Dna: The Secret of Life Read online

  PLATES

  Plate 1. 1953: Francis Crick (right) and me with our model of the double helix.

  Plate 2. The key to Mendel's triumph: genetic variation to pea plants.

  Plate 3. Notoriously camera shy T. H. Morgan was photographed surreptitiously while at work in the fly room.

  Plate 4. Eugenics as it was perceived during the first part of the twentieth century: an opportunity for humans to control their own evolutionary destiny.

  Plate 5. "Large family" winner, Fitter Families Contest, Texas State Fair (1925).

  Plate 6. Scientific racism: social inadequacy in the United States analyzed by Harry Laughlin as an umbrella term for a host of sins ranging from feeblemindedness to tuberculosis. Laughlin computed an institutional "quota" for each group on the basis of the proportion of that group in the U.S. population as a whole. Shown, as a percentage, is the number of institutionalized individuals from a particular group divided by the group's quota. Groups scoring over 100 per cent are overrepresented in institutions.

  Plate 7. The physicist Erwin Schrödinger, whose book What Is Life? turned me on to the gene.

  Plate 8. Erwin Schröder's What Is Life?, published in 1944.

  Plate 9. A view through the microscope of blood cells treated with a chemical that stains DNA. In order to maximize their oxygen-transporting capacity, red blood cells have no nucleus and therefore no DNA. But white blood cells, which patrol the bloodstream in search of intruders, have a nucleus containing chromosomes.

  Plate 10. Lawrence Bragg (left) with Linus Pauling, who is carrying a model of the a-helix.

  Plate 11. Maurice Wilkins in his lab at King's College, London.

  Plate 12. Rosalind Franklin on one of the mountain hiking vacations she loved.

  Plate 13. X-ray photos of the A and B forms of DNA from, respectively, Maurice Wilkins and Rosalind Franklin. The differences in molecular structure are caused by differences in the amount of water associated with each DNA molecule.

  Plate 14. The chemical backbone of DNA.

  Plate 15. The insight that made it all come together: complementary pairing of the bases.

  Plate 16. Bases and backbone in place: the double helix.

  (A) is a schematic showing the system of base-pairing that binds the two strands together.

  (B) is a "space-filling" model showing, to scale, the atomic detail of the molecule.

  Plate 17. Short and sweet: our Nature paper announcing the discovery. The same issue also carried longer articles by Rosalind Franklin and Maurice Wilkins.

  Plate 18. Matt Meselson beside an ultra-centrifuge, the hardware at the heart of "the most beautiful experiment in biology".

  Plate 19. The Meselson-Stahl experiment.

  Plate 20. Arthur Kornberg at the time of winning his Nobel Prize.

  Plate 21. The impact of mutation. A single base change in the DNA sequence of the human beta hemaglobin gene results in the incorporation of the amino acid valine rather than the glutamic acid into the protein. This single difference causes sickle-cell disease, in which the red blood cells become distorted into a characteristic sickle shape.

  Plate 22. The genetic code, showing the triplet sequences for messenger RNA. An important difference between DNA and RNA is that DNA uses thymine and RNA uracil. Both bases are complementary to adenine. Stop codons do what their name suggests: they mark the end of the coding part of a gene.

  Plate 23. From DNA to protein. DNA is transcribed in the nucleus into messenger RNA, which is then exported to the cytoplasm for translation into protein. Translation occurs in ribosomes: transfer RNAs complementary to each base pair triplet codon in the messenger RNA deliver amino acids, which are bonded together to form a protein chain.

  Plate 24. François Jacob, Jacques Monod, and André Lwoff.

  Plate 25. The cell's protein factory, the ribosome, in all its 3-D glory as revealed by X-ray analysis. (For simplicity, this computer-generated image does not show individual atoms.) There are millions of ribosomes in every cell. It is here that the information encoded in DNA is used to produce proteins, the actors in life's molecular drama. The ribosome consists of two subunits (orange and yellow), each composed of RNA, plus some sixty proteins (blue and green) plastered over the outside. Here the ribosome is caught in the act of producing a protein. Specialized small RNA molecules (purple, white, and red) transport amino acids to the ribosome for incorporation into the growing protein change.

  Plate 26. A plasmid as viewed by the electron microscope.

  Plate 27. Herb Boyer and Stanley Cohen, the world's first genetic engineers.

