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Bold Science: Seven Scientists Who Are Changing Our


World
Anton, Ted.
0716735121
9780716735120
9780585359946

cover

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Bold Science
Seven Scientists Who Are Changing Our World
Ted Anton

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Text design by Cambraia (Magalhes) Fernandes


Library of Congress Cataloging-in-Publication Data
Anton, Ted.
Bold science: seven scientists who are changing our world.
p. cm.
Includes index.
ISBN 0-7167-3512-1
1. Science. 2. ScientistBiography. I. Title
Q171.A614 2000
509.2'2dc21
[B]
99-059969
2000 by Ted Anton. All rights reserved.
No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a
phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or
private use, without written permission from the publisher.
Printed in the United States of America
First printing 2000
W. H. Freeman and Company
41 Madison Avenue, New York, NY 10010
Houndmills, Basingstoke RG21 6XS, England

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To the memory of Harry Anton,


who taught me to be bold

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Science could explain people, but it could not understand them.


E. M. Forster, Howard's End

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Contents
Acknowledgments

xi

Introduction

The Book of Life


Craig Venter's Shotgun Genomics

On the Road
Susan Greenfield and the Magus

31

Worlds in Profusion
Geoff Marcy's Planetary Astronomy

55

Dangerous Liaison
Polly Matzinger's Evolutionary Immunology

79

How Much Fun This Is


Saul Perlmutter and the Supernova Cosmology Project

103

The Art of the Woodpile


Gretchen Daily and Nature's Services

123

Drawn to Truth
Carl Woese and the Archaean Revolution

147

Conclusion
Intimate Science, Big Questions

169

Index

179

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Acknowledgments
In writing this book I conducted more than one hundred and fifty interviews with researchers all over the world. I
thank them all for taking time from their busy schedules to speak with me. Some who gave more than their share
of time include, certainly, Craig Venter, Susan Greenfield, Geoff Marcy, Polly Matzinger, Saul Perlmutter, and
Gretchen Daily. Without their patience and honesty, Bold Science could not have been written.
Many other researchers generously gave of their time, and I acknowledge their critical assistance. I want to give
special thanks to those who went out of their way to assist me, including Ralph Wolfe, Tony Kerlavage, Aravinda
Chakravarti, David Smith, Carl Pennypacker, David Stahl, Gary Olsen, Ron Schwartz, Paul Butler, Steve Emmett,
Ephraim Fuchs, Debra Fischer, Peter Atkins, Steve Maran, Susan Barns, Kevin Apps, Robert Kirshner, Paul
Erhlich, and Alexei Filippenko.
I want to acknowledge especially a group of research assistants, including Aimee LaBrie, Belinda Gordon,
Stephanie Duschene, and the guiding insights of Eileen Murphy. The University Research Council at DePaul
University provided a Summer Research Grant and two Competitive Research Grants during the course of my
work. When I began my travels in Seattle, Kim and Patrick McRoberts generously provided a roof and good
company. Without that assistance this book could not have been written.
Several friends and colleagues read the manuscript in various stages of completion, including James Fairhall, Stan
Cohn, Liam Heneghan, and Jonathan Gross. I thank my DePaul University students who read and commented on
chapters.I benefitted enormously from their insight. Other readers who brought critical wisdom include Ann
Finkbeiner, Rick McCourt, and Deborah Blum.

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In thanking all these people I hasten to add that any mistakes in this book, in its observations and conclusions, are
distinctly my own.
At W. H. Freeman and Company I thank especially Michelle Julet, whose excitement and wisdom helped guide
this project, as well as wise and patient project editor Georgia Lee Hadler, designer Cambraia (Magalhes)
Fernandes, production coordinator Julia De Rosa, and excellent copy editor Andrew Kudlacik. Thanks too to my
agent Ellen Levine, who guided the business of making the book. A most special appreciation goes to my wife
Maja, who once again bore with me in the travel, long hours, and rollercoaster of writing.
This is a book about the loopy, fast action of thought. A researcher lingers after a lecture, runs into a stranger, or
sticks to an idea beyond what anyone else thinks is worthwhile. No matter how many interviews an author
conducts, retracing this creative process is a difficult proposition. Retelling the incidents that lead to a new insight,
combining many minds working together in painful failures and childlike obsession, is a little like naming the
unnameable. Recollections may vary. In relying on personal interviews to reconstruct some events or thought
processes, I checked what I was told against the statements of other participants and published sources. In the case
of one minor figure, I have indicated a name change to protect an individual's privacy.
What follows is my attempt to capture the excitement of new ideas transforming our time. The best one hopes for
is a fair representation, marked by metaphor and approximation, for a process that remains at its heart a mystery.

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Introduction
It seemed an endless plane flight from Tokyo to Washington, D.C. It was 1990, before the time of air phones and
laptop computers. For hours over the blackness of the Pacific, thirty-four-year-old researcher J. Craig Venter was
alone with his thoughts.
Memories from his Japan tour slowly wafted into his mind, He enjoyed giving talks on his conventional research
into the biochemistry of the mind, but what had really captivated him and his Japanese audience was the infant
study of genomics, the complete genetic program in the cell's nucleus. For years the Holy Grail of unlocking how
DNA operated, how it shaped identity and life and death, had riveted the attention of science, But despite all the
advances in the study of DNA, identifying even a single human gene took many years. The problem seemed
staggering: humans had perhaps one hundred thousand genes, a fly had more than ten thousand. The solution of
life's ultimate mysteries lay, it seemed, far in the future.
Even though Venter was a successful researcher, with many articles to his credit, he was dissatisfied. As a young
man growing up in California, where he struggled in school and preferred surfing and sailing, he had disliked
science. He discovered his calling in an unlikely place, in Vietnam, where he learned at a field hospital and
orphanage that life was unimaginably fragile and that no time should be wasted on anything less than central.
Though he was bald now and to all appearances a typical government researcher, he still had the thick arms and
drive of a competitive swimmer, one who felt angry about science's inertia. He peopled his lab with younger
assistants who, like him, shared an obsession with attacking first principles and the biggest questions.
Many of the Japanese scientists he met shared his speculative passion, and he enjoyed the give-and-take of
discussion with them. The

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problem in genetics had to be solved by breaking through to the entire human genetic sequence, all at once,
complete. To do that, he and others felt, one needed robots attached to computers, capable of analyzing thousands
of DNA sequences at once. The trouble was that leaders in the field saw no chance of making this happen soon. If
it was the solution, they said, it lay in the distant future with tremendous government spending. The abyss between
knowing the rules of the game and actually playing it yawned like the night outside Venter's plane window.
But something nagged at Venter. As he sat on the plane a part of his mind kept returning to the body's own
mechanisms. The body knew how to find the right DNA automatically, and if he could tap into that, perhaps using
very ordinary tools and connecting them in a new way, he could unlock the genetic code on a huge scale. It would
transform the field by making the big picture visible. Then anything was possiblethe keys to heredity, disease, the
shimmering structure and meaning of life.
We live in a unique time in the practice of science. With the end of the Cold War's easy money and big-budget
projects, many researchers began, out of necessity, using common technologies across disciplines. In this small,
creative, complex-systems exploration, researchers found they could unlock the fundamental processes of life,
thought, and the universe on a new scale. By combining the cheap tools of personal computers, remote sensors, the
Internet, and basic artificial-intelligence systems, they began to open an exhilarating and frightening era in
genetics, ecosystems, cosmology, and neuroscience.
Many books have discussed this dawning century of scientific triumphof engineered life, accelerated intelligence,
and new mastery of nature's complex systems. But no one has explained how this new millennium will happen.
How do certain individuals at a certain moment in history lead their fields in a transformation of scale?
This book profiles seven researchers of opportunistic science in key fields that are changing our world. Their
scrappy creative approach results partly from a new fusion of unrelated fields, with professionals and amateurs
collaborating around the world instantly, much as the Renaissance grew from Europe's discovery of travel, of
Arabic, Oriental and classical knowledge, and from the breakdown of social hierarchy. In part, this new fluidity
arises from the intense expansion of science media and interaction with the public. Most of these scientists are, in
some measure, stars. They take advantage of the Web, newspapers,

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magazines, television, radio, and books to invite the public to join them on the edge of history.
While past generations have produced beautiful theoriesof DNA's double helix, quantum theory, and the nature of
the universe and our psychesthey were generally unable to apply these ideas. Darwin's theory of evolution gave us
a dynamic model of life's history. Einstein's theory of relativity and the discovery of the expanding universe
opened our perspective. The conception of these theories depended on simplifying evidence from the real world.
The most fundamental problem remained: to master how such theories operate in a real universe of chance and
accident, the world that science calls complex systems. We knew from Darwin that species evolve, for example,
but how does this happen at the cellular or molecular level? Today we are unlocking such questions.
What happened in the twentieth century, though, was the development of gigantic science, ever more specialized
and bureaucratic, an approach that gave us triumphs like the atom bomb, high-energy physics, and moon landings.
We began to think of all science as big science, when the truth was the most important discoveries have often been
made by fairly small, sometimes amateur, even accidental projects. Since the time of Galileo science has usually
been loopy, interdisciplinary, and humanistic as, well, any art form. And just as the telescope helped Galileo
transform a vision of the cosmos to a larger scale, today the combination of computer, remote-sensing, and other
technologies offers smaller, innovative teams the opportunity to transform our vision. Seeing and understanding the
big picture of evolving organisms, climate systems, or star systems, has become for the first time a real possibility.
A book telling the story of these seven research teams in such vastly different fields is itself a kind of experiment.
Since I was a child I have always been fascinated by big questions, and by the minds that turned on them. Where
does thought come from? How did the universe begin? How does knowledge advance? I loved books that showed
a life of the mind in all its detective-thriller suspense. As I began pursuing the question of who was leading this
creative science, I lurked at conferences like something of a spy, talking to experts, field leaders, and funding
agencies, I learned that the ''three great themes in science in the twentieth centurythe atom, the computer, and the
gene," to quote National Institutes of Health Director Harold Varmus, were combining to "revolutionize the
twenty-first century," in the words of physicist Michio Kaku. But how, I wanted to know, and who? The names of

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creative researchers were not difficult to uncover. The same names, I found, cropped up time and again at
conferences and in articles.
I have chosen to focus on fields in the midst of change, on the verge, possibly, of a new way of understanding the
world. These fields include genetics, with the imminent completion of the entire human genetic identity potentially
"the single greatest scientific advance ever made," according to National Institutes of Health's Francis Collins.
Craig Venter developed of many of the techniques driving the gene revolution. Neuroscience too is a field in the
midst of chaotic change. The first woman ever to head England's venerable Royal Institution, Susan Greenfield,
embodies in many ways the current controversies in the study of the mind. Ecosystems and astronomyour world
and othersare also exploding into new scales of vision. The extra-solar planet-finder Geoffrey Marcy and the
supernova explorer Saul Perlmutter have fundamentally altered our understanding of outer space. On our planet,
the new link of economics and ecology led conservation biologist Gretchen Daily to explore a multidisciplinary
view of nature. In health, many have written of a coming era of extended life through engineered body parts and
new disease treatments, toward which immunologist Polly Matzinger is linking classical thought and cutting-edge
medicine. Finally in biology, the discovery of new forms of life, perhaps vaster than all the life we knew until now,
has caused an upheaval largely as a result of the pioneering work of evolutionist Carl Woese.
This book proposes that the inner workings of discovery hold clues to the meaning of our time. In their mistakes
and victories, cooperation and cheating, patience and ruthlessness, hype and insights, these people hint at a new
moment in science, when small teams could think in a much bigger way than ever before. I found them remarkably
open to discussing their thoughts on the question of coming fundamental shifts in science, If they had not been so
willing, I could not have gone very far. I thank them for taking time from their packed schedules to talk with me.
This book is written to uncover their habits of mind in the suspense of unfolding ideas. I choose seven
representative stories, placing them side by side as a kind of comparative biography or narrative in a grand search
for the keys to today's creativity. I picked these researchers because they demonstrate different methods and
approaches to the architecture of change. Not all of them use computers, nor are all of them completely accepted in
their fields.
Many belong to newer or less known institutions, or come from private companies. Some are deeply controversial.
A few are making

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fortunes. Portions of their work are questionable and contradictory, as some put themselves out on the edge of
what science is or should be. They are significant because their research is helping to shape the policies and
discoveries of our time. Picking them, however, I leave others out. Ultimately, this book's goal is not to provide a
comprehensive view of the present, but to uncover the manners of thought shaping the future.
Just as the last century saw a shift in economic power based on the machine-tool technologies of oil and electricity,
today we are seeing a similar shift based on the synergy of the new machine tools of computers and biotechnology.
These innovations in connections, of ways of orchestrating the world and seeing it whole, are changing what
science can see. This change in what science can see amounts to a change in what scientists are. This collection
explores how certain personalities came to the front of their fields at a pivotal moment. Thinking about them
reveals, ultimately, the mystery of the human mind and the universe it apprehends.

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The Book of Life:


Craig Venter's Shotgun Genomics
1
It was hot. The Quonset hut hospital smelled of dust, antiseptic, and diesel fuel. The sun glared. Helicopters raised
an hourly din. Outside Danang, in Vietnam, Craig Venter evaluated the wounded as they were flown in. Twentyone years old, he decided who was to be saved and who was too far gone to waste precious resources on. Dodging
rockets every night, he hated his job and yet was morbidly fascinated by it. A poor student who preferred surfing to
his California high school, he stumbled into wartime triage by scoring highest of thirty thousand Navy service
people on an intelligence test.
He saw first-hand life's incredible caprice. One boy, for instance, died of a small bullet wound to the head. There
was barely a nick. Venter helped with the autopsy, studying the boy's brain to see what had happened. The bullet
had left barely a trace, he told a reporter later, with no other apparent damage. He was staggered that this would be
enough to kill someone. Another time Venter saw a soldier, barely eighteen, with multiple wounds, who had lost
most of his intestines. Doctors gave him a few hours. In the hospital, though, he lived for weeks, talking about how
he wanted to get home and play basketball. How was it, Venter wondered, that one boy lived "without any guts,
out of sheer determination" while another, with barely a nick, died?
After he returned to his parents' home in suburban California, Venter kept asking himself big naive questions. Why
did he live while

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all around him friends were dying? He signed up for community college in San Mateo with the idea of becoming a
doctor in the Third World. He had seen villages bombed, children orphaned, and thousands of young men die.
Gradually the idea of becoming a doctor came to be no longer enough. "What," he was asking himself, "is the
mechanism of life in the first place?"
Thirty-three years later Craig Venter was still asking those questions as he stood on the brink of making one of the
single biggest contributions ever to understanding human identity. At a new biotechnology company called Celera,
sitting in farmland a commuter train ride north of Washington, D.C., Venter was closing in on a first index ever of
the three billion bits of information in the entire human genetic code. Cited as one of the three most influential
scientists of our century by The Times of London, he was beating a $3 billion U.S. government joint effort with a
consortium of university laboratories to open a new chapter in the history of biology.
Most of us are aware of the genomics revolution, if not of the term. A gene is a single unit of life, a genome the
entire set of genes in an organism. A short time ago, it took years to sequence, or analyze, a single human gene.
But to be understood, genes cannot be studied individually. With one hundred thousand genes in a human, each
with thousands of letters, genes operate together with other tissues, complex biochemical interactions, the
environment, and chance, to make us what we are. To understand truly about disease, aging, identity, life, and
death, one must know the whole genome. Obtaining that knowledge required multiple disciplines, automated
techniques, creative financing, and a capacity to gamble.
The headlines surrounding the human genome, however, hint at the deeper shift in thoughtfrom the reductionist to
the inclusive, the cell to the whole organism, the gene to the genome. Like the eighteenth-century furor over
surgery, the genomics revolution is an upheaval that extends far beyond science, complete with the passions, anger,
violence, hyperbole, ethical conflicts, and financial bonanzas engendered by any sudden leap in human capability.
"This is an exponential explosion," says Venter. "A hundred years from now we'll see this as a pivotal moment in
human history."
At the center of the maelstrom, Venter was sitting in a comfortable office with two of his standard poodlesCricket,
asleep on the floor, and Shadow, edging me off his spot on the armchair by the fireplaceon the winter day I first
visited him at his first research institute in 1997. Attached to his office was that of his wife, fellow geneticist Claire
Fraser. He had decorated his walls with a framed astrology read-

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ing from the day he first published an organism's whole genetic imprint, a note from a Renaissance weekend with
Bill and Hillary Clinton, and a model of his yacht, the Sorcerer. Driven and combative, he ran an informal lab. He
let his assistants play rock and roll, loud. In the middle of a thought, he leapt to the window to point out a winter
rainbow outside. He searched on the conference desk for a snapshot of a Caribbean double rainbow taken from the
Sorcerer.
He was rich. At the center of controversy, Venter was launching rockets while he transformed the practice of
biology. That a researcher could become wealthy from the study of human genes was a hallmark of a new science
of complex systems changing our lives and the way science happens.
All this had been accomplished against almost impossible odds. After struggling in high school and serving his
tour of duty in Vietnam, Venter "started his education from scratch," he recalled. "Things were not handed to me
on a silver platter." He began as an obscure biologist who was turned down for an initial government grant in
genetics.
The most visible sign of the genomics revolution is Venter's race with the $3 billion joint government and
university effort called the Human Genome Project, which plans to spell out the human genetic code by 2003.
This, it could be said, is the traditional science approach. Venter planned to get it done by 2000. This, it could also
be said, is one form of a new way of doing science.
Why did this scientific quest become a race, and how did Craig Venter, an outsider to traditional science, become
its leader? This revolution was made by linking tools. Venter's automated DNA sequencers and computer assembly
programs together form an unlikely Renaissance magician's kit that promises to transform culture. They are already
changing the way we live. To understand how, we must begin in an Austrian monastery.
2
Johann Gregor Mendel (1822 1884) was a monk fascinated by weather, sunspots, time travel, and plant hybrids. He
bred pea plants to discover underlying patterns in life, as Enlightenment scientists had uncovered them in the
heavens. Over many years in Brno, in Moravia, he grew thousands of short-stem and long-stem plants, then

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crossed them. He catalogued some twenty-eight thousand different results. From this chaos he intuited laws
dictated by a living information carrier.
In 1944 physicist Erwin Schrdinger followed with the book What Is Life? His book suggested that "genes,"
Mendel's information carriers, were not merely symbolic but physical entities that operate according to laws as
discoverable as those of the new quantum physics Schrdinger helped pioneer. The book inspired Francis Crick, an
English researcher taking too long to get his Ph.D., and a brash, frizzy-haired young American, James Watson. In
Cambridge, they began seeking Schrdinger's and Mendel's "information carrier," not in proteins, where most
contemporaries were looking, but in the acids, or DNA, of the cell nucleus.
Crick and Watson built a model in their lab basement. Racing with the famous Linus Pauling in California, they
were missing a key piece of information. Stymied, Watson was allowed to sneak a look at the London researcher
Rosalind Franklin's slides from her x-ray crystallography (a technology that uses crystals as refractors of x-rays) of
DNA. Franklin could not yet interpret her eerily beautiful "x" images, but Watson and Crick suspected exactly
what they showed: DNA came in the form of a double helix. For that they won the Nobel Prize.
About the time Watson and Crick were drinking glasses of champagne in Stockholm, Craig Venter was growing up
in the San Francisco suburb of San Mateo. Born in 1946, he had two brothers and a sister. His father was an
accountant, his mother a painter. Venter loved to surf, but struggled in high school because he could not remember
facts, This hurt him in the rote education of the 1950s, making him suspicious of those who wielded facts like
weapons. "I cannot visualize," he later told New York Times reporter Lisa Belkin. "When I close my eyes, I can't
picture my wife. I can't picture my boat."
After high school Venter headed for Newport Beach, where he worked at night to support his surfing during the
day. He could sense the momentum of the water ten waves in advance, intuiting the best ones to ride. With the
Army about to draft him in 1968, he enlisted in the Navy so he could compete on its swim team. While he was in
training, however, President Lyndon Johnson announced the war's escalation and the end of military athletic teams.
Venter took the service's IQ test, scored highest, he claimed, and signed up to be a hospital corpsman.
Combat experience, along with work at a Vietnamese orphanage, drove him to a turning point. "I survived a year
where a lot of people

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around me didn't. Seeing villages bombed, treating children, I saw the best and worst of medicine. I saw the deaths
of thousands of people my age or younger," he says. "Coming out of there I felt I had to do something."
Returning to California, he enrolled at a junior college. In a required composition course during his first term,
Venter developed a friendship with his English teacher, Bruce Cameron. Cameron was new to teaching and felt he
lacked insight into his well-to-do students, many of whom were experimenting with drugs. He noticed Venter
though, who had taken to wearing Ben Franklin eyeglasses, for his "intelligence, wit, and insecurity due to his poor
academic performance in high school." In the 1960s spirit, Cameron offered to let his students devise their own
assignments if his were not "congenial to their style of learning." Venter was the only one to take up the offer, He
wrote a series of stories about the failing health of a chainsmoking English teacher. The teacher was diagnosed
with lung cancer. "Craig knew the grisliness of surgery," Cameron recalled, smiling, of his days as a teacher and
smoker. "When the patient was on the operating table, he described what the lungs looked like, everything." The
two became lifelong friends.
Venter began stopping by to talk with Cameron about a book he was reading, The Double Helix by James Watson.
In his coming-of-age story, Watson opened to the world the loopy and unlikely manner in which the DNA
breakthrough happened. Years later Venter would complain that he had no mentors; what he did in science was too
original. If there was one, he said, it was the Watson of The Double Helix. Combining brashness and brilliance,
with a strong hint of self-promotion, the story foretold some of the controversies of Venter's own future.
Watson and Crick had ended their short paper announcing their discovery in 1953 with the thought that DNA
"suggests a possible copying mechanism" for genes. At the time Venter was reading the book, others around the
world were feverishly building biochemical tools to explore how the "copying mechanism" works. Venter left San
Mateo after a year. He headed for the University of California at San Diego, where he earned a B.A. in
biochemistry and went on for a Ph.D. in physiology and pharmacology. What he did not know was that he would
soon join the DNA race, and morehe would completely change its rules, bringing him head up against its hero.

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3
In graduate school Venter was told there were no questions left in biology; it would be hard to find a doctoral
thesis worth writing about. He finished his B.A. and then a Ph.D. in a record short span of six years. Selected to
join the lab of Nobel Prize-winning biochemist Nathan Kaplan, he studied heart cells and their adrenalin receptors
"Those cells kept beating even if you put them all alone in a glass dish. They just never stopped. I had to figure out
why."
From Kaplan he learned how to think outside the assumptions in a field. Kaplan's lab connected him to the very
beginning of the study of cellular biology. "Kaplan was trained by Fritz Albert Lipmann, who was trained by Otto
Meyerhof, who invented the field," Venter recalled. But Kaplan was no longer as successful as he had been. "He
had two hundred people working for him. He'd have a dozen good ideas a day, but the lab lacked the organization
to act on them." From the beginning, Venter saw how wonderful ideas will falter under poor management.
With his doctorate, Venter was offered a professorship and his own lab immediately at the State University of New
York at Buffalo. This was an unusual leap; he skipped the usual postdoctoral tutelage under a "master." The leap
made it easier to retain his creativity, he felt, to trust his intuition. Driven by some sense of being an outsider, by
what he had experienced in his life, Venter worked at his heart cells, switching eventually to brain cells.
The years passed in Buffalo. He applied for promotion and tenure and was approved. He published papers and gave
talks. He sailed. He moved gradually from adrenalin receptors in the heart to the brain, as he became fascinated
with the chemistry of thought itself. He took a second position as associate chief cancer research scientist in
Roswell Park, Maryland, and applied for a position in neuroscience at the great national laboratory there.
Before he left Buffalo, Venter met graduate student Claire Fraser. When she graduated with her doctorate, one of
his competitors offered her a postdoctoral position. Venter asked her to marry him. "She agreed on the condition I
never use that as a recruiting device again," he says.
He landed a prestigious position as Section Chief in Neurology at the National Institutes of Health. At NIH, he
became increasingly interested in the early rumblings of gene research. The code controlling adrenalin receptors of
course had to lie in DNA. Young assistants

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gravitated to his intuition and supportive, challenging style, his "savvy for knowing the next big idea," says Tony
Kerlavage, who joined him in 1985. Venter encouraged the good-natured Kerlavage to play with the new personal
computers just being marketed by Apple. Then the first scientific paper came out announcing that a brain receptor
gene had been sequenced, "We made a dramatic switch," recalled Kerlavage, "and set to learning molecular
biology."
The quest to read the sequence of DNA had long drawn the attention of the most adventurous and interdisciplinary
minds. One pioneer was England's Fred Sanger, who made the first big step in molecular genetics ten years before
Venter became interested. In 1977 Fred Sanger developed a technique in which DNA strands (which can run up to
six feet long) could be snipped, amplified, and analyzed in a gel. Although he had won a Nobel Prize years earlier
for his work with proteins, Sanger earned another for this early tool for linking genetics, molecular biology, and
biochemistry. He made the first gene map of a simple virus, containing nine genes in all. But a virus is merely a
snippet of DNA. Subsequent improvements brought ways of identifying genes in many microscopic forms of life,
not just viruses, but it was still a painstaking, expensive, and Sysiphean task, taking many years and hundreds of
thousands of dollars to isolate a single gene.
The cell's genetic machinery was daunting, combining beauty and expediency. The double helix of DNA is a
spiraling ladder of four different organic bases. Each of the thousands or millions of ladder rungs is made up of a
pair of chemically linked bases. Long series of these "base pairs" make up a single gene. Series of genes in turn
make up the forty-six chromosomes (twenty-three each from mother and father) in the nucleus of a human cell.
The genes transfer their hereditary information to the rest of the body via messenger ribonucleic acid (mRNA), a
worker molecule that transcribes as a copy of the sequence of bases in a gene; the mRNA then migrates to one of
the cell's ribosomes, or protein factories, with its message. There the message is read to create the proteins that will
make our characteristic bodies and mindsour blue or brown eyes, nasty or sweet temperaments, our penchants for
opera or heavy metal, our capacity to dream or surf. The race was on to unlock the secrets of DNA.
The people who began building the tools to pursue the Grail of gene sequences were business partners, rivals, and
colleagues who often had moved over from other fields. They included the eccentric

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researcher Kary Mullis, at the University of California at San Diego, who manufactured his own hallucinogens and
thought of his technique for reproducing genes in a test tube while driving with his girlfriend late at night, Mullis
coined the term ''democratic science" for the small-team approach his technique made possible. Others began
identifying genes for diseases, hereditary flaws, longevity. "I realized that this was where the real golden era was
happening," recalled the leather-jacketed, motorcycling University of Michigan physician-by-training Francis
Collins, who went on to identify the gene for cystic fibrosis and then, in 1993, to direct the government's Human
Genome Research Institute. "I was completely blown away."
4
In deciding to pursue genes in the mid-1980s, Craig Venter faced several basic problems: first of all, his milliondollar lab was supposed to be studying neurology only, and second, isolating genes was still a slow, laborious
human process that required a great deal of squinting to read enormous reams of data. Analyzing a single gene, one
that produces a protein that serves as an adrenalin receptor in the brain, was taking him more than ten frustrating
years. "I vowed never again," he says.
The trouble was, life had very little to do with single genes. You can never say that Cain slew Abel because of a
faulty gene. To understand behavior, you need to trace the complex biochemical pathways by which a gene might
translate into a trait. To do that you needed the entire genetic sequence, the precise order of the rungs of the DNA
ladder. It was the advantage of a top-priced topographical chart over a pocket world atlas for hiking through a
dense uninhabited forest. You needed more than a map, you needed the sequence. "A genome 'map' just has crude
landmarks, like towns," said Tony Kerlavage. "A 'sequence' has every address on every street of every city."
DNA is powerful software. If one could ever fashion a DNA computer, it could pack a hundred trillion times the
information stored in a current computer, according to physicist Michio Kaku. The task of separating the bits of
such a potent code seemed impossible. Then

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Venter stumbled on a Nature article by Leroy Hood, who was at Caltech at the time. Hood had devised a way of
attaching a different-colored fluorescent dye to each of the four DNA bases, with a laser beam to track them, a first
step toward a machine that could decode genes rapidly and automatically.
Venter took it upon himself to meet Hood, whose paper changed the landscape overnight. In 1987 Congress
approved the first budget for the Human Genome Project, the seemingly quixotic quest to sequence all one hundred
thousand human genes, under the directorship of none other than James D. Watson himself. That year, Venter got
his lab named as NIH's test site for a prototype automated DNA sequencer. He connected with the high-tech firm
Applied Biosystems and assigned lab assistant Jeannine Gocayne to make the prototype work. Venter sensed he
had found a key in Hood's sequencer, one that Hood was not fully utilizing. Critics would accuse Venter of never
doing original work himself. Hood for instance, envisioned the machine, and Gocayne became one of the best
researchers pursuing automated analysis. But it was Venter who then put the two ideas together, parts into whole,
theory into application. "I'm more the orchestra conductor," he said, but he was also envisioning the music.
At NIH, Venter now gained support from James Watson himself. Watson saw in the DNA sequencer a way to
harness the "copying mechanism" of life. But the path was difficult. Neither of them was overstating the humble
machine's capability. The DNA sequencer was merely a tool.
5
Pursuing the sequence of thousands of genes, researchers faced two seemingly impassable roadblocks. The first was
that only 5 30 percent of the human genome is ever expressed ("turned on") in a cell. These are the genes that do
the actual work of lifegiving us our health or disease, adapting to changes in our environment. They make a liver
cell a liver cell, a kidney a kidney, an ovary an ovary. The other 70 95 percent of hereditary material is therefore, it
appears, attic trash left over perhaps from long extinct species. No one knows the purpose of the enormously long

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strings of dormant, or junk, DNA stashed in the chromosomes like old tourist key rings of the Sears Tower in a
forgotten drawer. But the cell is a cosmic pack rat; it throws little away save for what is dangerous. We are, in
short, walking museums.
While this junk DNA offered tantalizing possibilitieslike being able to trace the history of evolution from primal
cell to humanit makes gene indexing almost as formidable as combing a meadow for four-leaf clovers. To get to
the expressed genes one had to waste months or years wading through an overwhelming amount of junk.
By the time Venter left for a lecture trip to Japan in 1990, other researchers had suggested using the body's own
devices to discard the so-called junk DNA. Several American and Japanese scientists talked about using RNA, the
worker molecule, as a natural sifter of the wheat from the chaff. Messenger RNA transcribed only expressed genes,
automatically ignoring the inactive. It was clonable, manipulable, and as industrious as the beating heart cells
Venter had studied twenty years earlier.
On his long plane flight home Venter thought and thought about the problem. For hours over the blackness of the
Pacific, he let his mind wander. DNA is like a book. If the whole genome is the entire book, messenger RNA
represents the abridged version, a Cliff's Notes of important passages. With the help of Sanger's techniques, he
mused, one could turn the single-stranded RNA back into DNA, into a double-stranded synthetic molecule called
complementary DNA (cDNA). Indeed, several labs were already searching cDNA collections, or "libraries," that
had been created from mRNAs extracted from particular tissues or cultured cells. They were looking for specific
genes that had already been related to some illness or trait, spending months and months sifting and analyzing. The
trouble was, that each time you went looking for a gene, you had to sift through the same libraries again and again.
Why not sequence all the different cDNA molecules at once, organizing them into one master index? You could
build a library that a future researcher need simply consult, rather than search everything again and again.
This idea, making use of shotgun cDNA cloning (so named because the cloned colonies looked like grapeshot), had
the potential to be a "totally new discovery process," said Tony Kerlavage. "It's not driven by looking for a single
thing, but by asking, well, what's here? Let the organism tell you," It was a eureka moment. Venter could barely
contain himself waiting for the plane to land at Dulles.

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But when he got to his NIH lab at Bethesda, almost everyone told him he was wrong. Another team had tried the
shotgun approach in muscle tissue. They had found only a few genes for proteinsactin and myosin. All he would
end up with, they said, would be the same old same old genes for routine tissue.
One person who listened, though, was a young beginning postdoc from North Carolina, Mark Adams. They held
one ace; because Venter was in neurology they were searching in brain tissue, not muscle. Venter assigned Adams
to partly sequence brain cDNA from available libraries and analyze the results with their new computer program.
Almost immediately they began coming up with new genes. Brains, it turned out, contained a glut of new genes.
They switched to the testis. It too, perhaps not surprisingly, was rich in new genes. They were discovering
hundreds. Excited, Adams and Venter met with Kerlavage to name their revolutionary technique. Suddenly, it
seemed, the whole genome was in reach. One could complete in weeks what took other researchers whole lifetimes.
Kerlavage suggested the term "expressed sequence tags" for the short sequences of bases that they were using to
uniquely index the cDNA molecules without reading their entire sequences. The name stuck.
The idea of expressed sequence tags (ESTs) marked the first breakthrough, but a second advance a few years later
was even more important in Venter's minddevising the computer program to reassemble the pieces of information
they generated. The EST libraries were the genetic equivalent of scissoring up the Sunday New York Times into
hundreds of thousands of tiny fragments. The challenge of reassembling them properly meant devising a program
that would look for partial sequences that were repeated in different cDNAs, which implied that they overlapped. It
was a gargantuan task.
The genomics revolution was about to be launched. Soon they would be on the leading edge of a new complexsystems science they had simply been observing and critiquing. They now saw the capability of seeing the world
whole, and eventually of manipulating it. The revolution came not from expensive technologies, but rather from
creative connections among existing toolsautomated analysis, personal computer, and, eventually, the Internet. But
a professional crisis had to happen first.

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6
The more success Venter had, the more his star rose. He was appointed to head a multidisciplinary team to explore
the uses of the shotgun method. Convinced he had the technology in his lab to nail a good portion of the human
genome, he applied for some $10 million for EST research. He was turned down, he was told, mainly because he
was asking for a huge chunk of what was then a humble Human Genome Project budget. Venter felt, however, that
Watson had undercut him. Venter's speedier approach, he suspected, might cause Congress to question the much
larger amount of money it was spending on the more conventional slower method of sequencing.
Venter continued, locating by June 1991 some 347 human genes and, within a year, 2,375 more. By the end of
1992 he had found another 4,448. The rest of the world had only uncovered about 2,000. As he achieved greater
mastery, however, his relations with other researchers cooled. Venter's shotgun technique was obvious, they said; it
was simply a new relationship, not a new discovery. "He got lucky," complained one researcher. "Anyone could've
done it." Other criticisms were not so muted.
Such objections would be a common theme for almost every one of Venter's innovations; others had seen it, but he
was the first to make it work. Meanwhile, he was identifying twenty-five new genes every day. In 1991, under the
urging of the NIH Technology Transfer Director Reid Adler, the NIH sought to patent hundreds of the ESTs
Venter had located. The irony of what followed was that Venter never applied for the patent for himself; in fact, he
and Mark Adams opposed the idea at first. "NIH sought the patent. But everyone was out to get me." Venter said.
"It was a very difficult time."
Patents of new techniques in government-funded research are common, indeed critical for the free flow of ideas
(why tell others about your technique if you do not get the credit for it?). Insulin is commercially available today
because the technique for isolating the human gene that encodes it was licensed and used to implant the gene in
pigs. The furor over patenting of genes like insulin, though, had been building. Critics asked: How could you
patent a human gene? How could it belong to someone? The response is that patenters invest in developing
sophisticated techniques that isolate, artificially extract, or enhance the gene. Expressed sequence tags, the NIH
argued, were a technique that enabled researchers to generate and use genetic information.

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The patenting of ESTs, though, made researchers even angrier. ESTs were not whole genes, just snippets. How
could you patent a snippet of something whose uses you did not yet know? Researchers exploded, "The idea of
having to buy information that so many of us need, its not science," said one. In cover stories from The Wall Street
Journal to The New York Times, their anger focused on Venter. By now his combative reputation amongst them
exceeded his own combativeness, which was considerable. Years later, in fact, the American Association of
Inventors was considering him for its annual award for innovation. They could not believe it when he told them he
did not have a single patent to his name.
The worst part was that the NIH's James Watson, famous with reporters for his cutting wit, led the assault. Watson
called the idea of EST patents "sheer lunacy." Watson's assistant claimed, "any monkey could do it!" Days later,
The New York Times reported, a scientist in Venter's lab came to work dressed in a monkey suit. Friends took a
photograph of him reading a book by Watson.
The upheaval transformed careers. Responding to the general problem of ethics in patenting genes, James Watson
decided to devote a significant percentage of the Human Genome Project budget to a study of morals, inviting
science critics to participate. Shortly thereafter, he left the Human Genome Project altogether, returning to his post
as Director of the innovative Cold Spring Harbor Laboratory. Turned down by NIH, Venter was pursuing ESTs on
his own. But still, he felt like a target. The assault got so bad he contemplated leaving science completely.
Others had glimpsed the future, however, and saw the money it could generate. A Wall Street venture capitalist,
Wallace Steinberg, had been following Venter's work and understood its enormous implications. With the new leap
in capability, one could search efficiently for genes to cure cancer, resist AIDS, delay the aging process, or select
for intelligence and athletic prowess. Researchers could seek unknown genes in isolated populationsNew Guinea
tribes, Amish familiesthat offered unimagined qualities of health and resistance, qualities potentially worth a
fortune. While Venter had often received business offers, Steinberg had something completely different in mind, in
scope and independence. In 1990 he called to offer a onetime-only deal: $70 million of his clients' money and
Venter's own institute. All Venter had to do was enter into an agreement with a former Nobel nominee, William
Haseltine. Venter would do the research science, and Haseltine's company, Human Genome Sciences (HGS),

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would figure out the profitable applications. Wallace Steinberg would handle the selling.
At the time, Venter and Claire Fraser sat and talked it over. The stakes were enormous. But the possibilities
dwarfed what you could imagine. "The complete genome revolution has not yet begun. We're still in the early
phases of it," said Venter,
The revolution was scientific, of course, but it also signaled a tidal shift in the management of science and of the
vast fortunes that would soon be pouring into even obscure molecular biology research. Venter signed on with
Steinberg and Human Genome Sciences, Genetic research would never be the same.
7
Venter founded The Institute for Genomic Research (TIGR) in an abandoned industrial park on July 6, 1992. He
eventually moved to a sleek building a few miles down the road, where he installed the brass tiger outside the
upperstory office he shared with Claire Fraser. At TIGR Venter challenged computer scientist Granger Sutton to
devise software to reassemble the bits and pieces of cDNA by patterns of recognition. They dubbed the program
the TIGR Assembler. Combined with the EST method, it offered the possibility of seeing the big picture, the whole
genome of an organism.
Venter did not want to sever his ties to academic science. In 1993 he met Hamilton Smith of Johns Hopkins
University, who had won a Nobel Prize for his work on restriction enzymes, at a bioethics meeting in Spain. Smith
was sitting in the hotel bar when Venter introduced himself. "I knew him by reputation," the avuncular Smith
recalled, "which wasn't very good at the time."
As they began talking about how they had gotten into science, though, they realized they both had been changed by
their time in the military. Smith had worked at a naval dispensary and hospital during the Second World War.
Their talk continued over dinner. "We hit it off so well, Craig asked if I wanted to be on the advisory council for
TIGR," Smith recalled. At their first board meeting Smith suggested that they sequence the entire genome of
Haemophilus influenzae, a bacterium that

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causes a number of ailments, including ear infections and even meningitis. Smith was an expert on Haemophilus.
No one had sequenced a whole genome before; it would be a tremendous leap if they could do it. Understanding
this one might mean new medical treatments. "But we took it strictly as a test case for the shotgun method," said
Smith.
Smith encouraged Venter to apply for money from the NIH. "Given his reputation, it was strictly in their face," he
recalled, laughing." "E. coli was taking them ten years, and costing $10 to $12 million dollars." TIGR said that they
could do their bacterium, with its two million base pairs, for half a million.
Waiting for word on their application, they began working on their own, "Craig doesn't accept 'it can't be done' as
an answer," said Mark Adams. That independence was vital, because in January 1994, the NIH turned them down.
The rejection letter noted that "to date there is no successful example assembling two megabases of finished
sequence and no indication that this can be achieved by the TIGR group."
Venter framed the letter and used it to drive his staff. The small team stayed up late at night working to complete
the first free-standing organism's whole genome. They were already nearly 90 percent done. When they emerged in
May, Venter announced the feat at a microbiology conference: the first complete script of a living organism ever;
with Hamilton Smith, they displayed the full color-coded map of the H. influenzae genome. The accomplishment
was so revolutionary that Science put Haemophilus influenzae on its cover. Later TIGR published in Nature its
colorful sequence of thirty-five thousand human genes.
The imagery was fascinating: the genomes looked like cubist colored wheels with radiating spokes of tags and
numbers. They were soon joined by more genome sequences, including those of the pathogens that cause syphilis
and Lyme disease. TIGR's published papers became for a time the most quoted in all of science. The images
seemed to suggest infinitely rich possibilities in their comparison, The human genome looked remarkably similar to
that of most every other living creature, past and presentmice and worms, bacteria and algae, mastodons and
jellyfish. Our different races have virtually the same genome. Aborigines and Eskimos, Kikuyu and Caucasians,
Muslims and Jewswe have far less diversity than, say, fruit flies. The evolutionary messages were profound.
The more he looked at the pictures, however, framed like art in the entrance hall of TIGR, the more Venter felt
impatient and frustrated. It became apparent that genome sequences themselves would offer no

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intuitive breakthrough. "I looked at this thing we had tried so hard to get," Venter said, "and I expected to see some
magical answer there."
The grumbling about the lucrative finances of his research institute increased. Venter was growing dissatisfied with
the manner in which Human Genome Sciences delayed findings to see if there were profitable applications. The
original agreement had been that HGS would delay only a small percentage of data, and only by six months. "I
found out," Venter told Discover's James Shreeve, "they lied."
Haseltine responded that no delays in publishing data were ever invoked. Whatever the truth was, the relationship
between the men was deteriorating. Wanting once and for all to separate himself from the charges of opportunism,
and also ready to cash out, in the spring of 1995 Venter sold his 10 percent share of HGS stock for $9 million. It
seemed a staggering gain, but when the stock tripled over the following five years it showed, Venter maintained,
that his interest was always in the science, not the money.
The controversies, however, were just beginning. TIGR had launched a spectacular trend. Soon other
pharmaceutical companies ("big pharma") were gambling huge sums on research into genetic treatments for
obesity, disease, and psychological disorders. "Venter's paradigm shift wasn't scientific," said Maynard Olson, "It
was managerial.'' Overnight, biochemistry conferences shifted from sleepy gatherings to high-stakes conclaves of
scientists, patent attorneys, investors, and hustlers. In back hallways paper-givers in rumpled suits pitched new
techniques. With growing investment came a new culture of secrecy. "There's a fear that labs aren't publishing,"
Stanford researcher David Cox told Science. "It could become a nightmare."
In Salt Lake City in 1994, for instance, Myriad Genetics, Eli Lilly, and the Lilly subsidiary Hybritech paid $14
million for commercial rights to develop the discovery of the BRCA1 gene, linked to breast cancer. In 1995 in
California, the biotechnology firm Amgen paid $20 million for the exclusive right to develop a gene thought to
regulate obesity. In 1997 Roche signed a deal to develop a small company's gene and the associated protein linked
to inflammation. Today, not only insulin but many drugs are available because of patented human genes. "There
was a huge shift. Where once the pharmaceutical companies were five to ten years behind the scientific
community," Venter said, "now they're five to ten years ahead."
Defenders of the trend pointed to the last century, when formidable scientists like Thomas Edison (who cofounded
the preeminent journal Science as a way of speeding both information and investment)

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and George Westinghouse turned their prowess into control over new corporations like General Electric and
Westinghouse. The risks new investigators take are enormous, and financial support would be impossible without
the hope of a payoff. Detractors, however, noted that Edison and Westinghouse waited until their products were
marketed to earn their money.
There was a limit even at TIGR. Arguments broke out every time Venter sought to publish a new finding and
Haseltine told him to wait to see if there was a commercial application. Still, there was a lighter side. When Venter
published an obscure research article suggesting that humans probably had only sixty thousand genes, fewer than
the one hundred thousand often cited in the science literature, he received an angry telephone call. "What do you
mean sixty thousand?" Wallace Steinberg's voice screamed over the receiver. "I just sold Smith Kline Beecham a
hundred thousand!"
What Venter wanted most of all was to pursue the big questions. In June 1996 with its third organism sequence, for
instance, TIGR entered into a profound controversy in fundamental biology. They published a sequence of a
strange organism called Methanococcus jannaschii, which survived in thermal vents around volcanoes deep in the
ocean. The organism was vitally important because it represented a new form of life, theorized by University of
Illinois researcher Carl Woese, called archaea, the kind of life form astronomers thought would survive on other
planets and moons. But more important, archaea illustrated Woese's controversial theory about the evolution of life,
which could alter the structure of biology itself.
Woese's idea was attacked, but sequencing the genome helped prove his point. The fact fact that 56 percent of the
Methanococcus genes were completely unknown to biology hinted at "how little we know about life," said
University of California molecular biologist David Smith. The world became a far more mysterious place.
For pure science research, the genomics challenge became to marry Mendel's classical genetics with the new
molecular genomics, theory with application. In 1996 at a Renaissance weekend with the Clintons, Venter talked of
the incredible potential of genomics for the most basic science of biology. "You could track the entire history of
life on Earth, theoretically, by looking at all the nonexpressed genes." The journey had come full circle from its
beginning in an Austrian monastery a century and a half ago.
As his business experience with Human Genome Sciences grew more and more uncomfortable, Venter watched as
other researchers

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took off after fundamental biology. Researchers began trying to harness many of the complex functions of the
body's mechanismsits antibody production, cell signaling, techniques of rejuvenation and repair. The applications
touch fields from germ warfare to extraterrestrial life, from cystic fibrosis to depression. But no single thinker, it
seemed, had triggered one leap as Watson and Crick had. "Genomics is rather more like the interstate highway
system," said Maynard Olson. "Using existing technologies, a system was created that changed the culture."
Finally, for Venter, the relation with HGS became beyond repair. Wallace Steinberg died in 1995, and in 1997
TIGR split with HGS. In so doing, Venter claimed he lost $38 million in future profits. The next day TIGR
published all its genomic data on its website.
8
Venter of course was not the only player in the genomics revolution. As with the computer industry, the first phase
of genomics was the entrepreneurial tool-making phase, and small, creative, and interdisciplinary labs like Venter's
drove it. When a General Electric researcher visited Maynard Olson's early laboratory in St. Louis, for instance, he
was shocked. Twenty times more money and manpower, he said, went into a new refrigerator model than into the
early work on genomes. "There were no published tables," Olson said, of the reluctance of engineers to help him
design his machines. "No specifications. We had to invent it as we went."
Researchers sold their art as goal-driven and cheaper than much of the big-ticket research of the Cold War. They
resembled impresarios of the gilded agemen like Edison and Insull, who built the infrastructure of the electric age
and also enriched themselves. When the first wires were strung, no one could envision the computers they would
power. Maynard Olson looked a little like comedian Dana Carvey's character Garth, and he functioned as all
around gadfly in the field of hype. He punctured pie-in-the-sky claims about exotic technologies. Ironically, the
biggest naysayers of the genomics revolution were the traditional geneticists. "The idea is not to get lost," Olson
reminded a San Francisco audience of microbiologists in 1997. "You have to make this an interdisciplinary
science."

