounted through contemporary' articles and documents CHAPTER 5: DNA, DOLLARS, AND DRUGS Cooke, Robert Dr Folkman's War: Angiogenesis and the Struggle to Defeat Cancer New York: Random House, 2001 Hall, Stephen S Invisible Frontiers: The Race to Synthesize a Human Gene New York: Atlantic Monthly Press, 1987 Tells the insulin-cloning story with verve Kornberg, Arthur The Golden Helix: Inside Biotech Ventures Sausalito, Calif.: University Science Books, 1995 The foundcr of several companies describes the rise of the biotechnology industry Werth, Barry The Billion-Dollar Molecule: One Company's Quest for the Perfect Drug New York: Touchstone Books/Simon & Schuster, 1995 The story of Vertex, a company typifying the biotech approach to the pharmaceutical business C H A P T E R 6: T E M P E S T IN A C E R E A L BOX Charles, Daniel Lords of the Harvest: Biotech, Big Money, and the Future of Food Cambridge, Mass.: Perseus Publishing, 2001 Fascinating account of the genetically modified food controversy, emphasizing the business side and focusing primarily on Monsanto McHughen, Alan Pandora's Picnic Basket: The Potential and Hazards of Genetically Modified Foods New York: Oxford University Press, 2000 Spotty introduction to some of the issues, including scientific ones, behind the controversy CHAPTER 7: THE HUMAN G E N O M E Cook-Deegan, Robert M The Gene Wars: Science, Politics, and the Human Genome New York: W W Norton & Co., 1994 Brilliantly comprehensive account of the origins and early days of the Human Genome Project Davies, Kevin Cracking the Genome: Inside the Race to Unlock Hitman DNA New York: Free Press, 2001 Continuation of Cook-Dccgans story, bringing it up to the completion of the first draft of the human genome Sulston, John, and Georgina Ferry The Common Thread: A Story of Science, Politics, Ethics, and the Human Genome Washington, D.C.: Joseph Henry Press, 2002 Personal account of 417 Further Reading research on the worm and of the British end of the Human Genome Project Sulston's disdain for individuals and companies profiting from the human genome sequence drives his story and his science CHAPTER 8: READING GENOMES Bier, Ethan The Coiled Spring: How Life Begins Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2000 Comfort, Nathaniel C The Tangled Field: Barbara McClintock's Search for the Patterns of Genetic Control Cambridge, Mass.: Harvard University Press, 2001 A scholarly but approachable account of the lite and work of Barbara McClintock Lawrence, Peter A The Making of a Fly: The Genetics of Animal Design Boston: Blackwcll Scientific Publications, 1992 Now out of date but still an excellent introduction to the excitement generated when genetics meets developmental biology Ridley, Matt Genome: The Autobiography of a Species in 23 Chapters New York: HarperCollins, 1999 Hugely accessible introduction to modern studies of human genetics CHAPTER 9: OUT OF AFRICA Cavalli-Sforza, L L (Luigi Luca) Genes, Peoples, and Languages Translated by Mark Seielstad New York: North Point Press, 2000 Personal account of human-evolution studies by the field's leader Olson, Steve Mapping Human History: Discovering the Past Through Our Genes Boston: Houghton Mifflin, 2002 Balanced and up-to-date account of human evolution and the impact that our past has on our present Sykes, Bryan The Seven Daughters of Eve New York: W W Norton & Co., 2001 CHAPTER 10: GENETIC FINGERPRINTING Massie, Robert K The Romanovs: The Final Chapter New York: Random House, 1995 The story of the Romanovs' murders and of how DNA fingerprinting established the authenticity of the remains and unmasked impostors Scheck, Barry, Peter Neufeld, and Jim Dwyer Actual Innocence: Five Days to Execution and Other Dispatches from the Wrongly Convicted New York: Doubleday, 2000 From the horses' mouths, an examination of the power of DNA fingerprinting to exonerate the wrongfully convicted Wambaugh, Joseph The Blooding New York: Bantam Books, 1989 Exciting account of the first use of DNA fingerprinting to apprehend a criminal CHAPTER 11: GENE HUNTING Bishop, Jerry E., and Michael Waldholz Genome: The Story of the Most Astonishing Scientific Adventure of Our Time—The Attempt to Map All the Genes in the Human Body: New York: 418 Further Reading Simon & Schuster, 1990 