  Plate 28. Recombinant DNA: cloning a gene.

  Plate 29. Paul Berg with his viral Honda.

  Plate 30. A P4 laboratory, the ultrasafe facility required for biomedical research of lethal bugs such as the Ebola virus or for developing biological weapons. During the late 1970s, scientists using genetic engineering methods to do research on human DNA were also required to use a P4 laboratory.

  Plates 31 & 32. Wally Gilbert (left) and Fred Sanger, sequence kings.

  Plate 33. Time magazine marks the birth of the biotechnology business (and looks forward to a royal wedding).

  Plate 34. The Sanger method of DNA sequencing.

  Plate 35. Phil Leder with his "Harvard" onco-mouse.

  Plate 36. The effect of eons of artificial selection: corn and its wild ancestor, teosinte.

  Plate 37. Bt cotton: cotton genetically engineered to produce insecticidal Bt toxin thrives while a non-Bt crop is trashed by pest insects.

  Plate 38. The full complement of human chromosomes highlighted by chromosome-specific fluorescent stains. The total number of chromosomes in each cell's nucleus is 46 – two full sets one from each parent. The genome is one set: twenty-three chromosomes – twenty-three very long DNA molecules.

  Plate 39. Kary Mullis, inventor of PCR.

  Plate 40. Amplifying the DNA region you're interested in: the polymerase chain reaction.

  Plate 41. The genome project goes commercial: William Haseltine and Craig Venter.

  Plate 42. International collaboration: British and American scientists were the first to complete the sequencing of the genome of a complex organism, the nematode, C. elegans. The project's leaders, Bob Waterston and John Sulston, still found time to relax.

  Plate 43. Mass production meets DNA sequencing: MIT's Whitehead Institute.

  Plate 44. What our genome looks like: the major features of a small human chromosome, number 20.

  Plate 45. Barbara McClintock, discoverer of mobile genetic elements.

  Plate 46. Fruit fly faces. On the left is a normal individual, with a pair of feathery antennae protruding from its forehead. On the right is an antennapedia mutant, in which the antennae have been replaced by fully formed legs.

  Plate 47. Proteomics: the 3-D structure of a cancer-causing protein, BCR-ABL. The fusion of the two genes caused by a chromosomal abnormality leads to the production of this protein, which stimulates cell proliferation and may cause a form of leukemia. Shown in purple is a small molecule drug, Gleevec, which inhibits BCR-ABL function (see Chapter 5). It is with 3-D information like this that drugs will in the future be designed to target particular proteins. This representation of BCR-ABL's structure does not show the details of the atoms or individual amino acids, but nevertheless accurately reflects the protein's layout.

  Plate 48. Mary-Claire King.

  Plate 49. The mitochondrial DNA human family tree.

  Plate 50. Out of Africa and beyond: Our species originated in Africa and spread out from there. Estimated colonization dates are based on mtDNA data.

  Plate 51. How genetic fingerprinting works.

  Plate 52. Alec Jeffreys, father of DNA fingerprinting. />
  Plate 53. Nancy Wexler holding a child with early-onset Huntington disease, Lake Maracaibo, Venezuela.

  Plate 54. Genetic mapping of a disease gene. For convenience, only two generations and a few individuals are shown. If the analysis is to be statistically powerful, information is required from a large number of related individuals.

  Plate 55. David Vetter, whose inherited immune system disorder made him susceptible to the slightest infection, was raised in a sterile world and became the original "bubble boy".

  Plate 56 & 57. Fluorescent staining for chromosome number. A cell nucleus (dark blue) is probed for chromosome 10 (light blue) and chromosome 21 (pink). The image on the far left shows a normal karyotype with two copies of each chromosome; in the other, we see a Down karyotype, which has an extra copy of chromosome 21.

  Plate 58. Trofim Lysenko measuring wheat plants in a rare burst of empiricism on a collective farm near Odessa, Ukraine.

  Plates 59 & 60. The impact of just one gene. At top, a normal mouse mother is highly attentive to her offspring. The mother below, lacking a functional fos-B gene, ignores her newborns.

  Plates 61 & 62. The cultural wonder that is Homo sapiens. Two contrasting notions of chic: Paris 1950s and the highlands of Papua New Guinea. Evolutionary psychology seeks the common denominators underlying all our widely divergent behavior.