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That the revolution occurred in such a short span of time with initially slack funding was remarkable. It was driven
not by technology, but by people making new connections. The people pursuing gene sequences picked on the
nascent technologies to connect biology and information science. By the early 1990s, for instance, Stephen Fodor,
a Santa Clara, California, programmer bored with chemistry, formed the biotechnology company Affymetrix and
began trying to link superconductors and DNA in DNA chips. The Affymetrix GeneChip may change the way we
attack disease by allowing scientists to create enormously complex models that track mutations. Yet within a few
years, younger researchers were creating less expensive do-it-yourself microarrays in much the same way that the
Linux free software challenged Microsoft Windows.
The Internet became the medium of choice for the publication of hugely complex genomes. ("We can't publish
genomes on paper any more," says Tony Kerlavage. "They're too long.") You can find parts of the human genome
at the website for the National Human Genome Research Institute. Funding agencies, seeing the results of work by
people like Venter and Fodor, began actively promoting genomics' multidisciplinary systems approach. At the end
of 1997 Vice President Al Gore held up the nickel-size Affymetrix device at a White House briefing, declaring it
medicine's "most exciting new tool.''
The new paradigm of life became information. "Biology is no longer a life science, but an information science,"
announced Leroy Hood, by then at the University of Washington, in 1997. It seemed by then that Venter was
entering a mature phase of yacht racing and public speaking, much like James Watson himself. Then came Celera.
By early 1998 TIGR was pursuing all sorts of possibilities. In the spring, with air strikes again pounding Iraq,
Venter and a pair of other researchers met with President Clinton and the cabinet to discuss genomic approaches to
defense against biowarfare. We could build battlefield DNA sequencers, Venter promised. We could find the
organism and know exactly what it was in a matter of seconds, giving us the key to combatting it. Much as Galileo
sold his telescope to governments as a military tool and to philanthropists as a tool of art, so too Venter proved a
good showman as he returned to his battlefield inspiration for science.
He had his eye on old friend who was coming out with a new, incredibly efficient DNA sequencer. Mike
Hunkapiller and Venter had been rivals in the late 1980s, in the days of the first sequencer.

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Hunkapiller had been a postdoc with Leroy Hood, the one who actually developed Hood's laboratory model into a
working sequencer. Now a vice president of Perkin Elmer, he was bringing out a new model sequencer, the API
3700, orders of magnitude faster than the 370s Venter used. By the spring of 1998 he and Venter were closing on a
deal that would once again transform conventional genomics researchlinking the medical giant Perkin Elmer and
Venter's expertise to go after the human genome for a fraction of the cost of the government effort. They would
build a whole new institute up the road and call it Celera after the Latin celer, meaning swift.
The pace was increasing so fast that even some of Venter's closest colleagues felt it. Venter's secretary Lynn
Holland kept the balance on the flying projects. "I'll get a call when he's on the plane and it'll be, uh oh, Craig has
another idea."
Not wanting to repeat the mistakes of the past, Venter and Hunkapiller called in NIH's Francis Collins, who had
taken over the government Human Genome Project from James Watson. On May 8, 1998, Venter called Collins to
meet the next day with them at Dulles Airport. There, the two moved fast. They told Collins they were forming a
joint venture to use Perkin Elmer's ABI 3700 machines to pursue the human genome. They thought they would
succeed in a maximum of two yearsand did not want to upset the government project, which was projecting a
seven-year deadline.
Collins was a little nonplussed. But three days later, a press conference was called to announce the formation of
Celera to pursue the human genome in competition with the government's consortium of eight universities and the
Sanger Center in England. Collins appeared on the panel, looking uncomfortable. "I don't think these two efforts
will compete," he said gamely. "I think there's room for both approaches."
Indeed many critics were claiming that Venter's approach was too fast, too haphazard, to get an accurate genome.
Venter countered that Celera's genome, made with what was described as a "HAL-size computer," would be even
more accurate than the government version. "When you hear arguments that what we are doing here can't work,"
he said, "it's just because it's beyond the imagination for most scientists . . . dealing with tens of millions of pieces
of DNA at a time and having a computer solve all these massive calculations."
Celera was an incredible leap in capability, and the human genome was only part of a grander plan to sequence a
thousand major species in the next decade, laying the foundation of an electronic information

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empire. By now the world had heard much of such leaps. Venter sailed his yacht Sorcerer in the Newport to
Bermuda yacht race, the sail sporting an image of his face wearing a wizard hat. He went on a whirlwind speaking
tour, beginning with an invitation from an old nemesis, James Watson. Speaking at Cold Spring Harbor, Venter
was criticized for the "quick and dirty" approach Celera was taking. "Far from us being the evil empire, we as a
corporation are providing them with the tools and reagents," he responded to The New York Times, "to try to
compete with us."
As work progressed, he traveled to address the Nobel committee in Stockholm. He traveled by rented jet to
countless trade shows, talking about the new era of the genome and arranging potential deals. He met with Smith
Kline Beecham, at an exposition called Bio '98 in Manhattan. Someone asked him to dance in a tophat with two
girls on stage, and he refused. "There're some things I will not do." By October, Celera announced yet another link,
this with Compaq computers, which would provide the hardware for the human genome search.
The burden of Celera's speed fell once again on his group. Tony Kerlavage helped coordinate the efforts of three
hundred ABI 3700 machines. He gave a talk at a chaos-inspired session at the American Association for the
Advancement of Science (AAAS) conference in January 1999, in Anaheim. The session's title was "Managing
Massive Data Sets in Mathematics, Science, and Technology." When I saw Kerlavage there, he spoke of the frantic
pace. "It's . . . been interesting," he said of his past few months, We chatted in the bookstore, where I bought gifts
for my nine-and eleven-year-old children. "Here," he said, handing me a book. ''This is a good one." The title was
Perspectives on Genetic Patenting: Science, Religion, and Industry in Dialogue.
Later, in 1999, Celera collaborated with several universities in completing the genome of the fruit fly. Anticipating
the historic day when the entire human genome was completed, Venter planned to make a "consensus human
genome" available to the public on a DVD disk, and to give academics a cut-rate subscription for the full database.
The commercial rate for access, however, was pegged at $5 to $10 million a year. The uncertainty in the planned
subscription fee suggested the risk of genome investment.When the government group finally finishes, by contrast,
its database will be free.
For all the hoopla, the genome projects were mainly a start to the much more complicated ongoing work of
understanding how genes operate. "We're attempting to understand the essentials of life," said Venter. "It's like
coming into a dark room and turning on a light so you can see."

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9
Genetics has advanced at such a dizzying pace, with new genes being identified almost daily, that it belongs to
myth: as science it thrives as metaphor, as a spur to see the world whole. The pursuit of gene function will
overtake gene indexing as today's race. Predicting or treating disease with genes is unbelievably difficult. So many
factors are involved, so many mutations, chemicals, processes, and fail-safes, that we are barely beginning to see
some of the pathways by which disease develops. Researchers are using their new tools to shift away from looking
for single genes responsible for disease (like cystic fibrosis or sickle-cell anemia) to identifying genes that
contribute along with other factors to more complex diseases (like Alzheimer's, diabetes, and heart disease).
Complex diseases are not caused simply by single genes, but by a combination of genes and environment.
What does the genomics revolution mean? If we could learn how a body uses its DNA library to attack an
unknown disease, for instance, the savings in drug manufacturing would be tremendous. It means perhaps a cure
for cancer or AIDS and unassailable solutions to unsolved crimes. It promises new understanding of the evolution
and essence of life on Earth and elsewhere in the cosmos. Much of our so-called "junk" DNA is not junk, for
instance. It carries a history of lost genes in much the same way a writer keeps basement files or an overcrammed
closet where rediscovered ideas can spur fortunate inventions, species improvement, evolution. Like its pursuers,
DNA is a consummate multidisciplinarian and opportunist, a plagiarist of good ideas.
Most of all, the current upheaval means a fundamental change in the philosophical assumptions of genetics. Once
thought to be a dry process governed by Mendel's laws, today inheritance is seen to be incredibly fluida universe
governed by accident and will. Unlocking the whole genome, researchers now see life as a million chemical
pathways through a labyrinth of tendencies, statistical probabilities, and sheer inventiveness. "Having the human
genome sequence will force a fundamental change in the way we think about every other biological problem," says
Mark Adams.
A new interdisciplinary approach has given rise to a new fundamental approach to science, with most of its
innovations coming from researchers outside the envelope of their fields. Venter's contribution was to see the
connections. He did not invent automated DNA sequencing, Leroy Hood did. He did not make it work, Jeannine
Gocayne

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did. He did not create ESTs, Mark Adams did. He did not build the TIGR Assembler, Granger Sutton did. He did
not build the library to sequence the first full genome, H. influenzae, Hamilton Smith did. He did not create the
incredible computer flowcharts for assembling the human genome at Celera, Tony Kerlavage did.
What Venter did was something none of these people could do: he envisioned the relations among computers,
sequencers, established libraries, and unknown organisms to glimpse each next wave before it happened. The steps
that he took would be repeated countless times, in many fields of science almost simultaneously. They included his
interdisciplinary approach, bringing in biologists like Adams, computer scientists like Sutton, and technicians like
Jeannine Gocayne. Perhaps Venter's inability to see a mental picture is complemented by greater creativity in
intuiting precisely the technological links that will work. He described this skill as intuition. "I just saw in a flash
that the breakthrough was in linking the machine to the computer, applying remote sensing to basic artificial
intelligence." Exponentially upping the power, he achieved a synergy that made it possible to take on the whole
genome itself. It could be simply that he was the first to imagine such a possibility. Like the medical corpsman
working with what he had in a Vietnam battlefield, he had taken the most pragmatic approachmixing existing
technologies and pushing to get the most out of what he had.
The investor Wallace Steinberg considered himself an intuitive thinker, and he likened Venter's intuition to having
a dozen computers working on a single problem in parallel. Venter had many of the other clichd elements of
intuitionvision, trust in his ideas, the ability to foresee which wave to ride. But most of all he would not let
colleagues let go of a dream. Like each of the researchers to follow in this book, Venter pushed science to a
process-oriented outlook.
For all of the controversy, Venter was always open to the public, willing to take his time to answer questions about
his work. He read widely, thinking about the larger implications of the gene revolution, and convened a special
ethics panel when it seemed the possibility for engineering life forms was worth pursuing. He relished books like E.
O. Wilson's Consilience, on the future link of science and the humanities, and Anne Sayre's Rosalind Franklin and
DNA, about the forgotten woman in the gene quest. He raced his yacht,whose largest sail he decorated with a huge
drawing of himself in a wizard outfit. His was an American story, and he often repeated the idea that the support
for his innovation was only possible in this country.

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Venter also learned how to manage a laboratory from the mistakes he had seen Nathan Kaplan make. He put
together the backing that allowed him to go outside the National Institutes of Health and the National Science
Foundation, essentially bureaucratic institutions bound by political agendas. It could be that this trick of managing
without losing the upstart edge is his greatest accomplishment, a requisite of complex-systems science.
By contrast, maintained Cameron, "Watson and Crick's achievement was simple. By the early 1950s someone was
going to get the double helix. Linus Pauling was close. What Craig did is far bigger. No one was close to pulling
together the backing and intuition to pull off shotgun sequencing. No one had imagined it."
What is the relation between such imagination and a personality? When the history of twentieth-century biology is
written, it could well be that the humble connection of small and large, theory and practice, computers and
biomimicry, harnessing RNA to do a researcher's work, will stand out as a much larger and symbolic innovation
than the discovery of the double helix itself.
The new paradigm of biology, rightly or wrongly, has become information. In time, this will change. But for now,
DNA is pure thought, good and bad ideas locked inside a microscopic cell. "There's nobody who's been in this spot
before," said Venter. "It's the opposite of the end of science. It's really the beginning."

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On the Road:
Susan Greenfield and the Magus
1
In 1974 a lanky twenty-two-year-old senior named Susan Greenfield was filling out yet another graduate
application in her room in Oxford, England. The Velvet Underground blared from the record player and cigarette
smoke hung in the air. Applications to the Royal College of Art, a design school, and a physics program lay strewn
about her room. Greenfield had long legs and bright dark eyes with a glint of urgency. A flop of long blond hair
hung to her shoulders. She was about to graduate and was trying to decide what to do with her life. It was driving
her crazy.
She had begun at Oxford as a philosophy major four years earlier, but quickly despaired of the field's endless
deconstruction of language. She switched to psychology, but soon felt frustrated by the interminable experiments
into rat reflexes. She wanted to pursue big, fundamental questions. She was obsessively energetic and stubborn. "I
was really prancing around, applying for lots of barmy courses, not really having much direction," she said. Talking
with her tutor, experimental psychologist Jane Mellanby, she kept coming back to her interest in the human mind.
Why did we act the way we did? What was the basis of thought? "Well," Mellanby leaned back, thinking.
"Wouldn't it be a hoot to be a neuroscientist?"
Mellanby recommended her to Oxford researcher David Smith. At the time, neuroscience was in its infancy;
Oxford had one of the few doctoral programs in Great Britain. Science, it seemed, could

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more easily peer outward to the most distant stars than look inward to the organ that created its own laws.
Smith was working in his biochemistry laboratory when Susan Greenfield interrupted him. The room was small
and drab, the hallway outside painted a dull green. She told him she was fed up with psychologists and
philosophers treating the brain as a black box. She wanted to unlock the processes that made it work. She glanced
at his worktable. "What are you doing?" she asked.
"I'm working on acetylcholinesterase," Smith said, in his precise Oxford accent.
"What's that?" she asked.
"It's an enzyme that breaks down acetylcholine." He watched her. "Do you know what that is?"
"I think so," she said, "It's released from nerves."
"Do you know what the reaction is?"
"I don't have any chemistry."
Smith paused. The whole point of neuroscience was to analyze the chemistry underlying human thought. But
though he looked like a typical researcher in his wirerim glasses and his portly white labcoat, he could appreciate
the quirky bit. He was willing to listen as Susan Greenfield took a deep breath and began. Neuroscience had
contented itself for too long with minor questions, she said, while the strict boundary between it and the humanities
held research back from the really important thing, consciousness itself. She talked fast, jumping from idea to idea.
"But she had a vision," he recalled years later. "She knew what she had been taught wasn't the right way, and she
wanted to find the new way."
Smith decided to send her to the department chair, Sir William Paton, a distinguished, slightly balding, pipesmoking archetypal Oxford don. One of the last great scholars of science, he read Plato and asked tough,
penetrating questions. After grilling Greenfield, he called on Smith. "What do you think," he asked, "about Susan
Greenfield?"
"I don't know, what do you think about Susan Greenfield?"
She was a huge risk is what he thought. But Oxford made a point of encouraging people to take such risks. The
system required students to talk to faculty from other disciplines. Around each Oxford college dinner table there sat
teachers from the sciences and humanities, taking the time to talk and listen and confront each other. Taking a risk
on the quirky or eccentric, the difficult, the lost, was what Oxford was all about. So, they decided to take a risk. On
Susan Greenfield.
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Until recently science said very little about the mystery of consciousness, even though philosophers had filled
libraries with books on it, and even though science could say a great deal about the three-pound, moist and soft
organ that creates it. Research into the brain had been going on for hundreds of years, fascinating especially those
with a creative bent. Craig Venter began as a neuroscientist. Later, the young physicist Saul Perlmutter haunted
neuroscience conferences. But the self presented such a deeply complex problem, beginning with the fact that
every human self was different, that serious researchers ultimately gave up on it as unknowable.
Perhaps for that reason, brain research's early breakthroughs had come by accident. In the late nineteenth century
the researcher Nicolai Golgi, for instance, accidentally dropped a slice of a human brain in a jar of sulfur nitrate.
Discovering the lump two weeks later, he found thousands of tiny branches stained blackish by the nitrate. He
called them "neurones." The field of neuroscience was born in mishap.
In the following eighty years a host of findings, accidental and planned, began to unlock the electrochemical
pathways of neurons. As researchers pursued the intricate details of brain wiring and activity, they learned that, if a
supercomputer tried to replicate all the functions of the brain, it would require enough electricity to heat and light
one hundred thousand homes. But as for the big picture, the question of exactly what a thought is, the mind
remained as much a black box as it did for Renaissance magicians, who called thoughts "phantasms" and attempted
to manipulate them through alchemy, astrology, and a diet of leaves or honey.
Consciousness was the ultimate mystery. What is the imagination? How does it work? The ancients believed
thoughts were images. Religions placed intelligence in the mind of God. Literary modernists tried to recreate it in
"stream of consciousness" passages. Everyone mused about the organ that made us dream or do poorly in school,
win a Nobel Prize or embezzle a bank. But no one in science attacked the question of consciousness. It was too
big, too slippery, too . . . dangerous. Taking it on would require a new kind of research involving many disciplines
linking complex electrophysiological and biochemical systems with the abyss of the emotions and even
individuality, trying to chart the chaos of whim and logic. By the middle of the 1990s, however, the time was right.
Science exploded with big theories and bigger egos, attempting to do just that.

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2
At first glance Susan Greenfield might seem an unlikely candidate for a leader of the first wave of a new complexsystems science. Her father's father came to England from a Polish shtetl, ran a chocolate factory in London's East
End, made and lost a fortune. Her mother ran away from an upper-class boarding school to become a chorus girl.
Her father had a "spirit," she said. "Things sort of fell out of the sky. He never really connected with the work ethic
too much." Her mother was Church of England, her father Jewish. Both were deeply curious, big talkers, and "very
carpe diem," she recalled.
Born in 1950 in London, Greenfield was older than her brother by thirteen years. Her mother was theatrical, given
to asking sweeping questions like: "Is the red I see the same as the red you see?" Her father was an electrician who
gave her a tinkerer's confidence in thinking a problem through. Growing up, Greenfield felt like an outsider. When
she wanted to wear a cross to school like her friends, her mother made her also wear a Star of David. They were
on the low end of middle class, and, though her school friends went on foreign holidays or were chauffeured home,
Greenfield found her solace in the county library. In high school, or A levels, in west London, she studied Latin
and ancient history. She took ancient Greek from a teacher named Veronica Lemon who became one of her early
mentors. Greenfield loved discussing questions like why do people go to war, why fall in love? She found her
answers in the classics. She devoured The Bacchae of Euripides, for instance, relishing its identification of our
animal and human natures with the forces of wine and bread. She also had to study mathematics, rigorously.
Energetic, passionate, flitting from subject to subject, she earned the lifelong nickname Springy from her friends.
"The training to seek motive came from the humanities," she later said of her education, "and steel-trap proof came
from mathematics."
She won a place to read classics at Oxford's St. Hilda's College, the last women's college at the school. Lying just
over Magdalen Bridge on the grassy bank of the River Cherwell, St. Hilda's had a strong literary tradition, with
author Barbara Pym as a tutor and students who became leading critics of postmodernism. Greenfield joined an
adventurous group of women who clamored in argument over cheap bottles of wine on the dormitory steps on
winter evenings. In the evening, students and faculty rode by on bicycles on the cobblestone streets as the smell of
dried leaves and dinners rose in the air. Their traditional black gowns billowed in the dark over hooded sweatshirts
and jeans.

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Finding philosophy at Oxford too linguistic, she approached Jane Mellanby about psychology. "My first impression
was of a very enthusiastic and extremely scatty person. She was speaking about all different things at once,"
recalled Mellanby. Mellanby got her started in a crash course in basic science. But Greenfield soon found
psychology to be wanting, too. "It was all rats pressing bars. It was very vague, with no hard science." She
nevertheless produced an impressive undergraduate thesis. "She brought together physiology, anatomy, and
behavior. It was very original," Mellanby recalls. ''People weren't doing that much then. It was bold and unusual."
Accepted into the doctoral program in neuroscience, Greenfield worked in a third-floor laboratory of the cramped
pharmacology unit. Her shared lab room smelled of formaldehyde and ashtrays, but it looked out on a lone,
beautiful copper beech tree. She had to work twice as hard as everyone else. She stayed up late at night, building a
two-pack-a-day smoking habit as she pored over organic and inorganic chemistry texts. A few people made fun of
her. An obnoxious Australian mocked her constantly. She borrowed the department's textbook on
acetylcholinesterase and spilled coffee all over it "much to every one's annoyance," recalled Smith. But she turned
her weakness into a strength. "I studied longer and I took a broader view than others," she says. "I wasn't afraid to
say, I don't understand." Her work paid off: by her second year, she applied for and won a general scholarship at
St. Hugh's College. She found the Australian and "gave him two fingers," she recalled.
As her parents had lived, so she followed her instincts, drawn by the unusual, the nonclassical, "the odd bits, like
an obscure enzyme secreted by a neuron," she said. Such interest in the "odd bits" had of course led to many
science breakthroughs in the past, like Bernoulli's seventeenth-century models of coiled wires that led indirectly to
the modern calculus of variations. She followed up on Smith's work on acetylcholinesterase, but "she knew how to
take it further," Smith observed.
The story of acetylcholinesterase offered a parable about a researcher following his instinct. The enzyme had been
discovered in 1914, when the English scientist Henry Dale could not figure out why the effect of the nerve
transmitter acetylcholine on the heart and other muscles was so short-lived. Rather than assume his experiment was
being done incorrectly, Dale had a flash of insight about the ways nerves signaled each other, one "which was
absolutely crucial if the signals were to be clear and unambiguousthe immediate destruction of the transmitter
chemical once the signal was sent," Greenfield later

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wrote. The neural transmitter acetylcholine was broken down by acetylcholinesterase. The story of Dale's faith in
his intuition made an important impression on Greenfield.
By the 1980s acetylcholinesterase was commonly regarded as a protein tightly bound to the cell membrane, whose
main function was simply to kill the messenger acetylcholine after its message was sent. The Nazis had used it to
develop the nerve gas sarin, which blocked acetylcholinesterase and thus paralyzed its victim. Before Greenfield
joined the group, however, Smith and an Australian colleague Ian Chubb found acetylcholinesterase in the cerebral
spinal fluid, suggesting that it must be released by neurons. "This was a heretical idea," Smith recalled. "Nerve
cells were not thought to release proteins at all, they were just thought to release the small neural transmitters," he
said. "The idea . . . was just completely way out."
Smith more or less stopped there. But Greenfield, with her background in experimental psychology and her passion
for odd bits, wanted to know what acetylcholinesterase could be doing so far from where acetylcholine played a
role. Greenfield's pursuit of the second function of acetylcholinesterase became her doctoral thesis project. She
decided to put electrodes into the brain of a rat to see if she could get neurons to release acetylcholinesterase
directly. To do so, she needed to learn electrophysiology, which brought her to the office of John Stein, a vision
expert at Magdalen College at Oxford. The son of a major industrialist, Stein became a close friend, mentor, and
fellow poetical seeker of truth, who stayed up late into the night talking with her about the artistry of science. He
taught her the delicate technique of implanting electrodes in a cell and sending a pulse, enabling the researcher to
measure the imbalance in ions by which nerve cells created an impulse. She never became very good at the
technique, but she learned well enough to show something startling: parts of the brain rich in the enzyme
acetylcholinesterase secreted a certain important protein in massive doses, and the other parts did not.
"It was innovative," Smith observed. "It seems obvious in retrospect, but it wasn't at the time." Greenfield had
shown the ability to branch out into a new field to deal with a problem that more senior researchers evaded. "She
could see very clearly the simple experiments to give the answers. Not the unnecessarily complex sophisticated
stuff," Smith said. "You have to have a knack for peering through all the fog and see exactly what needs to be
done. Susan had it." Yet she was only beginning.
"I want to prove this protein does something in the brain," she told Smith.

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"Why do think it does anything?" he said. For him it was enough of a surprise that nerve cells secrete proteins, but
to think that the protein had a larger function was extraordinary.
She thought acetylcholinesterase, the signal destroyer, held a crucial secret to brain function, to development and
disease. If it was crucial to development, she speculated, then it might also play a role in degeneration. She wanted
to explore its effects by squirting it directly on neurons and studying what happened. This would be extremely
difficult. To do it she needed to learn about the biochemistry of the nervous system almost from scratch. "I thought
she was crazy," Smith said, "but I didn't say so. I thought, if she wants to do it, let her do it."
After earning her doctorate in 1977, she produced two major publications demonstrating a link between
acetylcholinesterase and the brain signaler dopamine. Dopamine was central both to brain development in an infant
and to its degeneration in an elderly person, as well as to Parkinson's disease. She found reassurance for her focus
on the obscure enzyme, which few others were following, in a book by researcher Anne Silver that speculated that
acetylcholinestrase could be a key to brain signaling. Greenfield was not afraid to go out on the same limb.
"Surprisingly few scientists are happy to take risks," she recalled. "If you say anything about me, say that I took
risks."
She wanted to understand what was going on with acetylcholinesterase at the molecular level. "She had
imagination," observed John Stein. "That's not mere instinct, not mere intuition, that's how science works. Or good
science."
3
In a lecture hall at a neuroscience conference in Lausanne, Switzerland, Greenfield sat in the audience talking to
her graduate student about the recent discoveries about dendrites, the filament-like branches of neurons. She was
saying how important it would be to understand their chemistry when a small, white-haired man in front of her
turned to her. He was one of America's premier neuroscientists, the Colombian-born Rodolfo Llinas. At New York
University, Llinas was developing sophisticated

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electrochemical techniques to map the brain's activity. "Come to New York," he said to her.
She did come in 1981 and 1982, spending most of her money to live in a closet-size apartment near the United
Nations on Manhattan's East Side. She dodged derelicts on her way from the lab. She made few friends and very
little money. She learned a lot from Llinas, especially about paying attention to the way brain regions interacted. It
was a difficult and exhilarating time, a "rollercoaster," she later recalled. Watching Llinas, she saw a top researcher
willing to tackle big questions, making mistakes but moving on. "We worked very hard, and he made me think
very hard and then challenged what I thought," she recalled. It was a struggle, but she finally succeeded in
developing a new technique for measuring acetylcholinesterase on-line, in the brain, using a light-emitting
chemical.
For his part, Llinas was impressed. "She was very young, just beginning, but she was very smart. She knew her
biocemistry. And she was hell on wheels, always ready to try something new. I think she was very strongly
influenced by her time in the United States," he recalled. "She saw a different rhythm than in Europe where
science was more restrictive, and the emphasis was more on being a professional science accountant rather than a
true explorer. We discussed this a lot." Llinas took her to New York's exclusive Century Club, encouraging her to
practice science that took risks, even if "you end up with egg on your face. If you reach for the stars," he said,
"you'll never get lost."
By the end of her second fellowship, she had changed considerably. She owed a great deal to Llinas but also
chafed under his ego as she gained more confidence. She admired him yet found him "caught by his own vanity."
As the heat grew and new leaves uncurled in Washington Square Park, she began to focus her diverse interests. She
was coming, forcefully, into her own. Most important, by 1982, she was publishing, in Nature and other leading
journals, three major papers charting the important "novel" functions of acetylcholinesterase. With these, Susan
Greenfield made her debut.
When she returned to Oxford, Smith was amazed. "By God, she showed acetylcholinesterase affected nerve cells in
a sophisticated way. It caused ion channels to be opened, which may be a good thing in small amounts, but if you
have too much of it can kill the cell." She was showing what she had speculated to Stein, that if
acetylcholinesterase played a key role in development, then it also played a

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key role in degeneration. Greenfield saw it could be related to cell loss in Parkinson's disease, and could be
exploited for an improved therapy. At that time, though profit-driven research on Alzheimer's and Parkinson's was
growing intense, only two other, Latin American, researchers saw the intuitive connection she was making.
She now had her own small lab. As a postdoc she had contracts with no teaching obligations. She woke at 5:30
AM and worked until 11 PM, unless there was a party. To unwind she hung out at the King's Arms, with its rugby
scores on the walls of smoky, warrenlike rooms. It was the happiest time in her research life and the most
pressured: she had to build a track record fast.
Greenfield's push for an interdisciplinary approach to the prize of thought itself made her something of an outcast.
"I can't understand why you're not interested in consciousness," she told Smith, who was becoming more of a rival
than a mentor. "It's not that I'm not interested. It's just that it's so far away from understanding," he said.
In 1983 she was eating in a Chinese restaurant in Oxford with philosopher Susan Hurley, the wife of a friend.
Discussing their research problems, they saw they were climbing "the same hill, but from different directions."
They hatched an idea for a series of lectures on consciousness by the world's top names from the humanities and
sciences. Even though the series was not formally announced, it drew an overflow crowd every month. Famous
thinkersthe University of California's John Searle, Oxford's own Roger Penrose, and Llinas himselflectured and
allowed their papers to be collected in a book, Mindwaves, coedited by Greenfield. Published in 1985, it presaged
the coming interdisciplinary, complex-systems explosion in the field and in science generally. For Greenfield, it
meant more. "I had come full circle back to my original interest in philosophy and the Greeks. I'd spent all these
years out in the wilderness, doing nuts and bolts stuff, and I was now in my thirties and feeling much more
confident." Such a one-two combination, strong science and strong arts, small picture and big, marked her career
from then on.
With the book in hand Greenfield applied for a medical professorship at Lincoln College. It was a prestigious post,
like that of associate professor in the United States. "Oxford is peculiar in this regard," said senior chemist Peter
Atkins, who was on her review committee. "Everyone has two jobs herea university lectureship, and a role as tutor
in a college." Atkins was impressed by her rigor as a tutor. Here was someone who had been forced by ignorance
to work hard and expected her students to do the same. "She would take a tough line, which is what Lincoln's
medical students need," he said.

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Election to the post of professor put her in the elite of her profession. She was regarded with authority but still
wore her black leggings and high Parisian black boots, her striped tights and bright pink tops. Lincoln, with its
august tradition, was not used to someone like her. Howard Walter Florey had isolated and purified penicillin at
Lincoln College, winning a Nobel Prize and giving birth to the age of modern antibiotics. Her office sat at the top
of a rickety wooden staircase, attached to a private reading room that provided the day's newspapers, fresh fruit,
cheeses, and sherry. The professors' meals were prepared sumptuously. Greenfield chainsmoked, arguing over
dinner at high table with Atkins, a chemistry researcher whose texts had been translated into some twenty
languages. They sat with other faculty in the great oak dining room, built in 1427, which had a hole at the apex of
its vaulted wooden ceiling for the original cooking fires.
Atkins disliked her smoking and disagreed with Greenfield's theory of consciousness. She believed thought was
profoundly deeper than what a computer could ever do; he argued that machines one day would think better than
we did. In a computer, she replied, a switch is either on or off. In the brain, there are many differing grades of "on"
or "off." Neurons could be very receptive to electrochemical signals, slightly receptive, or not receptive at all.
Also, neurons in different locations of the brain were involved with the same thought processes. The reductive link
of region to functionthe left-brain, right-brain crazewas completely misguided. While some regions roughly
corresponded to certain functions, the mind was much more subtle than mappers let on. If the brain lost one
function, like sight in one eye, it rewired itself to use different regions and make up for the loss.
Consciousness was in her view generated by shifting groups of neurons firing by the tens of thousands rapidly all
over the brain. She called these neurons "assemblies" and urged her colleagues to look at how they differed in
different people. "For most scientists, subjectivity is the dirtiest word," she says. But you could say nothing
substantial about consciousness, she felt, until you could explain why everyone is so different.
At the same time, she pushed her work on acetylcholinesterase. "She was fighting a lone battle. People just thought
she was . . . a little crazy," Smith recalled of her ideas about the brain chemical. "She'd published in peer-reviewed
journals but for ages she couldn't get any funding from government sources, partly because people just," his voice
lowered to whisper, "couldn't really believe it."

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4
In the late 1980s, Oxford's way of life, at least its struggling pharmacology lab, was under assault. For a few years,
pharmacology was slated for removal altogether. Greenfield and Smith scrambled for money. Smith talked to
numerous corporations. The directors of Squibb, Britain's enormous pharmaceutical company, asked him to
organize a neuroscience symposium so they could understand the field's financial promise. Along with other
members of the department, Greenfield presented her research on Parkinson's and Alzheimer's diseases. "She was
the one," Smith told me, "who most impressed them."
Greenfield joined Smith in the negotiations with Squibb. There was an enormous potential drug market among
aging baby boomers, if her ideas were correct. Greenfield excelled at putting her ideas before an audience. "She
made connections no one else saw," Atkins said. "Albert Szent Gyrgyi, a Hungarian biochemist, once said science
consists of seeing what everyone has seen, but thinking what no one else has thought. That was her ability," In
1987, in exchange for intellectual property rights to the work of its neuroscientists, Squibb gave the Oxford
University Pharmacology Department twenty million pounds, the single largest university grant ever offered in
England.
Critics leapt on the grant, claiming it was a Faustian pact that traded off a scientist's objectivity for a sleek office.
"In fact, it takes so long for papers to be published," Smith responded, "that we have never had to delay publishing
a finding to suit Squibb." There was nothing new about patronage of science, and Oxford merely got on the
biotechnology bandwagon early.
"In the old days you didn't need very much money, you could be very scruffy and deliberately inefficient. I don't
think that works any more," Greenfield said. Galileo after all, father of modern science, called the moons of Jupiter
he discovered the "Medicean stars," after his wealthy benefactors.
The accelerating discoveries in the mind led the last years of the millennium just past to be dubbed the "decade of
the brain." Top researchers raged over consciousness, flinging enormous books and egos and theories back and
forth. On one side were the "physicalists," like Tufts University's Daniel Dennett, who thought of neuron
assemblies as "multiple drafts," MIT artificial intelligence expert Marvin Minsky, who was trying to build a
machine to think, and Rodolfo Llinas himself, who saw consciousness as simply one of many products

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of routine electrochemical impulses. On the other side were the "mysterians," including physicist Roger Penrose
and evolutionary psychologist Steven Pinker. They saw consciousness as more like tragic mystery, a sum greater
than the parts of neurons and physiochemistry, infinitely beyond the capability of a machine. The field was in
crisis. Bernard Baars, a psychologist at the Wright Institute, in Berkeley, California, compared the chaos to the
state of physics right before Newton.
Greenfield's theory of consciousness showed the quality of compromise, incorporating elements of many sides of
the debate. Unlike most of the giant tomes that were coming out, her book Journey to the Center of the Mind was
short, clear, fun, and sensible. Writing it as a form of relaxation on weekends, she moved easily past the de rigeur
disquisitions on Plato to stake out a middle ground. She saw the mind as something like one of the conferences she
chairedwith disparate concentric groups of neurons ignited at different times, their attentiveness or receptiveness
ebbing and flowing, forming changing assemblies. Beautiful electrochemical images of the brain showed fleeting
electric patches or networks of thousands of neuron branches firing as a mind listened to a single sentence. She
insisted that science pull apart the processes by which these neuron assemblies formed and changed. This made her
a mysterian, but more: an artist of complex systems, in the way that neurologist Oliver Sacks called for science to
restore the humanities to its core.
Reminding scientists that no two minds thought alike, she repeated her claim that consciousness research could
claim no victory until it said something about individual differences. Virtually no one in science had taken up this
overarching problem. For the mentally ill or hyperactive children, medicine was making seemingly great,
profitdriven strides with psychotropic drugs, but no one really understood why Ritalin, for example, worked
differently in different people, nor why the same neurotransmitters in healthy minds create our different
personalities. Science had reduced its vision too narrowly. Mind and emotion, rational and irrational, were as
inseparable for science as they were for Euripides. "A computer cannot think because a computer cannot feel," she
wrote. "The problem lies in the strategy that, by building machines that get better and better . . . the missing
ingredient, the feelings that are the essence of our awareness will somehow materialize. It is like adding ingredients
to an increasingly subtle and impressive curry, in the hope that the taste will spontaneously emerge as that of
Baked Alaska." This realization was the critical step into the new science of complex systems that she would
champion.

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At Lincoln College, Atkins's and Greenfield's arguments over consciousness had the "happy quality of being
without resolution and so they could continue every night," Atkins recalled. First they were seated next to each
other by chance, and "then by design." Meeting at meals solved the problem of going out on dates, and they
married in 1992, In a tiny village registry office, Atkins's daughter from a previous marriage served as best man.
Greenfield's younger brother, whose childhood fear she had explored in her book, was chief bridesmaid. Their
honeymoon was to take one day off. But Susan Greenfield did make one key concession: she agreed to stop
smoking.
5
In 1994 Greenfield appeared on a late-night television discussion "only one man and his dog would watch," she
says. Attractive, quick-witted, she caught the attention of the Royal Institution, England's premier body dedicated
to the communication of science to the public, dating back to 1799. Every December the Royal Institution chose a
leading scientist to conduct its televised "Christmas Lectures" for children. Past lecturers had forged an important
British tradition, featuring such personages as the Institution's founder Michael Faraday, the astronomer Carl
Sagan, and, more recently, Oxford naturalist Richard Dawkins. That year, Susan Greenfield became the first
woman in history to give the Royal Institution Christmas Lectures. She was a huge success.
That success led to a BBC series and a popular book on the brain. She had also begun writing a regular newspaper
column for The Independent, a task she would complete on "Sunday afternoons, as other people might take up
gardening," she said. "It helps me see the wood for the trees." In her column and public lectures around the
country, she weighed in on such topics as discrimination against women and the need to combine disciplines to
pursue consciousness. She was enthusiastic and inspiring in a "vivid, imaginative way," commented The Times. Her
communication with the public also energized her research, her graduate student Steve Emmett noticed, by forcing
her to slow down and simplify. In early years "she talked so fast people

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in the group could not keep up," he recalled. "Now she had to become more understandable. It was good for the
group."
In her articles and appearances she did not merely perform: she put a researcher's thought process on public display
as it unfolded. When she attended a conference session that made her disagree violently, her readers knew about it.
When an ugly rumor about a female scientist was passed to her, her readers knew of the offensiveness of rumor
mongering. When writing for TV made her realize the importance of metaphors in scientific theory, her audience
learned as she learned. When September rolled around and she thought of the time consumed by one-on-one
tutoring with undergraduates, her readers learned of the value of teaching in research. At the second annual
international conference on consciousness at the University of Arizona, in 1996, which drew over a thousand
delegates from a number of fields, Greenfield spoke on a panel that included Rodolfo Llinas, telling her readers
other revelation there as to why computers would never be as smart as humans: "No computer can laugh, or fall in
love, or feel remorse. . . . To me, emotions are the building blocks of human mentality." Writing as she lived, on
the go and out loud, was a high-wire act in the style of Beat writer Jack Kerouac. She pushed herself by purposely
going out on a limban uncomfortable place for most academics. "It helps me keep the wider perspective other
researchers lose," she explained.
Her public persona also left her exposed at times with what might seem foolish or imprecise ideas out in print on
the World Wide Web. "I love venture capitalists," she once said. "They're the swashbuckling pirates of our time."
At one website she was quoted as worrying about evildoers "hacking" into someone's consciousness. She
contributed ideas to a CD of songs to take to a desert island (her selections included I Heard It Through the
Grapevine, Brown Sugar, and Non, Je Ne Regriette Rien). This willingness to become a public pundit, and her
success with it, enraged some of her colleagues. "Scientists . . . are nervous about speaking on anything that is
outside of expertise, whereas media people stray across a wide range of subjects," she told The Times."When they
ask, I always say yes.''
She fed on the delight of curious minds that did not take themselves too seriously. While the audience for such fun,
and creative, mulling about science had been there as long as science, electronic outlets were exploding. Greenfield
suddenly became perfect for her historical moment. In 1989 her fellow English researcher Stephen Hawking,
having labored a long time to produce the beautiful if somewhat unintelligible book called A Brief History of Time,
saw it

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become a huge international bestseller. The audience for the Star Wars movies, the popularity of science books that
followed Hawking's, and the rise of cable television channels such as Discovery, and The Learning Channel, as
well as the World Wide Webwhere the 1996 Mars Pathfinder mission site quickly became the most viewed website
in historyall created opportunities for science pop stardom in the 1990s. Few had seen a scientist like Susan
Greenfield before.
Greenfield's public outreach not only raised science's profile in Great Britain, it also helped her to step back and
see the big picture. One rainy Sunday afternoon (British science owes a lot to a climate that encourages
introspection), she stretched out on a couch in her countryside home and jotted down the recently discovered
features of acetylcholinesteraseits role in Alzheimer's and Parkinson's diseases and fetal development, the fact that
in fetuses acetylcholinesterase had the same form it had in Alzheimer's patients but different from that in normal
mature adults, its perplexing way of popping up in different regions of the brain. In a series of elegant experiments
with rats, Greenfield had seen acetylcholinesterase disappear in the extracellular space around the substantia nigra,
a microscopic brain organ vital to movement. She knew, of course, that the chemical was related to muscle
function. UCLA researcher Nancy Wolf, writing about global neurons unlike neurons of any other area in the brain,
noted that global neurons shared one featurethey all contained acetylcholinesterase. Looking at her list, Greenfield
felt more than ever that the chemical was a key to brain health. The difference now, with her Oxford professorship,
media success, and a series of increasingly convincing results published in peer-reviewed journal articles (eight in
1995, seven each in 1996 and 1997), was that she could mobilize resources. As her audience widened, her research
intensified. Typically, she turned to another field to take the next step.
A year earlier she had approached her Oxford colleague, cell biologist David Vaux, for help in developing a
technique for tagging acetylcholinesterase with a fluorescent dye, to track it in the brain. As Vaux grew interested
in her work and in the new discipline of comparative genomics, Greenfield suggested they join forces. Using their
different fields of expertise, they began looking for the part of the acetylcholinesterase molecule responsible for its
unknown functions. Perhaps it could be responsible for the way Alzheimer's and Parkinson's diseases killed brain
cells.
With some modest early success, Greenfield talked to Sir Martin Wood, director of Oxford Instruments, a private
company that helped

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Oxford researchers develop ideas with the backing of venture capital. He and colleague David Thomas encouraged
her and Vaux to outline a draft patent application for a peptide they had begun isolating and suggested that they
form a company to go after Alzheimer's and Parkinson's. By December 1997, Wood had raised six hundred
thousand pounds for their research, Greenfield and Vaux's company, Synaptica, was born. She enjoyed the deal
making, excelling at its required clarity and bluster. "With venture capitalists, bankers in the city, captains of
industry, publishers, politicians also, one has to become multilingual. I found that very challenging."
Many other start-ups around the world were seeking a cure for Alzheimer's and Parkinson's diseases, anticipating
the profit from an aging baby-boomer generation. The difference was that Greenfield convinced her investors and
the public she could do it by focusing on acetylcholinesterase. The drug giant Pfizer had just launched a new
acetylcholinesterase inhibitor for Alzheimer's. "They have spent absolutely millions but they've not been novel in
any way," said her assistant Steve Emmett, one of the first people hired by Synaptica. "Tacrine was the standard
acetylcholinesterase inhibitor for Alzheimer's. They've modified the drug chemically and tried to make it better.
They're not trying to make a breakthrough whereas people like us are having to be intuitive and insightful. That's
the only way you're ever going to cure a disease."
Starting with a handful of people, Synaptica grew "like a hydra" said Vaux, bringing in young researchers from
multiple disciplineselectrophysiology, molecular biochemistry, genomics, animal behavior. They occupied part of
the third floor of the new pharmacology building, the labs close to each other to encourage communication. They
met weekly to discuss their workseeking molecular binding sites of acetylcholinesterase, synthesizing peptides and
testing themleading to the biggest question: What, exactly, could they market? "We start off a lab meeting from a
reductionist point of view and then build up to what we're really seeing with our animal models, and then we'll
build a hypothesis," said Steve Emmett. "It works really well." The reason was Greenfield's knack for finding the
right path. ''Springy's intuition is legendary," says Emmett.
Because of her breakneck pace, though, other researchers began to take pot shots. The University of London's
Michael Lacey challenged her findings on acetylcholinesterase. A few of her younger researchers and postdocs,
listening to her glowing talks, found Greenfield too idealistic and cheery about the depressed state of science in
England. She could be difficult, too, if you were not getting

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results. But she worked harder than most of her competitors. She was working by 5:30 AM and at the office by
7:30. "She doesn't leave until 7:30 at night, so she knows how long you're there," Emmett says. "She sets really
tight deadlines."
Squarely built, friendly, totally bald, Emmett benefited from her intuition. The son of a Royal Air Force engineer,
Emmett had been a bike racer until an accident sent him plunging into a ravine. His injuries healed, but he gave up
bicycling and, one month after the accident, at the age of twenty, lost all of his hair. He was reluctantly considering
dentistry as a career when he visited Greenfield at Oxford. Hearing of his interest in natural toxins, she asked if he
wanted to go to Uruguay for a year to work on snake toxins that could be used to manipulate acetylcholinesterase
(the toxins paralyze victims by eliminating acetylcholinesterase). She told him to think it over. A few months later
she phoned to say, well, he had one day to decide. On the phone he said yes, then hung up and panicked. "I studied
snakes for two weeks at the London Zoo and crammed from my Spanish phrase book on the plane," said Emmett of
the speedy turnaround. "It was fantastic."
It also, often, worked. Outside Montevideo, Emmett found a snake called the green mamba, which produces a toxin
called fasciculin. It binds to acetylcholinesterase "at a very special location, where most other inhibitors don't,"
enabling Synaptica to study the enzyme in greater detail. Emmett's success only added to the group's awe of
Greenfield's intuition. "If you can have divine inspiration," said Emmett, "I think she's probably got it."
6
Such inspiration, some said, was not all divine. Science is a quest for truth, and while "most sci entists are just
beavering away at the details," David Smith noted, "Susan is a visionary who galvanized a field. The risk, and she
and I have discussed this, is she's not very good on detail. That's not a criticism, that's just saying there're different
ways of doing science. That's why she has a good partnership with David Vaux at Synaptica."
Even within her group, Greenfield's bold approach sometimes raised a question when younger people presented
their results. "The science

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must be good," Steve Emmett noted, adding: "She's very enthusiastic to see positive results. It can be difficult
sometimes to make her appreciate control and negative data. When she does, she is quick enough on her feet to
take this data in the context of her global hypothesis."
Greenfield suggested that negative data, an experiment "not working," might be a clue to a deeper breakthrough if
one shed one's assumptions. Part of shedding one's assumptions was to bring many techniques from different
disciplines to big problems. "Because I'd come from an unusual background anyway," she said, "I hadn't been
brought up in one thing or another, I could range freely among these different disciplines, smashing through these
different barriers, not having the complete difinitive expertise in any one."
Like Craig Venter in genomics, Greenfield delighted in rattling traditional science. "The problem is that very few
people have any ideas," she said. "Safe is a word that goes much better with sex than science." Assailing one
researcher's caution in a journal, Greenfield lambasted his criticism that acetylcholinesterase's novelty might be due
to lab contamination. "Whilst one cannot prove that there is no contaminant . . . any more than we can prove that
there is not a tea pot orbiting Mars," she wrote for the staid journal Neurochemistry International, "at the very least
the scenario is unlikely." ("I loved that one,'' said Emmett.) She criticized New York University's Joseph LeDoux,
whose book The Emotional Brain described emotions in rats. "The most interesting thing about emotions is that
you're feeling them," she says. "If you're not feeling then that's only reflex and that's all he's got." She dressed in
mini-skirts with high heeled Parisian boots, and looked good in them, as if to demonstrate to younger women they
need not worry so much about acceptance. "I tell them to take risks. What is the big problem if you are wrong?"
Once her secretary gave her pink hair dye as a joke. Afterward, it would not wash out, so she walked around with
pink-streaked hair for days.
Around her, the arguments about consciousness were reaching a white heat as different disciplines entered the fray.
Daniel Dennett despaired when a science journal asked him for a round-up of works on consciousness. The
intensity of the debate was "almost ridiculous" he told The New York Times, taking aim at physicists like Penrose:
"There's a discipline that is even more ignorant about the brain and even more arrogant than philosophy." John
Searle assailed philosopher David Chalmers's book on the subject in The New York Review of Books, saying that
both Chalmers and Daniel Dennett made the "same dumb mistake" in assuming there is such an entity as the self,
Fueled by promising research into the development of an infant's

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mind, neuroscience played a leading role in the popularity of science in the media. Brilliant, articulate, pretty,
funny, self-deprecating, and scathingly critical, Greenfield was the quintessence of interactive science, But there
was a danger. Neuroscientist Christof Koch warned, "We're going to be called to account in five or ten years . . . if
the results aren't delivered."
In June 1998, Greenfield ascended to a pinnacle in science in Great Britainshe was named Director of the Royal
Institute, poised to play a leading role in communicating the agenda of science to the public, Reading about it in
the paper, her old classics teacher, Veronica Lemon, could not believe that this was the same Susan Greenfield who
had loved The Bacchae. The appointment gave her a voice as the premier researcher in the country. "It means
prestige and money and power," says Emmett, beaming. Characteristically, she meant to use the role as a way of
fostering the big picture, practical dreaming, and bringing more women and students from diverse backgrounds to
the study of science.
The appointment opened all sorts of opportunities, as did her sixpart series on the brain for the BBC. She and
Atkins were invited to tea at Buckingham Palace. The BBC flew her all over the world in pursuit of the best
researchers. However, the appointment also brought into focus a long-felt but denied issue.
In her early days of struggle, Greenfield would have been the first to deny the notion of sexism in science, but the
higher she rose the worse she felt it. "It isn't like someone pinching your bum; in fact it would be easier if it were
like that. It's much more insidious and subtle, and it gets worse the higher you go," Greenfield said. "How are you,
young lady?" a member of Parliament greeted her at a committee meeting. She wrote in a column about the
whispered insinuation that one woman in science "had slept her way" to the top. At a party, a department head
introduced her to a student as "one of my professors." If she had been a man, she wondered, wouldn't he have
introduced a tenured professor by name?
She made sure that there was a mix of men and women at Synaptica, and brought many women up with her. One
was her assistant, a single mother of two and former advertising executive who, like her, had a working-class
upbringing. "Susan is unconventional," said Sandie Lowe, "and I think she is intrigued by those with an
unconventional background, especially if there might be a weakness. She would love the opportunity to nurture that
person if she sees that potential. It's kind of a risk thing."