Still one of the best accounts of the early days of hunting human disease genes Gelehrter, Thomas D., Francis Collins, and David Ginsburg Principles of Medical Genetics Baltimore: Williams & Wilkins, 1998 A short and readable textbook on modern human molecular genetics Pollen, Daniel A Hannah's Heirs: The Quest for the Genetic Origins of Alzheimer's Disease New York: Oxford University Press, 1993 Captures the thrill of the chase and highlights the awfulness of the disease Wexler, Alice Map-ping Fate: A Memoir of Family, Risk, and Genetic Research New York: Random House, 1995 Searingly honest testimony from Nancy Wexler's sister CHAPTER 12: DEFYING DISEASE Davies, Kevin, with Michael White Breakthrough: The Race to Find the Breast Gancer Gene New York: John Wiley & Sons Inc., 1996 Story of immensely hard work, dedication, ambition, and greed Kitcher, Philip The Lives to Come: The Genetic Revolution and Human Possibilities New York: Simon & Schuster, 1997 Philosophical and ethical discussion about how to use what we have learned of human molecular genetics Lyon, Jeff, with Peter Corner Altered Fates: Gene Therapy and the Retooling of Human Life New York: W W Norton & Co., 1995 Includes a good account of the treatment of the two girls with ADA deficiency Reilly, Philip R Abraham Lincoln's DNA and Other Adventures in Genetics Cold Spring Harbor, N.Y: Cold Spring Harbor Laboratory, 2000 Essays on topical issues written from the unusually informed perspective of a physician-cum-lawyer Thompson, Larry Correcting the Code: Inventing the Genetic Cure for the Human Body New York: Simon & Schuster, 1994 Account of the development of gene therapy, including the Martin Cline episode C H A P T E R : W H O W E ARE Coppinger, Raymond, and Lorna Coppinger Dogs: A Startling New Understanding of Canine Origin, Behavior, and Evolution New York: Scribner, 0 Overview of the enormous differences, in body and mind, among dogs Crick, Francis H C The Astonishing Hypothesis: The Scientific Search for the Soul New York: Scribner, 1993 A materialist perspective on the problem of consciousness Crick concludes that we are "no more than the behavior of a vast assembly of nerve cells and their associated molecules." Herrnstein, Richard J., and Charles Murray The Bell Curve: Intelligence and Class Structure in American Life New York: Free Press, 1994 More talked about than read Jacoby, Russell, and Naomi Glauberman, ed The Bell Curve Debate: History, Documents, Opinions New York: Times Books, 1995 Collection of eighty essays about and reviews of The Bell Curve 419 Further Reading Lewontin, R C, Steven Rose, and Leon J Kamin Not in Our Genes: Biology, Ideology, and Human Nature New York: Pantheon Books, 1984 The academic left's response to Wilson's Sociobiology Mendvedev, Zhores A The Rise and fall of T D Lysenko New York: Columbia University Press, 1969 Firsthand account by a scientist who suffered from the Communist Party's control of Soviet science Pinker, Steven The Blank Slate: The Modern Denial of Human Nature New York: Viking Penguin, 2002 Pinker, Steven How the Mind Works New York: W W Norton & Co., 1997 Evolutionary psychology outlined by one its most eloquent proponents Ridley, Matt Nature via Nurture: Genes, Experience, and What Makes Us Human New York: HarperCollins, 2003 Soyfer, Valery N Lysenko and the Tragedy of Soviet Science Translated by Leo Gruliow and Rebecca Gruliow New Brunswick, N.J.: Rutgers University Press, 1994 An account from someone who knew Lysenko Wilson, Edward O Sociobiology: The New Synthesis Cambridge, Mass.: Belknap Press of Harvard University Press, 1975 Proposes an evolutionary explanation for much of our behavior 420 ... manifestation of the wrath of God or the mischief of demons and devils; sometimes as evidence of either an excess of or a deficit of the father's "seed"; sometimes as the result of "wicked thoughts" on the. .. forces—found the messy complexity of biology bewildering Maybe, they suggested, the processes at the heart of the cell, the ones governing the basics of life, go beyond the familiar laws of physics... only dreamed of But the climax of the first fifty years of the DNA revolution came on Monday, June 26, 2000, with the announcement by U.S president Bill Clinton of the completion of the rough draft