  Table of Contents

  About the Author

  By the Same Author

  Title Page

  Copyright Page

  Dedication

  Author's Note

  PLATES

  Introduction

  CHAPTER ONE BEGINNINGS OF GENETICS: FROM MENDEL TO HITLER

  CHAPTER TWO THE DOUBLE HELIX: THIS IS LIFE

  CHAPTER THREE READING THE CODE: BRINGING DNA TO LIFE

  CHAPTER FOUR PLAYING GOD: CUSTOMIZED DNA MOLECULES

  CHAPTER FIVE DNA, DOLLARS, AND DRUGS: BIOTECHNOLOGY

  CHAPTER SIX TEMPEST IN A CEREAL BOX: GENETICALLY MODIFIED AGRICULTURE

  CHAPTER SEVEN THE HUMAN GENOME: LIFE'S SCREENPLAY

  Picture Section 1

  CHAPTER EIGHT READING GENOMES: EVOLUTION IN ACTION

  CHAPTER NINE OUT OF AFRICA: DNA AND THE HUMAN PAST

  CHAPTER TEN GENETIC FINGERPRINTING: DNA'S DAY IN COURT

  Picture Section 2

  CHAPTER ELEVEN GENE HUNTING: THE GENETICS OF HUMAN DISEASE

  CHAPTER TWELVE DEFYING DISEASE: TREATING AND PREVENTING GENETIC DISORDERS

  CHAPTER THIRTEEN WHO WE ARE: NATURE VS. NURTURE

  CODA OUR GENES AND OUR FUTURE

  Notes

  Further Reading

  Acknowledgments

  Index

  Also Available in Arrow Evolution

  Critical Mass

  DNA

  Born in the US, James Watson won the Nobel Prize for Physiology or Medicine in 1962 for elucidating the structure and function of DNA, along with the Englishmen Francis Crick and Maurice Wilkins. After studying and teaching at Harvard and Cambridge Universities, he has worked at the Cold Spring Harbor Laboratory in New York State for the last three decades, for most of that time as its director. He is the author of a number of books, including the international bestseller The Double Helix.

  ALSO BY JAMES D. WATSON

  The Molecular Biology of the Gene

  (1965, 1970, 1976, coauthor: 1987)

  The Double Helix: A Personal Account of the

  Discovery of the Structure of DNA (1968)

  The DNA Story: A Documentary History of Gene Cloning

  (coauthor: 1981)

  Recombinant DNA (coauthor: 1983, 1992)

  The Molecular Biology of the Cell (coauthor: 1983, 1989, 1994)

  A Passion for DNA: Genes, Genomes, and Society (2000)

  Genes, Girls, and Gamow: After the Double Helix (2002)

  DNA

  The Secret of Life

  James D. Watson

  with Andrew Berry

  This eBook is copyright material and must not be copied, reproduced, transferred, distributed, leased, licensed or publicly performed or used in any way except as specifically permitted in writing by the publishers, as allowed under the terms and conditions under which it was purchased or as strictly permitted by applicable copyright law. Any unauthorised distribution or use of this text may be a direct infringement of the author's and publisher's rights and those responsible may be liable in law accordingly.

  ISBN 978-1-4070-9624-7

  Version 1.0

  www.randomhouse.co.uk

  Published in the United Kingdom in 2004 by Arrow Books

  7 9 10 8

  Copyright © 2003 by DNA Show LLC

  James D. Watson has asserted his right under the Copyright, Designs and Patents Act, 1988 to be identified as the author of this work

  This electronic book is sold subject to the condition that it shall not by way of trade or otherwise, be lent, resold, hired out, or otherwise circulated without the publisher's prior consent in any form other than that in which it is published and without a similar condition including this condition being imposed on the subsequent purchaser

  Published by arrangement with Alfred A. Knopf,

  a division of Random House, Inc., New York

  First published in the United Kingdom in 2003

  by William Heinemann

  The Random House Group Limited

  20 Vauxhall Bridge Road, London SW1V 2SA

  www.rbooks.co.uk

  Addresses for companies within The Random House Group Limited can be found at: www.randomhouse.co.uk/offices.htm

  The Random House Group Limited Reg. No. 954009

  A CIP catalogue record for this book

  is available from the British Library

  ISBN: 978-1-4070-9624-7

  Version 1.0

  For Francis Crick

  AUTHORS' NOTE

  DNA: 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.

  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 proje
ct, 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.