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At the top of her profession, Greenfield's experience of women's difficulties did not end. "The subtle patronizing,
or being ignored in committee meetings, or being slightly put down, . . ." she said shortly after learning of her
ascendancy. "You would look ludicrous if you complained about it," she said. "You just have to absorb it or try to
make a joke of it, but that's very hard," Greenfield asserted on the eve of taking on the Royal Institution, its musty
creaking staircase decorated with portraits of the men of science of Great Britain.
7
One of my favorite pastimes as a child was to pause on my walk home from school and retrace my thoughts of the
previous quarter of an hour. I loved the dreamlike, bizarre associations that led from fantasies of piracy, to
interstellar heroics, to girls. The connections of my thoughts fascinated me. They were clues to a mystery that
could entertain me for hours. What is intuition? Craig Venter likened it to the speediest and most powerful of all
computers, mixing factors and alternatives boiled down by the heart and mind to the simplest and strongest
likelihood. "Connections are what I do," Venter said. The famed biologist Barbara McClintock likened it to a
Buddhist form of "seeing," in which the scientist achieved almost a mystical union with the subject. Greenfield
detests the comparison to computers. "You might as well compare the mind to a bowl of spaghetti, because it has
much more in common with the mind than a computer."
Above all, Greenfield's journalistic writing, her theatrical dressingboots, sweeping black skirts, pink streaks in her
hairher sense that life is a game and that the harder one works, the harder one should play, are part of a personality
that seeks the big picture, and sees no reason to waste time in getting there. She moves with lightning speed, which
I learned after I asked when I could come to Oxford from Chicago to visit. "Well, next weekend's good," she
replied.
"Once she's made her mind up she sees absolutely no reason for delaying," says Lowe. "You can't try to slow her
down. You know it's quite frustrating sometimes what you have to go through, with procedures and bureaucracy.
Sometimes people think Susan cannot handle too many tasks. The answer is that they can't. She can." Though

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she learned to focus her research, her life thrives on the same "scattiness" that Mellanby observed three decades
earlier. "It's no good telling her she can't do something," says Lowe. "With Susan, you have to find a way so she
can fit in twenty things in an hour."
Standing outside her new London apartment, a perk of the Royal Institution Directorship, she stared out at the line
of black taxis waiting to get to Piccadilly. She was telling Atkins about an idea. She wanted to put a bar and
restaurant into the Royal Institution building. There would be a salon of science for Royal Insitution members
where anyone could bump into someone who was interested in science. There were sports bars, why not a science
bar? It could work, she said.
Is it that a researcher stumbles onto something in her early twenties, which by incredible luck turns out to be the
crucial missing link in the most sought-after diseases in her field? Or is that she is such an enthusiastic
communicator that she makes investors believe she has found a critical link that most others are ignoring? It is
safest to say, "perhaps a little bit of both," but that would be ducking the question. When asked if her investors will
get their money back, she responded, "Maybe. That's the whole point of investment capital." The slow accretion of
evidence at Synaptica suggests something at least significant is going on with acetylcholinesterase.
Ironically for a thinker who flitted so much from field to field that she struck many as too scattered, her heroes are
people like Dale and Florey, who stayed on a topic for years and years after what seemed to be thudding defeats in
the laboratory. Greenfield has always stayed on her enzyme, but brought to it an interdisciplinary passion and
entrepreneurs skill. Step by step, learning electrophysiology, and then molecular biology, collaborating with experts
in genomics and animal behavior, placing tubes in rat's brains and then funneling in cholinesterase, watching their
behavior and studying their brain cells after they were killed, she pushed deeper into the basic mechanics of mind.
She did all this while mounting a uniquely successful public life in science, eclipsing those who scoffed at her in
her early years. Perhaps it was because she ranged so widely in her media appearancestraveling the world for the
BBC series in 2000, for instancethat she could stay focused on a single major thread in her own research. Like
Dostoyevski's gambler, Greenfield placed her bet early and followed it through.
Academic science has meant for her, paradoxically, being more practical than most researchers in the past. "She
sees the consequences

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in what might initially be perceived to be an academic connection," says Atkins. "It's a part of her global vision,
not only in people getting together," to attack consciousness as a whole, as a complex system, "but also for the
practical consequences of her work."
A typical weekend at the country home outside Oxford used to mean shutting themselves in their respective studies
to write books, but for Greenfield all that has changed. "She's in the nerve-wracking mode at the moment, doing
the Directorship of the RI and also the BBC series she signed up for, and the prospect of maintaining momentum at
Synaptica is probably as daunting now as when the Christmas lectures were being done. More so," says Atkins. Her
single biggest challenge was to find the time to stay in the laboratory. By the end of the school year in June 1999,
she had resigned her tenured position at Lincoln in order to devote full time to the Royal Institution and Synaptica.
Perhaps her work was not brilliant at first, but it showed the necessary quality of being inevitable in retrospect.
Greenfield saw a commonsensical approach and had the novel idea of not allowing anything to keep her from
pursuing it. Immediately. Of her place in this moment in the history of science, Greenfield saw a field in "desperate
need of a paradigm shift. This is rather sad that people are now preoccupied with the minutiae of things and the
basic premises are all rock hard, like . . . the brain region has very specific functions," she said. "It drives me nuts,
because the mind is . . . a highly dynamic, changing organ, otherwise you'd always have the same consciousness."
The complex-systems challenge of neuroscience, along with the explosion of popular interest in the topic, made
her "perfect for her moment in history," said Sandie Lowe. Swift, rigorous, a little crazy, she brought a humanist's
approach to individuality to a discipline bent on reduction and abstraction. She considered using her media stardom
to push the experiments that would test her theories. When she despaired of getting the time to do her experiments,
she planned to use her BBC series on the brain to conduct imaging experiments on humans to test her theory of
consciousness. "I can use the program to persuade someone to let me run experiments on camera," she said. "You
could manipulate different neuron assemblies and see if you could predict certain cells getting bigger." When I
checked back with her a year later, she had found something more valuable in doing the series. "It is a refresher
course in advanced neuroscience, because we're going into areas like vision and language that are not my area at
all. But I'm revisiting and interviewing all the leading scientists in it, and that is a fantastic way of seeing the wood
for the trees."

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Thinking of what there is fundamentally new to be learned in science, she mentions a favorite book, The Magus, by
John Fowles. The story of a wealthy, mysterious trickster who embroils a young Englishman in a deadly game of
self-discovery on a Greek island, the novel plays with issues of truth and fiction. Early in the story, the narrator
awakens from a nap on the beach to find that someone has left a copy of T. S. Eliot's poem "Little Gidding" by his
towel. A passage is marked:
We shall not cease from exploration
And the end of all our exploring
Will be to arrive where we started
And know the place for the first time.
In the ordinary, the obscure, the seemingly known, the selfhere, the young man soon learns, is where the most
frightening and important mysteries lie.

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Worlds in Profusion:
Geoffrey Marcy's Planetary Astronomy
1
In 1904 the venerable George Ellery Hale founded on Mount Wilson, near Pasadena, an observatory whose work
challenged astronomy's beliefs and practice. With its turn-of-the-century sixty-inch telescope and its later, 1950s
vintage one-hundred-inch telescope, the forbidding mountaintop observatory epitomized the twentieth century's
assault on the cosmos. Using its telescope built with gears that might have driven the Titanic, Edwin Hubble
discovered the expansion of the universe on Mount Wilson in 1929. His student, the bomber-jacketed Allan
Sandage, made godlike pronouncements with each new set of galaxies he photographed there. No women were
allowed; its dorm was nicknamed the Monastery. Researchers wore ties to dinner (Hubble wore a tie even when up
all night in the cramped metal viewing cage suspended two stories above the ground), and hierarchy dictated the
seating arrangement. A rite of passage was to move up from a clothespin-clasped dinner napkin to one held in a
wooden ring. The rules would have been funny if they were not taken so seriously. Phenomenally successful, pinescented Mount Wilson represented the very best of the old astronomy. By the 1980s, it also represented the most
ossified.
In 1982, a smallish, dark, affable postdoctoral candidate named Geoffrey Marcy was standing in the shower stall of
the Monastery. He felt desperate. He had won one of the two prestigious Carnegie Postdoctoral Fellowships
awarded annually at Mount Wilsonfor a project on the magnetic fields of stars' atmospheres. It was a very

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difficult, complex experiment, almost impossible, and it was going poorly. Marcy was convinced the fault lay with
him. He lacked the stuff to make it in astronomy. Perhaps everyone else knew it. He paced the halls of the Carnegie
Institution on Santa Barbara Street in Pasadena, from his mailbox to his office to the coffee machine, glimpsing the
open offices of famous astronomers. He thought they must realize how unfit he was. He woke up every morning in
pain. It had gotten so bad that a year into his two-year fellowship, when he learned that the medical plan would
cover psychiatric help, he began seeing a therapist. This could not be the way for a human being to live, he
thought. He was nice, athletic, smart, and successful at trying to please others. But he was going crazy.
Part of the problem was the incredible difficulty of his project. Even a routine star produced almost completely
chaotic magnetic fields. He had gone through agony to make little progress in understanding the complex
maelstrom of star atmospheres. Perhaps, he thought in the shower, that was why he had picked the project, because
it was so difficult no one could challenge him. Worse, even if he did succeed, neither he nor the world would care
very much. Magnetic stars was such an arcane subtopic its few experts all tended to be a little paranoid.
Soaping himself down in the tiny stall, Marcy foresaw a lifetime of incremental steps, visiting the same
conferences, seeing the same faces, arguing over the same bits of jargon, specializing in ever more arcane pursuits.
The idea disgusted him.
Somewhere in his therapy sessions he had realized that he was always trying too hard to please others. It had
ruined some relations with women. He realized that no one at Carnegie cared enough to push him to please them.
Crushed under the load of research, appearances, conference presentations, they could not care less what he did.
He shuddered in the yellow-green stall, looking down at the graffiti etched in the soap dish. He was selling himself
short to pursue an arcane topic to please people who did not notice. He realized it was a mistake. He felt it deeply.
He realized that his only hope was to find a project that captivated him. Other researchers might pursue topics
simply for their career value, but not him. If it did not move him it was not in him. Usually the Ph.D. process
pounded out this devotion to childlike questions; it was considered a critical flaw. But Marcy realized if he was
ever going to make some contribution to the grand march of progress, he had to conjure up a project that, success
or not, he truly loved.
What he really loved, what had brought him onto his parents' rooftop as a child to gaze at the sky, from there to
highest honors in

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astronomy at UCLA in 1976 and in graduate school, was planets. Not our familiar solar system of planets orbiting
our sun; no, what he really wanted was the romantic, audacious, quixotic quest for the trillions of planets that must
orbit other suns, those parallel worlds holding the possibilities of life and intelligence, the dream that drew in
anyone who ever gazed at the sky. Unknown distant planets, imagined but never seen, held his soul. It wasn't the
planets themselves he wanted, it was the idea that there was so much knowledge out there, so many worlds, so
much richness that no one was even looking at. In the hot spray of shower water he sensed, with a flash that jolted
him with fear, that if such was the case then he should pursue them. What was the point of all his education if could
not go after the simplest, biggest dream of all?
The roadblock was that the search for planets outside the solar system, called extra-solar planets, was considered
"unsavory"the whole thing smacked of science fiction, just this side of looking for little green men. Inside the solar
system, space probes in the 1970s had beamed back disappointing, barren pictures of Mars and Venus. If our solar
system's best candidates looked dead, the chances of finding other solar systems seemed even deader, Textbooks
barely mentioned them.
The challenge was in part technical. Because they emit no light, distant extra-solar planets could not be seen except
as reflected starlight, but the brilliant suns they orbited always overshadowed them. The technology would seem
never to cut through this immense block. No one had a clue how to get past it. The search was strewn with bogus
claims.
Yet Geoff Marcy had one quality other, more pedigreed, flashier postdocs lacked: if he believed in what he was
doing, he would not let go. Because he had accepted at Mount Wilson that he "was not in the fast lane, not going
to invent some amazing new formula the world would marvel at." he might as well go for broke. He already
considered himself a "fully fledged failure."
Why not? Turning off the water, he decided. He would pursue planets orbiting other suns. He would present
himself as he truly was. If he was going to be judged and rejected, at least it would be for something so extreme
and moving to him personally he would gamble his shortened career on it. "It came down to something deep for
Geoff," his thesis advisor Steve Vogt said. "For him this was a form of artistic expression. Like a sculpture or a
painting, science was a deep expression of his soul." For such an approach, self-discovery had to precede
discovery.

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2
Ever since Galileo ground his lenses and pointed his handmade telescopes at the moon, the most creative and risky
of astronomical endeavors had been to seek other worlds. In a terrifying, empty cosmos, planets are the sanctuaries.
The Renaissance philosopher Giordano Bruno was one of the first to speculate openly that the universe might hold
infinite planets; he was burned at the stake for his ideas in 1600. Planets caused even such seminal thinkers as
Johannes Kepler, the man to revolutionize our understanding of our solar system, to wax in wild speculation. When
the younger Galileo wrote him that four moons orbited Jupiter, the ecstatic Kepler wrote back that they must have
been placed there by God for the enjoyment of the Jovian people.
Growing up during the 1960s and 1970s, in Granada Hills outside Los Angeles, Marcy hung a poster of the solar
system on his bedroom ceiling. He spent every day at the park, playing baseball, football, basketball. At night, at
eleven years old, he would lie in bed, staring at that poster, memorizing the names of the moons around the planets.
Phobos and Deimos, Fear and Evil, spun like giant misshapen snowballs around Mars. Jupiter's moons, Ganymede
and Callisto, Io and Europa, held a slight promise of life. Uranus had Miranda, Saturn Titanhe stared at them until
he was cross-eyed.
His childhood was otherwise pretty normal. He played the cello. He played football and loved to leap to knock
down a long pass. His mother had majored in anthropology and earned a B.S., but she stayed at home with him.
His father was a mechanical engineer working on jet airplane design. Both had a sort of scientific bent but they
"were not particularly what you would call academic intellectuals." They emphasized schoolwork, but genuine
curiosity more.
When he was thirteen his parents, noting his interest in astronomy, bought him a used four-inch-diameter
telescope, which he parked on the flat roof of the family home. Standing amidst the thicket of TV aerials on the
other neighborhood roofs that were picking up "Lost in Space" or "The Twilight Zone," he stared and stared at the
planets, watching their movement and imagining. Nothing amazed him more. Venus glowed its cordial, cool
morning iridescencewaxing and waning in its motion like the moon; Mars angrily beamed orange; Jupiter swung
across the ecliptic like a monarch, requiring twelve years to complete one orbit. This was as close to the sacred as
he could get.

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The planet he liked looking at most was Saturn. Not only could he see its rings swooping from the flattened
yellowish saucer, but he could also watch its giant moon, Titan. Titan had a nitrogen-rich atmosphere much like
that of primordial Earth. Reddish brown hydrocarbons, the building blocks of life, blanketed its frozen surface,
perhaps even falling as snow. Night after night he watched as Titan wound around Saturn, completing its orbit in
just 16 days. ''I was amazed you could come back the next night and the night after and see this moon moving
around. It was mind blowing. I kept a notebook with sketches of the positions of Titan relative to Saturn. I actually
figured out the orbital period and compared it to the experts'," he said. "I was bang on."
Majoring in astronomy at UCLA, he managed to hold onto that awe, enough so that, when he himself went on to
teach, his students would award him with the highest evaluations. He then took his doctorate at the University of
California at Santa Cruz, where he worked with tinkerer Steve Vogt on the design of instruments for his star
magnetism studies. "I was in my first year as an assistant professor and Geoff was this very smart graduate
student," Vogt recalls. "It was more a collaboration than a teacher-student relationship. 1 learned as much from
him as he did from me." This openness from teacher to student, and relationships like the one with Vogt, marked
Marcy's entire career, putting him in line to lead the new interdisciplinary astronomy that would challenge the
hidebound Mount Wilson.
So did his devotion to childlike questions. The university controlled a somewhat Gothic observatory built in the
Diablo Mountains near the northern California coastLick Observatory. Named for an eccentric nineteenth-century
mogul, James Lick, who originally wanted to build himself a pyramid in the middle of San Francisco, Lick
Observatory stood on top of remote Mount Hamilton, flanked by a diner in a Quonset hut where the astronomers
ate. The highest winds on Earth were recorded there according to a plaque in the cramped control room, which,
with its 1950s technology, resembled more a college radio station than a professional observatory. Bobcats and
mountain lions roamed the surrounding precipices. One night when it was pouring rain, Marcy stayed up talking
and talking with a student named Todd Lauer. They were waiting to see if the weather cleared, in which case they
would observe. About three in the morning they opened their midnight snacks provided by the dinersandwiches,
chips, cookies, and an apple. Marcy began speculating about extrasolar planets. There had to be some way of
detecting them, he said. How could stars harbor planets and there be no way to find them?

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Planets exert gravity on the suns they orbit. The stars wobble. You could measure the star's wobbling he said.
Lauer went on to run his own institute. Marcy forgot the conversation, yielded up like a dream from his
unconscious, until years later, when Lauer reminded him of it.
At Mount Wilson the competition and hierarchy stifled him, and he would remember that years later. "I thought I
just didn't have whatever it takes. So I thought well, maybe I shouldn't push myself to be in the fast lane." It was
the 1980s, and "upwardly mobile" was the cliche among his old high-school friends. Marcy told himself he was
"downwardly mobile." With his softspoken willingness to be awed, his absolute enthusiasm over the slightest blip
in an experiment, he was the opposite of the all-knowing graduate from the glitzier schools. He still played the
cello avidly. He felt daunted about declaring to the world he was into the ''madness of astrophysics."
It did not help that in the 1980s the bottom fell out of government and university funding. Applying for teaching
jobs after Carnegie he received only one offer, from San Francisco State University. An enormous city institution
following an open admission policy, San Francisco State required him to teach three classes a semester, two huge
lectures and one lab course. He was exhausted by dinner. With his other duties, he worked forty hours a week. A
research institution might have required one or two courses a term from him. The job seemed to foreclose cuttingedge research. "The effect was dramatic," he says. He could publish maybe one paper every three or so years,
instead of the three a year a full-time researcher should.
For seven years he struggled in his tiny cubicle of an office on the tenth floor of cinder-block chic Thornton Hall.
There was no secretary and the photocopy machine was usually broken. He had to fix the oscilloscopes before labs.
He got hold of an early VAX minicomputer, and generally had to fix that too. There was no choice. He had to get
out a screwdriver, pull out the back plate, pull out the boards. It was ridiculous, spending the few hours he had free
to fix a computer.
For seven years he could not attend the usual conferences. His work flowed opposite to the current fads, but then
again it could not be shot down since he did so few presentations. His student evaluations scored among the
highest in the college. His science was a form of teaching; like art, it was meant to communicate, as the great
physicist Robert Wilson once said, and to connect, as the novelist E. M. Forster wrote. With the rise of computer
astronomy, he could do the new intuitive science he envisioned on the cheap. He turned disadvantage to advantage,
but no one, none of his later colleagues at Harvard and Berkeley, would ever know how hard it was.

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3
From his beginning planet search at Carnegie, Marcy approached the problem of searching for distant planets by
using his knowledge of the complex systems of stellar measurement. Because a large planet exerts a strong
gravitational pull on the star it orbits, if you take careful enough measurements of a star's motion over several
weeks you should see, if it has a planet of Jupiter's size or larger, that the star wobbles a little. You could not see
the planet directly because of the star's overpowering light, but you could see it indirectly by looking for tiny
variations in a star's radial velocitythe speed with which it receded or approached Earth. Using a spectrometer to
measure subtle changes in the wavelength of light from sun-like stars, Marcy planned to use the Doppler effect, by
which light waves from a receding object lengthen, shifting them to the red end of the spectrum, to find the star
wobbles and thus, he hoped, extra-solar planets. If a star swayed to and fro because of a planet's gravity, its light
waves should cyclically lengthen and compress, even if by an infinitesimal amountsay 1 part per 10 million for a
planet Jupiter's size.
He gave up a good part of his life to the search. After teaching all day he headed home to Berkeley at six in the
evening, ate a quick dinner, then worked until midnight. The next morning he awoke at seven do the whole
schedule again. "Geoff was more motivated and efficient than most anyone," a Berkeley researcher, Gibor Basri
said. "He amazed me." The same motivation that had Marcy practicing his cello late into the night, classical and
jazz, kept him going through those grueling years. ''Things were sacrificed," he recalled of that time. "I didn't get
married. Some girlfriends came and went. But it was exactly the way I wanted to run my life."
His first attempts were crude. In the beginning he could only hope to detect, at best, planets with masses at least
five times that of Jupiter. No theory really allowed for planets that big. "It was far fetched, but then again, I thought
there was no reason planets could not be that large," he says. "Why shouldn't they?" He then had to wangle time at
Lick, because it was reserved for University of California researchers, not San Francisco State teaching faculty. "I
had to talk and talk with the director, and even then, because I had no formal access, I could only get the crumbs,"
he said. "When the sky was white with a full moon, I'd get the telescope. Two nights every six months." The ironic
thing was, while everyone else was going after distant galaxies, which required pristine viewing conditions, Marcy
could do

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his work with nearby stars even in fairly dense smog. It was dirty astronomy, and he felt it. When they sat for
dinner in the tiny Quonset hut set high on the snowy mountain, the wind howling outside, a group of astronomers
huddled together in a claustrophobic cabin, they talked about their work. When Marcy said he was looking for
planets, the others looked at each other, wondering if he was joking.
The idea of such giant planets seemed heretical and Marcy's approach to them impossibly complex. He needed help
but his work was so loopy and isolated he could not seek a colleague to assist him. He could not even admit to
searching for extra-solar planets in his grant proposals. Instead, he wrote that he was looking for brown dwarfs,
stars not quite big enough to become full-fledged stars but too big to become planets. For help he turned to an
undergraduate who found the idea so wild and outlandish that he could give his "heart and soul" to it.
Paul Butler was a tall, thickset, outspoken, bearded student who had "the only interdisciplinary major in chemistry
and physics I'd ever heard of," said Marcy. Like Marcy, Butler also grew up in the Los Angeles suburbs, building
his own reflector telescope at the age of fifteen. Disheveled in his usual blue work shirt, white pants, and white
sneakers, he was more of an intellectual than Marcy, avidly reading the science fiction of Robert Heinlein and
"grokking" at a young age Kepler, Galileo, and Giordano Bruno. "Bruno was like the Magic Johnson of his time,"
Butler said. Marcy, by contrast, was a painfully slow reader who loved to linger over an author's words, drinking in
the style. By seventeen, Butler was taking college physics and chemistry, and ended up taking so much chemistry
that he simply took a double major. Butler met Marcy in the fall of 1985, and by the summer Marcy was putting
him to work.
Their dream of detecting such a small movement in a giant star a hundred light years away, on the order of the
speed that one bicycles across town, required some incredible yardstick. No one had the technology to do that when
they started. But in 1985 Marcy read a paper entitled "Stellar Radial Velocities," in a conference proceedings, that
made his pulse race. Bruce Campbell and Gordon Walker, at the University of British Columbia, had a yardstick:
hydrogen fluoride, an odorless, colorless, and deadly gas. Hydrogen fluoride absorbed certain signature
wavelengths, leaving a telltale grid of black lines on a star's spectrum. Placing the gas in a vial over their detector,
Campbell and Walker could compare its grid with many observed spectra to seek the shift that would give away a
star's wobble. They had been at it for almost ten years in the 1980s. In retrospect, if they simply

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expanded their search, they might have been first to find a distant planet. "They were doing better than I was,"
Marcy said. "I thought well, I better either give up, or adopt some of their approach."
Marcy and Butler were not about to mess with the highly explosive chemical, Butler's chemistry background
became critical as they searched for an alternative. They spent a year travelling to libraries, speaking to worldrenowned chemists, consulting tones. Marcy was on vacation in Cameroon in Africa with a girlfriend, taking bush
taxis, thinking the whole time about that gas, when Butler called. Over a crackling line Marcy heard him say,
"Iodine."
Iodine possessed an intricate and stable absorption pattern. The wobbles they were seeking were incredibly slight,
one-thousandth of a single pixel in a detector of two thousand pixels, but the spectrum grid of iodine was accurate
enough "to give them God's own spectrum" said Vogt. They worked on their computer code, designed to pull out
variables like a star's twinkling, the Earth's rotation, the sun's spinning outward to the edge of the Milky Way. The
code resembled somewhat the assemblers Venter used for gene sequences or, more precisely, the codes highenergy physicists used to analyze their billions of particle accelerator collisions. One spring semester in college,
Marcy had written a perfect little fugue. It was one of the most joyful artistic creations of his life. Sometimes, on a
few very lucky nights, writing the code felt like that too.
Coupled with their increasingly subtle computer programs to pick out the variation they were looking for while
blotting out the background noise, the iodine-cell approach seemed a good one, at least to them. They began taking
readings at Lick Observatory. With its treacherous, winding road that closed down in winter, the remote facility
was especially apt because it had specialized in measuring the radial velocities of stars since its opening in 1901.
They had a terrible time at first. It was gritty work. The observatory was icy cold, open to the winter nights so that
the mirror would not fog. They started with a list of stars to catch every night, then waited months or years to
digest the data. If the planets they sought had orbits as long as Jupiter's, they would not know if they had anything
for another twelve years!
Butler fought to get their software working. The code combined a million numbers into one, simulating hundreds
of physical interactions; it was difficult, frustrating, lonely. "There was no one to turn to for help, no textbook or
expert," he says. Problems would take him a year, sometimes more, to solve. A million pathways led to the wrong
answer with no signpost to the right one. It did not help that an optical flaw in the lens of their spectrograph caused
much of the error.

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Nor did it help that they operated on a budget averaging about $30,000 a year from 1987 until 1995, much of it
simply Butler's salary. It was less than science on a shoestring, it was small-team slash-andburn science for
nothing.
Others too began going after extra-solar planets. Teams from Harvard and Canada and elsewhere devised bizarre
methods for planet detection, like interferometrythe blocking out of starlight by sequencing the rays to cancel each
other out. They were making all sorts of competing claims, always disproved in the end. Marcy and Butler gave the
world little reason to think their approach would work. Reporting on the project at Harvard's Center for
Astrophysics in the summer of 1992, Butler talked about the complications of carrying out a full physics-based
computational model of the observed spectra, along with the six hours of mainframe computer time required to
analyze one ten-minute spectrum exposure. "They just laughed," he recalled. Of the four competing groups,
conferees put the little San Francisco State group in "third or fourth place."
Indeed their first publication announced failure. Of sixty-five stars they studied painstakingly in their first years,
they found "absolutely nothing. It was quite a stunning paper in fact," Marcy recalled. "Although I think my
honesty helped me gain some credibility. There were so many false detections that it was a refreshing twist to
publish a paper saying we found none."
Marcy still had two small critical triumphs in the early years. One was to win a NASA Innovative Research
Projects Grant in 1992, funding designed for original or crazier projects that might otherwise wither. The other was
in meeting Susan Kegley, a chemist who came to San Francisco while waiting to begin a tenure-track assistant
professorship at Williams College. A friend working on the search for extraterrestrial intelligence introduced them.
They hiked and shared a passion for Brahms. They tried duets on flute and cello, and on piano and cello. "I wasn't
as good as Geoff," Kegley says. He called her his goddess. Kegley helped him persevere through bigger and bigger
runs and failures. Steve Vogt also kept in touch and, when he was chosen to build the High Resolution
Spectrometer for the state-of the-art telescope at the Keck Observatory, in Hawaii, he secretly created a niche to fit
his former student's iodine cell.
They kept on taking readings and building enormous data banks on computer disk, scanning the closest sun-like
stars for a wobble. Their errors were still too large, they felt; the smallest movement they could detect was on the
order of six meters per second. This would not net

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them a Jupiter. Basri advised them to process their data anyway; if there were planets several times Jupiter's size, as
Marcy had speculated years earlier, they might already have detected one. Marcy went against his intuition and
disagreed. Despite their lack of success, it was one of the longest periods of sustained focus they would ever know.
As the power of their computers increased, they could bring less sweat and more intuition to bear on the problem.
Marcy had his love, his project, his students, and his cello. He was happy. Then the bottom fell out.
4
Science competition is unlike competition in any other field. Artists, lawyers, doctors, writers, and athletesall
compete with a vengeance. But they have many paintings to paint, cases to win, novels to write. In science there is
only one first to make a discovery.
In Geneva, Switzerland, in October 1995, a large, streamlined, government-funded team assembled by Swiss
astronomer Michel Mayor discovered the first extra-solar planet, a lugubrious gas giant five times the size of
Jupiter, sitting so close to the star called 51 Pegasus (or 51 Peg) for its location in the constellation Pegasus, they
were practically kissing. It was strangest planet ever seen, a monstrous blast-furnace-hot ball of gas closer to its
star than Mercury was to our sun. It raced around its sun in an unbelievable four days. It seemed impossible. How
could it look like that and do that? How did it get there at all?
Mayor and his colleague Didier Queloz announced the finding at a meeting in Florence, Italy, simultaneously
submitting their paper to Nature. Word of the cataclysm spread around the world instantly by e-mail, reaching
Butler and Marcy, who were already at Lick with the good weather. They raced to play the losers role of verifying
the discovery. They were stunned to see exactly what Mayor had seen, a gigantic planet. When Ted Koppel
interviewed them for "Nightline," Marcy played the gracious colleague. He said it was the most exciting moment of
his life, confirming the existence of an extra-solar planet. Deep inside, though, they felt differently. They had been
scooped. If they had processed all the data on their hard disk sooner, they might

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have been first. Well, if you can't be first, Butler thought, at least you can be the best. They had to get more
computer power, fast.
For any other astronomer, the announcement would have been devastating. But Marcy hung onto an inner
excitement. "For all of those years we were never sure we would ever find anything." He thought of his close friend
Jill Tarter, the SETI director portrayed by Jodie Foster in the movie Contact. "Her project, costing millions of
dollars, expending every ounce of intellectual ability they have, might never succeed."
More important, they helped save their Swiss colleagues. Incredibly, to Marcy at least, Nature had asked for
revisions to the paper. This was fine, the astronomers felt, but the unconscionable condition the magazine placed on
the possibility of publication was to embargo, or forbid publicity. "It wanted to have its cake and eat it too,"
reasoned Marcy. Years later, when Marcy would become the darling of every magazine and television program in
the world, he would remember. But by being there to verify the Swiss finding, they managed to get some critical
publicity out of what could have been a disaster.
Still it hurt that Mayor was well funded, while they had been turned down in 1994 for mainstream National Science
Foundation and NASA grants. If they had any hope they had to kick themselves into gear. To process their data,
they needed lots of computers immediately. Butler spent most of the latter half of October observing 51 Peg with
the little auxiliary telescope at Lick and sending out e-mail pleas for computer time. By November three research
groups at Berkeley donated some, Marcy flashed a defiant smile. "Our technique is better," he said. There were
going to be more planets, a flood of planets, and they were going to find the money and get them.
5
It did not take long. They already had two good candidates, and now that they knew such planets could exist, they
went after them with a vengeance. One planet, orbiting a star in the constellation Virgo, was even bigger than the
monstrous 51 Peg, six and a half times the size of Jupiter and about half as close to its star at its closest approach
as Earth is to the sun. It was so

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big it resembled more a stillborn or brown dwarf star than a planet. More puzzling, sometimes it swung so close to
its sun that it should disintegrate in a cataclysmic tide of gravity, then it slingshotted out deep into space. Such an
orbit was called eccentric, and it doubled the most eccentric orbit of our solar system. It was, in short, a monster
that posed deep problems for traditional ideas of how solar systems form and behave, of cosmology and chemistry.
At least their second planet, orbiting 47 Ursae Majoris, looked somewhat familiar: 2.4 times the size of Jupiter, it
sat out from its sun only a little farther than Mars from ours. By December 1995 they had enough data to trust their
plotted orbits. Marcy had been asked to give a morning talk at the annual January meeting of the American
Astronomical Society in San Antonio, Texas. They decided to announce their shattering news then. Butler felt
exhilarated, but Marcy was terrified of being scooped. "We had been through it once and did not want it to go
through it again," Marcy said. They spent a nervous holiday rechecking their data, monitoring e-mails and
intercontinental gossip, not wanting to appear too interested in the doings of Mayor and their rival HarvardSmithsonian group. "We couldn't bear to lose our little babies we had nurtured for two years. It was very difficult,"
Marcy said.
A rumor nevertheless got out at the conference, and the night before his talk he called Susan from Texas. "I think
you better fly out here," he said. He stayed up until 1 AM working on his transparencies, going over the words he
would use. He lay down to sleep. He watched the clock go to two and then three. The last time he remembered
looking, the clock said 3:45 AM, and then the radio was summoning him to wake.
Scheduled to speak at 8:45 AM, he had to fight through a crowd standing shoulder to shoulder down the hallways.
The double doors were jammed shut by graduate students in jeans and colleagues in ties and rumpled jackets.
Faces peered at himsome expectant, some smiling, some angry. People were packed outside the double doors,
craning their necks. A British television crew that had been kind to their group and thus tipped off by Marcy,
began rolling as he walked in. Bulbs flashed.
What a change from the morning fourteen years earlier when he stood in the shower lamenting his shortcomings!
In modest tones, Marcy described their findings. He felt the sweat in the small of his back, but once he began
talking all his doubts vanished. He downplayed the discoveries so much that graduate students turned to each

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other, asking What's he saying? At the end his colleagues in the San Antonio auditorium stood and applauded. The
guy who had doubted himself so much he took a full-time teaching job, who thought he came in second in the
biggest discovery of a lifetime, felt vindicated.
He was not prepared for the world reaction. "Paul and I were whisked around in limos from one TV station to
another. We didn't even know which station we were being driven to. We just got in the limo and they'd take us
somewhere and some moderator would ask us questions for twenty minutes. Chaos was in control." Commentators
noted his collaboration with a former student, and the triumph of a small unfunded team run by a teacher. For
once, it seemed, coming in second was better than coming in first. "It also helped that Geoff was an American,"
observed Basri. "The science media were in place to promote the story."
The real story was the planets themselves, so odd and disruptive, defying the paradigms of astronomy. Prior to
Marcy and Mayor, no one would have expected gas giants to have four-or five-day orbits so close to their suns.
The planets suggested richly mysterious possibilities by which solar systems could form, making the universe
suddenly more dynamic and creative than anyone had thought. That these weird giants circled so close to their
suns suggested they had been smashed into place, because the traditional theory of a gas cloud coalescing would
not put a gigantic planet beside a star. Solar systems resembled demolition derbies, with asteroids, planets, and
fragments blasting each other into new orbits, spreading the molecules of life's building blocks at the same time.
They showed an odd beauty, the kind that belongs to the underside of things, like the dense, potent egg smell in the
air in the moment before lightning strikes. Suddenly our solar system shed its plodding logic and rut.
We had evidence of its racy past: the cratered moon and Mercury showed that our solar system was once a
barbaric place. Little Mars had volcanoes and valleys far larger than Earth's, and even Earth had a cataclysmic
crater beneath the Caribbean Sea and Central America suggesting ancient Armageddon. Asteroids hurtled to
remind us that, if not for Jupiter's beneficent gravity, Earth might have been pummeled to bits. The Marcy universe
seemed chaotic, willful and creative as a child's tantrum. It betokened a revolution not only in astronomy, but in
"chemistry, biology, meteorology, and geology," Marcy said on the McNeill-Lehrer News Hour. Suddenly there
were many more things in heaven, as Hamlet says, "than are dreamed of in your philosophy." Space became
romantic again.

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6
NASA decided that extra-solar planets were hot, and it poured money into their pursuit. Buying a large portion of
viewing nights on the new, state-of-the-art Keck Telescope, NASA turned to Marcy and Butler to spearhead the
search. But another disaster struck. One of the grant judges tried to have himself declared principal investigator of
their project. He wanted to use their painfully constructed iodine cell himself to search for planets. Marcy and
Butler fought back, with great difficulty because he was one of their judges. Eventually, they prevailed, but the
stress fatigued them. They had now snagged twenty nights a year for their computer search on the world's best
telescope.
With celebrity, they also found corporate sponsorship. Noting that their software ran on Sun Microsystems hard
drives, the corporation agreed to supply them with their best computers in exchange for appending their logo to the
team's website. Never would they have to beg computer time again. Their scrappy, small-team, Silicon Valley
approach to science had worked, or so it seemed.
Vogt had left a space for their iodine cell in Kecks special highresolution spectrometer, nicknamed High Res, and
with that they moved into an expanded search mode with an international, Internetlinked, lean network. Butler won
a position at the Anglo-Australian Telescope in Australia, which gave them access to twenty nights a year on the
largest telescope in the Southern Hemisphere. During the time he lived in Sydney, Butler would join Marcy at Keck
in Hawaii almost monthly. In addition to observing, Hawaii provided a beautiful meeting place for plotting
strategy.
A new team member and returning graduate student, Debra Fischer, took over their old Lick Observatory slot.
Fischer had done her undergraduate work at the University of Iowa, and then came to graduate school at San
Francisco State after marrying and having three children. She was, if anything, even more rigorous and feisty and
single minded than Marcy and Butler. Marcy completely overthrew the sexist, hierarchic old system he had
suffered under at Mount Wilson. They ate and partied together, and he continued to host his undergraduates one
night a year at his and Kegley's home.
Combining telescopes, they increased their precision and power dramatically. They coordinated the search around
the world by email, instantaneously. Marcy and Vogt took readings from the Keck in Waimea, sending them by
Internet to Fischer at Lick in California,

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and then to Butler at the Anglo-Australian Telescope, and the combined numbers were coordinated, like the search
around the world, by e-mail instantaneously. Measuring the motion of a star a hundred light years away as it
waddles like a duck in a small pond, they calibrated the wobble against a fixed point. To do so, they had to take
out all the motions of Earth, whose own wobble shifted its axis a few degrees every twenty thousand yearsleading
to ice ages and global warming. Even the sun was not stable, because of Jupiter's pull. Using relativity theory they
marked each distant star against a fixed point in the Milky Way's center.
But something was lost, "the chance for sustained focus," observed Kegley. "That was critical, but now Geoff was
getting media requests and queries from all over the world. He answered them all." Marcy kept a very active
website; he felt it was critical to communicate his science, and even included family pictures of his coworkers. But
the drain on his time defied him. They were so busy they could not take the necessary time to improve their
computer programs. For some reason the program worked better at Lick than at Keck, though there should not have
been a difference. Lick was home. It became a special place for Debra Fischer. She loved the peaceful routine and
escape of night viewing on their telescope. "It's a time for me to get away and just focus on the important things."
She found the remoteness deeply inspiring. ''Four AM gets to be a little difficult, but I love the machines. There's
no 7 11, there's no gas station or anything else. It's just the Mount Hamilton diner for the staff."
Apparatus in hand, they began systematically searching the four hundred or so nearest stars. They began to pull in
planets, finding three more of the enormous eccentric type like 51 Peg. Then yet another cataclysm struck.
In February of 1997, in a letter to Nature, Canadian researcher David Gray argued that their "wobble" was not that
of a planet's gravitation at all, but of a star's pulsation. With provocative language Gray, who had written a major
text on using spectrometers, built his attack on a single abnormal measurement. To many, the tone of his piece
went beyond mere scientific debate; he was getting personal. But colleagues could not dismiss him. The letter
threatened to derail the entire planet search.
Reporters deluged Marcy with phone calls, e-mails, and continually repetitive questions. Newspaper cartoonists
lampooned him. Made furious by the time he was losing, as well as by the threat to

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their funding, he and Butler fired back in a website attached to their homepage. Gray was using a spectrometer
considered out of date, they said. He declined to offer his likelihood of accuracy. There was no evidence for the
pulsation of stars of 51 Peg's magnitude, but Gray took one odd number, most likely due to a mistake, and built it
all out of proportion.
Some colleagues, noting the Sun Microsystems logo on Marcy's Web page because it provided corporate funding,
felt his or Butler's rancor in responding had "gotten out hand," said one theorist. "It was bad for science." Butler,
ever open with his emotions, fired back. "If somebody supports you, you acknowledge it. Did anyone get mad at
Renaissance artists when they credited the Medicis for supporting their work?"
Over the next several months, four published articles, including one by MIT theorist Fred Rasio, refuted different
parts of Gray's claim. Then, almost a year after his article appeared, Gray published a letter of retraction in Nature.
To Marcy and Butler, the year seemed to have been nearly a total loss. The added stress and delays in research
pushed Marcy into taking up tennis, which he had played in high school, very ordinarily, and now discovered he
loved. He began playing every day, taking lessons from a student who was a pro, and developing partnerships with
friends on the court. It became important to him that his partner enjoy the match as much as he, a "complex,
multilevel kind of play."
The best way to go on was to work. With their methods honed and perfected, they took more and more readings.
The planets poured in, four in 1997, up to a total of thirteen by mid-1998. For the first time in human history,
mankind knew of more planets outside the solar system than inside. It was a tidal shift in the study of planetary
astronomy, and the momentum was building. None of the other teams from bigger institutions were finding any
planets at all. Some disbanded. CNN taped them at Keck. National Geographic profiled them. The New York Times
ran several features on them. Marcy, Fischer, and Butler felt they had many more planets, undiscovered planets,
sitting on their data disks. They simply lacked the time to process them because of all the media requests. Marcy
and Butler planned an all-out assault on the four hundred closest sun-like stars, to settle once and for all just where
the planets might be. What fraction of sun-like stars had giant planets? What fraction of planetary systems
resembled ours? Then they faced yet another completely unexpected challenge.

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7
One day in December 1997, Marcy was checking his usual twenty or so e-mails from around the world. The
romanticism of his quest and the openness of his website (it includes family pictures of many of the team, birthday
and graduation snapshots), attracted queries from all sorts of people. He always tried to respond to students, no
matter how late it kept him at the office. ("I'd tell him, you don't have to do every one, but he'd say, I really want to
talk to them," said Kegley.) One note caught his eye. A college freshman named Kevin Apps, from the University
of Sussex, England, asked if they would send him a list of their four hundred targeted sun-like stars. He wanted to
"assess their value as possibly planet-bearing," with the newest data from Hipparcos, a new European satellite. He
had purchased the Hipparcos CD ROM for the equivalent of $200.
Marcy did not discount him out of hand, as many scientists of his stature might have. Instead he talked with Butler.
Sending their proprietary list would be dangerous. "I didn't want Michel Mayor in Switzerland to know every
single move I make," But something about Apps's style made him think, "I'm going to trust this kid. Why not?" It
was the kind of move that had brought Butler to the search, the kind that had linked Vogt and Marcy. "I did
something I was scared to do. I sent him the list. To my surprise, about two weeks later he sent back an e-mail."
It changed their approach. It changed history.
Kevin Apps was a muscular working-class kid who wore his sandy hair cropped and his left ear pierced with a
large gold ring. He grew up in the end of a block of row houses in Crawley, near Gatwick Airport. His father was a
postman. In his bedroom he kept a poster of a NASA astronaut and pictures of his favorite bands. Graduated from
high school, he applied to the astronomy department in the University of London. He visited the glum, sootcovered city school buildings but, strapped for cash, decided he did not want to move away from his family and
friends. Instead, he took a job as an engineer at the local Duracell factory. Thus was his life set.
He worked, played soccer, and bowled in cricket, and on weekends went clubbing with his friends in town or, if
they were feeling adventurous, to neighboring East Grinstead. He liked to surf. He dreamt of the big waves, the
jaws of Hawaii's Big Island. He followed the news in popular astronomy magazines and then on the Web,

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which was where he learned of the careers of Marcy and Butler in 1995, much as his friends followed their favorite
professional footballers. He was so avid a reader that later he proved to know more insider gossip, certainly in
Europe, than Marcy himself. At night on their way home from the pubs Apps would nudge his friends, pointing up
at the planets as they blinked over the taillights of passing jets.
In February 1997 he was fired after Gillette bought out Duracell. Out on the dole with a severance package, he
spent his time sending resumes and going to interviews for jobs he did not want. At home, he learned his mother's
skin cancer had metastasized. Staying home to help his father care for her, he listened to her stories of growing up
in Brighton.
In April his mother died. His father moved out of the house, bequeathing it to him and his sister. Suddenly cut
loose, with enough money to do what he wanted for a time, he decided he needed to get away. "I'd lost my job,
and I needed to sort out what it was I wanted to do with my life," He found a travel package to Hawaii. He booked
a cheap Japanese hotel near one of the most dangerous beaches on the Kona Coast. He decided he would blow his
retirement money on the "holiday of a lifetime."
Apps spent a month on the big island, where he surfed every day, meeting the locals and hanging out. He traveled
up to tour the summit of Mauna Kea and the Keck Observatory. After he took the guided tour, he went up on his
own, and even did some observing from the summit's Visitors Center. It was mid-May. He knew that Geoff Marcy
and Paul Butler were up there. He looked at the twin giant domes of the telescope and wondered idly, Wouldn't it
be something if someday he could be working on that?
Returning in June he found some temporary work, just trying to find a job, and decided by August that finally he
would go to university. He applied to Sussex so he could live at home. Before the end of first term as an astronomy
major, he bought the Hipparcos CD ROM. Hipparcos was a joint European satellite cataloguing the first threedimensional map of the Galaxy. The first in a new generation of satellites, built inexpensively, making use of new
electronics, remote sensors, and smart materials, it was launching a new era of observation in astronomy and had
already played a key role in revisiting the question of the age of the universe. The CD ROM had just been
produced for the public. Apps wondered if Marcy and Butler had had time to consult the Hipparcos data. "I
thought, well, I'll ask. I was really surprised they responded. I thought, this is smashing!"

