Table Of Contenttransducing the
genome
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transducing the
genome
INFORMATION, ANARCHY, AND REVOLUTION
IN THE BIOMEDICAL SCIENCES
Gary Zweiger
McGraw-Hill
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DOI: 10.1036/0071381333
Contents
Acknowledgments vii
Introduction ix
1 Cancer, Computers, and a “List-Based” Biology 1
2 Information and Life 13
3 Behold the Gene 21
4 Working with Genes One at a Time 31
5 The Database 39
6 Getting the Genes 47
7 Prospecting for Genes with ESTs 61
8 ESTs, the Gene Race, and Moore’s Law 77
9 The End Game 87
10 Human Genome History 105
11 Comparing Human Genomes 117
12 A Paradigm in Peril 125
13 The Ancient Internet—Information Flow in Cells 135
14 Accessing the Information Output of the Genome 149
15 The Genomics Industry 161
16 The SNP Race 177
17 From Information to Knowledge 189
18 The Final Act 201
19 Future Prospects 207
Appendix: How the Patent Process Works 221
Glossary 235
Notes 239
Index 259
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Acknowledgments
Inspiration for writing this book came from numerous conversa-
tions in which scientists and nonscientists alike expressed great
interest in the human genome,the Human Genome Project,bio-
informatics, gene patents, DNA chips, and other hallmarks of a
new age in biology and medicine.There was a sense that history
was being made and that biology,medicine,and even our concep-
tion of ourselves would be forever changed.For some folks there
was tremendous excitement over the possibilities and promises of
genomics.For others there was trepidation and concern.However,
nearly everyone I spoke with agreed that many of the history-
making events and ideas were hidden from the public, and that
scientists and general readers alike would benefit from the per-
spective I had developed over the last decade.
Many of the ideas and insights that I present here came through
my work as a biologist in laboratories at Stanford University,
Schering-Plough Corporation, Columbia University, and Genen-
tech; in classrooms at various San Francisco Bay area community
colleges;consulting for several different biotechnology investment
groups; and through scientific, business, and legal work at Incyte
Genomics and Agilent Technologies.This work brought me in con-
tact with a vast network of people linked by the common goals of
advancing our knowledge of life and improving human health, a
perfectly primed source of help for a project such as this.
Several pioneers in the genomics revolution graciously shared
their recollections and insights with me.In particular,I thank John
Weinstein of the U.S. National Cancer Institute; Leigh Anderson
of Large Scale Biology;Leonard Augenlicht of Albert Einstein Uni-
versity;Walter Gilbert of Harvard University;and Randy Scott,Jeff
Seilhamer,and Roy Whitfield of Incyte Genomics.
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viii ACKNOWLEDGMENTS
I owe many thanks to coworkers at Incyte Genomics,who were
both terrifically forthcoming in sharing their enthusiasm and ideas
and tremendously supportive of my extracurricular activities. In
particular, I wish to thank Jeanne Loring, Huijun Ring, Roland
Somogyi, Stefanie Fuhrman, Tod Klingler, and Tim Johann. I am
also especially grateful for the support of my coworkers at Agilent
Technologies. In particular, I wish to thank Bill Buffington, Stuart
Hwang,Mel Kronick,Doug Amorese,Dick Evans,Paul Wolber,Ar-
lyce Guerry, Linda Lim, Ellen Deering, and Nalini Murdter for
their aid and encouragement.
I thank Donny Strosberg of Hybrigenics,Xu Li of Kaiser Per-
manente,Steve Friend and Chris Roberts of Rosetta InPharmatics,
Yiding Wang of Biotech Core,and Brian Ring of Stanford Univer-
sity for images and figures.Thanks to Karen Guerrero of Mendel
Biosciences for her encouragement and reviews and for educating
me on some of the nuances of patent law.
This book might not have been completed without the
steadfast encouragement and expert guidance of Amy Murphy,
McGraw-Hill’s pioneering “trade” science editor. I also thank
Robert Cook-Deegan for his insightful comments.
Finally, I offer my heartfelt thanks to Myriam Zech and
Karolyn Zeng for their friendship and advice,Martin and Martha
Zweig for their support,my daughter Marissa for her love and in-
spiration, her mother Andrea Ramirez, and my mother Sheila
Peckar.
Introduction
Institutions at the forefront of scientific research host a continual
stream of distinguished guests. Scientists from throughout the
world come to research centers,such as California’s Stanford Uni-
versity,to share ideas and discoveries with their intellectual peers.
It is part of an ongoing exchange that embodies the ideals of open-
ness and cooperation characteristic of science in general,and bio-
medical research in particular.
As a graduate student in the Genetics Department of Stan-
ford’s School of Medicine in the late 1980s,I attended several lec-
tures per week by visiting scientists.We heard firsthand accounts
of the latest triumphs of molecular biology, of newly discovered
molecules, and of their roles in human disease.We heard of ele-
gant, clever, and even heroic efforts to tease apart the molecular
architecture of cells and dissect the pathways by which molecular
actions lead to healthy physiology or sometimes to disease.And in
our own research we did the same.If molecular biology ever had a
heyday it was then.The intricate machinery of life was being dis-
assembled one molecule at a time; we marveled at each newly
discovered molecule like archaeologists pulling treasures from
King Tutankhamen’s long-buried tomb.What’s more,a few of the
molecular treasures were being formulated into life-prolonging
medicines by the promising new biotechnology industry.
Nevertheless, there was one guest lecture I attended during
this heady time that left me cold. I had been told that Maynard
Olson,a highly regarded geneticist then at Washington University
in Saint Louis,had helped to develop a powerful new method for
identifying genes associated with diseases and traits.But,instead of
speaking about this technology or the genes he had discovered,
Olson used our attention-filled hour to drone on about a scheme
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