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Receiving the list via e-mail from Geoff Marcy in late November 1997, he set to work on the gargantuan pile of
Hipparcos data. Night after night after finishing his homework, he filled the quiet hours in the house by "trolling"
numbers. On just the third star he saw a problem. "It was not what they thought it was. It was a giant star." A giant
star pulsates, meaning its signal varies too much to make the hyperaccurate readings Marcy needed. They would be
wasting time and money, one the worlds best telescopes, and months of studying their data. Apps thought,
"Blimey, oh Christ. They can't have realized this surely."
He plowed on and found more mistakes, reaching thirty in all. "I cropped up a couple of binaries, couple more
giants. I started thinking, well I have to tell them this." No one wanted them wasting Keck time, nor the years of
agonizing analysis. But then again he was a little fearful of approaching them. Sitting in his cramped bedroom
beneath his NASA poster, he wrote as respectfully as possible:
Dear Dr. Marcy, It turns out that a large fraction [of the target stars] are not main sequence stars but
subgiants and class III giants. . . . This may be a concern because . . . it probably reduces the likely number
of planet detections.
In San Francisco Marcy read his e-mail and laughed. "I thought, give me a break. Why did I ever e-mail this kid in
the first place? And I said OK, well, let me just look at one of them. And star by star by star, he was right, every
single time. Every single star he said was inappropriate, was indeed a useless star for our search. Out of four
hundred stars, he had found the thirty that were no good! And we were delighted."
In many ways Marcy's openness to correction reflected the same openness that had begun his fruitful collaboration
with Paul Butler some fifteen years earlier. He e-mailed his pleasure with the college freshman's work. He received
a response from Apps, asking, "By the way, may I suggest thirty replacement stars?" He had pulled out from the
Hipparcos list some likely nearby candidates.
For the first time since Galileo a complete amateur was contributing to the most expert team in extra-solar
planetary search. It was unprecedented, like a Little Leaguer coming into pitch the end of Game 7 of a World
Series. It never would have happened but for the trait of Geoff Marcy to work with students, going back to his old
days of insecurity, his days teaching Paul Butler, to the rise of the Internet and CD ROM technology, and a whole
new era in complex systems science.

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By September 1998, just nine months after he had stared up from the Visitors Center at the giant Keck telescopes,
Kevin Apps was helping to set the agenda for the use of the world's best telescope. A little more than three months
later, one of his suggested stars was found to hold a planet. At twenty-five suddenly he too was a media celebrity,
appearing in articles from The Independent to The New York Times to The Washington Post. He appeared with the
TV interviewer Johnny Vaughn on the hit morning show "The Big Breakfast." Within a few months, a well-known
bread company was approaching him about doing an ad campaign.
8
Astronomer Carl Sagan has said, "In all the history of mankind, there will be only one generation that will be first
to explore the solar system, one generation for which, in childhood, the planets are distant and indistinct disks
moving through the night sky' and for which, in old age, the planets are places, diverse new worlds in the course of
exploration." By the beginning of 1999, the leaps had been tremendous, to already knowing of some fifteen extrasolar planets, of which Marcy and Butler had found twelve. Their discovery of the fifteenth was as befuddling as
the first: it was the closestjust a scant fifteen light years awayand it orbited a red dwarfs star called Gliese 876, just
one-third the size of our sun. Red dwarfs are much more common stars than our sun, and much more long lived; a
planet orbiting a red dwarf gives strong evidence that planets form much more readily and are even more numerous
than we had long thought. "Planets appear ubiquitous, and planetary systems are extremely diverse," observed
Douglas Lin of the University of California at Santa Cruz.
The extra-solar planets posed huge puzzles for theorists, who wondered most of all how they had gotten into such
oddball orbitshad they been pushed by cataclysmic collisions or were they infant planets surrounded by swirling
clouds of dust and lethal asteroids? Lin and Japanese theorist Shigeru Ida opted for collision, picking up an obscure
theory propounded by an eccentric Russian, Immanuel Velikovsky, in a 1950 book called Worlds in Collision.

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Theorists joined the argument about the implications. Marcy and Butler for their part sometimes thought about the
vast new geologies and chemistries of such gas giants. They never tired of thinking about life on those planets,
even the gas giants, where water might be trapped in some layer of the atmosphere. Their work made colleagues
take a second look at our own neighborhood. We knew that it was once a very deadly placethe scars of the moon
or Mars or Mercury attest to an unimaginable violence of collision and explosion. Our moon was likely expelled
from Earth in a violent cataclysm stemming from an unbelievable collision. But on a vaster scale, it seemed that
our solar system "may be a very rare event," says Lin. "We are safe, but just safe."
Following on the quest for extra-solar planets, a whole new generation of NASA probes, built on the principles of
better, cheaper, faster that Marcy pioneered, are poised to open a new era of extrasolar planetary exploration. The
Space Interferometry Mission (SIM) will use complex wave-interference sensors called, aptly, interferometers, to
block out starlight and allow planets to be seen in silhouette, while the Terrestial Planet Finder (TPF) will take
"family portraits" of planet systems and atmospheres. "The first blue Earth-like planet we'll be able to see in about
a dozen years," predicted NASA's Dan Goldin. "When I see that, I will weep."
When Mount Wilson was founded in 1904, it opened not only a new astronomy, but a new way of doing
astronomy. Geoff Marcy's personal crisis as a young researcher on Mount Wilson led not only to a new
astronomyof weird new theories of planet formationbut also to a new way of doing astronomy. It was, first of all,
an astronomy of nice people working on interdisciplinary teams. It was also cheap astronomy, much as the Mars
Pathfinder and Explorer showed the world how probes could unlock the universe using basic video and electronic
and computer programs. It was a team effort, absent Mount Wilson's old rigid social order. Kevin Apps and Butler
and Debra Fischer can attest to that. Apps speculated that the reason Marcy was finding so many planets while the
better-funded Swiss astronomers Mayor and Queloz remained stuck at one was that Marcy, quite simply, was nicer
to people below him on the professional scale. Marcy used to coach Little League baseball, even though he had no
children. "I used to ask the boys, What position do you want to play?" he said. "The other coach thought I was
crazy."
How was it that a relatively obscure teacher forged the method of finding distant planets? How is it that much
better funded teams found many fewer? In the end, it was the go-for-it panic of a day in

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the shower, coupled with incredible drive to keep doing research every night after being exhausted from teaching,
and a good deal of luck. At the American Association for the Advancement of Science meeting in 1999 in
Anaheim, "uncle" Allan Sandage, father of twentieth-century astronomy, approached Paul Butler. "I saw you on
TV," he said. "I just wanted to tell you what you're doing is great." Butler demurred. A Harvard University Press
editor pushed up to him. "I want you to write a book," he said. "Come stop by when you're in Cambridge. We're
right across the street from the CFA.''
It would have been a moment to relish, but time was short. Butler had to race out of his conference to Cambridge,
and from there to New York. They were working on something bigger. Within a few months, they announced even
more astonishing news. They had found the first extra-solar system with multiple planets, around u Andromedae, a
sunlike star some forty-four light years away. This discovery, announced jointly with their former nemesis, the
Harvard-Smithsonian Center for Astrophysics, suggested that "our Milky Way is teeming with planetary systems,"
Debra Fischer said on the front page of The New York Times.
The momentum kept building, even as Marcy left San Francisco State for a position at the University of California
at Berkeley. In November 1999 came two more important announcements. One was the first direct observation of
an extra-solar planet, in the constellation Pegasus, as it dimmed a star's light by passing in front of it. The other
was the announcement of six more planets around other stars, bringing the total number of extra-solar planets to a
whopping twenty-eight. Announced by Steve Vogt (one of the planets had been described in a paper by astronomer
Nuna Linn, of the Swiss team), five of the new planets lay in the habitable zones around their starswhere liquid
water and, possibly, life could exist, most likely on the planets' moons.
Still they pressed on. Marcy and Butler are committed to finding Saturn analogues in the next few years, and to
being the first ones to find an Earth-type planet. Geoff Marcy could not have done it alone. Paul Butler could not
have done it alone. Only together could they have made the approach work. But what of the worlds that produced
such theories? "Sometimes in the middle of night we just look at each other and say, I can't believe we're doing
this," said Vogt.

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Dangerous Liaison:
Polly Matzinger's Evolutionary Immunology
I say Live, Live, because of the sun
the dream, the excitable gift
Anne Sexton, Live
1
When Polly Matzinger thought of the theory that would challenge nearly a century of immunology doctrine, she
was taking a bath. She was thinking about a problem, and she did her best thinking in the bath. She reviewed
papers for the journals Science and Nature in the bath, as well as for some of the journals in her field. While
soaking in the steaming water, she wrote the papers and presentations that stirred up a tempest among her
colleagues. The warmth of the water, smell of skin oil, and the ritual of settling in made her feel still and focused
and calm. What I needed was stillness and imagination, Einstein said in answer to the question about how he
uncovered the mystery of relativity. Imagination, he added, is more important than knowledge.
Lithe, small, short-haired, Matzinger was a laboratory chief at the National Institutes of Health in Bethesda,
Maryland, in 1991. She had trained border collies for sheep-dog competitions around the country. She had entered
science later in life than most of her colleagues and approached it from a different angle. She wrote syntheses

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and summaries. She spoke frequently to nonscientists. She did not like technology and computers. And she did not
like conventional wisdom.
At the time of Matzinger's bath in 1993, some experts were predicting that molecular immunology was about to
break through to a new era of unimagined longevity, when manmade hearts, livers, arms, and legs would extend
life almost without limit. The breakthrough would be supported by "a remarkable convergence of basic research in
some once-disparate specialties," according to science writer Boyce Rensburger, including molecular and
evolutionary biology and gene therapy. "The immortality of the single-celled organism is in us," Rensburger wrote,
a call echoed in articles and on television.
The trouble was, the human body is not nearly as easy to choreograph as the visionaries claimed. The primary
block is the immune system itselfthe many cells that protect us from disease and death every day. Sometimes the
immune system turns against the bodyin autoimmune diseases like multiple sclerosis, rheumatoid arthritis, Type I
diabetes, and lupus. Other times it rejects transplants of matched organs unless they are accompanied by massive
doses of immunesuppressing drugs that weaken the very person they are meant to help. More perplexing, the
immune system frequently does not recognize cancerous tumors until it is too late. Despite all the possibilities of a
new era in medicine, immunology's byzantine challenge made talk of immortality a bit premature.
In 1993 most immunologists were applying the techniques of cell biology, computer analysis, gene and bacterial
cloning, and basic artificial intelligence to the questions of what made the body attack infection and why. When a
foreign agenta virus, a bacterium, or a transplanted liverenters the body, it was known to be set upon by special
blood cells that arise in the bone marrow, which gobble up the invaders. Their theory stated that, shortly after
infancy, the body learns to accept what it recognizes as the self and attack elements it recognizes as nonself.
Proposed in the early 1940s by Macfarlane Burnet, the self/nonself model was confirmed in the cataclysm of World
War II by an urbane British doctor of Arabic descent, Peter Medawar, who studied the rejection of skin grafts.
Working with severely wounded veterans, Medawar watched with frustration as the body's own immune system
battled the grafts and prostheses meant to help the victim. After the war ended, Medawar's experiments with inbred
mice seemed to prove the self/nonself model. For their work, he and Burnet shared a Nobel Prize in 1960.
In the years thereafter, researchers sought to grasp and manipulate at a molecular level the complicated signals and
countersignals

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activating and running the immune system. However, as the studies became more rigorous, the picture became
cloudier. In some cases the body would not attack what appeared to be nonself, as with cancer tumors, and in other
cases it would attack the self, as in autoimmune disease. What exactly triggers the immune cells, and when does it
happen, and why? Those questions needed to be answered before researchers could begin to understand how the
immune system could be turned on or off, They were accepted as major challenges of late twentieth-century
immunology, but they were not what Polly Matzinger was thinking about in her bath.
It was instead clear to her, and a few others, that the self/nonself theory was not explaining a great deal that went
on in the laboratory and in life. Unlike her colleagues, who tinkered here and there at the edges of the model,
Matzinger felt that an entirely new model was vitally needed, and the place to look was not only in the databut in
the perception of researchers themselves.
The stakes were enormous. The riddle of exactly how the immune system worked occupied hundreds of
laboratories around the world spending billions of dollars; it was big business. The world, rocked by the first heart
transplants, had then seen the immune system unwork the miracles of surgeons. It had to be unlocked. If it could
be, anything was possible. Tissue engineering, which already helped athletes, offered the potential of one day
replacing our livers, lungs, and hearts with artificial organs, promising to extend our lives up to two centuries or
more. As with the genome, however, to reach such a vision immunologists needed the bigger picture, the entire
system, whole. Immunology was holistic, complex systems, interdisciplinary science of the most daunting kind,
and it made a giant roadblock in front of medicine's new millennium. "We saw the future," said one researcher,
"but no one knew how to make it happen."
As chief of the section on T-Cell Memory and Tolerance of the National Institutes of Health, Matzinger joined in
on the debates, stewing all the while about a deeper, more fundamental problem she saw in the entire model.
Self/nonself could not explain so many basic thingslike why a mother did not reject her lactating breast, or why a
teenager's body did not reject itself during puberty. The body was always changing, often radically. If human
puberty seems tough, she told her students, what about a frog's? What kept a tadpole's immune system from
recognizing its growing legs or its new red blood cells as nonself? What bothered her most was that few of her
colleagues even conceded this illogic. They thought they had the answers. Goaded by a young physician, Ephraim
Fuchs, whose brother had died of cancer,

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she sought a deeper logic to the immune system. They read avidly from authors on the creativity of science like
Arthur Koestler, Karl Popper, and Thomas Kuhn, discussing the overarching emperor-with-no-clothes problem in
their field. They argued about what kind of an immune system would make sense if designed by evolution.
Attractive, argumentative, and smart, Matzinger prided herself on challenging commonly accepted data if it
contradicted the philosophy of good ideas. Some said Matzinger did too much philosophizing and too little
experimenting and publishing in professional journals. Others said she rekindled the most time-honored approach
to science, synthesizing numerous studies into new ideas. She was verbal and smart and different, and she got
attentionfirst in a BBC series, then in women's magazine articles, then in keynote speaker engagements at major
science conferences in Europe and South and North America.
What she did with that attention inflamed some of her colleagues. An adept actress, she flaunted many of her field's
traditions. She once named her dog as a coauthor on a journal paper. Her curriculum vitae listed jobsyears of
playing jazz bass and piano, waitressing, carpentering, serving in the Church of Scientologythat few other scientists
would include. She even listed her former job as a Playboy Bunny at the top of the document. She drove with a
bumper sticker that read "Commit Random Acts of Kindness" while amassing $500 a year in parking tickets. She
admitted to "having a brain like a sieve" but challenged speakers' inconsistencies doggedly at conferences. She
played the piano and sang with a folk group, wore leggings and boots around the halls of the Bethesda complex.
Above all, she did not worship the prophets who promised a new era in immunology, not without reevaluating
what she saw as its faulty conceptual basis.
When she leapt out of that bath in 1993, dripping, "absolutely naked, running through my house," and screaming,
she had come up with a new model that threatened to turn her field, and the future of research, on its head. If true,
her idea could transform immunology. But was it true? Was she for real?
On that point, even some of her closest colleagues could become apoplectic. "People still will not give her any
credit," observed her NIH Director Ron Schwartz. "Polly is so refreshingly controversial," said Case Western
Reserve University's Paul Lehmann. "She's just what a scientist should benot by the book, not into systems and
structures, but sometimes she has to pay a price for it.'' At the beginning, she had little of the experimental data one
would expect, yet she managed to motivate dozens of labs to attempt a new immunology.

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Was she a harbinger of a new kind of interdisciplinary science, or the worst example of old-fashioned
dilettantism? The complaints about her resembled those about Craig Venter or Susan Greenfield, But Matzinger
took it to a new level. "Polly," Johns Hopkins University oncology professor Drew Pardoll once observed to the
magazine Elle, "is a very dangerous woman."
2
History often works by accident and mistake. For the seeds of revolutions look into the wings of obscure events
and trivial coincidence. In 1947, the same year Peter Medawar tested the self/ nonself theory, Polly Celine Eveline
Matzinger was born on July 21 in La Seyne, France, to a Dutch resistance fighter and a French former nun. Her
father, who had been sent to Dachau for assisting Jews, now worked odd jobs to support his painting and his wife's
pottery design. After moving to Amsterdam, the family made it to the United States, where Matzinger and her
younger sister were not allowed into a Long Island elementary school because they did not speak English. Her
father then took the family west, settling in Hollywood because Los Angeles County would allow his children to
attend school.
Matzinger and her sister were placed back a year because of their language. Bored and lonely, she later found
solace in her brother's beagle, named Trixie. At age eleven, Matzinger saved up dollars earned from sweeping a
candle shop to bring Trixie on a rope to a training school. "I told them I would pay them a dollar a week. They lent
me a leash and a collar and treated me like an adult."
By junior high, her father had moved the family to Watts, where she learned music from the first teacher to take
her seriously. For her senior year of high school, the family moved again, to Laguna Beach, where, feeling isolated
once again, Matzinger told the guidance counselor she wanted to quit. She skipped classes to attend a nearby
community college, where she made A's in some of the classes she attended. She also failed several that did not
inspire her. Her senior-class yearbook listed her as "Most Likely Not To Succeed."

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She kept up her dog training and music and did well with them, but little else. She attended junior college in music,
and the University of California at Irvine, but quit before graduating. She decided, she said, "that any job was
boring and so I would take only those jobs that would allow me to do what I wanted during the day." In her
twenties she cleaned bricks for two cents a brick. She ironed shirts at ten cents a shirt. Her favorite job was dog
trainer, which she loved for its "unspoken communication, like a marriage," She had a rare ability to listen to the
animals she worked with, letting them tell her how to teach them. The rest of her family was artistic, but she felt
like a talentless dabbler. After stints as a waitress and a carpenter, punctuated by gigs playing jazz bass for club
dates (she admired Charles Mingus), she moved to Boulder where she became a bumper pool Bunny at the Denver
Playboy Club. "It was a great job,'' she says. She enjoyed talking to people. She could listen intently, making
members think they were the only one in the room, as she did in telling me the story of how she ended up driving a
police squad car, in the middle of a snowy night, in her Bunny outfit.
One winter night her beat-up Volkswagen blew a tire, so she hitchhiked to work in the icy cold along Interstate 95.
Arriving late, she ran into a police detective named Duffy, who was waiting to give her a lesson in bumper pool.
When she explained that her car was broken down on the highway, he offered to fix it. The bell-bottomed detective
returned after a few hours to say her car was ready. When she thanked him effusively he paused. "Well, you could
do me a favor," he said. He wanted to use her car to go on surveillance at a "drug party." She hardly wanted to help
a narc, but she felt she owed him. He met her when she got off at three in the morning. The wind whipped up
cinders and sleet. She wrapped her tattered faux leopard coat around her. He showed her how to run the squad car's
lights and siren. She drove it almost all the way home, until a Boulder policeman pulled her over. "Is that, " he
asked, "your car?"
At the police station they checked their computer and found there was no Sergeant Duffy. "There had been a
Private Duffy in the tiny Green Mountain Falls police force," she recalled, "but he had been fired two years
before." Private Duffy had absconded with a squad car. When she heard that, she thought she had lost her
Volkswagen. But the next day he returned it, still insisting he was a detective.
From Boulder, Matzinger made her way to Davis, California, eventually waitressing at a bar called Mr. B's. She
liked chatting with two regular customers, one of whom was the University of California

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animal behaviorist Robert Schwab. If there was one thing she understood, it was animal behavior, When she
overheard them talking about deceptive mimicry, she chimed in that she never understood why a raccoon did not
impersonate a skunk to scare off predators. Schwab looked up.
"What," he asked, "made you think of that?"
Schwab began talking to her regularly, bringing in articles for her from Science, Nature, and Scientific American.
He encouraged her to finish her undergraduate degree and pursue science as a career. He even helped her fill out
the applications. "He gave me my life," she recalled in a BBC documentary. "And I never thanked him. When I
published the danger model I wanted to send it to him, but I didn't think it was good enough. I wanted some more
time with it." A few weeks later, he was dead.
3
In 1954 Peter Medawar's proof of the self/nonself theory was both elegant and simple. Medawar showed that, while
adult mice reject foreign skin grafts from other adult mice, a newborn mouse will eventually accept such grafts. He
concluded that the body's immune system will accept as "self" any cells it encounters early in life, while rejecting
as "nonself" any such cells encountered later in life. His model seemed so clear and inevitable, his prose so
reasonable, as to be unassailable. Medawar went on to something of a second career writing about the sociology of
scientific inquiry, penning books like Advice to a Young Scientist and The Art of the Soluble.
At the University of California in San Diego, Polly Matzinger began by studying the sex lives of fruit flies, but
under the pressure of answering an oral exam question, she had her first creative scientific idea. "It was in
immunology," she recalled. "When you come from a family of artists and you're not creative, and you find a field
you can be creative in, you switch." Under the mentorship of two leading immunologists, Mel Cohn and Richard
Dutton, she put to use her ability to communicate with animals, to listen, argue, and synthesize in the study of the
immune system.

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From the beginning as a graduate student, Polly Matzinger had felt uncomfortable with the self/nonself theory.
Even Medawar had seen as early as 1954 that it could not explain something as simple as why a pregnant woman's
immune system did not attack her own fetus. The fetus was foreign; why did the body's immune cells not react?
Medawar held that there must be some anomaly in female biology, not in his theory. Matzinger called that a
typically male response. Self/nonself had other, bigger problems. It did not explain phenomena like autoimmune
disease, when the body turns on itself, or cancer, when the body fails to attack foreign tumors. It did not explain
how we develop new tolerances as we grow older. If the body was always changing, it did not make sense that its
immune system, after infancy, always remained the same.
In the 1970s the stakes in immunology became suddenly enormous. Those were the heady years of the first heart
transplants. The accomplishments dazzled the world but then often ended in an ignominious death as the body
itself slowly rejected the lifesaving organ, or accepted it only with massive drug doses to suppress the immune
system. It seemed a cruel anomaly: the patient's body assaulted the organ that the surgeon had so brilliantly
implanted to save it.
The trouble appeared to be that each person's immune system was slightly different. We each evolve different
immunities picked up from the different illnesses we get, adding to the different sets of parental immunities we
inherit. The heart or liver from an organ donor, it was reasoned, could not be recognized as self by the patient's
own immune system because its genes were different from the patient's. The patient's system then attacked.
In the following years, several advances in molecular biology began making it possible to understand what was
going on down to the level of the molecules in the cell, unmasking how the body recognized nonself in the
immunological model. The mysteries of cell recognition, signaling, life, and death, began to open. It was known
already that the most important immune system signaler is the helper T lymphocyte, a white blood cell that
stimulates other cells to action. A T cell recognizes an invader by its antigens, molecules presented on the foreign
cells' surface. When it does so, the T cell starts to proliferate and causes an army of B cells (producers of
antibodies among other things) to proliferate, too. How did all this happen? Not as simply as Medawar imagined, it
was turning out.
Mel Cohn at the Salk Institute, in La Jolla, California, was a leader of the research into the signals of the immune
system. Across the ocean Australian researcher Kevin Lafferty, who would become a

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Matzinger supporter, was studying the complex mechanisms of antigen-presenting cells, which first encounter,
engulf, and digest an alien cell or a virus, then activate other immune cells by "presenting" the pieces to them. The
question was, what triggered the antigen-presenting cells themselves?
In 1976 Cohn invited Matzinger to go in his place to the most important world conference on immunology, held
every decade or so at the august Cold Spring Harbor Laboratory run by James Watson. At the end of the meeting
she met a young, rumpled Yale researcher named Charles Janeway. She became good friends with Janeway, who
came from an august family in immunology. In 1917 Janeway's grandfather Theodore was called on by the U.S.
Army to diagnose doughboys who were falling ill. He lived long enough to uncover pneumonia, and then died
from it himself. In the 1930s his father, Charles senior, had been a pioneer in the field. The younger Janeway
would later cowrite the definitive text in immunobiology and preside over the national immunological association.
He was traditional science, she an upstart, and she wondered if one day she would ever be invited to speak at a
conference as important as Cold Spring Harbor.
In her forays into professional meetings, being attractive was "an advantage and disadvantage." With her reputation
as a former Bunny, she could always get senior scientists to talk with her, she said. It was just hard to get them to
talk science. Inflamed by the meeting, though, she began to take off. Before she earned her doctorate she was to
publish or coauthor four papers in major journals, all attacking the question of what mechanism switched on the
immune system. She was proposing a model that seemed at first unlikely, but then turned out to be exactly correct.
It was "an important, creative argument early in her career," observed Ron Schwartz of the NIH.
But for her fourth paper, she committed an act that might have doomed her career. Refusing to write in the usual
scientific passive voice ("steps were taken") and too insecure to write in the first person ("I took the steps"), she
instead invented as coauthor her afghan, Galadriel Mirkwood, so she could write "we". The Journal of
Experimental Immunology, which published the article by Matzinger and Mirkwood, was incensed when it learned
of her deception. It banned her from its pages.
Being such a passionate speaker, an actress, and a debater who deliberately tweaked boundaries all put her in the
same dual-edged position. She was in immunology but not of it, "within and without" like F. Scott Fitzgerald's
Nick Carraway.

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4
In 1979 she returned to Europe for her postdoctoral work. First Matzinger went to Cambridge, where she was an
NIH overseas fellow working with immunologist Herman Waldmann. She then took a research position at the
Basel Institute for Immunology. Professionally it seemed a good match, but personally it was a disaster. There was
no place in Swiss society for an independent single woman, certainly not one who advertised herself as a former
Playboy Bunny, played jazz, drank and talked freely, and rode a BMW motorcycle.
Matzinger continued to demonstrate that she could perform seminal experiments, publishing papers in Nature that
examined the role of the dendritic cell and thymus in immune response. Dendritic cells, found in lymph nodes, the
spleen, and, in low levels, in the blood, are particularly active in stimulating T cells. She did pioneering work on
their function. Still "Polly didn't do a lot of reading in the literature. She tends to be much more of an intuitive
person. She did not do a lot of writing up," her later NIH section supervisor Ron Schwartz commented. She was
more a creature of meetings and discussions. Once, she kept Schwartz up until 4 AM arguing the night before he
was to make a major presentation. Hers was almost an improvisational form of science research, like jazz. "At
some point you realized you just weren't going to win," Schwartz said, "so you gave up."
In her last year in Switzerland, her beloveed afghan died. She was so depressed she drove her motorcycle well past
midnight, drunk, up and down the cobbled sidestreets. That was when she heard from Schwartz, who had just
become a section chief at the National Institute of Health in Cellular and Molecular Immunology. He could hire
two researchers.
Schwartz invited Matzinger to give a seminar in 1988, the same year she was asked to speak at the very Cold
Spring Harbor Conference she had aspired to more than ten years before. Schwartz wanted someone to provide "an
intellectual spark" and who could mentor younger scientists. She galvanized the audience. She would always be a
favorite with postdocs, attracting young people from as far away as Turkey and India, especially women. He
offered her a choice of two positions: one lower paying with the option of tenure, the other higher paying but
riskierit did not offer tenure.
Matzinger was not sure she wanted to return to a "country that didn't know it lives in the world," but it was a good
time to come. The National Institutes of Health would in a few years undergo deep

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changes under the leadership of Nobel Prize-winner Harold Varmus. Since 1937, when Congress founded the
largest and best-funded of the NIH Institutes, the National Cancer Institute, the NIH had epitomized the paradigm
of huge government-funded bureaucratic research. Franklin Roosevelt called it a war effort to eradicate disease.
Under Varmus, the NIH instead committed to creative, individual, big-picture, risk-taking basic science. Matzinger
chose the second, riskier position. "I figured if I can't do something in four years to make somebody want me, I
belong in another field."
Needing to earn tenure, she had to sit and put her thoughts on paper more regularly. She needed to do experiments.
On the first floor of sprawling Building 4 in Bethesda, her team worked side by side with Schwartz'sgiving plenty
of opportunity to share ideas in the open hall. She liked to write philosophical questions in magic marker on a
white board in the lab tea room, just as she wrote herself notes on a blackboard in her kitchen at home. A young
postdoc working with Schwartz, on a leave from his training in clinical medicine, began writing down answers.
Born in 1960, the dark, intense Washington-raised Ephraim Fuchs learned at the age of fourteen that his father was
suffering from colon cancer. At fifteen he learned that his talented older brother had brain cancer. After his
brother's death, Fuchs decided he would become the person to cure cancer. Coming to NIH in 1988, Fuchs was still
fairly new to the field. Schwartz put him to work figuring out how to create tolerance for transplant antigens. He
was "flailing around and not getting very far." The molecular biological revolution was sweeping labs around the
country, and Schwartz's interests veered more toward cellular systems than to the big-picture questions involved in
curing diseases that Fuchs yearned to pursue. When the cloning of genes for T-cell receptors became possible, the
problems of molecular immunology seemed finally within researchers' grasp. Fuchs was having trouble and found
in Matzinger an open door and fellow spirit. "With others, you had to make an appointment just to see them," he
recalled. "Polly was more of a classical cellular immunologist, so when I had problems with my experiments it was
easier to consult her."
Matzinger's more free-wheeling approach inspired and, sometimes, bothered him. "What's striking is that Polly
works from a priori principles. She starts out by saying, if I were a God designing the immune system, how would
I design it?" This philosophical, almost Aristotelian approach ran counter to the work of most other labs in the
field. "Many people just generate as much data as possible and try

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to extract information from the data," Fuchs said. He and Matzinger talked and talked about the problems in their
field and about the nature of science in general. They read Thomas Kuhn on the paradigms of scientific disciplines,
and Arthur Koestler on creativity. They read and then argued about Karl Popper, the historian at the London
School of Economics who took up such issues as whether the universe is ultimately open or closed, free or
predetermined. "Ephraim was a discussive type of guy," Matzinger recalls. Their metaphysical discussions opposed
the big technological approach of most government science. It was rare at any lab, at any time, and they needed to
bolster each other for their assault on immunological doctrine.
From the start, it was Fuchs who challenged the self/nonself theory. Thinking about cancer, he saw immediately
that the body did not behave the way the theory would predict. Tumors should have been assaulted because it was
clear they had antigens on them that were foreign. But researchers were spending years and millions of dollars
trying to get the immune system to work against them, to no avail. For a while Matzinger played the older, wiser
"grandmotherly" role, in her words, trying to explain how the discipline worked, but Fuchs would not let go.
Self/nonself, he argued, was philosophically and physically impossible. "Was it Heraclitus who said you can't step
into the same river twice?" he said. "The fact is the body is always changing. Tumors occur all the time, as do
bodily changes like puberty, and mutations, and the immune system doesn't attack." Fuchs had read the physicist
Richard Feynman, who described how, when a scientist proposes a breakthrough, he had to have the courage to
suggest that maybe the previous findings were, well, wrong. Gradually Matzinger stopped talking and just listened.
Perhaps the previous data were flawed. "Polly, one thing I have to give her a lot of credit for is she was able to
challenge some of the icons of immunology and say, well their reasoning had to have been wrong."
Around the world a few other researchers kept finding problems with the prevailing model, and strangely promising
results that contradicted it. In Australia's John Curtin School of Medical Research, for instance, cancer researcher
Kevin Lafferty found that an organ cultured in high oxygen is not rejected when it is transplanted because the
organ's dendritic cells died off, which was unexplained by the self/ nonself model. Others, like Janeway, were
stimulating the immune system to act against autoimmune diseases by combining bacteria with diseased cells. But
it was one thing to suggest that a prevailing theory required modification, quite another to propose a replacement. If
not nonself, then what triggered the immune system to attack?

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Matzinger got Fuchs to read Richard Dawkins, the Oxford animal researcher who had extended Darwin's theory of
evolution into many new fields. He first coined the term "meme" for a cultural riff that gets passed around much
like a successful gene. To Dawkins, and to his avid reader Matzinger, every aspect of life evolved to perpetuate the
genes of the species, "Once you start reading Darwin," Fuchs said, "there's no going back." But the self/nonself
theory seemed terribly inefficient in light of natural selection. It seemed to prevent the human immune system from
evolving to pick up immunities to some agents. What use was an immune system that could not adopt new
resistances? They spent months thinking and arguing about it. Matzinger sat on her cottage's back patio, working at
her laptop, absently tossing the ball to her sheep dogs. She was still doing her other research on antigens and T-cell
memory; in fact she was publishing at a new rate of two or three articles a year. But she kept thinking about the big
picture.
They decided that it was most likely, in an evolutionary world, that an immune system wired to prevent danger
would be more sensitive than one turned against everything foreign. The trouble was, what defined danger to the
immune system? "Danger" was just a metaphor. It sounded like a novel or movie plot device, not a scientific
theory. At this point, Matzinger stepped into her bath. As she watched the bubbles pop, she thought about the two
different kinds of cell death molecular researchers were uncoveringone programmed and healthy, called apoptosis,
the other sudden and unexpected, called necrosis. In programmed cell death the cell's contents remained inside the
cell wall. In sudden death, the contents spilled out. Those contents, it dawned on her as she watched the soap
bubbles pop, could signal danger.
She leapt from her bath, naked, dripping, racing through the house, her thick long hair tangled and wet. That was
it! The immune system responded to danger signaled by the sudden death of cells. That was why transplanted
organs were rejectedthe surgery caused severe trauma, killing many cells. That was why a mother did not reject her
fetus. That was why tumors did not trigger a responsethere was no necrosis when they began to grow. "The reason
I didn't see it was, I was really blinkered," Lafferty later recalled in a BBC documentary. "Everyone has to realize
that we're confined by our conceptual framework all the time, even though we don't know it." It was so simple.
What would be the most useful stimulus in evolution for an organism's survival? Danger, signaled by death of
cells.
Though she was excited, and Fuchs was too when she told him,

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the idea was no Archimedes-class revelation. Lots of people have ideas. She needed a triggering mechanism to get
herself out of the realm of metaphor and into the real world. She suspected the signaler was the dendritic cell,
whose functions she had been exploring, but she did not know how it distinguished between danger and safety.
One Saturday afternoon Matzinger was out in a Maryland farm field, watching her border collie herding sheep. At
one point the dog shot off to protect the bleating sheep. There was nothing there. A sudden sound or wisp of wind
had scared the sheep. She noticed the dog responded not to a menacing animal, but to signals from the frightened
sheep. Her mind worked. The bleating, she realized, signaled danger. In the body, perhaps the dendritic cell goes
into action not because of an invading organism, but because of the distress signal from necrosis of its own cells.
The bleating was the sudden spilling out of the cell's contents.
Now the theory began to take shape. Fuchs had been talking about the idea with her for months, but it needed rigor
and depth. It had to be airtight enough to be what Karl Popper called "falsifiable"that it could be supported or
disproved by experiment. Some of what she was saying had already been proposed by Charles Janeway in a
creative paper titled: "Approaching the Asymptote? Evolution and Revolution in Immunology." He had given that
talk at the 1989 Cold Spring Harbor conference, where she also spoke. Janeway had synthesized the latest findings
to suggest that the body's immune system responded not just to nonself but to patterns in antigens presented on
invading cells. Matzinger adopted what Janeway said and, as she liked to recall in lectures, "took one more small
stepand that step dropped me off a cliff." She broke entirely with the old model. "Hers was a profoundly deeper
idea than Janeway's," said Ron Schwartz. For once her sweeping, philosophical approach might beat out the more
precise voice of traditional science. ''Their ideas were similar," said Case Western Reserve University's Paul
Lehmann, who later tested their models, "but Polly was more cautious and philosophical. Janeway was plain
wrong, because in the absence of bacterial products you do get immune response. Polly may still very well be
right." Granted tenure in 1993 and promoted to section head, Matzinger built the confidence to put her ideas to the
world. But she needed a forum.
In 1994 the NIH researcher William Paul asked Matzinger to write the chapter on immunology for his annual
review. It was a nice recognition of her growing status, though more a review assignment than a creative one.
Matzinger turned it into her big chance: to write an original workmuch as Carl Woese would do later with his

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microorganisms. Night after night she reviewed the latest findings from around the world, synthesizing and
adapting them to what she snappily titled the "danger theory." She had not done any experiments yet, but the
whole thing fit so well with what others were uncovering. This was why the body did not attack cancer tumors; the
cells did not die until the cancer had advanced and metastasized. A mother's immune system did not attack her
fetus because fetal cells do not normally die by necrosis; the same went for a tadpole turning into a frog. The
seemingly mundane job of pulling together the latest news unleashed the rebellious part of her. With the same flair
for the dramatic that made her lectures so popular (she gave nicknames like "the schlepper" to the body's major
histocompatibility complex), that enthralled her audience with tales of mysterious police detectives who were not
what they appeared to be, she dropped her bomb in the most innocuous place possible, the Annual Review of
Immunology.
She contacted Fuchs to show him a draft of the paper and invite him to be the coauthor. At first her younger
collaborator was angry. "I had been discussing these ideas with her for months and then she had gone and written
them up. And she put things in the paper I did not agree with. But I have to admit she pulled it together and
explored the implications much more throughly than I had." She submitted the article with the title, "Tolerance,
Danger, and the Extended Family." And then she waited for the explosion.
5
New ideas can be accepted, discussed, rejected, or modified. Or they can be ignored, either because they are crank
ideas or because the field lacks the vocabulary for discussing them. Matzinger and Fuchs were met at first by
silence. According to Matzinger, researchers under thirty, especially those from outside the field, liked it but could
not go out on a limb. Those over fifty, especially those in the field, mostly disagreed. Those in between, the critical
audience who might listen and act on her ideas, mostly ignored it. Their silence was worse than disagreement. It
was to her a passive derision. She was a leading researcher who had been asked to write the round-up. It deserved
some kind of reaction.

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The lack of reaction may have come partly from the fact that others were on a similar track. Indeed, Janeway was
quietly furious, both with the idea and the way she went about presenting it as her own. "I have a personal grudge
with her because we presented the whole thing first. Basically, what we call innate immunity she calls danger.
We've done the experiments, we've got evidence. What she's saving is that anything that gives rise to an immune
response is danger and that anything that doesn't by definition is not dangerous. And that seems to me to be a
circular argument." She countered that her theory deeply extended Janeway's findings, which could not account for
the rejection of transplanted organs. But in one respect Janeway was correct. She needed data, She needed to show
that the sentry would be the dendritic cells. She needed to do an experiment.
In 1996, in the journal Science, Matzinger reported what she thought was one of the needed experiments. The
article, coauthored with Fuchs (who had begun the experiment in 1990, before leaving the NIH in 1991) and her
technical assistant John Paul Ridge, and titled "Neonatal Tolerance Revisited: Turning on Newborn T Cells with
Dendritic Cells," redid the famed Medawar experiment. This time they injected infant mice with foreign dendritic
cells that had been "activated" to trigger a reaction. If Medawar was right, that all cells in a newborn mouse were
tagged as "self," then there should be no immune response. If Matzinger and Fuchs were right, the cells should be
rejected.
The cells were rejected. This second time she proposed the danger theory, Matzinger recalled, "the shit hit the fan."
Business Week said she was "standing the immune-system theory on its head." The New York Times called her
model a "full scale challenge to the reigning theory of immunology." Even The Wall Street Journal noted that, if
accurate, her ideas ''would dramatically alter the development of anti-AIDS drugs, vaccines, and drugs to prevent
the rejection of transplants." When she presented her case directly to nonspecialiststo veterinarians, students,
clinicians, the publicthe response was electric, When she presented within her field, the response was fierce. Her
detractors wrote angry letters. Johns Hopkins University historian of science Arthur Silverstein bristled. Calling the
questions nothing new, he added: "it is unclear how the inferences and conclusions drawn by the authors could
have passed peer review."
Others started off with more common criticisms: They were "overinterpreting their findings," said Charles Janeway.
They confused the age of the cell with the age of the organism. All she had shown was that she could get an infant
mouse's immune system to react, But

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Janeway took deeper issue with her proselytizing to a lay audience, and so did others. "Maybe it's too close to the
field's roots as in snake oil salesmen, or alchemy," suggested Ron Schwartz. The reaction was insidiously
backhanded. In 1995 for instance, she was in Australia to present at a conference, and the BBC was filming for a
special on her called, "Turned On by Danger." Several researchers assailed her in the seminar, but only one would
go on camera.
The reaction seemed the response of a field whose main foundation is challenged by "an ontology," said a
supporter, Rochester University hematologist Neal Blumberg. Fuchs and Matzinger fired back a defense in Science
that noted how, almost two millennia before Copernicus, Aristarchus had proposed a heliocentric universe, only to
be laughed out of the academy until the academy was ready to hear the news. They cited Thomas Kuhn in defense
of the strength of their new paradigm. The difference in their idea, they said, was that their theory explained
anomalies in Medawar and Janeway. Some of the reaction did not make sense: Silverstein, for instance, said both
that they were wrong and also that they were adding little new to the old model first proposed by Burnet. Which
was it? they responded. If their idea linked them with Burnet, they wrote, "we could be in far worse company."
But the tempest had another effect: more than ever, Matzinger resolved to go over the heads of the arbiters of field.
Instead, she pressed her case directly to clinicians, students, and the public. In 1997 she was asked to give a
Special Topical Lecture at the American Association for the Advancement of Science meeting in Seattle, where
Venter and ecologist Gretchen Daily also gave major talks. She logged 100,000 miles in three years, breaking into
the public domain much as Greenfield and Venter and Marcy were doing. The difference was, she sought out the
publicity to motivate the acceptance of her ideas. In 1998 she was talking to veterinarians in Ontario, to
genomicists at the Institute for Human Gene Therapy in Washington, to researchers in Boston, New York,
Amsterdam, Sydney, and Auckland. Proclaiming her ideas to the world in the BBC documentary, in press articles,
in an Elle magazine profile written by Cynthia Fox, she further enraged her critics in the field. "Polly is doing this
kind of sales pitch. She's very good at it. Many scientists react to that as not science, though," her friend and NIH
supervisor Ron Schwartz commented, likening her to a kind of "Madonna figure,"
It was not just a new idea but a new way of offering ideas in a period of tremendous change in the access of
scientists to the media. "It could be that the legacy of [people like Matzinger and Venter], these

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prophets of the new frontier, is that they're open to teaching the public," said Schwartz. Her talent for promoting
her theory, not to scientists but to the general public, further exasperated her critics. Charles Janeway said, "The
bottom line is there are thousands of researchers doing important science in this field, and Polly is not one of
them." To others her penchant for publicity undermined the seriousness of her approach. "I think this accounts for
the utterly disproportionate anger I'd hear in the field. People ask me, how can you keep her at the NIH? Well,
from the start she's done very careful, very seminal experiments," said Schwartz. ''But people do not accept this.
Why?"
The theory pushed immunology to look inward, urging researchers to attend differently to each organism, which
was part of Matzinger's talent for training dogs but ran counter to the drift of Western science, "She said you
should make a different vaccine for each patient, and medicine was not ready for that," observed Pramod
Srivastava, a University of Connecticut immunotherapist. "She's given a vocabulary to contain thoughts that
perhaps were not being thought about. She said the words. Words are like trap doors. They can let you into new
rooms, new universes. The language she used for danger is a very powerful trap door."
The larger community of science recognized the "trap door" intricacy and freshness in her contribution that
engendered the anger in her field. The journals Science and Nature invited her to review papers for them. She
became a regular review contributor to Nature, as was Susan Greenfield. She served on grants review panels at the
NIH. She became a much-sought speaker at major conferences, especially those outside the conservative, datadriven United States. Multilingual and multidisciplinary, she connected with European science in a way none of
her rivals did. She became the first woman ever to give the prestigious Grabar Lecture at the annual meeting of the
French Society for Immunology. She gave keynote addresses at the German, British, Canadian, Austrian,
Scandanavian, and Dutch immunological societies, as well as at the annual meetings of nonimmunologists in the
United States, including geneticists, ethicists, and transplant surgeons. But, in the end, was she right?

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6
"No number of lectures, seminars, or other verbal communications," Peter Medawar wrote in Advice to a Young
Scientist, "can take the place of a contribution to a learned journal." Arthur Silverstein suggested there was no way
to test her theory. With her international travels, she was slow to build the data she needed to convince her field,
but other researchers that she hooked took up the slack. These included Gus DalGleish of St. George's Hospital in
London, Allan Kirk at the U.S. Naval Hospital in Bethesda, and Pramod Srivastava.
Allan Kirk and David Harlan of the U.S. Naval Medical Research Center were among the first to jump on
Matzinger's idea. Kirk began working on kidney transplants, making them "take" without using immunosuppressive
drugs, as the danger theory promised. He had promising results in mice and moved on to rhesus monkeys. By
August 1997 he was announcing results of an experiment using a synthetic protein that made it possible for an
immune system to tolerate a mismatched kidney without any immunosuppressive drugs, and the story was big
enough to make it into The New York Times Science Section. By June he was holding a press conference to
confirm what Leslie Spring of the National Kidney Foundation called "an amazing breakthrough," the use of
synthetic antibodies to mimic a safety signal in rhesus monkeys. In November 1998 the technique was providing a
model that could be applied to the autoimmune disease Type I diabetes, and Kirk joined with the Diabetes
Research Institute at the University of Miami to develop a human treatment. "We lose ten people every day
because I'm not working fast enough," he told reporters. By February 1999 the National Institute of Allergy and
Infectious Diseases inviting him to join an expert panel to develop "a new paradigm'' to revamp the dialogue
between clinicians and theorists like Matzinger.
Gus DalGleish of St. George's Hospital recalled being electrified by Matzinger's talk at the American Association
of Immunology Conference in New Orleans. He had been treating melanoma patients with a vaccine created from
their own tumors, and Matzinger's theory provided a new framework to explain the results: the immune system had
to be stimulated to see the tumors as dangerous. Within two years he was seeing a threefold increase in the survival
rate of his patients. "It's not stopping the disease," he cautioned, "but it's slowing it so one can go in and remove
the tumors." As for the other cancers, Matzinger had success in convincing major researchers, like Michael Lotze
of the University of Pittsburgh School of Medicine, who suggested that,

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her "strong intuitive sense for the biology is right and what she calls 'danger' is largely right." At the National
Cancer Institute, researcher Francesco Marincola suggested that her theory "explained a lot of phenomena
molecular immunologists" were seeing. "The old model is definitely wrong," he said. "Matzinger's theory is a
historic intellectual step. It's the only one going in the right direction." But she still needed her molecular handle.
She got one hint from an unlikely place.
In India many years earlier, the budding paleontologist Pramod Srivastava had been helping temporarily in the
Center for Molecular Biology, where he puzzled over the fact that a cancer vaccine worked against only the single
tumor it came from. "What molecule could be so valuable, so polymorphic, as to account for this?" he wondered.
Thinking he might be onto the discovery of a mechanism as profound as that of antibodies, he began doing
experiments. Not knowing immunology, he came at the problem as straight biochemistry. What he was led to was
very humble, not antibodies at all but a kind of protein called "heat-shock" because cells manufactured more of
them when they were heated. Because heat-shock proteins could replicate the antigenic handle on a tumor, they
appeared to be the body's internal mechanism for signaling.
Srivastava had been thinking about his heat-shock proteins for about fourteen years, when he came across
Matzinger's article for the 1994 Annual Review of Immunology. The danger metaphor caught his interest because it
offered a "very powerful" new way of thinking about his own work. "I remember just feeling quite excited. It
seemed that there was something important for me in that idea." Coming from India, he felt her idea of the way
cells died held an important message. It "resonated very deeply," he said. Rather than a lockstep immune system,
Matzinger saw a flexible system requiring flexible, personalized treatment. At the 1995 summer International
Immunology Congress in San Francisco, one of his postdocs who had heard her talk came to him, breathless with
excitement. That was it: Srivastava had to call her. The beauty to him was that she confirmed his own shift of focus
from outside to inside. Before that, the immune system had always been considered to be outward looking in the
old technical approach of self/nonself. "Hers was this very powerful idea, to listen to what the body is telling you. I
found it very powerful scientifically, as far as its testability and implications, and metaphorically as far as its
admonition to return to a traditional medicine of close observation. I felt the objections to her were mainly a
cultural block."

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Like Kirk, Srivastava set to work, first with mice, then rats, then sheep. By 1998 he was hosting the first
International Conference on Heat-Shock Proteins, with another scheduled for 2000. He cofounded Antigenics, a
biotech start-up, and prepared for clinical trials. He became involved in a series of studies at New York's Memorial
Sloan Kettering Medical Center and Houston's M. D. Anderson Center. Small numbers of patients suffering from
melanoma or renal or pancreatic cancer were treated with vaccines made from their tumors after they had been
removed, with promising results. The trouble was that the procedure was expensive. Still, other biotechnology
companies, including Intracel in Rockville, Maryland, were following up on the idea, putting them into the pages
of The Lancet and on the front page of The Wall Street Journal.
The danger theory offered one of several possible avenues for clinical treatments, and Srivastava did not see it so
much in conflict with Janeway as extending his ideas. Yet within her field Matzinger 's ideas remained more
problematic than they should have been. Paul Lehmann of Case Western Reserve University, for instance, tested
the validity of her theory against Janeway's. In the summer of 1999 Lehmann published his findings in the Journal
of Immunology. Of the three possible interpretations of what he saw, Janeway's idea he felt was proved the most
wrong "because in the absence of bacterial products you still get immunity." Matzinger's was more likely accurate,
but a little too simple and clean. "Danger is not a single quality," Lehmann cautioned. But for her contribution to
shaking up the field, he was effusive. "Thousands of labs depended on self/nonself discrimination, and she
suggested they reconsider this. She's done a wonderful thing," he said. Her theory worked well for clinical
hematologists Joanna Heal and Neal Blumberg, who wrote letters to Science supporting her work.
As for Matzinger herself, the dispute bothered her even as she stuck to her challenge. "Janeway's theory cannot
explain why the immune system rejects transplants. I can." The debate could be boiled down to scientific issues,
but the dismissiveness and the rancor were difficult to understand. "I used to be really close friends with Charlie
Janeway," Matzinger said. "It just makes me really sad."
There was nothing new about scientific rivalries spurring research. "The kind of rivalry between Janeway and
Matzinger, that's the real history of science," said Schwartz. Nor was there anything new about a proposed theory
outstripping the technical proficiency of the day. When Copernicus proposed his new theory of the heliocentric
solar system, his idea could not be tested, wrote historian of science Karl Popper. It first of all offered a new way
of interpreting old findings.

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"That was also true of Einstein and Darwin at the time of their findings," said Northwestern University historian of
science David Hull. "There was no way at that moment to test their findings." Neil Blumberg, perhaps too glibly,
called the objections to Matzinger a typical response of the "professional scientist heavily invested in an old
model."
Part of Matzinger's effect on immunology came from her international stature, which inspired a generation of
students. Her nurturing passion attracted the minds of Kamala Tirumalai, who came from Madras just to work with
her, and Oral Alpan, who came from Istanbul. Tirumalai was impressed not so much by her big-picture thinking
but by her incredible command of detail. "In my first experiment I had amassed all this data," she recalled. "Polly
spotted right away the three anomalies in all the tables that made for my conclusion." When Matzinger needed
more direct proof of the danger model, Tirumalai and Alpan proposed an experiment with sheep. They hoped to
answer a challenge made by Mel Cohn, to show that organisms can be immunized against their own
proteins,"which would be one of the most direct proofs of the danger theory," says Alpan. The three of them,
working with one of Matzinger's border collies, began heading out once a week to immunize their sheep and test
their blood. "There are days when you're in the lab until 3 AM," says Alpan. "But the main thing she demonstrates
is a way of thinking science. We're not here just to publish. She wants you to go out and spend a day at the ocean
just thinking about if what you're doing is important. Then she listens.''
Matzinger offered a counterweight to the technicians of science who loomed preeminent at the millennium. An
outsider, working with a small team, she brought a holistic approach to transform a field. "It is not the correctness
of a theory which I wish to discuss, but its boldness," Karl Popper wrote. Great scientists, seeking the levels
beyond the levels of reality we see, engage almost in a kind of mythmaking, Popper said. They build on what
comes before.
During a normal week, all three of them would bring her border collie in a Toyota Corolla to round up the sheep
they would inoculate, preparing the data for a future paper. "She makes you excited about what she's excited
about," said Kamala.
I felt that excitement when she asked my opinion of what other researchers had said of her. She made me feel that I
was helping to advance research in much the way she made me a co-conspirator in her story of a mysterious police
detective, in what Schwartz said of their late-night talks. The final summer of the millennium for her

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included dog training and sheep-herding contests almost every free weekend. On Saturdays she was out in dewdrenched Maryland fields, moving through the mist.
There was a revolution going on in the way we think about transplantation biology, and researchers like Matzinger
were coming at the problem from science's humanist beginning. From the beginning of her own education
Matzinger had questioned immunology's half-century-old model, but it was not until she read some good books on
evolution that she was prepared to think creatively about that model. She left questions on a board and listened
when one of her younger associates, Ephraim Fuchs, responded. Like the young cosmologists featured in the next
chapter, she participated in a regular journal reading club with all of her assistants, keeping up on the newest
questions both inside and outside her discipline.
Her new model offered a highly fluid, interactive, discerning immune system that changed as an organism changed.
It introduced a body operating by dynamic processes rather than the fixed rules of immunology doctrine. Moving
between small picture and big, professional audiences and the public, she had presented both a new way of
thinking and presenting one's thinking. "I can't think of another scientist who has been more influential in helping
me make sense of the phenomena I observe in the clinic," noted Alan Kirk. What seemed impossible seems very
possible now."

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How Much Fun This Is:


Saul Perlmutter and the Supernova Cosmology Project
1
Graduate students called the home of Nobel Prize-winner Luis Alvarez "The Castle." Monday nights they raced
there after their afternoon seminars and quick dinners, climbing the steep flagstone steps beneath low-hanging
clouds, as drizzle raised the scents of bougainvillea and pine high in the hills of Berkeley, California. Inside, they
could hear arguments rage in the living room with its baronial stone fireplace and commanding view of San
Francisco Bay, as senior researchers tried to prove each other wrong. Everyone ate Oreo cookies and gulped
slippery beers, watching as casserole dishes were tilted to imitate the Earth's axis or the curve of gravity.
The terror of the meetings was that each week one student had to report on a new finding or hot science rumor.
Alvarez and the others would grill the speaker, interrupting every few minutes, demanding clarification of a
statistic or contradiction, until gradually the group moved on to the latest controversies and gossip in physics or
science or just about anything. Tall and blond at seventy, Alvarez had won a Nobel Prize for the particle physics
discoveries made with the bubble chamber he had invented. Since then he had moved among different fields,
looking for fundamental questions. He started companies and they succeeded; he started branches of physics and
they caught on. He could have rested on his achievements, but instead he lunched

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with students (the "young pricks" he called them) rather than colleagues ("old farts"). He worked with
undergraduates and graduates. He invited them to his home. Once Alvarez invited physiologist Marion Diamond to
dissect a brain on his coffee table. When she was done, Alvarez squeezed the cerebellum, then tossed the rubbery
lump into the air. The lessons of those evenings boiled down to one thing: all science is crazy passion.
Into this group in 1982 came twenty-two-year-old Saul Perlmutter, a hawknosed, long-haired, slight, nice, quicktalking Harvard graduate raised near Germantown in Philadelphia. On those Monday nights he watched and
absorbed the many lessons. If a mystery lay outside your field, he learned, you did not give up. You learned the
new field. It was better to have a wide-ranging curiosity, to know a little about a lot of things, than to know a lot
about a little. Most of all, he absorbed the confidence to shake up new fields if that was where desire took him.
Perlmutter had been raised by two graduates of the academy: his father was a chemical engineer and his mother a
social worker. Though Jewish, he had attended a Quaker school in Philadelphia. He played the violin and lived on
a tree-lined block with working-class and professional families, playing baseball in the street and rooting for the
Phillies. The idea of pursuing truth across many fields energized him.
Saul Perlmutter wanted to pursue fundamental physics but felt depressed by its unwieldy bureaucracy. In the 1980s
high-energy physics was practiced by four-hundred-person teams, working on the world's three or four biggest
particle accelerators like the anonymous builders of gothic cathedrals. As a child he had loved building Rube
Goldberg contraptions based on nature's simplest mysteries, like the way a rotating bicycle tire turns against the
direction you push it. He came to California for big questions, innovative science, and for the Lawrence Berkeley
Laboratory (LBL).
Perched at the top of a steep hillside, the Lawrence Berkeley Lab was a unique government institution. Founded in
1931 in an abandoned clapboard engineering building, it helped pioneer a new science of nuclear cyclotron physics
that cut across the traditional disciplines of chemistry, physics, and engineering. By the 1980s however, Lawrence
Berkeley Lab physicists were again looking to a new interdisciplinary science. This time they were getting into
cosmologythe study of the universe as a whole, its beginning and end, the kinds of big questions once relegated to
philosophy. Probing infant galaxies, distant star clusters, tidal nebulae, and dying stars, they hoped to learn about
the size and shape of the universe and, therefore, its age, without the aid of

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billion-dollar budgets and physics machines. In the very distant and the very large, conventional physics broke
down, making fertile ground for basic research. Toward that end, the lab was developing the technologies for using
a monster telescope that it hoped would be built at Hawaii's Mauna Kea peak, Looking into the deepest recesses of
the heavens the Keck, it was believed, would capture the pyrotechnics of deep spaces power physics, much as the
early Berkeley cyclotron had done for earthbound physics.
At Berkeley Perlmutter met an enthusiastic Californian, Carl Pennypacker, who specialized in cosmic rays. With
his moustache, glasses, and awkward speech, the twenty-two-year-old Pennypacker would lug fifty pounds of
equipment up a mountainside in the rain if he had to. In sixth grade, Pennypacker had worked out for himself the
mathematical proof that the square root of 2 was always irrational. He never forgot the incredible rush that he felt,
in his room, unveiling a law of God. Seeking that same adrenalin rush, he joined Alvarez's group as a Berkeley
undergraduate.
Perlmutter and Pennypacker worked primarily for Alvarez's protg, the Bronx-born Richard Muller. On those
Monday nights of beer and cookies, they watched "how Luis's mind worked," said Pennypacker. They saw an
independent, impatient, intuitive thinker, willing to admit his mistakes but ready to savage those of others. Alvarez
thought the plan of American physics for a giant Superconducting Supercollider was ridiculous, for instance. He
considered the $4-billion, twenty-mile circular Texas tunnel a machine with no imagination. Indeed, its final
political defeat after millions had already been spent signaled the demise of cold war, big science.
Watching Alvarez, the two graduate students witnessed how such a bold approach could transform a science and
capture the popular imagination. Back in 1979 Alvarez's son Walter, a geologist, had discovered an odd layer of
black dust containing rare isotopes of iridium and niobium in rock that was some sixty-five million years old.
Other similar discoveries around the world seemed to link the dust layer, which could have been generated by an
asteroid impact, with the extinction of the dinosaurs. Luis and Walter Alvarez proposed just that: an asteroid
collision had blanketed the Earth with dust, obliterating the sun, lowering temperatures, and killing off the
dinosaurs. The idea, cutting across disciplines like climatology, geology and astronomy, electrified the world,
enraged traditional researchers, and eventually made the front cover of Time in 1985.
The idea that such a tiny clue as a layer of dust could hint at such a profound secret of existence, exploding into the
world's attention,

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grabbed hold of Carl Pennypacker and Saul Perimutter, who watched the drama unfold. "We learned there was no
limit," Perlmutter recalls, "and that you could use one field to change another."
What could they do to match that? They decided to attack cosmology, For much of the twentieth century,
cosmology had been dominated by a handful of great men with access to the big telescopes on Mount Palomar and
Mount Wilson. People like Edwin Hubble and Allan Sandage controlled the libraries of carefully culled
photographic plates that built the dogma of galaxy classifications and the supposed expansion rate of the universe,
its birth and fate. They uttered pronouncements like "Nebulae are found both singly and in groups of various
sizes." As the writer Dennis Overbye observed, "You could hear the intergalactic winds creaking" through their
prose. For all the swashbuckling at LBL, students felt haunted by the suspicion that this great triumphal era of
astronomy was ending. There were many more physicists and cosmologists than ever before, and funds were
drying up. Some told students that there was nothing left to discover. "The kind of research that made science grow
for so many years, where you bring in young people and nurture them and they become great scientists, boy that's
becoming very hard," observed Muller, after the tremendous success of his early career. "When I started in 1969, I
could look around and see a lot of people having a wonderful time. I don't think that's true anymore."
Then Saul and Carl came along.
2
Cosmology in the second half of the twentieth century was the quest for two numbersthe expansion and
deceleration rates of the universe. If you knew those you could figure out the greatest mysteries of all: how the
universe began and how it would end. The problem was measuring these numbers. What sort of yardstick could an
Earthbound observer use to measure the expansion rate? In the 1950s an eccentric thinker at Los Alamos, Stirling
Colgate, suggested the best measurements might come from supernovae, or dying stars.

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When a massive star runs out of nuclear fuel, its outer layers collapse onto its core, setting off a final catastrophic
explosion. For a few seconds, it gives off more energy than all the stars of an entire galaxy. For the next three or
four weeks the spectacular death cloud glows with the brightness of ten billion stars. The dying star spews out a
rich dust of carbon and complex atoms, seeding the universe with the building blocks of life. We are all walking
stardust or, more prosaically, the garbage of supernovae.
Scion of the toothpaste family, Stirling Colgate became known at Los Alamos for concocting schemes that were
either crazy or way ahead of his time. Supemovae could be seen very far away, Stirling Colgate observed. They
also seemed to be fairly uniform in brightness, which depended mainly on what kind of star they originated from.
Brilliantly radiant, they could serve as the calibrated candles cosmologists desperately needed. Colgate built his
own automated telescope to search for supernovae.
For cosmologists willing to take on the biggest questions, distant supernovae posed a quixotic goal. If you could
somehow find and measure those superbrilliant explosions on the edge of the universe, you would have a shot at
learning the age and fate of the cosmos. Indeed, in 1977, in a popular book called The First Three Minutes,
Harvard physicist Steven Weinberg was among those who carried Colgate's idea further, suggesting that one should
try to measure the redshift of the spectra of distant and relatively uniform supernovae. Redshift is a measure of
speed based on the Doppler effect: the light waves from rapidly receding objects are longer than those of a
stationary object, shifting their spectrum toward the longer, red end in the same way that the sound of a receding
police siren shifts down in pitch as it races away from you. If one could measure the speed of the most distant
observable objects in the sky, said Weinberg, one could learn how fast the universe was expanding and, thus,
critical facts about its age and beginning.
Astronomers knew all this; the problem was finding the distant supernovae and measuring their light. Until the
twentieth century we could not hope to spot them. Observers on Earth with the unaided eye saw only about one
supernova every few centuries, and these were close by. With better telescopes the search for dying stars became a
quest for amateurs like Robert Evans, an Australian priest who tracked them in his backyard, using a ten-inch
telescope. Evans memorized each sliver of sky, seeking any short-lived brightness that appeared where no star
existed. His years of searching produced some forty supernovae, none of them very distant. He demonstrated what
could be accomplished, however, as Evans helped mark a twentieth-century comeback for amateur astronomers.

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Hearing of automated military telescopes that tracked the sky for incoming missiles, Luis Alvarez proposed a
systematic automated search for supernovae, using robotic telescopes to scan the sky and computer programs to
compare fresh images with old ones, identifying objects that were not there before. But he was too embroiled in the
controversies over the dinosaur asteroid to follow up on the idea. Richard Muller started a supernova search group
with Pennypacker, but they had less success than Evans when they began.
In their search for a big project Pennypacker and Perlmutter grabbed supernovae. "We always had in our heart and
minds to use these to measure the universe," said Pennypacker. "Because that's the Holy Grail of cosmology and,
you know, a major intellectual, cultural achievement if we could get that." They bet that improved computers, with
more automated telescopes and sharper video light detectors, could raise viewing power exponentially. "We came
from a generation that was comfortable with throwing a computer at a problem," Perlmutter said, In conventional
astronomy, taking a spectrum of a distant starfiguring out what it was made of by breaking up its lightcould take a
month. With new sensitive electronic detectors, spectra could be nailed in minutes. At least, that was the idea.
More than simply a line of research, it was a new way of doing astronomy. They would go into the night without
an agenda; the sky would tell them what to do. High-speed computer programs could digitize the information
immediately, enabling them to send it around the world (first by fax and later by e-mail), then instantly command
two or three of the world's best telescopes to focus simultaneously on a distant star's three-week death dance. That
way they could increase their viewing power enormously. Huge amounts of data, near instantaneous processing,
wide fields, state-of-the-art detectorsthe whole project was an almost ridiculously daunting adventure. It was
guerilla astronomy.
Fortunately they were at the Lawrence Berkeley Laboratory, where they could get the initial funds without a huge
review process. Muller contributed some of the money that flowed in from some of his other grants. Pennypacker
initiated the search. A Danish group had tried a similar approach but they lacked the followthrough and technology
and support. "It's similar to genomics," said Harvard's supernova specialist Robert Kirshner, "in that the technology
progressed very rapidly." In the hills near Berkeley, Pennypacker helped automate the University of California's
humble Leuschner Observatory. A three-quarter-meter telescope, every minute it looked at a different galaxy.
From 1986 to 1989 they found twenty supernovae among nearby galaxies.

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For distant supernovae they needed the newest technologies in charge-coupled detectors (CCDs) sensitive to ultralow light levels. Light was collected on a silicon wafer and then read out by a computer. A good photographic
emulsion might capture 5 percent of the light hitting it; a CCD nabbed 50 to 80 percent. Their Monday nights at
Alvarez's house gave them a secret weaponcultivating insiders at nearby Silicon Valley, they heard about and
nabbed "the very best new detector the moment it came out," said Pennypacker.
With their small early success, Pennypacker used LBL funds to collaborate with Warrick Couch to build a new
camera on the Anglo-Australian Telescope. The camera was one of the widest-field systems on a large telescope,
and it was dubbed the Pennypacker F/1 system for its new optics. They enlisted a senior data expert, Gerson
Goldhaber, who had survived Nazi Germany and helped to discover several fundamental particles at LBL. With his
white beard, Indian shirts, and calm deliberative manner, ready to plot their data points as he had plotted the bursts
of energy in the earliest particle accelerators, he brought a steadying hand to the small, nervous group. They
needed better computer programs, Muller said. Perlmutter had already developed them, "I decided then that Saul
was directing this project and, since I wasn't ready to be a follower, I dropped out," Muller recalled.
Australia made for an idyllic four months for Pennypacker and his wife and two children. It was like America in
the 1950s. They were living the best of what science could be: you get an idea, get money, travel, and spend a year
looking at the sky. In a beautiful national park high atop the hills east of Sydney, Pennypacker set to work. Once he
had the machines up and running, he transmitted their data to Berkeley by a fledgling Internet link developed by
NASA's AMES Research Lab. Driving home, he would see kangaroos skipping along the highway.
They struggled, however, with poor sky conditions. When you observe through a computer you do not see clouds,
you see lousy numbers. Frequently they told their operator to go outside and just look up to see why their programs
were not working. The clouds prevented them from finding a single decent supernova. It was a disaster. "We
almost gave up," said Pennypacker.
Instead, they rethought their entire approach. Even if they had had better conditions, their technology was still not
good enough to find the incredibly faint smudges they sought on the edge of time and space. They built a new
camera from scratch, making the most of Perlmutter's skills as a young engineer in his family's garage, and sought
a collaboration with the Royal Greenwich Observatory in the Canary Islands. The Cambridge group there was
studying quasars

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distant, mysterious sources of gigantic energy pulses. "I said, why don't we work together and use the data for
different purposes?" Perlmutter was proving adept at coaxing precious telescope time, becoming an operator and
politician in their desperate days. In the isolation of the Canary Islands' remote mountaintops, with their howling
winds, their collaboration began.
The Canary Islands provided an ethereal backdrop for staring into the farthest reaches of the sky. At the top of the
mountain, as in the film Journey to the Center of the Earth, eerie lava formations towered over a volcanic crater.
At night the stars blasted out at full volume. The Milky Way glowed like a torn bridal dress. There they got their
first supernova with the new telescope in 1992. It took three weeks, but once the data had been analyzed they knew
something vital: the idea worked.
The collaboration with the Royal Greenwich was vital because the Supernova Cosmology Project, the grandiose
name they gave themselves, was under fire from their funders in the early 1990s. They had spent a lot of time and
money in Australia and gotten nothing. Theirs was not a project that would pay off in a year or two, they argued. It
might take ten. They said they wanted to do a new kind of digital, holistic astronomy. They would use the
developing Internet to coordinate the search in the Canary Islands with the world's best telescope, the LBLdesigned Keck Observatory in Hawaii, and with the Hubble Space Telescope itself.
Still the project was placed under external review. "We were fighting for our lives," recalled Pennypacker. On the
review board was Harvard's Robert Kirshner, the highly respected supernova researcher. Because Perlmutter had
been trained in physics, he struck some traditional astronomers as an interloper. The problem, according to
Kirshner, was the huge uncertainty in the search.
He pointed out that not all supernovae have the same brightness. "By 1991 we'd found a bunch that were extra dim
and extra bright. It would be like looking at lights on a highway and not knowing if you were seeing a truck or a
flashlight on a nine-volt battery," Kirshner said. "While Saul kind of charged ahead, some of us were very
worried." Their rate of supernova discoveries was discouragingly low, he wrote to the National Science Foundation
and the Department of Energy, and the margin for error in interpreting their brightness unacceptably high. The
review caused a snowball effect that threatened the whole project, "We had to fight like crazy to keep it alive,"
remembered Pennypacker. Kirshner, he felt, "was leading the charge against our survival."

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Some good results came from the struggle, however. They recruited from their Cambridge collaborators a young,
even-tempered spectroscopist named Isobel Hook, who thought their search was the most exciting thing in
astronomy. She agreed to analyze the spectra of light from their supernova, telling them if what they had was a
very distant, or ''high redshift" object. They decided to make their main telescope the Cerro Telolo reflector in the
Chilean Andes. Viewing conditions were better there. When the external review finally proved favorable enough to
continue, they started turning out distant supernovas. "By 1992 we got our first one, and by 1995 we found seven,"
Perlmutter said. Seven exploding stars, anywhere from six to eight billion years old. Our own sun was a second
generation star, formed from the debris of objects like these.
Perlmutter spent much of his time either in front of a computer or on the phone, cajoling extra viewing time from
other teams sharing the telescope, in much the same way he had jerry-rigged his childhood Rube Goldberg
contraptions. It was unbelievably difficult. Who would have thought of the great Luis Alvarez having to wheedle
time from a competitor? But even Alvarez, now seventy-four, agreed to assist them, by pitching in to manually
check their data, a time-consuming, arduous task. Perlmutter had such a childlike enthusiasm he was often
successful in getting other senior researchers to cede prized telescope time, despite the fierce competition for it.
Because they were not trained as astronomers they brought in a supernova expert, Alexei Filippenko, who had a
knack for getting attention. With his bushy eyebrows and open face he was a favorite of undergraduates at the
University of California at Berkeley, demonstrating concepts by throwing a tennis ball into the air. He could also
offer them institutional access to Keck. He and Perlmutter, however, had egos that did not mesh well.
Their nights were much more pressured than those of traditional astronomers, "heart-stopping, heart-sickening
ventures," as Kirschner later put it. Nervously they watched and waited, ready to take whatever the sky gave
themwhatever blew up. It was a heroic and unlikely method: first, one team at the Cerro Telolo telescope in the
Chilean mountains ran the search, taking the CCD images. Then, three weeks later, Chile took a new set of images,
and they transmitted the data back to Berkeley, using a compression technique because the Internet was not fully
established. A team in Berkeley compared the two sets of readings. They either called them into the newly built
Keck Observatory in Hawaii, or someone flew from Berkeley to Hawaii with the candidate list of supernovae.
Then Hook and Perlmutter would look at the spectrum and trigger the data to telescopes around

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the world, including the Canary Islands, Chile, and a telescope in Arizonahoping what they had was a dying,
unimaginably distant star. If not, they moved on to the next object. When they found something it was Hook's job
to decide if the spectrum they got was indeed a supernova. With the whole team looking over her shoulder, she had
a few minutes to give a thumbs up or down. When nothing was going on, Hook played rock and roll loud to keep
them going through the nightVerve, maybe, or Radiohead. "I'll never forget the first supernova," recalled Hook. "It
was at 1.4 redshift, not terribly high compared to what we get now, but it was such a beautiful spectrum and you
could see every detail. There's no question that it was a Type I-A supernova. I mean it looked so good, it
guarantees the project works." The image looked like a Mondrian painting. "Since then, we've been getting really
good spectra at higher redshifts where no one has gone before. I think to the earlier generation (of astronomers), it
seems sort of magic."
With restored funding from the National Science Foundation, Perlmutter hired a few more postdocs and graduate
students. The team now totaled twenty; they had "a presence." Some began giving papers at conferences. The
Berkeley lab increased its support. At the end of a Keck telescope run, they would take time off to swim at Hapuna
Beach, laughing and choking on salt water. At the end of the whole run, everyone came back to Berkeley from
their distant locationsChile, Hawaii, Tucson. They gathered at the home of Gerson Goldhaber and held a party. For
each supernova they found, they cracked open a bottle of champagne . . . eventually working up to twenty bottles.
Success stiffened the competition, however, from inside and out. From inside, Carl Pennypacker realized there was
no room for two group leaders and decided to pursue a project he had been thinking about a long time. He wanted
to bring in public high-school students to work with the raw data the group used, giving students the thrill of
cutting-edge discovery. Winning support from the National Science Foundation and the Department of Energy, he
began the "Hands-On Universe" program. He sent their data to California high schools by Iternet, where students
analyzed it virtually at the same time astronomers did. Students began discovering objects like new asteroids from
the information, giving them a bit of the rush Pennypacker first felt doing his math proof as a sixth grader. He
remained a member of the Supernova Cosmology Project, but turned over its leadership to Perlmutter.

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From outside, a rival international team of astronomers began copying their technology to compete with them.
Calling themselves the High Z Supernova Project (Z stands for redshift), they claimed to be a looser, more
sophisticated collaboration. They would pay closer attention to the nuancesthe precise filters and corrections
needed to understand the exact nature of the spectacles they were seeing. They would gather less data but analyze it
more carefully. Rather than cookie-cutter physics, they would practice real astronomy. Alexei Filippenko defected
to join this group, led by none other than Harvard's Robert P. Kirshner and his former student Brian Schmidt. "The
other group took pride in the fact that they didn't know anything about the folklore of the field," said Kirshner.
"Brian felt we could do what they were doing, only better."
Both groups were pioneering a new astronomy combining "big telescopes, great communications, and great
computing power," said Filippenko. Several other projects were also practicing this kind of interdisciplinary
cosmology. The Sloan Digital Sky Survey was using robotics and computers to provide the first three-dimensional
map of the entire universe with a sky search that, like Perlmutter's work, would be available immediately to
amateurs by the Internet. Using new robotics, cheap materials, software, and basic artificial intelligence systems,
NASA and the European Space Agency were planning several deep space probes to explore the universe's
beginning. NASA's MAP (Microwave Anisotropy Probe) and the European Planck satellites, for instance, would in
2005 and 2007 map in minute detail the ripples in the cosmic background radiationthe echo of the Big Bang. Like
the supernova projects, these linked particle physics with deep space astronomy by exploring how protons,
neutrons, and electrons first formed out of the cosmic soup.
"We're at the beginning of a new astronomy," said Alan Guth, the MIT theorist who in 1979 wedded cosmology
and physics with his theory of inflationthat the universe expanded exponentially in first fraction of a second. Now
astronomy was trying to understand what the universe was like in every moment of its growth. "When I was
younger I thought these parameters were unknowable forever. Now they're within our grasp. It's amazing. It really
is."
Perlmutter had not invented the opportunistic, shotgun approach, but the international team he directed had made it
work. But if the supernova cosmologists felt vindicated, they also now felt the hot breath of others gaining on them.

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3
In September 1997, sitting in his cramped office in Berkeley, Gerson Goldhaber was studying the group's data
points, the end product of months and years of work and dreaming. On graph paper he had plotted points from all
thirty-eight supernovae. He routinely looked at the grouping to anticipate what they were learning about the age
and future of the universe. For months he had noticed that all the supernovae were piling up at the lower end of the
scale, meaning they were farther away and farther back in time than commonly accepted theories of cosmic
expansion would have predicted. He kept thinking that the bunch would spread out as their precision improved.
Instead what he now saw was a giant spike, almost exactly like the spike he had seen forty years earlier when he
discovered the fundamental particle called the mu meson. He nearly jumped out of his chair.
What the spike showed was that, far from decelerating as all the astronomy texts claimed, the universe was actually
accelerating. This acceleration had been suggested by only one person, Albert Einstein, who called it lambda and
used it to counteract relativity's prediction that universe should collapse on itself. Einstein quickly abandoned
lambda as being a preposterous cosmic fudge factor. But the data Goldhaber was examining said they were seeing
some kind of universal constant, a mystery engine driving the cosmos. At a hastily convened meeting on
September 24 they argued into the evening. Several on the team urged caution. They were just getting legitimate
acclaim. They dare not blow it on such an outrageous finding. Better to wait, gather more information. "Gerson
says he will keep working on this," the minutes of the meeting read. Then, in italics, Goldhaber was quoted as
saying, "I've been known to make mistakes."
In December 1997 Saul Perlmutter was staying up all night at the Keck Observatory. Taking camcorder pictures of
the sky from the peak of Hawaii's tallest mountain was a lonely job. Oxygen was only 60 percent of that at sea
level and the night sky, stretching over the observatory's twin domes, disoriented viewers at three in the morning.
He had a constant headache. Every so often the telescope operator put on his down jacket, went outside, and slid
through the snow to look up and check that the three-hundred-ton machine was pointing out above the clouds.
Steam rose from a volcano. Above him, seven-billion-year-old starlight roiled and spun. They worked all night and
caught a few hours of sleep in the day.

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Perlmutter and Hook again worked frantically, analyzing the images and directing where to point the telescope
with nanometer precision. Ever since their meeting with Goldhaber their work had a new urgency. Perlmutter was
going to present their findings at the biggest science conference in the world, the American Astronomical Society
(AAS) conference in January in Washington. What would he say? He e-mailed the targets to the Canary Islands,
Chile, Arizona, and California, and ultimately to the Hubble itself. Then they waited anxiously. Isobel Hook had a
few seconds to analyze each image from the top of the mountain. They argued, talking with the telescope operator
by video teleconferencer. When she had some time, Hook liked to go outside and look up at the starlight coming
from the edges of the universe, all the way to where she stood at the volcano's bottom in a breeze that smelled of
bougainvillea.
Perlmutter dropped the phone to check the computer screens again. Hook and Perlmutter decided when they had a
good spot, assigning the greatest telescope in history, the Hubble Space Telescope in orbit two-hundred-forty-five
miles above them, to look at a distant smudge of a star in the throes of death. Using this approach to detect
supernovae on the fly and transmitting this information around the world instantly, they were coming close to
realizing their dream.
They were also racing another group. They plotted their findings on a graph, matching the distance of the stellar
explosions against their velocity as they were swept away by cosmic expansion. Their data made for a perplexing
line. Everyone was buzzing about it at Hapuna Beach on their last day. The line curved up at its end, as Goldhaber
had suggested, meaning that indeed the universe was not decelerating as all the texts said, but was accelerating. If
it was real it would make the announcement of a lifetime. But their uncertainty was high; too many things could be
wrong. Did they have the correct color measurements? Why did their analysis now disagree so much with an
earlier one? Perlmutter caught a flight to Berkeley, where he had a morning layover to race to the lab, run the
numbers, print out a poster, and race back to the airport, where he hopped a plane to Washington, D.C. with the
graph stuffed in his briefcase, heading to the annual meeting of the American Astronomical Society.
I saw him present his findings that January. He was disheveled, having just jumped off the plane after staying up all
night. From devices as common as the light detectors used in camcorders and the Internet, he said, they had
evidence suggesting that, contrary to theory, the universe would expand forever into a lonely infinite night.
Reporters mobbed him afterward.

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Surrounded in the press room of the Georgetown Hilton, Saul Perlmutter was the star of the AAS meeting. He was
offering a possible solution to one of the biggest questions of cosmology. Fortunately, four other researchers on his
panel, using more conventional methods, had gotten roughly the same result. After he gave his talk, reporters
clustered around him for an hour, asking question after question. How could you take the Hubble, writers asked,
steer it into position, and watch the death of a star lasting all of three weeks, from seven billion years ago?
It was a great place to report findings because the funding directors of the National Science Foundation and the
Center for Astrophysics were all there. Their story played not just in The New York Times, but in newspapers and
on TV news all over the country. It was enormous news, telling us that "some kind of new physics is happening
now," Princeton astrophysicist David Spergel told The Washington Post. Perlmutter discovered that he possessed
the traditional cosmological talent for publicity.
But he chose to play down their more spectacular results. One reporter, James Glanz from Science, commented on
the implied cosmic acceleration in their data while two others hinted at it later. In the hall afterward I joined
Perlmutter as he hung out with some of the other young astronomers, still happy to answer questions, checking out
what they were doing. For the rest of their lives, however, some in his small group would question their caution.
4
The following month a much smaller meeting was scheduled at Marina Del Rey in California. There both
supernova groups were to speak. Acceleration, the idea that objects in space were moving faster and faster away
from each other was a monumental discovery, on the order of Edwin Hubble's first observation, in 1927, that the
universe was expanding. If the universe was accelerating, the entire foundation of physics was shaky. It meant a
completely unknown force or energy was at work.
The problem for the Perlmutter team was that their margin of error, or error bars, were still too great, they felt, to
make such a stu-

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pendous announcement. But the competing group now had had access to their data since it had been announced.
What should they do? At Marina del Rey Perlmutter showed their data with the error bars, saying they had
"evidence" for acceleration but not proof.
Then Alex Filippenko rose to address the group. Well, he began, savoring the moment, either you have a discovery
or you don't. We have evidence, and our error bars are much smaller and better understood. We have for the first
time real evidence of a new "antigravity" force at work in the cosmos.
Afterward a commotion broke in the conference room. Again it was James Glanz of Science who got the story first,
though other journalists soon followed. The curve on the top of the High Z graph pushed the cradle of physics off a
cliff. "Somewhere between amazement and horror," said High Z coleader Brian Schmidt of the Mount Tromlo and
Sliding Spring Observatory in Australia. "Magical," said Michael Turner, theorist of the University of Chicago.
"It's crazy," said colleague Rocky Kolb, who compared the discovery of the missing matter in the universe to the
Marx brothers movie in which more and more people crowd into a stateroom, leading to chaos.
If the universe was expanding faster and faster, not only were the texts wrong, but something like 70 percent of the
universe's energy was missing. This mysterious energy was driving the unheard-of acceleration. The finding was so
amazing that many theorists balked, rightfully so. "Extraordinary claims require extraordinary evidence," cautioned
Turner. "The competitive urges," added another theorist, "have driven both these groups out onto a limb where they
shouldn't be."
While the two teams set to work on supporting their claim, Alex Filippenko had to take off for a long-scheduled
eclipse cruise, mostly for retired couples. It was fitting that the youngest member of the High Z team, the soccerplaying Adam Riess, suddenly found himself on the "McNeil-Lehrer News Hour" (his father's favorite show),
discussing the meaning of space and time. "(They) asked me, 'Why should people care about this?'" Reiss recalled.
"I said, well, 'Why am I on this show?'" Riess had done most of the grunt work. For once a postdoctoral jobseeker
got the acclaim. Younger than any other group member, Riess was proof of a new astronomy taking hold. ''This
was something most of us thought we would just never know," he said, echoing Guth's words.
As for the Perlmutter team, after all their work, all the rejection, the criticisms leveled against them rankled: they
were too bold or not bold enough, and in either case they were mere physicists, too sloppy for the finely nuanced
art of astronomy. Kirshner gave them no credit

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in his discussions in the press, even though it was their method that made the discovery possible. "He got the credit
because he came from Harvard," complained Pennypacker. "They have better press agents," said the normally
equable Gerson Goldhaber. The bad blood between them, embarrassing for all, became even, well, badder.
"Hey, what's the strongest force in the universe?" Kirshner told The New York Times. "It's not gravity, it's
jealousy." Photographed in front of the august Harvard-Smithsonian Center for Astrophysics, he grinned in
triumph.
5
The announcements of the findings had stirred up so much puzzlement and sheer disbelief that Perlmutter, Riess,
and Kirshner were all called to a showdown at a conference in May 1998 at the Fermi National Accelerator
Laboratory. In the Illinois prairie, theorists and experimenters came together for a gathering called "Where Is the
Missing Energy?" The theorists were desperate to question and challenge the findings, and to know more. The
giant particle accelerator at Fermilab provided a fitting backdrop, because it was the machine that solidified the last
piece of the Standard Model of physics and the cosmos.
While cicadas chimed outside, researchers grappled with the discoveries. If, as most thought, the cosmic soup had
exploded exponentially in the Big Bang, doubling in size every instant in its first trillionth of a second, it seemed as
though, for its first seven billion years, the universe had indeed been slowing down. The evidence from the
supernovae experiments suggested, however, that at a critical point, when the density had lessened, another
repelling force had kicked in, pushing matter out faster and faster.
The force seemed to be Einstein's famous "cosmological constant," added in 1917 to his theory of general
relativity. Einstein added it because relativity seemed to predict the universe should collapse under its own weight.
When Edwin Hubble discovered the expanding universe, Einstein discarded his constant as "the greatest blunder of
my career." Now it was resurrected, If the universe was accelerating, some previously unknown enormous energy
existed.

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Was the missing energy Einstein's cosmological constant, or something more dynamic that varied over time? "It's a
monumental issue," said Princeton's Paul Steinhardt. "It means a significant fraction of what's out there we weren't
even thinking about a few years ago. That's why it's particularly important to understand whether it's something
fairly uniform and static, or something dynamical and changing. It's monumental both for fundamental physics and
for cosmology."
What was going on? Steinhardt called the missing energy "quintessence," after Aristotle's fifth element.
Quintessence was fundamental mystery, a roadblock that seemed a precursor to a radical shift in scientific thought.
Was quintessence the same as dark matter, the unseen stuff that seemed to clamp down on galaxies like a waffle
iron? It seemed not. It appeared rather, that this energy or force had an effect only after some seven billion years,
during which time the expansion did decelerate as standard theory predicted. Once the density of the universe fell
below a certain point, however, the "antigravity force" kicked insuddenly revving up the outward explosion of all
matter. The answer lay in supernovae evidence. "Not only would it tell us what the universe is composed of, where
it came from, and where it's going, but it would tie together the laws of physics," Paul Steinhardt said to reporters
at a special luncheon at Fermilab. Over the clacking of plastic forks and whirring of tape recorders, he said: "It
must emerge from a fundamental law of physics, and we need to know which form it is, not only for cosmology,
but for people who are trying to develop the holiest grail of allunified theories of fundamental forces. You have a
new ingredient that you had not anticipated suddenly forced upon you.'' Endorsing the new interdisciplinary
approach, he added: "It's an opportunity for cosmology to provide a gift to particle physics."
Within a few months the ground would shift once again, as more observations plotted on neat graphs, shown on
overhead transparencies, and reproduced in Science and popular newspapers confirmed that the universe began to
accelerate about halfway through its 14.2-billion-year history. What was this exotic energy that opposed the natural
self-attractive gravity of matter? Whatever the answer, the two supernovae teams had taken the search for the true
nature of the cosmos out of the realm of philosophy and into that of science. "In science you usually have a
tradition you must match," said Perlmutter. "Do your data fit the tradition? In this field, there is no tradition, no
previous data. It's completely uncharted."
At the end of the Fermilab meeting, while Telemann from a state high-school flute competition echoed in
Fermilab's great hall,

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Perlmutter and Adam Riess gathered over a coffee table, comparing problems with their graphs while the laughter
and jokes of weary participants rose around them. The tension of the grilling in the conference was over, and
Kirshner, Guth, Steinhardt, Turner, Kolb, and others made plans for Saturday night in Chicago. The Supernova
Cosmology Project was still sensitive about the manner in which their technique had been adopted without credit
being given. Kirshner and Filippenko resented their rivals' accusations. The tensions between the two teams were
personal and emotional but, more importantly, they were philosophical: do you want fewer observations done more
carefully or more observations done less carefully? Yet in the end, Perlmutter and Riess were just two young kids,
scribbling on a napkin that I walked over and retrieved later, sipping coffee and trying to make a contraption work.
Prior to the last decade of the twentieth century, new cosmology results came in rarely. Once every few decades
some data would really change things. "We are now entering an era where we are able to probe simultaneously the
universe in its very early times, intermediate times, and present time," said MIT's Alan Guth. "It's amazing, it really
looks like in the next five, maybe ten, years, all the questions that seemed completely open all these years are going
to be nailed down. I think in five to ten years we will know if the universe is flat or open or closed, and we will
know quite accurately what the Hubble constant (expansion rate) is, and we will know quite accurately what the
mass density is, and whether there's a cosmological constant or not. All those questions seemed totally open five
years ago."
Combining computers, robotics, the Internet, and video sensing, cosmology was heading either toward confirming
what we think we know, or toward revolution. Not everyone agreed, however, that cosmology and physics were
entering a new era. Lawrence Berkeley Lab's Richard Muller, for one, disagreed. "Louie Alvarez told me in the last
few years of his life, that if he had to go into physics today, he would never make it. He said he just couldn't stand
the bureaucracy." As to what Perlmutter had done, Muller said: "To do a project that takes as long (as
Perlmutter's), you would not get the support today. Perlmutter was lucky he was at LBL, and still he paid a price.
He had to give up faculty positions. He had to take personal risks, have a job where his salary would not be
guaranteed, that kind of going out on the personal edge. There aren't too many people like Saul around these days."
Even Perlmutter admitted it had been difficult, and wondered aloud where such innovations could come today. To
answer that, one

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must look at how he did it himself. "Perlmutter was successful because he went after big questions," said Carl
Pennypacker. "You forged ahead even though you did not know how you would pull it off. That was a gift from
Luis. At LBL there was an atmosphere of support. You could be aggressive, because you got some money to
begin." They were also close to several other industries and leading departmentsthey managed to get hold of the
best cameras and computer programmers.
Perlmutter had the support of parents and mentors. He and Pennypacker were opportunistic and practical, and
lucky. At the time they started, the technologies of the Internet, the space telescope, the robotic and computerdriven searches all became viable. The confluence of technologies did not make the project inevitable, but possible.
To make it happen he had the model of Alvarez, the resources of LBL, the guidance of Goldhaber, and even the
rivalry to spur competition. He had also a rare quality of being genuinely nice that made people want to help. He
cajoled extra telescope time around the world. He helped guide a large international team. Being nice, it struck me
once again was almost a requirement of bold complex-systems science if you wanted to inspire others to your
cause.
At the end of 1998, Science named the accelerating universe the "Breakthrough of the Year," New supernovae
were pouring in, and what was accepted as the team decided to name them alphabetically after classical composers
rather than by numbers as they had been doing. By spring, they had Albinoni, Brahms, and clear evidence that
showed the universe changing speeds. Of course, nothing in cosmology is ever completely clear. "What do you
think of lambda Uncle Allan?" an astronomer asked Allan Sandage at a 1999 conference. "Not much," he replied.
In 1600 Galileo Galilei, a thirty-six-year-old professor of mathematics at the University of Padua, heard of an
instrument for making distant objects appear close. It was invented in the Netherlands out of spectacle lenses, but
there it was used solely for military purposes. Galileo was the first to direct it at the moon and the sky, make
systematic notebooks of what he saw, and shake the intellectual edifice of Europe to its foundation. Years before
the Supernova Cosmology Project, a Danish team had pursued the same goal with robotic telescopes operated by
computer. But the technology was not quite good enough, and they gave up.
Each technological advance sharpened our vision of the cosmos, to the point it seemed we could uncover its precise
age and, thus, a vital clue to its beginning. "We get an age of 14.2 billion years," Adam

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Riess told me at the Fermilab meeting. "To me, that you could answer such a thing is amazing. I mean, it started
out that we thought we were the in the center of the solar system. So, okay, we're not at the center. Fine. So then
we learned that the matter we're made up of may not make up most of the universe, it may be darker. Now we're,"
he paused as I looked at the napkin he and Perlmutter had been scribbling on, "now we may be learning that even
the kind of energy we're used to thinking about, the kind of energy that affects us day to day, may not make up the
majority of the kind of energy in the universe. So we may be totally unrepresentative in any way. We don't fit in,
we are not normal, and our intuition could be totally wrong. We might not be seeing what most of the universe
does, what most of the universe is made up of. I think that's quite amazing."
Timing, the techniques of another discipline, technology, complex networking, and imagination marked the new
cosmology. It did not seem to be the end, but the beginning. When I showed Perlmutter the napkin he had been
scribbling on, he laughed. "What people don't realize," he said, "is just how much fun this is."
The latest Supernova Cosmology Project proposal was to build an entire satellite, called Supernova Accelerator
Probe (SNAP), to track two thousand supernovae a year and perhaps nail the exact identity of what seemed a new
mysterious force in the universe. If the satellite was approved, it would be up and running by 2007, based on the
successes of the two teams. Like two competing orchestras, the supernova groups worked from a confluence of
several disciplines and approches and instruments to create a new era in cosmology. In fact, Perlmutter had just
heard that planet finder Geoff Marcy played the cello, and he needed one for his string quartet. He was about to
pick up the phone and call.

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The Art of the Woodpile:


Gretchen Daily and Nature's Services
1
Three young women lived upstairs above their bakery in a cement building in a small town near the southern edge
of Costa Rica. San Vito had a bullring where only fake bullfights took place and a few small grocery stores lining
a main street with no streetlights. In the morning the smells of pastries like tres leches, or "three milks," rose like
the scents of flowers outside the bakery. In the evening the odor of bread baking with cheese in the middle brought
workers into the Panaderia from the coffee farms and ranches dotting the mountains, taking the time for a quick
chat before dinner.
Thirty-one-year-old conservation biologist Gretchen Daily found any excuse to stop by the Panaderia to eat a
couple of cocadas, coconut sugar puffs, after returning from her work in the warm damp fields. She liked the
women in the shop and often picked up vital information from them. Her favorite was Magaly Chaves-Len. The
bakery's sales of bread and pastries paid for her tuition at the local community college. She often asked about
Daily's research.
Lanky, with unruly blond hair and steel eyes, Daily rose before dawn to snoop around in people's backyards, farm
fields, and bits of forest, carrying binoculars and a note pad to record the birds that thrived in habitats altered by
man. Birds like the tropical gnatcatcher, blue-crowned motmot, scarlet-thighed dacnis, and different kinds of
tanagers raised a huge call, like a symphony. "It's so beautiful it's almost like not working," said Daily's graduate
student Jennifer Hughes.

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Daily was leading several experiments and collaborations that sought to fundamentally extend the study of ecology,
centering on which species are likely to survive human impact. Directing a small research group, she was asking
big questions about the complex interactions of nature and our role in it. Studying birds, moths, butterflies, beetles,
and mammals, developing remote sensing by satellite of ecosystem health, she wanted to develop a scientific basis
for the policies needed to sustain Earth's life-support systems.
To some critics the questions were too big, the work too much a leap of faith. "You have to start somewhere," was
Daily's reply. Humans were setting off the sixth great extinction spasm in Earth's history. Thousands of species
seemed to be disappearing every year. Even one species lost contained an encyclopedia's worth of genetic
information. If humans dominate the Earth, Daily reasoned, then scientists needed to study how plants and animals
will survive in human-altered habitats. It was an integrative, interdisciplinary science of tradeoffs, asking: what
was the net benefit or cost of society's protecting the next unit of an ecosystem? Indeed, what opportunities could
come from the environmental crisis? Yes, the questions were so difficult as to be beyond the view of usual
science. It was a lot easier to work in a laboratory. But that did not mean you gave up.
For most of its history, ecology focused on pure nature in isolation from humankind. Landmark studies by Edward
Wilson on the bees of the Canary Islands established the benchmark of "island biogeography," the study of species
on secluded bits of land. This seminal work was the model by which all future work was measured. But the trouble
was, most ecosystems rarely worked as isolated islands in a human-dominated world. Pollinators of wild plants
and crops nested in town parks, vacant lots, or along railroad tracks. Nature in turn provided wealth to citiestheir
raw material, pure air and water, flood and drought controls. Where others had studied islands, Daily studied
interactions. She called her work "countryside biogeography."
It was no mere academic debate. Daily's work, which put her in Newsweek's Century Club and on the front pages
of newspaper business sections, was to help governments quantify the services of nature, as part of a tidal shift in
the way we think about animals, plants, climate, and the proper human relationship to the fragile planetary skin on
which we live. Whenever policy debates came up, the problem was that developers could always quantify the jobs
and money generated by new construction. No one quantified the value of the lost services of nature, like climate
regulation, protection from flooding and other

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disasters, or production of food and the ingredients of medicines. She wanted to provide governments with that
accounting. "What was nature worth?" a New York Times profile of her once asked. "For you, thirty-three trillion
dollars," it answered erroneously.
Many changes were making her analysis of ecosystems services more and more of a possibility. First, new tools
like remote sensors, advanced computer software, and satellite imaging made it possible to develop more and more
complex measurements of nature's activity. Second, a new approach to doing science, combining disciplines like
meteorology, economics, ecology, biology, and chemistry, made the time right for interdisciplinary researchers
willing to take the risks. Third, Daily made a point of going outside traditional science to work with people from
all walks of life and all over the worldbusiness people, mothers, villagers, movie producers, farm laborers. At the
San Vito Panaderia and in the fields, she consulted the husbands who hunted and the children who knew the
beetles and insects better than the hunters. The farmers explained which crops they planted and why. She insisted
that her graduate students learn Spanish before coming. Daily was also one of the few ecologists who consulted
with corporate and economics experts and leaders, trying to understand the problems through their eyes. She
wanted nothing less than to throw off the old Romantic idea of nature isolated against humanity, an opposition as
old as Wordsworth and as sweeping as Virgil and Plato.
She had about a dozen such projects going at once. She was writing a feature on biodiversity and happiness for a
National Geographic book, coauthoring three articles under submission to peer-reviewed journals on topics like
her work in San Vito, writing grant applications, teaching undergraduates, making public appearances all over the
world, advising the U.S. government, and devising partnerships for ecobusiness ventures. Any one of these
projects was a few years out of a single career. "It's a curse," Daily said of her passion to pursue science that
mattered, "but sometimes I feel if I don't do it, so few will."
That she carried out her big-picture research in the public eyeon television, in radio, and in popular magazines was
yet another risk she took. Some researchers criticized her approach as far too broad and sweeping. Others extolled
it. "She's fearless. She's a hero to me," said her department chair, Harold Mooney. "She's what science should be,"
said her longtime collaborator Paul Ehrlich.
It was not easy. Always she felt pressure: she should be doing more. She could be doing more. But it was not
impossible, she said. What was the point of science if not to answer the biggest questions

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of how the living world was going to survive? At the Panaderia, she and Chaves-Len talked about putting on a
party. The women would bake and the scientists would hang out with the children. "Let them see what the blond
lady does in the back yard," they decided.
2
The study of ecology and nature, and our place in them, probably goes back as far as human history. The ancient
Greek Theophrastus wrote about the relation of living things to their environment in the time of Aristotle, and by
the nineteenth century the infamous Thomas Malthus was plotting the fluctuation of human population with food
supply. In the first half of the twentieth century, however, interdisciplinary ecology began to take off as botanists
and biologists in Europe and the United States studied the flow of food and energy in natural systems. In the later
twentieth century, the conceptual basis of a new science of ecosystems finally became widely accepted. It was the
product of about a half-dozen other sciences, including climatology, microbiology, conservation, ecology, and
population studies. It remained a somewhat suspect, hybrid science, retrospective and descriptive. When human
pollution began threatening 3.8 billion years worth of evolution, however, the study of ecosystemsanimal, plant,
geological, climatological, and human relationshipsbecame front-page news. The furor over air pollution, acid rain,
algal blooms, declining fish catches, and death of forests was further ignited by the publication of biologist Rachel
Carson's Silent Spring.
About the time the furor was beginning, in 1964, Gretchen Daily was born in Washington, D.C. After living in the
United States and Germany her first two years, her family settled in California, in the San Francisco Bay Area,
where she grew up as a tomboy climbing trees and wandering the foothills encircling the bay. When she was
twelve her father, an ophthalmologist, decided to show his children other parts of the world. He joined the U.S.
Army to serve in the medical corps overseas. From him she inherited a pragmatic idealism and willingness to leap
over boundaries that would serve her well.

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Her father took his family to Frankfurt, where she attended a private international school. She studied eight
subjects, learning French and German as well as English. "I saw the difference between an American education
and a really fine European school. I had a great biology teacher," she said.
In the late 1970s, though, the dollar plummeted and her parents transferred her to a free Army school in Frankfurt.
It was an early experience of the link between international economics and people's lives. One science teacher there
was the school's main drug dealer. "On our first day of class he barely reached the Ds in his roster," Daily recalled.
Still, some great teachers reached students, and Daily learned something of life in the real world.
She also witnessed the explosive convergence of international politics and the environment. By the late 1970s acid
rain had become a huge concern in Germany. News photographs of stricken stretches of the Black Forest earned
the blight the ominous name Waldsterben (forest death). Daily did an all-year after-school project on pollution in a
local river, winning an international high-school science competition. But still she had no particular ambition.
Some school friends were skiing and putting off the Army. "I would have become a ski instructor," she said. "But
my Dad wrote away for college applications. He made me apply to Stanford." With her straight As, she got in.
Returning to California as an undergraduate she pursued first German literature, then geology. It took her a while
to find her way into biology, where at first she felt overwhelmed. She was used to "doing nothing and getting an
A." Now she was with people who already knew the material she struggled to learn. A deep insecurity set in, but
she used it to drive herself harder than her friends. She joined the ski team and served as a docent at the local forest
preserve.
She lucked out by walking into the biology laboratory of Paul Ehrlich. The small, voluble Ehrlich was a major
scientist who had put ecology on the map, for better and worse. With his wife, Anne, Ehrlich educated and
browbeat the American public about the ill effects of the human assault on the environment. He attacked
Americans' faith in superabundant natural resources. A big early success as an author was his appearance on "The
Tonight Show" in 1970 to talk about his book The Population Bomb, which then became a bestseller. Authoring
forty similar books, appearing a total of twenty-five times on Carson's program, he became one of the most visible
public scientists in the country. He also committed gaffes that earned the enmity of many colleagues and
conservative critics, offering scenarios

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for massive food riots in the 1980s, worldwide starvation, and a nuclear attack on the United States. In some ways
Ehrlich's worst enemy was his mouth.
But to Daily, Ehrlich was one of the few scientists willing to tackle the world's biggest problems in the public
arena. He showed that a scientist could make mistakes and yet keep fighting in public for a cause. He and others
also supported her. "I was lucky to have senior faculty telling me not to worry, it was risky and sometimes painful,
but worth it." She joined Ehrlich's research group at the Rocky Mountain Biological Laboratory near Crested Butte,
Colorado, where she proved to be resourceful in gathering data and in analyzing it in innovative and creative ways.
She learned how to seize opportunities. One day, for instance, as she and Ehrlich were walking an alpine path, they
heard a loud tapping in a willow. They peered inside to see a woodpeckera red-naped sapsuckerchiseling away at
the wood. The bird continued without noticing them. As they watched, hummingbirds and warblers came along to
get the sweet sap pouring from the chiseled bush. "This is great," Ehrlich said. "Stay here, Gretchen."
She sat for hours, taking notes as chipmunks and squirrels joined the group. Thus began a study that would extend
many months, into years, as Daily returned again and again to spend hours videotaping and recording, swatting
flies and sticking to research that kept expanding. Eventually she demonstrated the subtle interactions of a fungus
that weakened the trunk of aspen trees and a bird that nested in such trees, feeding on the sap it made flow from
willows, with the communities of squirrels, chipmunks, hummingbirds, wasps, butterflies, and other species in the
ecosystem. As it would many times in her career, a nature walk with a friend led to a study of complex
communities of animals and plants, even when they seemed to have no obvious interaction. "The disappearance of
a single species," she noted years later of that research, "could precipitate a wholly unanticipated unraveling of
community structure." The first study produced her first published paper, cowritten with Ehrlich: "Red-naped
Sapsuckers Feeding at Willows: Possible Keystone Herbivores." Appearing in American Birds eighteen months
after she graduated with her B.S., it was a coup for a budding ecologist.
She wanted to pursue her master's degree. In coursework she focussed mostly on math, but in research she
rebelliously expanded, linking with several prominent women. Mentors are important to all who are young and
creative, but they are probably more critical for women going into science. Baylor University mathematician
Vivienne

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Malone Mayes, the first black faculty member hired at Baylor, has spoken of the significance of her teacher Evelyn
Boyd Granville, one of the first two black women to receive a Ph.D. in mathematics in America. At Stanford,
Daily answered an ad posted by the nonprofit Worldwatch Institute's Sandra Postel. She worked with Postel to
investigate global warming, acid rain, and integrated pest managementthe use of natural predators to attack crop
pests. Postel taught her to develop research that could shape policy, science that mattered. ''Even then," Postel
recalled, "Gretchen was torn between which direction to gointo academic science or public policy."
After graduating, Daily headed back to Germany, where she struggled to decide what to do with her life while
studying the effects of acid rain. She realized that to make her mark in the world, academics was the route. "I could
have gone into law or politics, but after watching Sandra I could see the battle she had to face," she said. "Science
satisfies a lot of desires for me. It satisfies my curiosity in solving problems. It has all these rewards on its own,"
she said.
She decided to get her doctorate in conservation biology. She faced a problem. Virtually no programs offered the
kind of big-question, interdisciplinary approach she wanted. The only possibility was Stanford, which had a great
interdisciplinary tradition. The biology department even had a climatologist assigned to it. But, like most graduate
programs, it was reluctant to take the incestuous step of admitting its own undergraduate. She applied anyway,
causing a heated debate in the department. "Ultimately we made an exception for Gretchen," recalled Ehrlich. Four
years later she shared the prize for being the best graduate student in the Life Sciences Department.
Back again at Stanford in 1989, Daily joined a swirl of adventurous personalities gathering and sharing ideas,
coming from departments as different as ecology, law, climate science, international studies, population studies,
and economics. It was a rich moment of intellectual excitement. They argued late into the night in the dreary
lecture room of the biology building. Paul and Anne Ehrlich hosted dinners in their home, where Daily met visiting
professors and lecturers who shared her desire to pursue the biggest questions about Earth's future. They included
Cambridge University economist Partha Dasgupta, Berkeley University energy analyst John Holdren, climatologist
Stephen Schneider, ecosystem ecologists Pamela Matson and Peter Vitousek, and others. Realizing that a
multidisciplinary approach was necessary to understand the natural and man-made systems they wished to master,
they tried to learn about each other's fields.

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In the usual academic setting it was difficult to show one's ignorance. They preferred to meet socially, over dinners
with endive salads and sea bass cooked by Anne, while Paul served obscure good wine. Only with their guard
down could they begin to communicate at a gut level, beyond the professional jargon and posturing. Often in
science the most important ideas come from lunches, dinners, cocktail hours, and chance encounters. Cloning
pioneer Ian Wilmut picked up his key idea in overhearing a competitor's conversation in an Edinburgh pub. The
Ehrlichs liked to mix younger and older colleagues. They shared ownership of an airplane with the law school
dean, Paul Brest, and law school or international studies professors frequently joined in the conversations about
Earth's future and governments' role in shaping it.
Daily was most intrigued by the economist Partha Dasgupta, who was on leave from Cambridge, England, with his
wife. Originally from Dhaka, the capital of Bangladesh, he had been thinking deeply about the connections of
poverty, population growth, and the environment since his student days at the London School of Economics. A
former president of both the British and the European Economics Associations, Dasgupta was using his sabbatical
in California to furiously pursue interdisciplinary models. Daily was amazed that he had read all of Ehrlichs and
John Holdren's book, Ecoscience. Ecologists and economists rarely talked to one another unless it was to condemn
each other, "The book was huge and very technical," Daily recalled. "It made me think, I haven't read any
economics. Partha made me feel it's OK professionally to do this,"
For Dasgupta, the dinners were equally critical. As a student, in the London School of Economics library, he had
searched in vain for books that explained how natural systems interacted with human economies. He turned to a
catalog of publisher W. H. Freeman and Company, where he found Ecoscience. "It was absolutely fascinating to
me. I was searching but did not quite know the word 'ecology' at the time," said Dasgupta, who was doing work on
exploited resources like fisheries. "The book offered the beginning of a unified way of treating resource economics
and environmental economics under one intellectual scheme." Here he uncovered formulations of the same
problems he had been working on, in equations an economist could comprehend.
When he told Ehrlich he loved the book, "it was probably the first time Ehrlich ever heard an economist saying
anything good about him," Dasgupta recalled. Invited to dinner, Dasgupta put Ehrlich in touch with a Stanford
neighbor, Nobel Prize-winning economist Ken

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Arrow. "They had never broken bread together, even though they'd been colleagues for years." Two lecture series
were started. Leading thinkers were invited to talk to faculty from other disciplines, in much the same way Susan
Greenfield put consciousness on the map in an interdisciplinary lecture series at Oxford. But more important were
the dinners at the Ehrlichs', where "great natural scientists would show up, often with graduate students in tow,"
Dasgupta said.
For her part, Daily had thought of science as people in white coats, but that changed. "The possibilities were really
stimulating, even though careerwise there were a lot of disincentives to working with other disciplines. At first we
didn't agree on anything, but gradually we learned the language and the assumptions of each others' disciplines. It
was fun being a part of. The social dynamics played a prominent role in creating ideas."
Ignited by what she heard, Daily worked on the first thesis in the biology department to analyze policy as well as
biology. With the slightly grandiose title, "Interactions Between Populations and Resources," it sought to assess the
ultimate carrying capacity of "life on Earth." She later published sections of it in the British Royal Society
Proceedings. What is that going to accomplish? she recalled Sandra Postel asking. Thinking what to do next, she
resolved to do something that would have an impact in the real world. She had come a long way from red-naped
sapsuckers, but she was only beginning.
3
The interdisciplinary approach was difficult. It is one thing when a Nobel winner or senior researcher decides to
switch careers or make a name as a public intellectual. It is quite another for a young postdoctoral researcher to
attempt to learn more than one discipline. Stanford was the world leader in environmental economics. But given
the larger difficulties of making it in any single science field, and the limited time and resources available to her, it
was a little crazy.
A few were calling for science to return to its humanistic Renaissance roots. Some interdisciplinary projects were
pushed by

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North American and European government agencies. But it was immensely difficult to do good work in traditions
that each required years of study to master, and across different departmental assumptions so ingrained as to be
invisible. Academic departments existed for good reason. You did not want your English colleagues suggesting a
new treatment for cancer. The distrust of interdisciplinary work was often unspoken: back-hall gossipers suggested
such scholars could not make it in their own fields, they talked rather than did, they were publicity hounds who got
their information secondhandI have felt that way myself. Perhaps there is a natural discomfort with being exhorted
by someone not trained in your field. In science, moreover, the funding flowed down departmental lines. Being
outside of a department took you "out of the money," said Ehrlich. When Harvard Medical School's Athena
Andreadis derided her coming-of-age within medicine's "feudal parochialism" and "fiefdoms," she could have been
speaking of any scientific field.
Few in the 1980s were pursuing interdisciplinary research. "It's either feast or famine," said virologist Rita Colwell
of interdisciplinary science at traditional science conferences in 1994, before becoming director of the National
Science Foundation (NSF). "Either you're the keynote speaker or you're not on the program at all." Later the NSF
would require its Long Term Ecological Grant recipients to include research into the social science as well as the
natural science of the regions they studied.
Yet Colwell's work, as well as that of others, showed how interdisciplinary the world is. Colwell was studying the
resurgence of cholera and other pathogens like tuberculosis in the worldalarming epidemics because the diseases
were thought to have been conquered. Cholera was increasing because of polluted water supplies, brought on by
the decaying infrastructure of sanitation and health care in poor countries. To a virologist, then, research had to
encompass issues of social policy and public health. Disease was interdisciplinary, even if science was not.
With the economics of ecology, the small Stanford group began to develop a vocabulary and rules of measure. In
economics the standard measure was marginal valuethe extra wealth produced by one more unit of labor or a
commodity. At Stanford, Daily and others asked questions like: What was the marginal value of a single hectare of
rainforest? To answer, ecosystems had to become a weave of processes whose workings spread through time, from
forest to town, from agriculture to culture. They expanded the science to make it reach from the sun to the
joblessness of the young man raised on the street who

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might rob your research van. They became makers of worlds, scientists who slipped from investment ratios to the
daily routine of Third World families to the biochemistry of bees.
Daily pursued her postdoctoral work with energy-resource expert John Holdren. Amidst Berkeley's leafy hills,
Daily's interests widened. She coauthored papers linking climate change and food capacity, the spatial distribution
of sub-alpine butterflies, and "Figs and Fun," a how-to article of sapsucker secrets. Most she coauthored with
Ehrlich, and some readers noted her growing command of economics. "Paul's writing improved as a result of
working with Gretchen," said Dasgupta, as the two set out to link population studies and market economics.
Daily began showing the skills that made her special. From a father who joined the Army to travel abroad, she
inherited a practical ability. From her upbringing she brought an international ease with several languages. From
her time in an Army school, she relearned the necessity of understanding "the views of strangers, foreigners, and
enemies." From Ehrlich, Daily learned how to attack the biggest questions with confidence. She also witnessed the
dramatic conflicts and show business of science (Ehrlich was an NBC correspondent for many years) and the
pitfalls and potential of life as a public figure. Most of all, her colleagues observed, she worked harder at
collaborating than most anyone else.
She traveled to Australia and New Zealand, speaking on subjects as different as biodiversity, new computer models
for gauging climate change, and the effect of climate change on food production. She applied for a prestigious
Winslow Heinz Postdoctoral Fellowship as well as a Pew Fellowship dedicated to the issues of the environment
and humanity's future on Earth. Her younger brother in high school became interested in making business more
eco-friendly. She became more confident. "I had a lot of insecurities," she said. "But they might actually have been
an asset, keeping me more open to new ideas and making me strive to improve."
By the early 1990s other institutes around the world were pursuing the big questions of ecosystems and human
interaction. Nonprofit groups like the Santa Fe Institute in New Mexico, the Beijer Institute of the Royal Swedish
Academy in Stockholm, and the International Institute for Applied Systems Analysis in Laxenburg, Austria, sprang
up as the study of complex systems gained momentum, drawing on the romance of chaos theory. More researchers
felt a growing sense that science must finally overcome its own divisions to grapple with the overarching issue of
humanity's survival. The fate of the Earth became an acceptable question for scientific study.

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One of the most prominent such institutes was the Beijer in Sweden. Founded in 1977 by the Royal Swedish
Society and reorganized in 1991 as the International Institute of Ecological Economics, it was set in the stunning
Stockholm archipelago. After delicately prepared French dinners, invited fellows joined in talks about how to
attack the problems of the environment. Chaired by Partha Dasgupta, the institute sponsored annual symposia on
topics like poverty and environmental degradation. Gradually, out of these symposia came the hope for a new
approach to ecology, a new science.
The basics were clear if dauntingstatistical formulae for determining the abundance of a species through time,
Keynes's models of taxation and spending, Mill on social utility, Mead on family structure. Each new set of
variables, each new discipline, hid a universe of equations and assumptions, like trap doors. The vagaries of global
warming provided a good example of the difficulties. If done improperly, the simplest climate forecasts spaghettied
into infinite complexity.
Where did one focus? It seemed frighteningly limitless. Daily was interested in the services of ecosystems, in
issues of sustainability, in biodiversity, each a career in itself. By July 1992, at the age of 27, she was giving the
Beijer plenary address on population extinction, an amazing recognition for such a young thinker. But to truly
address the issues facing her field, she needed to be out in the field.
4
For years policymakers had grappled with the paradox that developing countries experienced the worst population
explosions and ecological devastation. They used energy inefficiently and lacked the basic services necessary to
build a sound social infrastructure. Why were poor families so big, the pressures of population most critical in
countries least able to confront them? One reason was that many Third World societies often were also the most
unequal and patriarchal. Gender inequity led to greater numbers of unwanted pregnancies, and societal inequity
allowed industries to devastate the land. Research could not fully confront economic ecosystems questions without
taking on issues of culture and power.

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In Costa Rica Daily found what looked like a success story. Costa Rica, a more middle-class country than its
neighbors, had managed to protect its unique natural resources. Dubbed "rich coast" by Columbus, it was split by a
series of volcanic mountain chains, some of the volcanoes still active. About a third of the size of Illinois, it
offered researchers twelve different ecosystems. With more than a quarter of its land protected, it had twenty-four
national parks, twenty-six protected areas, nine forest reserves, eight biological reserves, and seven wildlife
sanctuaries. Though it covered just 0.03 percent of the world's surface, it was home to more than 5 percent of the
planet's life-forms. Daily and Ehrlich began a series of field studies in the region surrounding the Las Cruces
Biological Station, documenting the response of various animals to different types of human activity. "Gretchen
has a talent for picking important problems," said Ehrlich, "and then sticking with them." Soon they were working
with local authorities, employing and learning from townspeople, and reaching out to local researchers.
By 1993 and 1994 Daily and Paul and Anne Ehrlich felt so strongly about including sociology and policy studies
in ecosystem research, they began writing a book called The Stork and the Plow: The Equity Solution to the Human
Dilemma. One key to escaping the population crisis, it argued, was to increase the equality of people in the world.
When women are given power over their bodies, birth rates fall. When farmers in poor countries own the land they
work, harvests increase. At the Beijer Institute and at Stanford, Daily talked a lot on bird walks with colleagues
about the relationship between social institutions, poverty, and population.
Published in 1995, the book sparked debate and controversy. It was no mere scientific treatise, but a broad
historical and cultural synthesis that linked subjects as diverse as birth rates and aspects of religion, witchcraft, and
homosexuality. Scientists could no longer simply look at nature, make measurements, perform tests, and announce
results. They must enter a two-way relation with the people and systems they studied. As ecosystem study became
more interconnected, involving human, plant, animal, geological, and climatic systems, the models became more
complex. Each refinement in one field forced a refinement in the others.
Daily had practiced these ideals in San Vito. She worked with local business, political, and church leaders. She
listened to the women in town. "Everyone knows Gretchen," said graduate student Jennifer Hughes. Daily hired a
fifteen-year-old, call him Luis, to help her identify animals and plants. He was really good at spotting butterflies,

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which she almost never could find on her own. When they hiked, he would remember the trees where they had set
their butterfly traps, ninety feet above the ground. Where she would find nothing, he could point out a coiled snake
or the paw print of the furry jaguarundi. He knew which wasps were harmless and which were dangerous. The
money she paid him was critical for his family.
Some reviewers, however, connected the book with Earlich's earlier doomsday predictions of famine and
ecological crisis. The anti-environmentalist brownlash movement, which had found a voice in Ronald Reagan,
made Ehrlich a favorite target. They claimed that he ignored the triumph of technology in supplementing natural
processes. He also ignored the fact that when resources become scarce their prices rise, in theory, and people
reallocate their spending and find ways to replace or renew resources, or do without. Ehrlich, they claimed, ignored
the give-and-take of humanity's oldest complex systemthe free market.
It was true that, in the twenty years since Ehrlich had published The Population Bomb, world food production had
increased, contradicting one of his main arguments. Ehrlich dueled weekly with the maverick economist Julian
Simon. In a famous bet, Simon offered to buy back five commodities after ten years if their prices rose. When the
prices fell Ehrlich lost, paying Simon $570.07. (Later Ehrlich and Holdren recast the terms of the bet, but Simon
would not take them up on it.) The rightists gloated.
Even with its flaws, The Stork and the Plow and an article with John Holdren on sustainable development sparked
researchers in other countries grappling with the problems they described. At the National University in Mexico
ecologist Gerardo Ceballos was galvanized. "I was seeking a way for dealing with the issues we faced," he
recalled. "Paul Ehrlich and Gretchen Daily were publishing important papers in the field." Ceballos was so taken
he headed to Stanford on a year's sabbatical to begin a collaboration, joining them in their field studies in Costa
Rica.
At about that time Ceballos was picking up Daily's work, a special position called the Bing Interdisciplinary
Research Scientist opened at Stanford. Funded by the chair of the Board of Trustees, Peter Bing, there were three
such endowed positions, the other two belonging to Ehrlich and former Food and Drug Administration Director
Donald Kennedy. Now the stakes escalated dramatically. It was the position for which Gretchen Daily had lived
her life. She had already begun to build a student following, helping along those who also wanted to do science
with a social impact. Because her work was

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scattered over so many fields, there was no traditional interview with a search committee. "We simply decided that
we had to find a position for Gretchen at Stanford," recalled Paul Erlich. They told her the position was "an
experiment," said Daily. She was elated. Sometimes, she felt, her whole career was an experiment.
5
Beginning at Stanford in the fall of 1995, she worked harder than ever. Though not required to teach, she played an
important role in devising a new interdisciplinary core science curriculum. Thinking about what she was going to
do with her virtually unique opportunity, she resolved to go after the biggest picture, to study, understand, and
evaluate the tradeoffs between humanity's expansion and the Earth's sustaining biodiversity.
She won a Pew Foundation Fellowship in Conservation and the Environment, joining in annual meetings at remote
sites where researchers argued about the interaction of society and nature. A mentor from this group was the
Oregon State University marine biologist Jane Lubchenco. Articulate and energetic, Lubchenco served on several
federal panels and professional committees. She liked Daily's enunciation of the study of nature's services and
encouraged the other Pew Fellows to pick up the idea. They could make sure policymakers had hard numbers on
nature's economic services like water and air purification and food and energy production, all done at a fraction of
the cost of artificial systems. Whenever new developments were discussed, politicians thought of nature "in terms
of parks and reservations," she said. "We wanted to talk about nature in terms of money,"
In 1995 at the White Stallion Ranch in Arizona, where paintings of buffalo stampedes and buffalo hunts covered
the lodge hallways, Lubchenco and economist Peter Vitousek invited about ten people to dinner outside under the
desert stars. They needed to put together the work on nature's services, Vitousek suggested. All their work was too
scattered. What about coauthoring a journal article?
It had to have heft, to have real data. But who could pull together their input? "Gretchen was clearly the most
qualified," recalled

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Lubchenco. Everyone turned to Daily. "When I did not back out fast enough," she recalled, "I was selected."
Daily was selected because she had discipline and interdisciplinary knowledge. She had above all an uncommon,
obsessive commitment. Once, for instance, her Costa Rica research was criticized because her traps missed the
butterflies flying high above the forest canopy. Daily took a trap and redesigned it from start to finish, seeking a
way to get it ninety feet up into the trees. She decided on using a slingshotting spider wire that shot up above the
canopy and then came down over a tree branch. She affixed a shutter that could be closed from down below. She
installed a suite of these new traps high up in the trees,
She took to the nature's services project, soon realizing that a single article could not hold all they wanted to say.
She suggested they turn the idea into a book. She began assigning chapters and pursuing collaborators, reaching
back to many of the different people she had met in her young career. Jane Lubchenco helped her procure grants
from the W. Alton Jones and Packard foundations. Lubchenco was president of the largest and most visible
research organization in the United States, the American Association for the Advancement of Science. It was a
profound platform from which to announce a wider effort to document the services of ecosystems. Lubchenco
decided to make nature's services a keystone of the 1997 annual meeting, in Seattle, where Bill Gates was due to
speak.
6
In the spring and summer of 1996 the ideas of the book were taking shape in working drafts of nineteen chapters,
cowritten by thirty-two authors assembled by Daily. She brought in economist Lawrence Goulder and her friend
Donald Kennedy to explain the theoretical model; Gary Nabhan and Stephen Bachman to discuss the disastrous
declines in numbers of insect pollinators, which threatened many wild and crop plants; Jane Lubchenco to examine
saltwater marine ecosystems services; and her old friend Sandra Postel to discuss freshwater services. She took off
on a lecture tour in Japan, returning to Providence, Rhode Island, to present a paper at the

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Ecological Association of America conference. She published eight coauthored journal articles during that year.
She was driving herself hard.
By the time they reconvened that summer to share their chapters at a Pew meeting in Purity Springs, New
Hampshire, Daily was exhausted. She had been travelling for weeks without a break. Often at Pew meetings she
organized the extracurricular hikes and adventures (she had inspired Lubchenco to go rockdiving in Jamaica), but
after canoeing the first midnight with the others, she returned to her room and collapsed with a fever.
Unable to join in climbing Mount Washington, she lay in bed and read manuscripts. Her depression and exhaustion
leaked into her language. ''If humanity is not suicidal," she wrote, "then it must begin to scientifically evaluate
ecosystems services." There was nothing new about this insight, of course. Plato had described the precipitous
result of overfarming in Greece in the fourth century BC:
Formerly, many of the mountains were arable. The plains that were full of rich soil are now marshes. Hills
that were once covered with forests and produced abundant pasture now produce only food for bees. . . .
The abandoned shrines at spots where formerly there were springs attest that our description of the land is
true.
How save the Earth? One had to first evaluate nature's services, in the universal language of self-interestmoney.
Pollinators alone were worth some $8.3 billion a year, larger than the gross national product of many countries.
Daily's chapter on soil, cowritten with Pamela Matson and Peter Vitousek, showed that up to one thousand years
are needed to regenerate one inch of lost topsoil. Norman Myers asserted that the value of life's genetic diversity
was quite simply incalculable.
The book, titled Nature's Services, appeared at the beginning of 1997 and immediately attracted attention. At
Columbia University, for instance, economist Geoffrey Heal was so intrigued by the book that he and Daily began
to collaborate. He offered to help her with international economics, if she could help him with conservation
biology. Like her, he loved the intellectual challenge of complexity.
In February, Lubchenco made nature's services the topic of her speech at the meeting of the American Association
for the Advancement of Science. While Bill Gates was predicting that biotechnology and information technology
would "dominate the twenty-first century," nature's services and interdisciplinary approaches were the buzz at

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the conference. If science did not step out and help shape policies on such broad issues, said Teresa Heinz of the
Heinz Family Philanthropies, it risked going the way of the medieval church.
When Daily, Paul Ehrlich, and Geoffrey Heal held their conference session, I had trouble finding a seat in the
packed auditorium. An article by Robert Costanza making similar arguments appeared in Nature, sparking further
debate. The idea had arrived.
To promote these ideas, Daily traveled to New York and Washington on an unusual book tour with economist
Geoffrey Heal, business consultant Michael Kleeman, and Donald Kennedy. With the tour, "Gretchen took the idea
of ecosystems services and put it on the map in a big way," said Jane Lubchenco. They met with editorial boards
and policymakers, finding enthusiastic audiences at Fortune and Time. Nature's Services put her in the center of
most newsmagazines, including US News and World Report and Newsweek, which made her pose in a tree,
bringing on an allergic reaction to tree moths. The business section of The New York Times ran a front-page piece
on it, and Science ran a laudatory review of it. Nature called it a must-read "for teachers, students, scientists, and
citizens at all levels of expertise." Washington Post columnist Tom Horton called it "the most important book on
the environment in years, a starting point for a desperately needed new view of Earth."
Reviewers considered Daily's contributions in the introduction, the coauthored chapter on soil services, and in the
conclusion, precise and well-grounded economically. Some of her colleagues loved it. Heal pointed out passages in
which she clearly admitted the limits of quantitative analysis, neatly laying out the problems and suggesting
mathematical solutions. He called the book a "quantum move" for her. Finally, it seemed, Daily's long years of
painstakingly identifying keystone species and spatial geographic computations were paying off.
Some critics, however, questioned the laxity of other scholars' contributions and confusions at the center of the
enterprise. Some contributors, reviewers noted, confused the economic terms "marginal" and "total" values. The
total value of say, pollinators was infinitesince there was virtually no way to artificially pollinate crops to sustain a
human population. But the marginal value of one species of bee, for instance, might be relatively small if another
species could serve the same pollinating purpose. Other entries, such as the one on fisheries, mistook the difference
between value and cost. The contribution on global warming was dubbed out of date by one reviewer.

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The articles, in short, varied in their command of economics. The accumulation of sloppy equations, mistaken
vocabulary, and shaky assumptions together had the effect of "dulling the impact," Issues in Science and
Technology noted. An important review in TREE (Trends in Ecology and Evolution) called it "highly inclusive, but
conceptually shaky."
The most fundamental criticism, however, was of the concept itself. Was it real science of the paradigm-shifting
sort, or a mere "curiosity," as the TREE reviewer put it, "like nineteenth-century attempts at a perpetual-motion
machine"? Some letter writers to environmental magazines assailed the authors as anthropocentric philistines
stooping to putting a dollar value on nature. Science fired back that such an ivory-tower view abdicated science's
role in the formation of policy. After all, the book billed itself as a start.
While many of the great theorists of the past had eschewed application, many more had become actively involved
in history. Galileo actively lobbied to make his telescope useful as a military tool. Einstein had proposed to
Franklin Roosevelt that the Germans were building an atomic bomb based on his theory of relativity. James
Watson and Francis Crick became outspoken leaders of the genomics and neuroscience revolutions their discovery
of DNA spawned. "While other scientists content themselves with tiny incremental research," said Michael
Kleeman, "Gretchen's after the whole enchilada."
Many ideas followed from this quest. If one gave nature a value, then one could sell shares in it, have people invest
in it. Could the preservation of the present systems be "privatized" so that corporations and individuals find
preservation in their interest? New York City spent $600 million to improve the Catskill watershed, rather than $4
billion to build a new water-treatment facility. Merck and Costa Rica devised a controversial joint venture to mine
the genes of plants and animals in the rain forest for potential pharmaceuticals. In Florida, some thirty wetland
banks were created, in which government paid a premium to companies to save and protect natural aquifers and
water-purifying marshes.
Some policymakers were listening. Vice President Al Gore used the concept in his speech on the new information
technology initiative he announced in early 1998. Columbia University's Geoffrey Heal suggested that countries
market their natural areas much as a CEO might take a company public. The ideas, which had been around for a
while, now gained momentum.

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<><><><><><><><><><><><>
For some time Daily had wanted to use satellite imaging, a technology many other researchers were using, to make
instant assessments of ecosystem health. She contacted the Costa Rican researcher Arturo Sanchez-Azofeifa. Yes,
he said, with the Landsat Thematic Mapper satellite, he would tell her when farmers were cutting forest. When
coffee prices rose, Costa Rica's forest suffered; when they fell, the economy faltered but ecosystem health
improved. The jovial, sweetfaced Arturo Sanchez had a personal tie to their work. His grandfather and many
relatives were farmers and "probably deforested as much as anybody in the region," he recalled. "This was a way
to put something back."
In the spring of 1998 Daily held her first fun fair for the children of San Vito, beginning an outreach effort that
became critical to her research, Sanchez, who was teaching at the University of Alberta, talked about how he
would use the satellites in the sky to study the forests and fields. One of the children asked if the butterflies died in
their traps. Daily went out to the van and pulled out a hand-made net trap, basically a cylinder of netting over a
bent coat-hanger frame, below which dangled a platform for bait. They used molasses, rum, and overripe bananas
to attract the butterflies, she explained. It smelled sweet and enticing. "The butterfly goes in here," she said,
patiently. "Then it eats the bait, gets a little drunk, and just rests nice and protected from predators and rain until
we check the trap and release it."
They had fun, but the good relations had a serious purpose. "The local people really helped for getting the real
picture of what was going on," said Gerardo Ceballos. Arturo Sanchez recalled warmly the Insane Wine Contest
hosted by Ehrlich at the biological station every day at five. Ehrlich would wrap boxes or bottles of wine,
sometimes local pineapple wine, and sometimes a vintage winewhatever San Vito had. They would serve it with
pan aejo (old bread) and make learned judgments on its qualities. Finally Ehrlich would unwrap it with a flourish,
and "it might just turn out to be vinegar or something," Sanchez laughed.

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7
Tired, excited, feeling scattered more than she wanted ever to be, Daily was becoming a science star. A leading
figure of the nature's services paradigm, she lectured all over the world. She gave talks in Spanish at Central
American universities, served on a committee of the President's Council of Advisors on Science and Technology,
and spent much of her time doing fieldwork in San Vito. She was a key participant in annual meetings at the Beijer
Institute and of the Pew Fellows. She was applying for grants, winning awards like the Newsweek Century Club
citation, and being called for quotes by everyone on El Nio damage, estimated to be $13 billion.
In early 1999 she flew overnight to San Jose, Costa Rica's capital, waited two hours to find her missing luggage
and equipment, grabbed a rental car and headed for a hotel where she had meetings with Costa Rican
collaborators. Gerardo Ceballos was coming separately from Mexico City. She felt lightheaded from lack of sleep.
She got stuck in San Jose's wicked morning rush hour. As she inched forward in the diesel and gas fumes, amidst
the rattling farm trucks and salsablaring car radios, she caught sight of something out of the corner of her eye. A
few seconds later her rear tire blew out. Sighing, she pulled over to the side of the road and got down to look
underneath the car.
From the car behind her a fortyish man approached her. He was dressed nicely in dark slacks and a white shirt. He
asked if she needed help. Something about him made her suspicious. "Do you live around here?" she asked.
"Right in that house over there." He motioned.
She got out from under the car to talk to him. He helped her, but right before the job was finished, he asked her to
unlock the car door to get another tool. In an instant, he snatched her nylon hip pack, tucked away between the
front seats. With it, her wallet and passport, and the well-dressed man, were gonehe was whisked away by his
accomplice, hiding in a car parked out of view.
Idiot, she thought to herself. What was she thinking? As it turned out, the family that did live in the nearby house
came out to help her. It's a new trick, the woman told her. One of the men runs in front of your back tire to lay
down nails when you are stuck in traffic. "We were suspicious, but he seemed so helpful we didn't intervene," the
woman said, while her son-in-law helped fix the tire. "You're lucky worse didn't happen." They reported the
robbery to the local police, and learned that the owner of the get-away car was part of a wellknown Colombian
crime group.

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By the time she reached the hotel a short time later, several hundred charges had already been made on her credit
cards. She checked her e-mail. She had a grant deadline the week she got back.
Crime was taking a turn for the worse in San Jose. Everyone had a story. People had been mugged or accosted and
hustled. The bottom had fallen out of coffee prices, and with the growing influx of tourists came Colombian and
other crime groups. Once a perfectly safe country, Costa Rica now offered some of the same problems they had
been studying.
It seemed that the arguments in The Stork and the Plow were proving themselves. On the other side of the world,
fires raged in Indonesia, launched by deforestation and desperation in the failure of Asian markets. Disease and
drug addiction were the scourge of Eastern Europe and Russia, driven by alcoholism, prostitution, and the decline
in living standards after the fall of communism. The fear of new viruses unleashed as development pressed deeper
into the African and Asian wilderness was now overshadowed by the resurrection of old viruses like tuberculosis,
propelled by the collapse of government health systems. With international travel the world was ever more
interdisciplinary.
Daily was busier than ever. Her life was no longer her own, she sometimes felt. She was scheduled to speak at the
World Economic Forum. Jane Lubchenco arranged for her to be one of the first group of Aldo Leopold Leadership
Fellows, giving her intensive training in dealing with the media. She spent a great deal of time giving talks to
nonscientists. No one disagreed that nature provided invaluable services to humankind, that it had to be protected,
and that scientific formulations must play a leading role.
The issues spun out from the concept of nature's services were becoming more and more complex. U.S. ranchers
who destroyed habitats could "rebuild" them elsewhere. In biotechnology a race was on to gain rights to genes,
gene pools in natural populations, and potential drugs from the natural world. The implications were staggering.
Meanwhile, the ecological devastation accelerated. "An observer from outer space," Daily wrote, "would likely
conclude that next to nothing was being done to arrest or reverse fundamental aspects of environmental
degradation." Since 1970 over two-hundred-fifty million people, almost the population of the United States, had
died of hunger. Since 1981 the total crop area of the Earth had shrunk by 5 percent. An area the size of Colorado
was abandoned each year because it was no longer viable to farm.

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Yet arguments against nature's services also continued. That the doomsayers ignored the great advances of the past
twenty years was the gist of an article in The Atlantic Monthly by Greg Easterbrook and, later, a more thoughtful
piece by Mark Sagoff. Decrying first of all the ecologist's tendency to sound like Chicken Little, they argued that
ecosystems science was full of holes. Though neither were scientists, they were good writers, and their ideas
caught fire.
"We don't highlight the successes as well as we should," Daily agreed. But she assailed Easterbrook's demagogic
use of isolated facts to weave a pattern that's "plain wrong," she said. The Earth was losing more natural lands
faster than at any time in its history. There's no value for a Brazilian rancher to keep up a hectare of rain forest.
She wanted science to give them that value.
Later in 1999, she learned that her assistant Luis had been falsifying data for months. She felt guilty for allowing
such a young man to be so critical to the research. She had no choice but to dismiss him. But she called on others
in town, like Jesus Ilama, church deacon, who fashioned guitars in his spare time. He became their star mammal
trapper. Another townsman, Randi Figueroa, specialized in butterflies. Still, they had troubles. Once a major bridge
was torn down to be replaced and they had to leave the car and walk several miles out of their way. Another time,
recalled Jennifer Hughes, Daily asked for a shovel to work on huge mounds of dirt that had been sitting for days to
be used to fill in the ruts of a road.
She kept going. They were getting good results, finding that even a small amount of preserved forest, say along
riverbanks or through gorges, will preserve significantly greater species diversity that would have been expected.
The possibility of maximizing tradeoffs was there, if only one knew where to look.
8
Imagine a world where you could open the business section of the newspaper and see precise, intricate
measurements, not of the unemployment or interest rate, but of the latest fluctuations in the nitrogen cycle or the
forest recovery in a country. It is a problem of our time that we pay such close attention to the latest tipple in

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business but little to the changes in the great wealth-producing machine that is the Earth. Today, for all the
enterprise of researchers, we are still doing only a little better than flying blind. This is where Daily's work is
important, as an early step toward understanding how the intensification of land use can be modified to maximize
the health of ecosystems.
Read only history books, and it becomes easy to think of advances and breakthroughs as somehow inevitable. It
would be easy to suppose right now that nature's services is an idea that must surely be catching on. More forest is
cut down every year than in the twenty millennia before ours. No one could doubt that eventually Earth's resources
will run out. Technology is great, but you cannot eat it.
Like Susan Greenfield, Gretchen Daily stuck to her earliest interests in the humanities and turned to lectures,
popular journalism, and collaborations to carry out her complex quest. Like Greenfield, she wrote frequently for
the press and tirelessly grabbed every opportunity to push an agenda she believed in. This got her into trouble but
it made it possible for her to work on a shoestring, as did Marcy, when the rest of science was not supporting her
complex-systems approach. Like Venter, she organized science panels at major meetings, especially at the oftdenigrated AAAS meeting.
The jury is still out on how much of a paradigm she is shifting. By her mid-twenties she had pushed to the front of
the most challenging goal of sciencethe study of Earth's sustainability and the future of our species. "Gretchen
drew in a broader range of expertise that turned out be absolutely brilliant," said Jane Lubchenco, new member of
the National Academy of Sciences. "But it's too early to say how countryside biogeography will play."
Sitting at the edge of the front row during her panel at the AAAS convention in Seattle, I watched her take
questions on nature's services and on the resurgence of El Nio. She had the uncanny ability to talk with people
from completely different fields. I was amazed at her breadth. When we met for breakfast at Stanford, she was
self-deprecating when a difficult question came up, or when she was challenged on the idealism of her quest.
Reporters called her to comment on every manner of climate and ecosystems disturbance. We face great scientific
uncertainties, Daily wrote, "but clearly most of the action is on the social side." To play tennis well, a friend once
told me, you have to play with no ego. I took that to mean, do not be afraid to fall on your face. Just get back up
and play.

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Drawn to Truth:
Carl Woese and the Archaean Revolution
1
In a cave in the mountains of Chiapas, in southern Mexico, thirty-five-year-old microbiologist Norman Pace
dangled from a rope. Below him the cavern's river dove down a waterfall and then down a much bigger eightyfive-foot cave drop called Fool's Falls. The slippery stone smelled of earth. Leading one party in an amateur
expedition to map the cave, Pace was laying a phone line to a camp a couple of hundred feet below the surface.
They needed the phone because when it rained, much of the cave flooded. You wanted a phone line to check the
surface weather. Otherwise you could die.
Rigged onto a seat sling clipped to the line, he lowered himself into the water, bobbing, spooling out line, letting
the force of the icy stream push him forward. The small, energetic Pace had been exploring caves since he was a
small boy in rural Indiana. He could tell you the date, June 22, when he had first followed two guides into what
seemed a routine cave in a state park. They showed him a hidden fourteen-hundred-foot crawlway, where a cool
dank wind blew from an enormous, newly discovered cavern deep inside. In his life as an amateur explorer, Pace
had uncovered several new caves and caves within caves. In Kentucky's Mammoth Caverns for instance, with its
gift shop and tour guides, he once peered up from the main trail and, spotting a shadow, climbed up to uncover a
new mile-and-a-half-long passageway.
Caving was a hobby he considered critical to his science. It taught him that much of what we think we knowwe do
not, really know. The

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most exciting possibilities often lay where you thought you should not be looking. "Exploring caves teaches you
that if you think it's all known, you fall prey to circular reasoning," he said, "into a paradigm of self-satisfaction."
Suddenly his anchor popped loose. One minute he was moored, the next minute he was dropping down into a
rushing torrent toward a precipice. The rapids ripped away his glasses, the spool, his pack, everything but his light
as he plummeted over the first waterfall. Halfway down, the rope above him yanked and caught. It snagged his
ankle, yanking him up directly under the waterfall, hanging upside down. Icy torrents of water poured into his
nostrils and mouth. He writhed, seeking a space to breathe. He was drowning.
At the time, Norman Pace was an associate professor in Denver attached to the National Jewish Center. He was a
leading researcher, on his way to election into the prestigious National Academy of Sciences for his work on the
physical structure of RNA. But his most exciting work, what he called The Search and likened to cave exploring,
had not yet begun.
Shortly before Norman Pace struggled in a waterfall in a Mexican cave, a friend at the University of Illinois had
come up with a discovery that shook the foundation of Darwinian science. Carl Woese, a physicist turned
evolutionist who was fourteen years Pace's senior, had always felt "drawn to truth." For years he had studied the
short sequences of bacterial ribosomal RNA, seeking the cellular keys to evolution. Most others were using DNA
technologies to launch the human genome revolution, but Woese, working mostly alone, was studying the RNA of
bacteria in a much bigger quest, for the history of life.
In that search Woese stumbled across an important discovery in 1976 and 1977. Studying a little-noticed group of
organisms he had found a whole new kingdom of life, a third domain that offered a new key to the origin of all life
on Earth. Funded by a small NASA grant for seeking extraterrestrial life, Woese was proposing a new concept of
life to the scientific world. But his ideas about the microscopic organisms he called "archaea," for the "ancient
ones," were being met with ridicule and hostility. Even he did not realize their full import. It was not enough to
have a good idea. He and others had to prove it, to explore and map its implications.
Struggling to pull his head out of the wall of rushing water, Pace had no thought of archaea. He was fighting as
hard as he could. His friends were pulling on the rope and yanking him back into the rushing torrent. He yelled but
they could not hear him. He pushed with all his strength into the water, bouncing against the current into the

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air where he grabbed hold of a slippery outcropping, hands bleeding, coughing and gasping.
It would take another decade or so, but together Norman Pace and the retiring Woese and others would usher in
what Science called a ''new era in one of biology's grandest, if most problematic pursuits: understanding the origins
of life." Woese laid the foundation, and Pace developed the technique, for uncovering a teeming universe of
unknown life, leftovers from primordial Earth, in overlooked environments like the bottom of the ocean, the
bubbling hot springs of Iceland or Yellowstone, the superhot minerals and rocks miles below the Earth's surface,
and watery sulfuric caves. As it would turn out, these strange organisms overran almost every environment on
Earth. They showed that our concept of species and kingdoms was incomplete; our tree of life was stunted; our
perception of species balance in the world was myopic. "Look at the visible world with a trained eye," Woese said,
"and you see microorganisms are the underpinings of everything," The normally staid journal Science called the
archaean discoveries "a new paradigm for understanding life on Earth." What followed transformed fundamental
and applied biology.
Much of this came from a friendship between Woese, an unusual and quiet thinker working alone in an unkempt
lab, and Pace, an adventurer whose near-death experience exemplified a spirit that recast the direction of a science.
What put Carl Woese on the edge of the biggest acceleration in the history of microbiology? Why did his
breakthrough lead others like Pace into discoveries no one had envisioned? The story of the archaea is a parable of
creativity and collaboration. It is a story of years spent outside the mainstream of a field, seeking the extraordinary
in the ordinary, following an idea as if your life depended on it. This is a story, ultimately, of the power of thought
and friendship to uncover an unseen universe in the forgotten crannies of the world.
2
For thousands of years, our understanding of life had been divided very simply between two groups, plants and
animals. With the seventeenth-century invention of the microscope, a new group was added, the microbes. There
matters stood until the 1930s, when a more scientific division was offered, based on the features of

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the cell, differentiating between the bacteria, or prokaryotes, on one side and everything else, or eukaryotes, on the
other.
About that time, Carl Woese was growing up in Syracuse, New York. Born July 15, 1928, he was the son of a
consulting engineer and a stay-at-home mother. He attended Deerfield Academy and then Amherst College, where
he loved physics and mathematics. He was shy in groups; he had a slight build and an offbeat sense of humor. He
liked to get to the bottom of things. "Ever since I was a kid," he once said, "I wanted not only to understand things
superficially, I wanted to understand them deeply." As a graduate student at Yale he gravitated toward evolution
and began pursuing biophysics, what we today would call molecular biology, which could offer, he thought, the
mathematical rules that governed life.
As he turned in his thesis, however, Watson and Crick were publishing their discovery of the structure of DNA.
Woese felt "I wasn't good enough to be a scientist." He thought he could never match them. He switched to
medicine for "two years and two days," but found it too cold-blooded. He returned to Yale for postdoctoral work.
At the time biology was split between two domains, one dominantWatson and Crick's cell biologyand one
subordinate, the older Darwinian study of evolution and natural history. Evolution was the nineteenth century,
exemplified by Darwin's pencil sketches of dodo birds and fossils and the eccentric spirit of the Renaissance
collector. Cell biology was the twentieth centurymathematical, brash, and promising to harness life as relativity had
done for the atom. The two sides had little to say to each other.
Within cell biology itself, the rage was to understand "translation," the complex biochemical interactions by which
DNA exercised its power in the cell. Two models of translation battled for acceptance in the late 1950s. One
model, proposed by the physicist George Gamow, argued that DNA interacted directly with the amino acids of the
cell to create proteins. Another, suggested by Francis Crick, argued that there had to be an adapter molecule. Most
of biology sided with Crick. Woese sided with Gamow. He shared the physicist's conviction that you could find the
principles that underlie the processes of the world. "Physics takes a complex world and makes it simple," Woese
said, half-laughing. "Biology takes a complex world and makes it more complex."
It was not too much of a leap for him to side with the iconoclastic. Woese was schooled in a rich tradition of
pursuing first principles. His mentor, Ernest Pollard, had worked with Chadwick, the discoverer of the neutron.
Chadwick in turn had been trained by Earnest

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Rutherford, Cambridge's pioneer of atomic structure. "It was like studying American history with the Adamses,"
Woese said. He landed a job doing basic genetic research at, of all places, General Electric, in a short-lived
corporate division. While he was there, a cellular building block called transfer RNA (tRNA) was discovered
elsewhere, and biology leapt on it as Crick's "adapter" molecule. For Woese, this apparent disproof of Gamow's
idea posed a crisis. Instead of abandoning his intuition, however, he decided that if the theory did not match the
facts, then the facts were incomplete. If nucleic acids did not interact with amino acids in cells now, he reasoned,
perhaps they had evolved from a time deep in the past when they did. "So I had to become an evolutionist," he
said.
With this quiet leap Woese offered to bridge the study of the cell and the study of evolution. To him this was
natural. "You can't sequence the same protein in two different organisms," he said, "without starting down the path
of becoming an evolutionist." In the field, though, he was trying to synthesize two completely separate disciplines.
If he was right, it was a stroke of genius. He was foreseeing dynamic change in a static study of cell structure,
somewhat as Newton had seen change in the static world of mathematics two centuries earlier. If he was wrong,
then he was crazy. His later students would comment that in discussion he did not distinguish too heavily between
great ideas and nutty ones; it was hard to tell the difference at first. Quiet and introspective, he thought instead
about how he was going to prove his idea.
3
When General Electric's stock plummeted, Carl Woese had to look for a conventional university job, which he
found at the University of Illinois in Urbana. Miles of feed corn and soybeans from Chicago, it might have seemed
a backwater, but it was forging a stellar tradition in microbiology. The great Salvador Luria, mentor to James
Watson, once taught there. Woese joined a rich group of colleagues like Ralph Wolfe and Sol Spiegelman, and
they eventually formed "the best microbiology department in the country,"

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recalled a student, Dave Stahl. Urbana afforded them the freedom to think independently. "It was a place you could
pursue your own ideas without interference," said Ford Doolittle, a younger postdoc who had attended Harvard and
Stanford, but came to Illinois to be with Woese.
Woese's lab was small. He did not waste time writing for grants and did not like to travel to a lot of conferences;
he was in the lab forty hours a week, accessible to students for questions. He attracted an unusual group of
"castoffs from other labs," said Mitchell Sogin, now the Director of the Woods Hole Program in Molecular
Evolution. "Not that they were any less worthy, but they just didn't fit normal molds." They included people whose
interests ranged more widely than straight microbiology, like Michael Bleyman, who went on to the University of
North Carolina but eventually opened a breeding program to preserve the gene pools of carnivores like tigers,
leopards, and jaguars, and Lee Sutton, a philosophy enthusiast who was in no hurry to finish his degree. They
gravitated to and learned from Woese's broad vision of what science should be, according to David Stahl, who
went on to become an award-winning microbiologist at Northwestern University. "But [science] is not often
practiced that way. Carl thrived on being an outsider."
They learned something else, that a career was not just about giving papers or winning the largest amounts of
money. "He treats science as though it is some sort of holy temple," said Mitchell Sogin. "It almost takes on a
religious tone, though not in a deity sense. He worships science. He worships truth."
Seeking the secrets of evolutionary history, Woese focused on bacteria, the most ancient of life forms. To do that,
he needed first a system of classification, much as Darwin had needed to classify the fossils and species he
discovered in his Beagle years before attacking the question of their history. While there existed extensive family
trees for animals and plants, at the time there was little for bacteria. The giants in the bacterial field, C. B. van Niel
of Stanford and his student Roger Stanier of the University of California at Berkeley, had struggled in the 1930s to
make such a tree. They declared it impossible to catalogue the blobs, cylinders, spheres, squiggles, and tubes that
infected old cheese or dotted a microscope slide. Just a handful of soil alone contained billions of microbes. They
were difficult to grow in pure culture, if too easy in your refrigerator, so biological work concentrated on the few
weeds, like Escherichia coli, that could be studied in pure culture. Because what we did know was mainly about E.
coli, it was then reasoned that everything else must act like E. coli. The intellectual inertia, Woese said, "was
astounding."

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Woese thought that if you wanted to understand any deep evolutionary question, "to go back to where Darwin was
unable to go . . . it was obvious that you needed to be able to see the relations among species. It was like going to a
zoo and not being able to distinguish a zebra from a lion." Coming from physics, he did not fear taking a fresh
approach. "I hadn't been trained as a microbiologist," he told Virginia Morell of Science,"so I did not have this
bias." In 1965 Linus Pauling and Emile Zuckerkandl found a way to make a universal tree, sounding a "clarion
call" in an article in the Journal of Theoretical Biology titled ''Molecules as Documents of Evolutionary History."
They showed that molecular sequences in cells offered an organizing principle for life's family tree.
Nabbing their idea, Woese focused on ribosomal RNAs (rRNA). Because the ribosome made the proteins that did
the work of life, the nucleic acid that it was made of, the rRNA, could have been the most ancient of nucleic acids.
RNA was also simpler and shorter than DNA, making it easier to study in those early days. It could be extracted
fairly easily and was found in all organisms. "It was the bar code of an organism," Woese said, "that identifies it
and at the same time relates it to other organisms."
In 1966, though, few tools existed to analyze RNA. Woese had to adapt a time-consuming method, called
oligonucleotide cataloguing, devised by Fred Sanger, the interdisciplinary figure who had already won one of his
Nobel Prizes. Like DNA, RNA is made of four different basesadenine, cytosine, uracil, and guanine. Sanger's
technique cut radioactively labeled rRNA into very short snippets, sorted the fragments by size and electric charge,
and exposed them together on X-ray film. The resulting transparency showed only cryptic groupings of spots, but
their arrangement gave Woese clues to the base sequence of the original rRNA. Over the years Woese began to
build up hundreds of these large films into a library of bacterial rRNA, which he stored in yellow Kodak boxes in
his closet. To study the transparencies he covered his office with light boxes, including one entire "luminescent
wall." He became the world's leading expert on them. "He stood there all day, every day, looking at these,
searching for patterns," said the University of Georgia's William Whitman. "Only three or four other people could
understand what he was doing." For relief, he did chin-ups on a bar in his office and drank Dr. Pepper. In a
cramped cluttered lab with its windows blacked out, he combined mind-numbing detail work with the broadest
possible quest. "None of us really had an appreciation for what Carl was trying to do," recalled Mitchell Sogin.
"I'm not sure he had a full appreciation for how it would work out."

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From 1966 to 1976 Woese taught his classes and slowly built up a library of about sixty bacterial rRNAs,
arranging their patterns into a fledgling bacterial family tree. Other researchers were sequencing proteins toward
the same goal, but the proteins were not as universal as rRNA. Woese published bacterial phylogenies in 1975 and
1976, helping to build confirming evidence that advanced cell structures such as mitochondria had actually been
external bacteria captured by other cells, eons ago, and incorporated symbiotically. He gave a talk in Paris where
NASA's extraterrestrial biology director, Dick Young, was in the audience. Afterward Young asked him to write a
grant proposal, the only time "that has ever happened to me," Woese said. Young provided a critical early grant of
$50,000.
With the money, Woese solicited suggestions from colleagues for good candidates to analyze. In 1975 Ralph Wolfe
suggested doing the methanogens. Little was known about these humble microbes that lived in sludge, mud, and in
the intestines of cows and humansstrange environments, some of which were as caustic as sulfuric acidproducing
methane gas. They needed no oxygen to survive. They were intriguing.
As he studied them, he became more and more puzzled. Their rRNA looked foreign. The transparencies were
missing the signatures of certain bacterial sequences. He told Wolfe that they must have run the wrong RNA. They
tried the experiment again. Over the months, he built his data in little green books that only he could understand. A
jazz aficionado, Woese once compared his work to listening to music. "You have to pick up on these faint tunes,"
he said. "And if you like them, you go to where you can hear them better." George Fox eventually coded the data
on punch cards, writing an early computer program to interpret it. "You could try to help him," Fox recalled, ''but it
was exhausting and he always did it himself anyway."
Since the 1930s life had been divided into two kingdomsthe prokaryotes, like bacteria, whose very simple cells
lacked a nucleus, and the eukaryotes, like the plants and animals, whose cells contained nuclei and developed
structures and organelles. With a jolt Woese realized he was seeing something remarkable. His microbes looked
like bacteria on the outside, but not on the inside. They were nothing less than an entire new kind of life, and a
bridge between bacteria and everything else. At first he thought it was impossible. But as he thought, he realized
the old two-kingdom model had never once been tested or verified. And it was wrong.
He confronted Wolfe in the hallway outside their offices. "These aren't bacteria!" he said.

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"Of course they're bacteria," Wolfe recalled responding. "They look like bacteria."
Ten years of staring at slides had taught Woese one thing: that the proof was not in a being's appearance, but in its
ribosomal nucleic acids. He checked and rechecked his data, convinced he had discovered an entirely new form of
life. Their primitive metabolism and extreme habitats suggested that these were very ancient organisms, perhaps at
the root of all life on Earth. He needed a good name to capture the wonder his discovery inspired, He settled on
"archaea" from the Greek archaios, ancient. In a last moment of self-doubt, he added "bacteria" to the end:
Archaebacteria, "Arkies,'' for short.
Woese called NASA to say he had an urgent announcement. NASA scheduled a press conference. It was kept a
low-key affair, without even Woese present, but on November 3, 1977, Woese's discovery made the front page of
newspapers around the worldThe New York Times, even his local paper.
That day Woese emerged from his office to bask in the expected public attention. He stopped to order a coffee at a
fast-food place in town. He approached the girl at the checkout. "Do you know me?" he asked. She smiled blankly.
Then she brightened.
"Oh, yeah," she said, "you're Bob's dad."
The response of his colleagues was far more discouraging. Some resented the news conference held the day before
the findings were published in The Proceedings of the National Academy of Sciences. "The reporters couldn't
understand it," recalled Ralph Wolfe, "so Woese called it a 'third form of life.' Of course that caused a lot of
confusion." Some suggested Woese had spent too much time in front of a light box. Because Woese abjured
conferences and few understood how to read his transparencies, he was viewed as a crank whose methodology was
suspect. He was not really a biologist. No one else was using his technique. Others said his rRNA tools could not
possibly answer the questions he was asking. The reaction was all the more difficult because it was insidious. No
one published a reply or attempted experimentally to refute his conclusions. Harvard's Ernst Mayr was a main
opponent. The day of the press conference, MIT's Salvador Luria called Ralph Wolfe. "You're going to ruin your
career," Luria said. "You've got to disassociate yourself from this nonsense!" R. G. E. Murray, editor of
microbiology's definitive text, called Bergey's Manual, would include archaea only as a subfield under bacteria.
Woese had hoped at least for a response from the microbiologists van Niel and Stanier. He never received one,
even though Stanier did write a note of appreciation to a colleague who later applied Woese's

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technique. "I'd read Structure of Scientific Revolutions," Woese recalled, turning to Thomas Kuhn's ideas on the
history of science to help survive the crisis in his career. "I knew exactly what was going on. First the field ignores
a new idea, then there's ridicule, and finally comes acceptance."
Only in Germany, where the celebrated microbiologist Otto Kandler immediately grasped the significance of
Woese's finding, was his work given the recognition he felt it deserved. Kandler arranged for the world's first
archaea conference to take place in 1981 in Munich, inaugurating an annual series. Knowing Woese's sense of
persecution, Kandler arranged for a church brass choir to greet Woese as he rose to address the conference. "That
was a jolly time," Woese recalled almost twenty years later. "Kandler was thoughtful, and he was open."
But even after a generation had passed, Woese remained sensitive, and he held on to his anger. "Even now,"
Norman Pace recalled, "he sometimes lashes out at people on whose shoulders he stood who, he thinks, failed him
because they didn't recognize archaea." Others remarked on the magnitude of his claim. ''It was a new idea and
people struggled to accept it," said Ford Doolittle.
Woese had not been looking for a new branch of life when he began his quest: he had been seeking the history of
cellular evolution. He wanted to find the Universal Ancestor of all life on Earth, and he returned to that quest after
announcing his discovery of archaea. Eventually he began reaping the rewards of a life of the minda MacArthur
genius grant, the Leeuwenhoek Award, microbiology's highest honor, and election to the National Academy of
Arts and Sciences.
The three-part tree of life he developed was startling. Most life is single-celled and invisible to the naked eye, it
showed, with plants, animals, and the rest of visible life only a small twig of an enormous tree. If microbiology
was going to apply what he discovered, though, it would require other scientists to seek more data and expand on
its implications. But no one was leaping to devote years of research to a controversial theory proposed by a cranky
personality. For his part, while he was "really taken with the concept of the Big Tree," Norman Pace was looking at
the physical structure of ribosomal RNA in a quest for better understanding of the cell and, eventually, things like
better medicines. He was not really interested in archaea for archaea's sake. He had little desire to be "Paul to Carl's
Jesus," he once said. But his friendship with Woese helped him realize that the older scientist was giving "a new
sense of the space of evolution," he recalled. Pace was attuned to mapping spaces because he was attuned to map-

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ping caves. He loved exploring and caves; the Woesean tree provided a profound new map with which to look into
both.
4
Growing up in rural Indiana, Norman Pace came to the University of Illinois as a graduate student in microbiology.
He did not work in Carl Woese's lab, but they talked a lot. In 1969 Pace went off to the University of Colorado in
Denver, where he stayed for fifteen years, rising from assistant to associate to full professor and exploring the
mountains and caves around Boulder, in Mexico, and elsewhere. He ended classes and conversations with "Let's
rock!" Short and scrappy, he was an ebullient teacher. Pace was captivated by the possibilities of RNA. He
compared the study of its architecture to the multidimensional thought involved in mapping caves. His harrowing
experience at Fool's Falls, and others in his explorations, had "shown me that not looking in the right place could
be the way to discover something new," he said. Talking to Woese, he began to realize that his map of life, using
RNA, was still incomplete. In the lab scientists had been able to cultivate only a fraction of the true number of
microbes. "Woese provided the . . . framework of evolutionary relatedness," he said. "But still we knew absolutely
nothing about microbial diversity in the world."
Many people became interested in RNA as the primordial essence of life, dating back earlier than the more
complex DNA. But they could not yet prove RNA was capable of reproducing itself, the sine qua non of life. In
1981, the same year as the first world archaea conference in Germany, the University of Colorado's Tom Cech
found something close: RNA could splice itself. When Sydney Altman at Yale made a similar finding, suddenly
evolutionists could look at early life and "contemplate an RNA world," wrote Walter Gilbert in Nature, in a
famous line that gave birth to a whole field of study. Cech came down from Boulder to speak, and Pace and
another Woese associate, Gary Olsen, were in the audience. "It was like, wow, this changes the world!" recalled
Olsen.
Around that time the deep-sea research submarine Alvin was finding enormous caches of unknown microbes living
around volcanic

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vents in weird communities with giant tubeworms and other creatures. Because archaea and their microbial cousins
thrived in nearboiling water, they were called extremophiles or thermophiles. Some fed on carbon dioxide, others
on hydrogen sulfide. The photosynthetic types did not use chlorophyll. They were, in a word, oddballs. Pace
became interested in them, however, because extremophiles had highly stable ribosomal RNA, and they could be
useful as he sought to understand the physical structure of RNA. He called a researcher for some sample cells. It
was 1984 and Pace was on sabbatical back at the University of Illinois. Pace waited, then wrote and called again.
Time was short. Still no cells arrived.
While he was waiting, Pace picked up a book by the University of Wisconsin's Tom Brock called Thermophilic
Microorganisms and Life at High Temperatures. It described the thick rugs of brilliant pink filaments of
hyperthermophilic bacteria living around Yellowstone's Octopus Hot Springs. Pace thought about the idea. "Hey,"
he burst out to his group. "Forget about waiting for cells. We're going to get a bucketful of mud and sequence
everything that's in it."
"But you won't know what the organism is," objected postdoc Gary Olsen.
"That doesn't matter. The RNA will tell us what we've got."
They all sat for a second, stunned, as the idea sunk in. They could just go out, suck up ooze along a tourist
pathway, and then randomly analyze it. For a century microbiologists had driven themselves crazy trying to
achieve pure cultures in a lab. "Just do it in the dirt," Pace said. They could do shotgun sequencing of genes straight
from the environment.
"Do you know what you just said?" Olsen asked. "You just transformed microbial biology."
5
In forgoing lab experiments on cultured micro-organisms Pace offered a new way of seeing, more akin to the
reality of life than what a traditional laboratory approach revealed. Microbes did not exist in the world as
designated "species" in petri dishes, they lived in teeming symbiotic communities in which they borrowed freely
from

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one another's food, waste, even perhaps their genes. The non-oxygen-breathing archaea, for instance, almost
always existed with organisms that did need oxygen. The seething throngs Alvin had discovered on the ocean
bottom showed that symbiosis, not independence, was a paradigm for life on Earth. Pace now offered a way to take
"a natural history approach to microorganisms," said David Stahl, something that Darwin and others had done for
plants and animals, but never before for the invisible world.
It was an assault on the whole idea of what a laboratory or a species is. It would also be fun. "The hot springs idea
was like another cave to Norm," said Ford Doolittle. "It gave him an excuse to go to Yellowstone. I would have
been afraid to try it."
Excited, a group including Pace, Woese, David Lane, Gary Olsen, and Dave Stahl headed off to Yellowstone in a
van in the summer of 1988. "It was a kind of pilgrimage," recalled Stahl. Amidst wandering tourists, they took
samples from the mud around the near-boiling pool. They stored the samples on dry ice, freezing them in a metal
cooler. They brought the van back to Illinois and started sequencing. In so doing they reversed Woese's approach.
"Carl Woese used the organisms to identify the ribosomal RNA," Pace said. "We used the ribosomal RNA to
identify the organism."
What they found was perplexingfragments of new organisms, each stranger than the last. They saw hints that the
diversity of life was far greater than had been uncovered in animals and plants. What Pace came to call "The
Search" really took off, however, in the early 1990s when a new postdoc and a refugee from graduate school in art
history, Susan Barns, joined Pace's group and came to Yellowstone seeking new sites to sample. She took an
interest in an obscure pool first noticed by another postdoc named Jim Brown. The steaming nine-by-twentyseven-foot cauldron sat tucked up above the usual hiking paths, its water boiling and spilling out into lower pools.
It was so unexplored it had no name, They called it Jim's Black Pool because of its most stunning characteristicits
utterly black obsidian sand. High in iron and sulfur, two prerequisites for archaea and thermophiles, it seemed a
great place to search.
Using a more advanced sequencing method that Pace had perfected, Barns took the DNA and focused on a
particular gene that was present, but different in sequence in each different microbial species. She amplified the
gene, cloned it in cultures of E. coli, and then sequenced DNA from the clones to identify the different forms of
this gene from the thousands of organisms sampled. By this method she found a new pair of archaea that looked
like the most primitive

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organisms ever discovered, dating back perhaps 3.5 billion years and suggesting that life began in hot pools much
like Yellowstone's. Then she began to find more. By the time she was finished, she had found thirty-eight new
species of archaea, some more different from each other than we are from plants. A normal biologist, studying
plants and animals, might make a career out of discovering one or two new species; Barns had discovered thirtyeight in one small pool. They tried to culture the new organisms in the University of Regensburg laboratory of Karl
Stetter, the world's premier specialist in culturing thermophilic microorganisms, but they could not get the most
exotic species to grow. By then they needed a name for the spring. The Park Service would not allow them to use a
person's name. Woese, a bit of a poet, suggested the name Obsidian Pool.
Once Barns had identified the astonishing diversity of archaea in the pool, Pace decided someone should look to
see how diverse the bacteria might be. He had a postdoc from New Zealand, Phil Hugenholtz, do the sampling.
Digging out the stromatolites, sticky rocks covered with oozing bacteria that are probably the most ancient type of
living community on Earth, he found an even greater diversity of unknown bacteria in the pool than archaea.
Obsidian Pool suggested that, contrary to common belief, archaea did not all dominate thermal pools. Bacteria there
outnumbered archaea fifty to one. Hugenholtz eventually discovered thirteen new families of bacteria, more than
doubling the known families of bacteria, all in one pool. "We've been ignorant of diversity everywhere," Barns told
Carl Zimmer from Discover, "this happened to be the place where it jumped out at us." And it was only beginning.
Similar discoveries of archaea, by researchers using Pace's method, extended their habitats into temperate and icy
waters as well. Jed Fuhrman of the University of Southern California and Edward DeLong of the Monterrey Bay
Aquarium Research Center, working independently, discovered archaea in huge numbers in the Pacific, both on the
surface and deep below. The search became "an obsession of mine," said DeLong, who discovered that about 15 to
20 percent of all microbial cells in ocean waters were archaea. As for Fuhrman, based on the ocean samples he had
taken, it seemed "there's a very good chance that these are the most common organisms on Earth."
Even before the explosion of new discoveries, Woese decided to take a year to write a critical synthesis. In
Germany and elsewhere new findings were arriving on top of each other but no one had organized and clarified the
significance of the study of molecular evolution.

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Published in 1987 in Microbiological Reviews, Woese's article, titled "Bacterial Evolution," sounded quite different
from any typical science review paper: "A revolution is occurring in biology;" it began, "perhaps it is better
characterized as a revolution within a revolution." Recounting the history of science's mistaken models of the tree
of life, Woese noted most of all how such incorrect paradigms had "stifled any real creativity." Explaining that
molecules were "chronometers,'' he offered an equation for determining the exact relatedness of organisms by their
gene sequences. While the article did break down the archaean and bacterial family trees, it also went further,
almost to a spiritual level, about the ultimate aim of biology. Observing that physics had abandoned its old
mechanistic view for a fluid, processoriented outlook, Woese argued biology must also shed its old reductionist
views to explore how "processes (evolution, development, mind) somehow underlie genes, cells, brains, etc., not
the reverse."
Representing much of what Woese had worked on for two decades, it linked microbial diversity and evolution
along with the latest findings from around the world. "It was a highly integrated article," said David Stahl, "in a
way that most microbiologists had not been thinking until that point." Others might give papers or take to the
airwaves; Woese thought and wrote. It worked. With three hundred citations in other journals over the next three
years, his article became one of the most cited science papers of the decade. The Woesean tree was soon hanging
in most every microbiology lab in the country.
One person who was stunned by the article was a computer scientists at Argonne National Laboratory near
Chicago, Ross Overbeek. "It was clear he was attempting something of huge significance," Overbeek recalled. "I
showed the article to my partner . . . He came back and said, 'There's more science on a single page of this than
you or I will do in a lifetime.'" Woese had indicated he was looking for a connection to a good computing group.
Soon Overbeek would lend the power of some of the world's best computers to the quest for the Universal
Ancestor.
With the advent of the age of genomics, one would need far more computing power to compare whole genomes
rather than just gene fragments. Woese foresaw a tremendous impact on the search for the origin of life. In 1988 he
proposed to the NIH a large-scale sequencing project for microbes. The proposal was turned down. The NIH
wanted to focus its resources on the human genome. Ironically, sitting on their review panel was then NIH Senior
Researcher Craig Venter.
It was frustrating. "The human genome is mere application; it's a drop in the bucket," Woese later said. "Here we're
on the verge of a

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new paradigm to change all of biology. Microorganisms are the underpinnings of the biosphere. They are the
evolutionary sources of our cells. Understanding the genomes of the microbial world is fundamental to
understanding how life got to be on our planet." As for the ecological debate, "We have to understand how the
biosphere works at the microbial level if we're going to be able to cope with man's stressing of it."
6
By the 1990s the U.S. Department of Energy (DOE) was ready to finance the sequencing of microbial genomes.
The extremophiles had tremendous energy and industrial potential. The microbes' oils could be used in hightemperature machinery. The fact they lived off sulfur, iron, petroleum, even could absorb radiation, made them
ideal as biotechnological answers to toxicwaste cleanup. Entrepreneurial companies like New England Biolabs
began selling archaeal Vent and Deep Vent polymerases, used in DNA sequencing and industrial enzymes, as
cleaning aids in detergents that removed pollutants like chlorine and bromine. The hyperthermophiles' resistance to
heat afforded the possibility for new thermal technologies, even cancer research.
At Yellowstone itself, the biomining of extremophiles became a controversial issue for the National Park Service.
There was nothing new about the issue. In the 1960s, Thomas Brock of the University of Wisconsin discovered the
first new microbe from a geothermal pool that he named Thermus aquaritus, or Taq. By the 1980s, Cetus
Corporation was using an enzyme from Taq to speed its DNA replication by polymerase chain reaction. By the
1990s the Taq enzyme was generating $100 million a year for Hoffman-La Roche, but no royalties went to
Yellowstone. The financial potential of the new organisms being discovered was staggering.
The DOE was also interested in the fact that microbes produced methane by the ton, offering incredible potential as
a new, clean totally renewable energy source. By 1993 the DOE was setting up a special microbial genome project
with grants, to chart the genomes of these

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potentially lucrative creaturesalmost the exact proposal Woese had made five years earlier. The University of
Maryland's Frank Robb arranged a meeting in 1994 at Craig Venter's world-leading genomics facility TIGR, with
Woese, Pace, Overbeek, Ford Doolittle, Gary Olsen, and others, to convince Venter to join in pursuing a DOE
grant for sequencing the genome of an archaean organism. Venter, of course, was mainly interested in the human
genome. The idea of using his vaunted computers to understand obscure bugs was less than inspiring
It was a difficult meeting of prickly egos, respecting each other but a bit wary. For years Woese had watched
millions being pumped into the Human Genome Project, while the much vaster need for microbial sequencing had
received very little financial backing. He wanted to go after pure science, feeling that "what we're doing here is so
fundamental, that it is inevitably going to have an impact on a number of applied areas," recalled Overbeek. He
suggested a variety of organisms to sequence jointly at TIGR and Urbana. But Venter, with by far the larger
facility, held the cards. "Craig did not want to let the data leave his lab," recalled Hamilton Smith.
After Woese gave his presentation the group headed out to lunch at a Chinese restaurant, where they loosened up
over a beer. There, Venter invited Woese to serve on TIGR's scientific advisory board and agreed to a
collaboration. By the time they were driving back to the airport, Robb recalled, Woese sat back and said: "Well,
the motley crew did it."
In the end Venter held onto the purse strings of the proposal, but formed a joint project with Woese to sequence
Methanococcus jannaschii, a methanogen isolated in 1981 by John Leigh, a graduate student in Ralph Wolfe's
laboratory, from sediment retrieved by Alvin from the base of a "white smoker" nearly three kilometers below the
surface of the Pacific Ocean. It was named in honor of Holger Jannasch, the pioneering researcher into the deepsea microbial life. Its genome would be the third complete one ever sequenced. "It was just a tremendously
exciting thing to be part of," said Overbeek.
What they found with M. jannaschii in 1996 was amazing. It lived in water from 48 to 94 degrees Celsius (118 to
201 degrees Fahrenheit), under pressure the equivalent of 200 atmospheres, enough to flatten iron. It lived on
carbon dioxide, nitrogen, and hydrogen. Oxygen killed it. "It's like something out of science fiction," exclaimed
Venter. "Not so long ago no one would have believed you if you'd told them such organisms existed on Earth." In
looking at its genes, the team led by Claire Fraser at TIGR found that 56 percent of the genes were completely

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unknown to science, unlike any found in any other creature in any branch of the tree of life. "It shows how little
we know about life," said Douglas Smith, a molecular biologist at the University of California at San Diego. Some
researchers even tried to connect it with the putative fossils on the Martian meteorite reported a week earlier.
The strangeness of M. jannaschii tantalized everyone, but other similarly odd organisms were turning up all over
the worldin Iceland, in Italy, at the bottom of the oceans, and down in the bedrock several miles below the Earth's
surface. Life as we knew it, oxygen-breathing or photosynthetic, quite likely made a smaller percentage of the
Earth's life than they did. Suddenly the scope of life humans had observed for thousands of years seemed woefully
incomplete. With all our studies of climate, pollution, and ecology, we could know little about the future of the
planet until we could unmask its underpinning, the microbes. And they held one more surprise, perhaps the biggest
of all.
7
In 1998 Claire Fraser at TIGR was sequencing two new intriguing extremophilesDeinococcus radiodurans and
Thermatoga maritima. D. radiodurans was fascinating because it absorbed radiation; it could have existed for eons
in space on the surface of a comet before it came splashing down on Earth. But Thermatoga, a rod-shaped
bacterium discovered in superhot mud in Vulcano, Italy, in 1986, provided a clue as to what came next, in the first
billion years of life on Earth. "It was chosen because it is near the base of the Woesean tree," said Craig Venter.
When TIGR finished with Thermatoga, researchers found something very puzzling. "A quarter of the genes are
most similar to archaea," said Fraser. As other newly sequenced genomes of microbes were completed, the
Woesean tree began running into problems. Computer simulations by TIGR's Karen Nelson, comparing sequences
of primitive bacteria and archaea, showed there were any number of family trees that could account for the gene
differences. The repetition of huge gene sequences suggested strongly that huge hunks of

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genes were freely swapped among organisms on early Earth. It made the search for the Universal Ancestor much
more difficult.
The idea of swapping, or lateral gene transfer, was not new. Woese had described it back in his first archaea paper
in 1977, calling it "reticulate evolution" and worrying it could make for "unmanageable complexity" in building
lineages. He felt gene swapping was so rampant among early organisms, one could not even think of them as
individuals in distinct families. They were more like a consortium where one swallowed a neighbor's genes if they
helped to insure survival. In June 1998, in the Proceedings of the National Academy of Science, Woese suggested
that the heritage of the earliest microbes should not be arranged in a hierarchical tree, but in radiating branches
from a single common ancestor. Some went so far as to claim that all of the planet's early bacteria came from a
single giant "global superorganism." As genes became more complex, and separate species developed, it was likely
that gene swapping became much less frequent. So the tree held, and the search continued.
Think of the Earth four billion years ago, an infant planet. No one knows what it was like. It may have been a
superhot ball of rock, rent by volcanoes and pounded by comets and asteroids. It may have had a yellow-green
atmosphere with greenhouse levels of carbon dioxide, sulfur, and hydrogen. Its oceans, filled with iron and
minerals and pummeled by electrical thunderstorms, could have been so hot they virtually boiled, sending up vast
clouds of steam. The safest place on this vision of early Earth would have been at undersea hot vents, and deep
within the rocks. There were likely no cells, no cell walls, just a soup of molecules attached to rocks or sand. Yet
somehow, some time very close to the origin of the planet, organic molecules grew more and more complex,
eventually forming molecules that replicate themselves, mutate. No one knows if they emerged spontaneously, a
feat close to "a miracle" according to Ford Doolittle, or from organic material brought to Earth from outer space.
For that matter, life could have originated in ice, where archaea also thrive.
But life started early in the planet's history, and advanced rapidly. "You put a selective hammer on it and it
happens fast," Pace told The New York Times. "It's shockingly fast, maybe just tens of millions of years." Three
billion years ago simple cells proliferatedbacteria and archaeawith no nuclei, just genetic material and protein
factories called ribosomes. They lived off hydrogen, sulfur, iron. Plagiaristic, swapping freely, "early life," in the
words of Antonio Lozcano, "was

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not chaste," Yet it produced the oxygen we now breathe, the environment we are striving so hard to save.
Step outside or open your refrigerator or pick up a handful of soil. You are looking at billions of unknown
organisms, most of which we have never identified. Some will have biochemical and catalytic properties we can
barely imagine. Some could live miles below Earth's surface, some in ice, some in boiling water. Yet they contain
within their genes the history of life, of us. If they were to die out, so would we. If we were to die out, they would
go on and on. Truly we are interlopers in their world.
Today most every microbiology text contains Woese's three-part tree of life, though general biology high-school
texts are still just catching up. The Woesean tree is "as familiar in some labs and classrooms as the double helix,"
reported The Scientist. Rarely has one science changed a world view so completely. Before Darwin, the purpose of
natural history was to reveal the divine ordering principle. The motivation of Carl Woese when he discovered
archaea was to seek out classification of microbes to answer basic questions about the evolution of life. "I was a
self-taught Darwinian," he said. "But the concept transcended Darwin."
What were the qualities of his creativity? He was obsessively driven, moving between the small picture and the
big. He was aware of the latest findings but "purposely avoided reading in the journals," observed George Fox. "He
felt it stifled his creativity." He was not too critical of himself or of others; a good idea and a crazy idea were
indistinguishable at the start. He listened to others. He viewed science as a holy quest. He valued the act of pure
thinking. "You have to have your own particular sensitivity to the world," Woese once said. "And there are parts of
it that are beautiful to you no matter what anyone else ever thinks. You see this all the time in artists. And you see
it in good scientists."
There were difficulties too. Many commented on his paranoia, his worry about what others were saying about him,
his feeling of never getting his due despite the enormous number of accolades bestowed on him. Yet he matched
his time perfectly. By remaining independent and sticking to first principles, he opened a new way of seeing. "He
had the quality of recognizing something when he saw it," said Gary Olsen. Then came the techniques of Norman
Pace to reveal the incredible hidden life in the most ordinary settings, like finding hidden caves within familiar
ones. Then came genomics to compare the enormous number of new genes and organisms being discovered

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Woese matched his time by thinking differently from most any other scientist, yet he used the tools everyone else
was using. "Not to be too mundane about it," said Mitchell Sogin, "but Carl is just smarter than everybody else."
By finding a whole new kingdom of previously unknown life, the archaean revolution should transform the study
of ecosystems, energy, genetics, Earth history, of life itself, offering a new understanding of biological time and
space. "What's really interesting is not what's going on now, though," Woese observed. "It's what's going to
happen."

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Conclusion:
Intimate Science, Big Questions
We live in the age of intimate science. Susan Greenfield wants to open a restaurant in the creaky rooms of the
Royal Institution. The Internet makes it possible to learn the cutting edge of a field from your bedroom, even the
insider gossip and, in some cases, raw data of international projects. You can manipulate the Hubble Space
Telescope from your office. Soon you may be able to buy a personal DNA analyzer. Imagine getting a few DNA
sequencers. You could think of a dozen excellent, potentially lucrative experiments looking for genes associated
with physical or mental prowess. Combining personal computers and the Web, you could form a company and an
international collaboration. Every day would be different; every day would challenge you to try out new ideas.
But these stories also hold something back. This work is gritty, daunting, complex, nearly impossible. To spot a
star forty light years away, wobbling at the rate one might ride a bicycle across Grant Park, is staggeringly
difficult. Perhaps it was fun, as Saul Perlmutter said of his supernovae, but there certainly are easier ways to make
a living. Graduate students still worry about the sorry state of funding over their pints at Oxford's King's Arms.
How were these scientists at different levels seemingly so successful? And what of their creativitywhat were the
traits of this new science of synthesis, of asking big questions?

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<><><><><><><><><><><><>
For clues to the practice of bold science, look first for mentors. Saul Perlmutter hung out at parties at the home of
Luis Alvarez, picking up the sheer excitement and confidence of a researcher unafraid to switch fields, speak up,
even look foolish. Craig Venter, by contrast, saw an example of what not to do in the lab of Nathan Kaplan, even
while avidly reading the story of James Watson. Geoff Marcy had crucial quiet support from astronomy giant Allan
Sandage. Gretchen Daily worked with Paul Ehrlich, learning how to promote her ideas in public while pursuing
colleagues from other fields, seeking out money, and always returning phone calls from journalists. What a hoot to
be a neuroscientist, the experimental psychologist Jane Mellanby told Susan Greenfield. Go, try it, Do not be
afraid.
Mentoring cuts both ways. It is also critical to be a good teacher to those who follow you. Many researchers teach
to pay for their research, but mentoring as an open collaboration with students is also critical. Imagine the Marcy
planet search without former student Paul Butler, or Marcy and Butler if they had not responded to an English
freshman's e-mail. They might still be burning expensive telescope time searching useless star systems. "Teaching
showed me how to think better about problems," Susan Greenfield wrote in her newspaper column, itself a forum
for teaching. Craig Venter kept a lifelong friendship with his college composition teacher, Bruce Cameron, even
giving him a job. Venter will also corral anyone who knows more than he does on a subject. At a conference in
Australia he grilled Norman Pace on the latest findings on diversity in microbiology. Carl Pennypacker left
research altogether to found the Hands-On Universe for elementary, junior, and senior high-school students. Last
spring my eleven-year-old son headed to school at midnight so he could manipulate by computer the onceforbidding Mount Wilson telescope with Pennypacker's program. A science theory or experimental finding is,
Einstein once wrote, a form of teaching.
Mentors are critical because, in trying to follow their childhood inner drive for big questions, most of these people
faced a brick wall. "There are no new questions in biology," Venter was told. He felt so let down by his rote highschool education he gave up on his mind for a while. Marcy felt so insecure on Mount Wilson he saw a therapist
for depression. Daily worried what conventional researchers would think of her. Polly Matzinger and Carl Woese
were at one time ridiculed in their fields. In graduate school, the universal reaction is one of self-loathing pounded
in through doctoral programs on subjects from Byron to biology.

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<><><><><><><><><><><><>
Having a mentor is critical, but it alone cannot account for the ways in which these people pushed their fields.
After mentors, it is critical to get into a position that allows freedom of thought. In general these people did not
follow conventional routes into giant laboratories. They worked outside of the main networks of their fields. Geoff
Marcy taught forty hours a week for much of his career. Without a secretary in his cinder-block office when he
was at San Francisco State, he often had to interrupt our conversations to take phone calls from strangers who saw
his name on the Web or on CNN. "I'm sorry," he would say. "Dr. Marcy is not in." But this post allowed Marcy
special intellectual freedom because no one bothered him about his research. By contrast, Perlmutter and Matzinger
largely avoided teaching, surviving on grants and fellowships within unconventional government laboratories that,
at least for a time, assisted them to secure the funds and instruments they needed. Still, Matzinger became a much
sought international lecturer and attracted talent from all over the world to the National Institutes of Health. Venter
founded his own company to pursue his ideas, as did Greenfield. Carl Woese and Gretchen Daily joined special
departments at unique moments in their histories. Daily joined in Stanford dinners at the Ehrlichs' mountainside
home, linking to a group that fostered independent thought.
To be independent, these thinkers had to overcome the fear of looking foolish. In the moment when you feel most
vulnerable, sweating and beyond your comfort zone, ideas happen. Certainly you may fall on your face, indeed
often you will. But this kind of navet, the childlike acceptance of mistakes, is a signal that you are pushing to
your limit. To do that you must also, of course, withstand criticism. Heart palpitating, Susan Greenfield first
entered the Oxford pharmacology building; Geoff Marcy got out of the shower stall stuck but resolved to pursue
planets. To ask big basic questions is immediately to look clumsy, to go back to the beginning.
These researchers clearly pursue the biggest questions, the ones that seemed slightly unsavory in their breadth and
depth. What is life, what is it made of? Where did immunity come from? What is the value of all the natural
processes of a given ecosystem? To attack such questions, one must combine sweeping vision with an obsession
with the specifics of a field. The intelligence is combinatory, linking three kinds of thoughtthe big interdisciplinary
vision of the dreamer, the handson, bench-smart qualities of an experimenter, and the street wisdom

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of the hustler. One needs the capacity to see broadly, but to balance it by moving from the specific to the abstract
and back again in ''two voices or episodes of thought," observed Peter Medawar, "imaginative and critical, which
alternate and interact."
At the imaginative level Craig Venter and Saul Perlmutter shared a fascination with the neuroscience and the
physiology of thought well before they moved onto genomics or astronomy, respectively. Susan Greenfield loved
Greek tragedy and myth, and sought in neuroscience an explanation for the truths of human existence. Marcy
wanted to seek the Grail of planets in astronomy. Gretchen Daily, raised in Europe, trained in biology but
immersed in economics, pursued the biggest question of allwhether we will survive as a species. This is wisdom in
the intellectual sense, but more in the creative unconscious way of an artist who seeks to explain why the world is
what it is.
One must also get one's hands dirty. Weak as her experimental skills were at first, Greenfield learned to improve.
Taking after her electrician father, she could sit down and set up an oscilloscope and show an ion buildup in a
single brain cell of a rat. From there she built her early elegant experiments showing the key role of
acetylcholinesterase in the brain. Perlmutter and Pennypacker lugged their equipment around the Berkeley hills,
grabbed new CCDs as soon as they came out of the factory, and built a telescope from scratch. Marcy collaborator
Steve Vogt built the world's best spectrograph, and Marcy cobbled together his iodine tubenow in the Smithsonian
collectionin the machine shop at San Francisco State's Thompson Hall. Polly Matzinger, for all the accusations that
she was only a good talker, demonstrated time and again she could conceive and execute "really important, seminal
experiments" noted NIH Section Chief Ron Schwartz, in papers published in Science and Nature. When it came
time to test her theory, she used her skills as sheep dog trainer to conduct her tests on, of course, sheep.
The third kind of intelligence is street smarts. The remarkable thing is that none of these thinkers, save perhaps
Woese, resemble anything like the solitary genius of the old mystical variety. We do not live in the age of such
geniuses, it seems. We live in the age of interactive, interconnected synthesizers.
Often when I checked in with Gretchen Daily or Saul Perlmutter they were on deadline to write a grant proposal.
Venter pioneered commercial links to science and then took them to a controversial height no one had imagined.
Greenfield founded her company Synaptica and kept the investors happy without yet showing much of a profit.
Marcy's computers were eventually provided free from Sun

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Microsystems in exchange for a logo on his websiteanother source of controversy. One might worry about a space
probe dotted with corporate logos, but these kinds of collaborations hearken back to the era of RCA and Thomas
Alva Edison, and further. One should judge, but also acknowledge, the utility of street wisdom in finding money to
make research happen today.
Each one of these researchers broke down important barriers by linking their science with their inner sense of
wonder. "Write what you mean to say," the writer V. S. Naipaul's father advised him. Practice the science you
mean to practice, one could add, that which springs from your passions and deepest questions. To do so one has to
break barriersbetween the amateur and the expert, the public and the private, and between the disciplines
themselves.
First, especially in astronomy, they broke the barrier of professional and amateur. An amateur, of course, loves the
field. The Australian priest Robert Evans found supernovae before any academic group could. Carolyn Shoemaker,
widow of planetary geologist Gene, was the first to sight the millennial comet Shoemaker-Levy 9. Anyone can
become part of the search for extraterrestrial intelligence (SETI) by downloading its screen saver. Kevin Apps
volunteered his time to work with the Marcy team.
The breaking down of walls between professional and public extends, more importantly, to the laboratory itself.
Norman Pace's revelation was that microbiologists could leave the lab and "do it in the dirt." Pace, Perlmutter, and
Venter all devised ways to allow nature to do their data crunching for them. "Human DNA is the best
supercomputer there is," Venter said of his EST method. The laboratory walls came down; the world in many cases
became the lab. This opportunistic approach lies behind some of Daily's ideas as well; the predators of insects will
count for you the number of insects in an ecosystem.
One must also break the barrier with the public. That Marcy coached Little League despite not having a child on
the team, and that when he coached he let the kids decide among themselves which positions to play, suggest a key
trait of bold science today. Because it requires cooperation, innovation, entrepreneurship, and continually launches
into new fields where one is ignorant, one must, above all, be nice. It was the best bit of advice my grandmother
gave me when I got married. Just be nice, she said. The day of the science czar, the autocrat of the giant telescope
or the dictator of the four-hundred-person high-energy physics team, have disappeared. There is no lack

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of ego and imperial administration in the major labs today, but for the scrappy success of these researchers, one
must be nice. In his office I listened as Geoff Marcy delivered detailed, complicated directions to his house on the
telephone. A former girlfriend was visiting him and Susan Kegley, he said, hanging up. Did he feel especially
proud or vindicated now that he was famous?. "Oh no," he said, waving his hand. "That's just planets. This is
friends."
Equality also emerges from these lives. Susan Greenfield made it a point on her research team to mix ages and
genders. A looser more collaborative social hierarchy was a driving force for Marcy and others who suffered under
an older, more rigid science order.
A powerful tool for breaking barriers is the media. All of these people have used and benefited from exposure in
magazines, newspapers, radio, the Web, and television. Paul Ehrlich showed Gretchen Daily that appearing on
television could be part of a seminal science career. These researchers answered phone calls and e-mails promptly,
speaking articulately and enthusiastically. They moved back and forth intellectually, within and outside their
groups, between their professional and public audience. Much has been written by historians of science about how
ideas must be pushed into the public eye. Craig Venter made the time right for shotgun sequencing. Venter and
Daily serve on several policymaking panels in Washington, D.C. Greenfield and Daily write regularly for
newspapers or television. Marcy, Perlmutter, and Venter are regularly written about. Daily pens editorials and
articles for newspapers and magazines. Susan Greenfield used her BBC series to check in with major thinkers in
neuroscience.
The relation was symbiotic. One appeared on TV because one could synthesize and explain clearly, and because
one could simplify, one gained an edge as a researcher. Such clarity of vision requires a researcher to put her or his
work in the tradition, communicating its meaning in history, Toward that end several read and drew ideas from
popular science books. Polly Matzinger's collaborator Ephraim Fuchs got his start with Robert Wright's The Moral
Animal. Venter was reading James Watson and, much later, the biography of Rosalind Franklin. Matzinger and
Woese read a great deal in the philosophy of science.
Once these researchers had an idea, they did not wait. If they had a motto it would be, "Do it now." When I first
talked with her on the phone, Susan Greenfield wanted me to catch virtually the next plane to England. Craig
Venter refused to wait another conventional ten years to sequence a single gene, having done it once. Saul
Perlmutter wanted

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to pursue supernovae when everyone else thought he should wait for new equipment. When you move fast, you
create your own luck.
A second motto would be, "Do it with what you have." Venters paradigm shift was that gene sequencing tools
available to anyone in the early 1990s were perfectly adequate for full-scale genomes, if one changed the
approachfrom single genes to shotgun sequencing of the whole genome and taking what you got. Greenfield
wanted to check the venom of Latin American snakes; she found a postdoc who could do it and got him some
money. Gretchen Daily never listened to those who argued we lacked the tools for the sophisticated measurements
of biodiversity she needed; she settled for keystone species, designed her own instruments, rolled up her sleeves,
and walked into the back plots and hedgerows of San Vito. Geoff Marcy, lacking the tools for finding Saturn-size
planets, said there must be a good chance planets Jupiter-size or larger exist. He went looking, and found them.
To pursue their dreams speedily, each of these researchers practiced a science of new connections. First it was the
mental connectionfrom precise to general, everyday to abstract. Next, it was a technological connection. To make
shotgun gene sequencing work, Venter had to connect the personal computer with the remote sensing of automated
sequencers, much as Daily began to use remote sensors on satellites to connect with researchers slogging through
fields in Costa Rica. Perlmutter connected the new technology of charge-coupled devices with multiple telescopes
around the world to find more supernovae in one night that had been observed in the previous thirty-five years.
When Kevin Apps e-mailed him from England, Marcy connected with a European Space Agency satellite to
pinpoint the stars he would search. In these prosaic ways the oft-trumpeted information revolution actually
surpassed the claims made by its supporters, assisting innovative connections among thinkers.
The new connections, more importantly, come in the form of adopting techniques from one discipline to another.
Venter moved from neuroscience to biomimicry to genetics; Marcy used chemistry and astronomy to rewrite
planetary science. Woese moved from physics to biology, Perlmutter from physics to cosmology. Matzinger was
never accepted by immunologists, but simply went over their heads, using the media to reach out to other
professional and public audiences. Greenfield moved from electrophysiology to genomics in her pursuit of
neurotransmission Daily was the most obviously interdisciplinarycombining economics, climatology, botany, and
ecology tirelessly with other international researchers to unlock the future of our world. "Interdisciplinary
connections are now absolutely fundamental,"

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National Science Foundation Director Rita Colwell told a research workshop in September, 1998. "They are the
synapses in this new capability to look . . . beyond the horizon. The interfaces of the sciences are where the new
excitement will be most intense."
These researchers often eschew the usual rounds of small talk, meetings, and conferences. They are consummate
battlers. When attacked, Polly Matzinger went over the heads of her critics. Craig Venter framed and photographed
his rejections and nemeses. Carl Woese and some members of Perlmutter's team would not keep quiet about the
injustices they needed to remedy. Some of these people frustrated and enraged me at times. Polly Matzinger would
sound so like an actress I would not know how much to believe. Venter could vacillate between kindness and
abrupt suspicion. Carl Woese was famously moody. They were sometimes charged with going out to the edge of
the verifiable in their claims and defying their colleagues.
There is a definite line in science, explained Ron Schwartz at the NIH, that "separates us from our origins in
sorcery." Some of these researchers walked very close to it. This is the nature of bold science. It was why some
colleagues disliked Matzinger so much. But your weaknesses are also your strengths, TIGR's Bruce Cameron said.
Craig Venter overextended in order to push himself and others. Greenfield set nearly impossible deadlines. Would
Synaptica's investors get their money back? I asked her. "Maybe," she said. "That's what investment capital is all
about.''
Finally, they share a sense of humor, seeing their work as a kind of game. "Nobody realizes how much fun this is."
said Saul Perlmutter. It is fun to watch their research in Hawaii, or in San Francisco, in San Vito or in the Thames
valley. If not experimenting they are either teaching, or giving conference papers, meeting with friends, going out
to dinner, traveling, and mainly talking about questions like the history of the universe or the kinds of planets that
might harbor life outside our solar system.
Many historians and philosophers have stressed many of these traits of creative science. Now, in a digital age when
so much has been written about the explosion of information, synthesisinterconnecting disparate pieces of
informationhas become the single most important creative skill. Insight can come from a variety of approaches, but
today it most often stems from new connections. These can happen by inspiration and mistake, as when Kekule
discovered the benzene ring in a dream of a snake eating itself. Synthesis, or complex-systems science, is most like
art. "Innovative science is closer to composing

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music or painting on a canvas than most people realize," Geoff Marcy said in his office. E. O. Wilson, in his book
Consilience: The Unity of Knowledge, described the coming convergence of art and science. "This is where the
edge of science really is," he once told me. "Art is the ultimate sythesizer."
Several of these researchers were amateur artists and all were effective communicators. Marcy played cello,
Matzinger piano, and Perlmutter violaall of them actively, Woese listened intently to jazz. When bringing their
ideas to the public, these thinkers found the right metaphor to simplify and explain. One of the best was Polly
Matzinger, whose danger model seemed glib to her critics, but brilliant to her growing number of supporters. "I
can't think of another scientist who has been more influential . . . ," researcher Allan Kirk said. "She has a
wonderful ability to hold down your nose in the data and make you see what is really there, recognizing as obvious
[what] I had not even noticed before."
In 1817 Samuel Taylor Coleridge wrote that imagination "reveals itself in the balance or reconciliation of opposite
or discordant qualities: of sameness, with difference; of the general, with the concrete; of the idea, with the image;
of the individual, with the representative." This combination marks the ability to intuit, a common theme among
these thinkers. "I look for relationships among fields," says Craig Venter. Intuition is the best computer because it
unconsciously weighs and values a huge number of variables before following a half-formed insight.
These are the traits of these creative research teams as we move from what Michio Kaku calls three centuries of
discovery to an age of mastery, from being observers of nature's dance to becoming its "active choreographers."
These traits are not new. Most science is usually haphazard, creative, accidental. These same qualitiesof moving
fast, thinking big, having a mentor, combining tools to create a synergy of increased observing powerhave been a
part of creativity since the time of Archimedes. It is possible they exist on some second level of pure existence
much as Plato wrote, outside of us on our dusty planet, outside of time.
What has changed clearly are the tools. Today's toolsthe computer, remote sensors, artificial intelligence,
automated DNA sequencers, telescopes, transgenic mice, magnetic and radiation imaging of the mindcan be
combined to create a synergy of effect. These tools enable the thinker to move faster and delve deeper into
questions than ever before. It is no longer an overwhelming leap to try to use the interplay of climate, nature, and
economics to plot the future of

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species on Earth, or to break down the million biochemical steps that lead to a thought. By linking such tools,
researchers are uncovering the processes of the universe in a new science of fluid, dynamically changing
relationships commonly called complex-systems science.
Such tools create a space for interactive research that privileges those who are, first of all, good at working with
others and open to young ideasas Marcy showed by welcoming Kevin Apps, or Venter in working with Mark
Adams, or Matzinger with Ephraim Fuchs. The current technology supports those who are open. It privileges those
who can adapt to change and move fast, like Susan Greenfield. It privileges those, like these thinkers, who use the
media effectively to advance their aims. You must be able to proceed, in a dark time, until the eye begins to see. It
seems, these stories attest, that as dark a time as ours is, is is also a joyous time for living a life of wonder.

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Index
A
ABI 370, 26
ABI 3700, 26
Aborigines, 21
accelerated intelligence, 2
acceleration, 116
acetylcholine, 32, 35 36
acetylcholinesterase, 32, 35 38, 40, 45 48, 51, 172
acetylcholinesterase inhibitor, 46
acid rain, 126 127
actin, 17
Adams, Mark, 17, 18, 28, 29, 178
adapter molecule, 150 151
adenine, 153
Adler, Reid, 18
Affymetrix, 25
Affymetrix Gene Chip, 25
aging process, 19
AIDS, 19, 28
alchemy, 33, 95
alcoholism, 144
Aldo Leopold Leadership Fellows, 144
algal blooms, 126
Alpan, Oral, 100
Altman, Sydney, 157
Alvarez, Luis, 103, 104, 105, 108, 109, 111, 120, 121, 170
Alvarez, Walter, 105
Alvin, 157, 159, 163

Alzheimer's disease, 28, 39, 45 46


American Association for the Advancement of Science (AAAS), 27, 77, 95, 138 139, 146
American Association of Immunology Conference, 97
American Association of Inventors, 19
American Astronomical Society (AAS), 67, 115, 116
American Birds, 128
Amgen, 22
Amherst College, 150
amino acids, 150 151
Amish families, 19
Andreadis, Athena, 132
Andromedae, 77
Anglo-Australian Telescope, 69 70, 109
animal behavior, 46, 51
Annual Review of Immunology, 93, 98
anti-AIDS drugs, 94
antibiotics, 40
antibodies, 86, 98
Antigenics, 99
antigens, 86 87, 89 92
"antigravity force," 117, 119
API 3700, 26, 27
apoptosis, 91
Apple Computers, 13
applied biology, 149
Applied Biosystems, 15
"Approaching the Asymptote? Evolution and Revolution in Immunology," 92
Apps, Kevin, 72 76, 173, 175, 178
Arabic, 2
archaea, 23, 148 149, 155 157, 158 160, 164 166
species of, 160
archaean, 149, 163, 167

Archimedes, 177
Argonne National Laboratory, 161

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Aristarchus, 95
Aristotle, 119, 126
Arizona, 112, 115
Arrow, Ken, 131
artificial intelligence, 2, 41, 80
artificial organs, 81
asteroid, 75, 105, 112, 165
astrology, 33
astronomy, 4
Atkins, Peter, 39 41, 43, 49, 51 52
Atlantic Monthly, The, 145
atom, 3, 150
atom bomb, 3
autoimmune diseases, 80 81, 86, 90
lupus, 80
multiple sclerosis, 80
rheumatoid arthritis, 80
Type I diabetes, 80, 97
B
B cells, 86
Baars, Bernard, 42
Bacchae, The, 34, 49
Bachman, Stephen, 138
bacteria, 90, 148, 150, 152, 154 155, 160, 164 165
bacterial cloning, 80
bacterial family tree, 154
bacterial phylogenies, 154
bacterial products, 92
bacterial ribosomal RNA, 148, 153
bacterial sequences, 154

"Bacterial Evolution," 161


Barns, Susan, 159 160
Basal Institute for Immunology, 88
Basri, Gibor, 61, 68
Baylor University, 128
H.M.S. Beagle, 152
beetles, 124
Beijer Institute of the Royal Swedish Academy, Stockholm, 133 135, 143
Beijer plenay, 134
Belkin, Lisa, 10
Bergey's Manual, 155
Berkeley cyclotron, 105
Big Bang, 113, 118
"big pharma," 22
Bing Interdisciplinary Research Scientist, 136
Bio '98, 27
biochemical interactions, 150
biochemical properties, 166
biochemical systems, 33
biochemistry, 13, 98
biodiversity, 125, 133
biologists, 126
biology, 68, 125
biomimicry, 30
biophysics, 150
biosphere, 162
biotechnology, 5
biowarfare, 25
birds, 124
Black Forest, 127
Bleyman, Michael, 152
Blumberg, Neal, 95, 99 100

botanists, 126
Brahms, Johannes, 64
brain receptor gene, 13
brains, 161
BRCA1 gene, 22
breast cancer, 22
Brest, Paul, 130
Brief History of Time, A, 44
British Broadcasting Company (BBC), 49, 51 52, 82, 85, 91, 95, 174
British Economics Association, 130
Brock, Tom, 158, 162; see also Thermophilic Microorganisms and Life at High Temperatures
bromine, 162
Brown, Jim, 159
brown dwarf star, 67
Brown Sugar, 44
Bruno, Giordano, 58, 62
Buckingham Palace, 49
Building 4, 89
Bunny 82, 84, 87, 88
Burnet, Macfarlane, 80, 95
Business Week, 94
Butler, Paul, 62 67, 69 77, 170
butterflies, 124
C
Cable News Network (CNN), 71
California Institute of Technology (Caltech), 15
Callisto, 58

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Cambridge University, 88, 129, 151


Cameron, Bruce, 11, 30, 170, 176
Cameroon, 63
Campbell, Bruce, 62
Canada, 64
Canary Island, 109 112, 115, 124
Cancer, 19, 28, 86
cancerous tumors, 80 81
carbon dioxide, 158, 163, 165
carbon, 107
Carnegie Institution, 55 56, 61
Postdoctoral Fellowships, 55
Carraway, Nick, 87
Carson, Rachel, 126
Silent Spring, 126
Carvey, Dana, 24
Case Western Reserve University, 82, 92, 99
"Castle, The," 103
catalytic properties, 166
Caucasians, 21
Ceballos, Gerardo, 136, 142 143
Cech, Tom, 157
Celera, 8, 25 29
cell biology, 80, 150
cell death molecular researchers, 91
cells, 150, 161, 165
cell structure, 151
cell walls, 165
cellular evolution, 156
cellular immunologist, 89

cellular keys, 148


cellular systems, 89
Center for Astrophysics, 116
Center for Molecular Biology, 98
Cerro Telolo, 111
Cetus Corporation, 162
CFA, 77
Chadwick, James, 150
Chalmers, David, 48
chaos theory, 133
charge-coupled detectors (CCDs), 109, 172, 175
chemistry, 67 68, 76, 125
Chile, 111, 112, 115
chlorine, 162
chlorophyll, 158
cholera, 132
cholinesterase, 51
Chubb, Ian, 36
Church of England, 34
Church of Scientology, 82
class III giants, 74
classification, 152
Cliff's Notes, 16
climate systems, 3
climatology, 126
Clinton, Bill, 9, 25
Clinton, Hillary, 9
cloning, 130
Cohn, Mel, 85 87, 100
Cold Spring Harbor Conference, 88, 92
Cold Spring Harbor Laboratory, 19, 27, 87
Coleridge, Samuel Taylor, 177

Colgate, Sterling, 106, 107


Collins, Francis, 4, 14, 26
Columbia University, 139
Columbus, Christopher, 135
Colwell, Rita, 132, 176
comets, 165
Compaq, 27
comparative genomics, 45
complex atoms, 107
complex diseases, 28
complex-systems science, 2 3, 17, 30, 34, 39, 42, 52, 74, 81, 176, 178
interdisciplinary science, 81
complementary DNA (cDNA), 16, 17
Congress, 15, 18
consciousness, 32, 39 44, 48, 52
conservation biology, 123, 129, 139
Consilience: The Unity of Knowledge, 29, 177
Contact, 66
Copernicus, Nicholas, 95, 99
cosmology, 2, 67, 106
Costa Rica, 123, 135, 141
Costanza, Robert, 140
Cox, David, 22
Crick, Francis, 10, 11, 24, 30, 141, 150 151
culture, 152, 160
cystic fibrosis, 14, 24, 28
cytosine, 153

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D
Dachau, 83
dacnis, 123
Daily, Gretchen, 4, 95, 123, 127 146, 170 175
Dale, Henry, 35 36, 51
DalGleish, Gus, 97
danger, 94, 96, 98 99
danger model, 85, 177
"danger theory," 93 94, 100
dark matter, 119
Darwin, Charles, 3, 91, 100, 150, 152 153, 159, 166
Darwinian, 150, 166
Dasgupta, Partha, 129 130, 133 134
Dawkins, Richard, 43, 91
theory of evolution, 91
de rigur disquisitions, 42
deceleration, 106
deceptive mimicry, 85
Deep Vent polymerases, 162
Deerfield Academy, 150
deforestation, 144
Deimos, 58
DeLong, Edward, 160
democratic science, 14
dendrites, 37
dendritic cell, 88, 90, 92, 94
Dennett, Daniel, 41, 48
Department of Energy, 110, 112
depression, 24
Hands-On Universe program, 112

diabetes, 28
Diabetes Research Institute, 97
Diablo Mountains, 59
Diamond, Marion, 104
Discover, 22, 160
Discovery Channel, 45
diseased cells, 90
DNA, 1 3, 16, 20, 26, 30, 141, 148, 150, 153, 157, 159, 162, 169, 173
automated DNA sequencing, 28
"base pairs," 13
brains, 17
chromosomes, 13
cloning; see Shotgun DNA cloning
complementary DNA (cDNA), 16, 17
"copying mechanism," 11
double helix, 3, 10, 30
genetic sequence, 2, 14
genome map, 14
junk DNA, 16, 28
library, 27
messenger ribonucleic acid (mRNA), 13
patents; see Patents
replication, 162
ribosomes, 13
testis, 17
DNA sequencers, 15, 25, 26, 169
API 3700, 26, 27
ABI 3700, 26
370s, 26
Doolittle, Ford, 152, 156, 159, 163, 165
dopamine, 37
Doppler effect, 61, 107

Dostoyevski, Fyodor, 51
drug addiction, 144
Duffy, 84
Dulles Airport, 16, 26
Duracell, 72 73
Dutton, Richard, 85
dwarfs, 62
E
E. coli, 21
Earth, 66
Earth history, 167
Easterbrook, Greg, 145
eccentric orbit, 67
Ecological Association of America conference, 139
ecology, 123, 125, 126, 130, 132, 134
economic ecosystems, 134
economics, 125
economists, 130
Ecoscience, 130
ecosystem, 2, 4, 124, 125, 128, 132, 134 135, 138 139, 142, 145, 146, 167
ecosystem ecologist, 129
Edison, Thomas, 22, 23, 24, 173
Ehrlich, Anne, 127, 129 131, 135
Ehrlich, Paul, 125, 127 133, 135 137, 140, 142, 170 171,

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174; see also The Stork and the Plow: The Equity Solution to the Human Dilemma
Einstein, Albert, 3, 79, 100, 114, 118, 119, 141, 170
El Nino, 143
electrochemical impulses, 42
electrophysiology, 33, 36, 46, 51
Eli Lilly, 22
Eliot, T.S., 53
"Little Gidding," 53
Elle, 95
Emmett, Steve, 43, 46 49
Emotional Brain, The, 48
energy, 167
engineered life, 2
Enlightenment, 9
environmental degradation, 134
environmental economics, 131
enzyme, 162
Escherichia coli (E. coli), 152, 159
Eskimos, 21
EST method, 173
eukaryotes, 150, 154
Euripedes, 34, 42
Europa, 58
European Economics Association, 130
European Space Agency, 113, 175
Evans, Robert, 107, 108, 173
evolution, 148, 150
evolutionary biology, 80
evolutionary history, 152
evolutionist, 151

expansion rate, 106


Explorer, 76
Expressed Sequence Tags (ESTs), 17 19, 20, 29
external bacteria, 154
extra-solar planetary exploration, 76
extra-solar planetary search, 74
extra-solar planets, 57, 59, 62, 65, 69, 75 77
extra-solar system, 4, 77
extraterrestrial, 148
extraterrestrial intelligence, 64
extremophiles, 158, 162, 164
Deinococcus radiodurans (d. radiodurans), 164
Thermatoga maritima, 164
F
Faraday, Michael, 43
fasciculin, 47
Fermi lab, 119, 122
Fermi National Accelerator Laboratory, 118
Fetal development, 45
Feynman, Richard, 90
51 Pegasus (51 Peg), 65 66, 70 71
Figueroa, Randi, 145
Filippenko, Alexei, 111, 113, 117, 120
First Three Minutes, The, 107
Fischer, Debra, 69 71, 76 77
Fitzgerald, F. Scott, 87
Florey Howard Walter, 40, 51
Fodor, Stephen, 25
Food and Drug Administration, 136
forest recovery, 145
Forster, E. M., 60
Fortune, 140

47 Ursae Majoris, 67
fossils, 152, 164
Foster, Jodie, 66
Fowles, John, 53; see also Magus, The
Fox, Cynthia, 95
Fox, George, 154, 166
Franklin, Rosalind, 10, 29, 174
Fraser, Claire, 8, 12, 20, 163 164
Freeman, W. H., 130
French Society for Immunology, 96
Fuchs, Ephraim, 81, 89 91, 93 95, 101, 174, 178
Fuhrman, Jed, 160
G
Galileo Galilei,, 3, 25, 41, 58, 62, 74, 121, 141
Gamow, George, 150 151
Ganymede, 58
Garth, 24
gene, 1, 159
gene cloning, 80
gene function, 28
gene indexing, 16, 27
gene pools, 152
gene sequences, 161, 164
gene therapy, 80
General Electric, 23, 24, 151
genes, 3, 159, 161, 166
genetic identity, 4

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genetics, 2, 4, 13, 23, 27, 28, 167


genetic material, 165
genetic research, 151
genetic sequence, 2, 14
genome investment, 27
genome sequences, 21
genomes, 8, 20, 21, 24, 25, 81, 161 162, 163
genomics revolution, 8, 9, 17, 20, 27
multidisciplinary systems approach, 25
genomics, 1, 24, 26, 46, 48, 51, 108, 141, 161, 166
geology, 68, 76, 127
Georgetown Hilton, 116
Gilbert, Walter, 157
Gillette, 73
Glanz, James, 117
Gliese 876, 75
global neurons, 45
gnatcatcher, 123
Gocayne, Jeannine, 15, 28
Goldberg, Rube, 104, 111
Goldhaber, Gerson, 109, 113, 114, 121
Goldin, Dan, 76
Golgi, Nicolai, 33
Gore, Al, 25
Goulder, Lawrence, 138
Grabar Lecture, 96
grafts, 80
Granville, Evelyn Boyd, 129
Gray, David, 70 71
green mamba, 47

Greenfield, Susan, 4, 31, 32, 34 52, 83, 95 96, 131, 146, 169, 171 172, 174 176, 178
guanine, 153
Guth, Alan, 113, 120
H
Haemophilus influenzae, 20, 21, 29
Hale, George Ellery, 55
hallucinogens, 14
Hamlet, 68
Hands-On Universe program, 112, 170
Harlan, David, 97
Harvard University, 60, 64, 104, 107, 108, 112, 118, 152, 155
Center for Astrophysics, 64, 77
Harvard Medical School, 132
Harvard-Smithsonian Center for Astrophysics, 118
Harvard-Smithsonian group, 67
Harvard University Press, 77
Haseltine, William, 19, 22, 23
Hawking, Stephen, 44 45; see also Brief History of Time, A
Heal, Geoffrey 139 141
Heal, Joanna, 99
heart disease, 28
heart transplant, 86
"heat shock," 98
heat-shock proteins, 98
Heinlein, Robert, 62
Heinz, Teresa, 140
Heinz Family Philanthropies, 140
heliocentric solar system, 99
heliocentric universe, 95
Heraclitus, 90
high-energy physics, 3, 104
High Resolution Spectrometer (High Res), 64, 69

High Z (Supernova Project), 113, 117


Hipparcos, 72 74
Hipparcos CD Rom, 72 74
histocompatibility complex, 93
Hoffman-LaRoche, 162
Holdren, John, 129, 133, 136
Holland, Lynn, 26
Hood, Leroy, 15, 25, 26, 28
Hook, Isobel, 111, 112, 115
Hubble, Edwin, 55, 106, 118, 169
Hubble constant, 120
Hubble Space Telescope, 110, 115 116
Hugenholtz, Phil, 160
Hughes, Jennifer, 123, 135
Hull, David, 100
human genes, 18
human genetic code, 8
human genome, 15, 17, 18, 26, 27, 163
consensus human genome, 27
Human Genome Project, 9, 15, 18, 19, 26, 163
Human Genome Research Institute (HGRI), 14

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human genome revolution, 148


Human Genome Sciences (HGS), 19, 22 24
human genome sequence, 28
human immune system, 91
human-altered habitat, 124
Hunkapiller, Mike, 25, 26
Hurley, Susan, 39
Hybritech, 22
hydrogen, 163, 165
hydrogen fluoride, 62
hydrogen sulfide, 158
hyperactive children, 42
hyperthermophiles, 162
hypothermophilic bacteria, 158
I
I Heard It Through the Grapevine, 44
Iceland, 149
Ida, Shigeru, 75
Ilama, Jesus, 145
imaging experiments, 52
immune response, 88
immune suppressing drugs, 80, 97
immune system, 80 82, 85 86, 89, 91, 97
immunobiology, 87
immunological societies, 96
immunologists, 81
immunology, 79 82, 86 87
Independent, The, 43, 75
industrial enzymes, 162
inhibitors, 47

innate immunity, 94
inorganic chemistry, 35
Insane Wine Contest, 142
Institute for Human Gene Therapy, 95
insulin, 18, 22
interdisciplinary science, 81
interferometer, 64, 76
International Conference on Heat-Shock Proteins, 99
International Immunology Conference (San Francisco, 1995), 98
International Institute for Applied Systems Analysis (Laxenburg, Austria), 133
International Institute of Ecological Economics, 134
Internet, 2, 17, 69, 74, 109, 112, 113, 115, 120, 169
Intracel, 99
invaders, 80, 86
Io, 58
iodine, 63
iridium, 105
iron, 159, 162, 165
isotopes, 105
Issues in Science and Technology, 141
J
Janeway, Sr., Charles, 87
Janeway Charles, 87, 90, 92, 94 96, 99; see also "Approaching the Asymptote? Evolution and Revolution in
Immunology"
Jannasch, Holger, 163
Jews, 21
John Curtin School of Medical Research, 90
Johns Hopkins University 20, 83, 94
Johnson, Lyndon, 10
Johnson, Magic, 62
Jones, W. Alton, 138
Journal of Immunology, 99
Journal of Theoretical Biology, 153

"Molecules as Documents of Evolutionary History," 153


Journey to the Center of the Earth, 110
Journey to the Center of the Mind, 42
Jovian, 58
Jupiter, 58, 61, 63, 65 68, 70, 175
K
Kaku, Michio, 3, 177
Kandler, Otto, 156
Kaplan, Nathan, 12, 30, 170
Keck Observatory 64, 69 71, 73 74, 105, 110, 111, 112, 114, 115
Keck Telescope, 69, 75
Visitors Center, 73, 75
Kegley, Susan, 64, 69 70, 72, 174
Kekule, 176
Kennedy Donald, 136, 138, 140
Kepler, Johannes, 58, 62
Kerlavage, Tony, 13, 14, 16, 17, 25, 27, 29
Kerouac, Jack, 44
Keynes, 134
models of taxation and spending, 134

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Kikuyu, 21
King's Arms, 39, 169
Kirk, Allan, 97, 99, 177
Kirshner, Robert, 108, 110, 113, 117, 118, 120
Kleeman, Michael, 140 141
Koch, Christof, 49
Koestler, Arthur, 82, 90
Kolb, Rocky, 117, 120
Koppel, Ted, 65
Kuhn, Thomas, 82, 90, 95, 156
L
Lacey, Michael, 46
Lafferty, Kevin, 86, 90 91
lambda, 114
Lancet, The, 99
Landsat Thematic Mapper satellite, 142
Lane, David, 159
Las Cruces Biological Station, 135
lateral gene transfer, 165
Lauer, Todd, 59 60
Lawrence Berkeley Lab (LBL), 104, 106, 108, 109, 110, 120
Learning Channel, The, 45
LeDoux, Joseph, 48
Leeuwenhoek Award, 156
Lehmann, Paul, 82, 99
Leigh, John, 163
Lemon, Veronica, 34, 49
Leuschner Observatory, 108
Lick, James, 59
Lick Observatory, 59, 61, 63, 65 66, 69 70

Lin, Douglas, 75 76
Lincoln College, 39 40, 43, 52
Linn, Nuna, 77
Linux, 25
Lipmann, Fritz Albert, 12
Little Mars, 68
Live, 79
Llinas, Rodolfo, 37 39, 41, 44
London School of Economics, 90, 130
London Zoo, 47
Long Term Ecological Grant, 132
Los Alamos, 106, 107
''Lost in Space," 58
Lotze, Michael, 97
Lowe, Sandie, 49 52
Lozcano, Antonio, 165
Lubchenco, Jane, 137 140, 144, 146
Luis, 135, 145
Luria, Salvador, 151, 155
Lyme disease, 21
lymph nodes, 88
M
MacArthur genius grant, 156
Magdalen Bridge, 34
Magdalen College (Oxford), 37
magnetic fields, 56
magnetic stars, 56
Magus, The, 53
main sequence stars, 74
Malthus, Thomas, 126
mammals, 124
Mammoth Caverns in Kentucky, 147

"Managing Massive Data Sets in Mathematics, Science, and Technology," 27


Marcy, Geoffrey 4, 55 77, 95, 146, 170 175, 177
marginal value, 140
Marincola, Francesco, 98
Mars, 57 58, 67, 76
Mars Pathfinder, 45, 76
Martian meteorite, 164
Massachusetts Institute of Technology (MIT), 41, 71, 113, 120, 155
Matson, Pamela, 129, 139
Matzinger, Polly 4, 79 101, 170 172, 174 178
Mauna Kea, 73
Mauna Kea peak, 104
Mayes, Vivienne Malone, 129
Mayor, Michel, 65 68, 72, 76
Mayr, Ernst, 155
McClintock, Barbara, 50
McNeil-Lehrer News Hour, 68, 117
M. D. Anderson Center (Houston), 99
Mead, 134
family structure, 134
Medawar, Peter, 80, 83, 85 86, 94 95, 97, 172
Advice to a Young Scientist, 85, 97
The Art of the Soluble, 85

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"Medicean stars," 41
Medicis, 71
melanoma, 97, 99
Mellanby, Jane, 31, 35, 50, 170
"meme," 91
Memorial Sloan Kettering Medical Center, 99
Mendel, Johann Gregor, 9, 10, 23
Brno, Moravia, 9
Mendel's laws, 28
meningitis, 21
mentally ill, 42
Merck, 141
Mercury, 65, 68, 76
messenger ribonucleic acid (mRNA), 13, 16
metabolism, 155
metastasized, 93
meteorology, 68, 125
methane gas, 154, 162
Methanococcus jannaschii (M. jannaschii), 163 164
methanogen, 154, 163
Meyerhof, Otto, 12
Michio Kaku, 14
microarrays, 25
microbes, 149, 152, 154, 157 158, 161 162, 164 166
microbes' oil, 162
microbial biology, 158 159, 162 163
microbial cells, 160
microbial diversity, 157, 161
microbial genome project, 162
microbial genomes, 162

microbial sequencing, 163


Microbiological Reviews, 161
microbiology, 126, 149, 151, 156 157
cultured, 158
microorganisms, 149, 162
cultured, 158
microscope, 149
microscopic organisms, 148
Microsoft Windows, 25
Microwave Anisotropy Probe (MAP), 113
Milky Way, 63, 70, 77, 110
Mill, John Stuart, 134
social utility, 134
Mindwaves, 39
Mingus, Charles, 84
Minsky, Marvin, 41
Miranda, 58
Mirkwood, Galadriel, 87
The Journal of Experimental Immunology, 87
mitochondria, 154
molecular binding sites, 46
molecular biochemistry, 46
molecular biological revolution, 89
molecular biology, 13, 20, 51, 80, 86, 150
molecular evolution, 152, 160
molecular genomics, 23
molecular immunologists, 98
molecular immunology, 80, 89
molecular sequences, 153
molecules, 161, 165
as "chronometers," 161
Monastery, 55

Monterey Bay Aquarium Research Center, 160


Mooney, Harold, 125
Morell, Virginia, 153
moths, 124
motmot, 123
Mount Hamilton, 59, 70
Mount Palomar, 106
Mount Tromlo and Sliding Spring Observatory, 117
Mount Wilson, 55, 57, 59 60, 69, 76, 106, 170
Mr. B's, 84
Mthanococcus jannaschii, 23
mu meson, 114
Muller, Richard, 105, 106, 108, 109, 120
Mullis, Kary, 14
Murray, R. G. E., 155
Muslims, 21
mutate, 165
Myers, Norman, 139
myosin, 17
Myriad Genetics, 22
mysterians, 42
N
Nabhan, Gary, 138
Naipaul, V. S., 173

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NASA, 66, 69, 72, 74, 76, 113, 148, 154 155
AMES Research Lab, 109
Hands-On Universe program, 112
Innovative Research Projects Grant, 64
Microwave Anisotropy Probe (MAP), 113
National Science Foundation, 110, 112, 116
National Academy of Arts and Sciences, 156
National Academy of Sciences, 146, 148
National Cancer Institute, 89, 98
National Geographic, 71, 125
National Human Genome Research Institute, 25
National Immunological Association, 87
National Institute of Allergy and Infectious Diseases, 97
National Institute of Health in Cellular and Molecular Immunology, 88
National Institutes of Health, 3 4, 12, 15, 17 19, 21, 26, 30, 79, 81 82, 87 89, 92, 94 96, 161, 171 172, 176
National Jewish Center, 148
National Kidney Foundation, 97
National Park Service, 162
National Science Foundation (NSF), 30, 66, 132, 176
National University of Mexico, 136
natural history, 150
natural toxins, 47
Nature, 15, 21, 38, 65 66, 70 71, 79, 85, 88, 96, 126, 140, 157, 172
Nature's Services, 139 140
Nebulae, 106
necrosis, 91 93
"Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells," 94
Nelson, Karen, 164
Neurochemistry International, 48
Neuron assemblies, 52

neurones, 33, 37
neuroscience, 2, 4, 31, 32, 52
neuroscience conferences, 33
neuroscientist, 31, 33
neuroscience revolutions, 141
New Guinea tribes, 19
New York Review of Books, The, 48
New York Times, The, 10, 19, 27, 48, 71, 75, 77, 94, 97, 116, 118, 125, 140, 155, 165
New York University, 37, 48
Newport to Bermuda Yacht race, 27
Newsweek, 124, 140, 143
Newton, Isaac, 42, 151
Nightline, 65
niobium, 105
nitrogen, 163
nitrogen cycle, 145
Nobel Prize, 10, 12, 13, 19, 20, 27, 33, 40, 80, 88, 103
Northwestern University, 100, 152
nuclei, 154, 165
nucleic acids, 151, 153
nucleus, 154
O
oligonucleotide, 153
Olsen, Gary 157 159, 163, 166
Olsen, Maynard, 22, 24
ontology, 95
opportunistic science, 2
Oregon State University, 137
organelles, 154
organic chemistry, 35
organic material, 165
organic molecules, 165

organisms, 148 149, 151, 159, 161 162, 166


oscilloscopes, 60, 172
Overbeek, Ross, 161, 163
Overbye, Dennis, 106
Oxford Instruments, 45
Oxford University, 31, 34 36, 38 39, 41, 45 47, 50, 52, 91, 169, 171
P
Pace, Norman, 147 149, 156 160, 163, 165 166, 170, 173
Packard Foundations, 138
pancreatic cancer, 99
Pardoll, Drew, 83
Parkinson's disease, 37, 39, 45 46
Parliament, 49

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particle accelerator collisions, 63


particle accelerators, 104, 109
particle physics, 103, 113, 119
patents, 18, 19, 22
pathogens, 21
Paton, William, 32
Paul, William, 92
Pauling, Linus, 10, 30, 153
Pegasus, 65, 77
penicillin, 40
Pennypacker, Carl, 105, 106, 108, 109, 110, 112, 118, 121, 170, 172
Pennypacker F/1, 109
Penrose, Roger, 39, 42, 48
peptide, 46
Perkin, Elmer, 26
Perlmutter, Saul, 4, 33, 104 106, 108 122, 169 177
petroleum, 162
Pew, 139
Pew Fellows, 137, 143
Pew Fellowship, 133
Pew Foundation Fellowship in Conservation and the Environment, 137
Pfizer, 46
pharmacology, 41, 46
Phobos, 58
photographic emulsion, 109
photosynthetic, 158, 164
physiochemistry, 42
Pinker, Steven, 42
plant hybrids, 9
Plato, 32, 42, 177

pneumonia, 87
policy studies, 135
Pollard, Ernest, 150
pollinators, 124, 139 140
Popper, Karl, 82, 90, 92, 99 100
Population Bomb, The, 127, 136
Postel, Sandra, 129, 131, 138
President's Council of Advisors on Science and Technology, 143
primitive bacteria, 164
primordial, 149
Princeton University, 116, 119
Proceedings of the National Academy of Sciences, The, 155, 165
programmed cell death, 91
prokaryotes, 150, 154
prostheses, 80
prostitution, 144
proteins, 150 151, 154
psyches, 3
psychotropic drugs, 42
pulsation, 70 71
Purity Springs, 139
Pym, Barbara, 34
Q
Quonset hut, 7, 59, 62
quantum physics, 3, 10
quasars, 109
Queloz, Didier, 65, 76
R
radial velocities, 63
Rasio, Fred, 71
Recording Company of America (RCA), 173
red dwarf star, 75

Gliese 876, 75
redshift, 107, 111, 112
rejection of transplants, 94
relativity, 150
remote sensors, 2, 3, 125, 175
renal cancer, 99
Rensburger, Boyce, 80
restriction enzymes, 20
"reticulate evolution," 165
rhesus monkeys, 97
ribonucleic acid (RNA), 16, 30, 148, 153 154, 157 158
ribosomal nucleic acids, 155
ribosomal RNAs (RNA), 153 156, 158 159
ribosome, 153, 165
Ridge, John Paul, 94; see also "Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells"
Riess, Adam, 117, 118, 120, 121, 122
Ritalin, 42
River Chewell, 34
Robb, Frank, 163
robotic telescopes, 108
Roche, 22
Rochester University, 95
Rocky Mountain Biological Laboratory, 128

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Roosevelt, Franklin, 89, 141


Rosalind Franklin and DNA, 29
Royal Air Force, 47
Royal College of Art, 31
Royal Greenwich Observatory, 109, 110
Royal Institute, 4, 50 52, 169
"Christmas Lectures," 43, 52
Director of, 49, 52
Royal Society Proceedings, 131
Royal Swedish Society, 134
Rutherford, Earnest, 151
S
Sacks, Oliver, 42
Sagan, Carl, 43, 75
Sagoff, Mark, 145
Salk Institute, 86
San Francisco State University, 60 61, 64, 69, 77, 171 172
San Vito, 123, 125, 135, 142 143
Sanchez-Azofeifa, Arturo, 142
Sandage, Allan, 55, 77, 106, 121, 170
Sanger, Fred, 13, 16, 153
Sanger Center, 26
Santa Fe Institute, New Mexico, 133
sarin, 36
satellite imaging, 125, 142
Saturn, 59, 77, 175
Saturn Titan, 58
Sayre, Ann, 29
"schlepper, the," 93
Schmidt, Brian, 113

Schneider, Stephen, 129


Schrdinger, Erwin, 10
What Is Life?, 10
Schwab, Robert, 85
Schwartz, Ron, 82, 87 89, 92, 95 96, 99 100, 172, 176
Science, 21, 22, 79, 85, 94 96, 99, 116 117, 119, 121, 140 141, 149, 153, 172
Scientific American, 85
Scientist, The, 166
search for extraterrestrial intelligence (SETI), 66, 173
Searle, John, 39, 48
Second World War, 20
self/nonself theory, 80 81, 83, 85 86, 90 92, 98 99
sequence, 151, 159
sequencing, 159
Sexton, Anne, 79
Shoemaker, Carolyn, 173
Shoemaker, Gene, 173
Shoemaker Levy 9, 173
short sequences, 148
shotgun genomics
shotgun DNA cloning, 16, 17, 18,
shotgun gene sequencing, 174 175
Shreeve, Jim, 22
sickle-cell anemia, 28
signaling, 98
Silicon Valley, 109
silicon wafer, 109
Silver, Anne, 37
Silverstein, Arthur, 94 95, 97
Simon, Julian, 136
simple cells proliferated, 165
single-celled, 156

Sloan Digital Sky Survey, 113


Smith, David, 23, 31 32, 35 41, 47
Smith, Douglas, 164
Smith, Hamilton, 20, 21, 29, 163
Smith Kline Beecham, 23, 27
Smithsonian Institution, 172
snake toxins, 47
sociology, 135
software, 125
Sogin, Mitchell, 152 153, 167
Southern Hemisphere, 69
Space Interferometry Mission (SIM), 76
Special Tropical Lecture, 95
species, 152, 158
spectra, 107
spectrograph, 63, 172
spectrometers, 70
spectrum, 62
Spergal, David, 116
Spiegelman, Sol, 151
Spring, Leslie, 97
Springy, 34, 46
Squibb, 41
Srivastava, Pramod, 96, 97 99
St. George's Hospital in London, 97
St. Hilda's College, 34 35
Stahl, David, 152, 159, 161
Stanford University, 22, 127, 131, 135, 146, 152, 171

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Stanier, Roger, 152, 155


star atmospheres, 56
star systems, 3
Star Wars, 45
Stein, John, 36 38
Steinberg, Wallace, 19, 20, 23, 24; see also Human Genome Sciences
Steinhardt, Paul, 119
"Stellar Radial Velocities," 62
Live, 79
Stetter, Karl, 160
stillborn, 67
Stork and the Plow: The Equity Solution to the Human Dilemma, The, 135 136, 144
stromatolites, 160
Structure of Scientific Revolutions, 156
structures, 154
subgiants, 74
Substantia nigra, 45
sulfur, 159, 162, 165
sulfur nitrate, 33
sulfuric acid, 154
sulfuric caves, 149
Sun Microsystems, 69, 71, 173
sunspots, 9
Superconducting Supercollider, 105
Supernova, 4, 106 116, 119, 121, 122, 169, 173, 175
Supernova Accelerator Probe (SNAP), 122
Supernova Cosmology Project, 110, 112, 120, 121
Sutton, Granger, 20, 29
Sutton, Lee, 152
swapping, 165

symbiosis, 159
symbiotic communities, 158
Synaptica, 46 47, 49, 51 52, 172, 176
synthetic antibodies, 97
syphilis, 21
Szent Gyrgyi, Albert, 41
T
Tacrine, 46
tanagers, 123
Taq enzyme, 162
Tarter, Jill, 66
T-cell, 86, 88
T-cell memory, 81, 91
T-cell receptors, 89
Terrestrial Planet Finder (TPF), 76
The Institute for Genomic Research (TIGR), 20, 21 25, 163 164, 176
scientific advisory board, 163
TIGR Assembler, 20, 29
theoretical model, 138
theory of evolution, 3, 91, 100
thermomicrophilic microorganisms, 160
thermophiles, 158 159
Thermophilic Microorganisms and Life at High Temperatures, 158
Thermus aquarius (Taq), 162
third domain, 148
Thomas, David, 46
thymus, 88
TIGR; see The Institute for Genomic Research
time travel, 9
Times, The, 8, 43 44
Tirumalai, Kamala, 100
tissue engineering, 81

Titan, 59
Titanic, 55
T-lymphocyte, 86
tolerance, 81
"Tolerance, Danger, and the Extended Family," 93
tones, 63
"total" values, 140
transfer RNA (tRNA), 151
"translation," 150
transplanted organs, 94
TREE, 141
Trixie, 83
tuberculosis, 144
tubeworms, 158
Tufts University, 41
"Turned On by Danger," 95
Turner, Michael, 117, 120
Twilight Zone, 58
Type 1 Diabetes, 80, 97
U
United Nations, 38
United States Department of Energy (DOE), 162 163
Universal Ancestor, 156, 165

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University of Alberta, 142


University of Arizona, 44
University of British Columbia, 62
University of California at Berkeley, 60 61, 66, 77, 105, 109, 111, 112, 114, 129, 152, 172
University of California at Irvine, 84
University of California at Los Angeles (UCLA), 45, 57, 59
University of California at San Diego, 11, 14, 85, 164
University of California at Santa Cruz, 59, 75
University of California, 23, 39, 61, 108, 111
University of Chicago, 117
University of Colorado, 157
University of Connecticut, 96
University of Georgia, 153
University of Illinois, 23, 148, 151, 152, 157 158, 163
University of Iowa, 69
University of London, 46, 72
University of Maryland, 163
University of Miami, 97
University of Michigan, 14
University of North Carolina, 152
University of Pittsburgh School of Medicine, 97
University of Regensburg Laboratory, 160
University of Southern California, 160
University of Sussex, England, 72 73
University of Washington, 25
University of Wisconsin, 158, 162
uracil, 153
Uranus, 58
U.S. Naval Hospital, 97
U.S. Naval Medical Research Center, 97

U.S. News and World Report, 140


V
Van Niel, C.B., 152, 155
vaccines, 94
Varmus, Harold, 3, 89
Vaughn Johnny, 75
"The Big Breakfast," 75
Vaux, David, 45 47
VAX minicomputer, 60
Velikovsky, Immanuel, 75
Velvet Underground, 31
Vent, 162
Venter, J. Craig, 4, 33, 48, 50, 63, 83, 95, 146, 163 164, 170 178
adrenalin receptors, 12, 14
brain cells, 12, 14
Haemophilus influenzae, 20, 21
Japan, 16
molecular biology, 13
National Institutes of Health (NIH), 12, 17, 19
Renaissance weekend, 9, 23
Roswell Park, Maryland, 12
Sorcerer, 9, 27
State University of New York at Buffalo, 12
Vietnam, 1, 7 10
Venus, 57
Virgo, 66
Vitousek, Peter, 137, 139
Vogt, Steve, 57, 59, 63 64, 69, 72, 77, 172
W
Waldmann, Herman, 88
Waldsterben, 127
Walker, Gordon, 62

Wall Street Journal, The, 19, 94, 99


Warrick Couch, 109
Washington Post, The, 75, 116, 140
Watson, James, 10, 15, 18, 19, 24 27, 30, 87, 141, 150 151, 170, 174
Double Helix, The, 11
wave interference sensors: see interferometers
Weinberg, Steven, 107
Westinghouse, 23
Westinghouse, George, 23
White Stallion Ranch, Arizona, 137
Whitman, William, 153
Williams College, 64
Wilmut, Ian, 130
Wilson, E. O., 29, 124, 177
Consilience: The Unity of Knowledge, 177
Wilson, Robert, 60
Winslow Heinz, Postdoctoral Fellowship, 133

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Woese, Carl, 4, 23, 92 148 157, 159 161, 163, 165 167, 170 172, 174 177
Woesean tree, 157, 161, 164, 166
Wolf, Nancy, 45
Wolfe, Ralph, 151, 154 155, 163
Wood, Martin, 45 46
woodpecker, 128
Woods Hole Program, 152
World Economic Forum, 144
World Series, 74
World Wide Web, 44 45
Worlds in Collision, 75
Worldwatch Institute, 129
Wright, Robert, 174
Moral Animal, The, 174
Wright Institute, 42
X
x-ray crystallography, 10; see also Franklin, Rosalind
Y
Yale University, 150, 157
yellow-green atmosphere, 165
Yellowstone, 149, 162
Young, Dick, 154
Z
Zimmer, Carl, 160
Zuckerkandl, Emile, 153

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