Ted Anton is professor of English at DePaul University. He is the author, most recently, of Bold Science and has written for Chicago magazine, the Chicago Tribune, and Publishers Weekly. The University of Chicago Press, Chicago 60637 The University of Chicago Press, Ltd., London © 2013 by Ted Anton All rights reserved. Published 2013. Printed in the United States of America 22 21 20 19 18 17 16 15 14 13 1 2 3 4 5 ISBN-13: 978-0-226-02093-8 (cloth) ISBN-13: 978-0-226-02095-2 (e-book) Library of Congress Cataloging-in-Publication Data Anton, Ted. The longevity seekers : science, business, and the fountain of youth / Ted Anton. pages. cm.—(From obscurity, 1980–2005—“Greater than the double helix itself,” 1980–1990—The grim reaper, 1991–1993—Sorcerer’s apprentices, 1991–1996—Race for a master switch, 1989–2000— Money to burn, 2000–2003—Longevity noir, 2003–2004—Betting the trifecta, 2005–2006—Defying gravity: the battle to find a drug for extending health, 2005–2013—Sex, power and the wild: the evolution of aging, 2001–2008—The rush and crisis, 2008–2010—Live long and prosper, 2009–2011—Centenarians in the making, 2011–2013—Fountains of youth, 2013—Reimagining age.) ISBN 978-0-226-02093-8 (alk. paper)—ISBN 978-0-226-02095-2 (e-book) 1. Life expectancy—Economic aspects. 2. Longevity— Economic aspects. 3. Life spans (Biology) 4. Old age—Economic aspects. I. Title. HB1322.3.A58 2013 612.6′8—dc23 2012043340 This paper meets the requirements of ANSI/NISO Z39.48–1992 (Permanence of Paper). THE LONGEVITY SEEKERS Science, Business, and the Fountain of Youth TED ANTON THE UNIVERSITY OF CHICAGO PRESS CHICAGO AND LONDON For my parents, Bertha and Gus Contents A Note on Purpose Preface PART 1. FROM OBSCURITY, 1980–2005 1. “Greater Than the Double Helix Itself,” 1980–1990 2. The Grim Reaper, 1991–1993 3. Sorcerer’s Apprentices, 1991–1996 4. Race for a Master Switch, 1989–2000 5. Money to Burn, 2000–2003 6. Longevity Noir, 2003–2004 7. Betting the Trifecta, 2005–2006 PART 2. DEFYING GRAVITY: THE BATTLE TO FIND A DRUG FOR EXTENDING HEALTH, 2005–2013 8. Sex, Power and the Wild: The Evolution of Aging, 2001–2008 9. The Rush and Crisis, 2008–2010 10. Live Long and Prosper, 2009–2011 11. Centenarians in the Making, 2011–2013 12. Fountains of Youth, 2013– 13. Reimagining Age Epilogue Acknowledgments Longevity Gene Timeline List of Longevity Genes Notes About the Author Index A Note on Purpose This story began with my interest in an article in the New York Times science section. In January 2001, I called the article’s subject, MIT biologist Lenny Guarente, who suggested I call the University of California at San Francisco’s Cynthia Kenyon. Over the next eleven years I became hooked on their science of longevity genes. I conducted more than two hundred interviews with scientists, investors, and students in their offices and labs. I visited and worked in labs, observed classes and conferences, and traveled from California to Crete to research the story of the science behind the dream of extending healthful life. To research the book, I attended conferences in Cold Spring Harbor, New York (2002); Hersonnissos, Crete (2004); St. Louis, Missouri (2006); Boston, Massachusetts (2008 and 2009); and Madison, Wisconsin (2010). I watched scientists teach classes, run their labs, and conduct journal seminars. I was a student for a day in the Woods Hole, Massachusetts, Genetics of Aging course. The following pages explore the social history of a science idea. A researcher grows up in a creative family, follows an obscure interest that appeals to them and no one else, and stumbles onto an exciting insight that alters a mode of thought. I am interested in the power of such ideas, revealing why some receive attention at a given moment and others do not. This book proposes that in such behind-the-scenes moments, one can discern crucial clues to the historical, technological, and social forces driving an era. Naturally, memories of such moments may vary. As much as possible I have sought to square my interpretation with the recollections of the scientists. I have been fortunate that the researchers themselves are recording the history of their field in professional journals, online and print interviews, conferences, and in their own books or oral histories. I consulted these works, talked to as many lab members as possible, and tried to match recollections with the record and those of other lab members. I went back to most researchers and checked the details of a scene. What follows is my attempt to recount the unfolding of an absorbing and disputed series of discoveries. If I quote a conversation, it is based on interviews or public documents. Picking certain researchers and discoveries, however, I leave others out. Ultimately, my goal is not to provide a comprehensive text, but a dramatic record of the personal, economic, and intellectual motivations shaping discovery in our time. One of these discoveries could reshape the way we experience our lives. In the race for longer, healthier lives, almost every discovery came under explosive disagreement. What role did accident or personality play in their unfolding? To what extent did public fascination and big money alter the course of science? Which of these findings, if any, may lead to significant applications? This book explores the relation of a unique science to its time and, in so doing, the relation of any science to any time. Preface The Laboratory of Molecular Biology sat at the end of Hills Road on the southern edge of Cambridge, England. In 1983 the weather had been so miserable that twenty-nine-year-old Cynthia Kenyon taped a yellow sun on her single window overlooking distant hedgerows and a lone traffic light. She was checking her experiments in her tiny three feet of bench space in a room in one of the leading institutions of molecular biology. The room was small and crammed with equipment, with cream-colored walls. Upstairs was a cafeteria strewn with newspapers and ashtrays. The laboratory smelled of coffee. She worked with spectacular people mostly in their twenties who were committed to science driven by ideas. Their main idea was that if you had a biological question, you studied it in a living animal, not in single cells. Lanky and tall, with short blond hair and freckles, Cynthia Kenyon had changed her career to join this group. The oldest of three who grew up in New Jersey and Georgia, she hated limits and disliked authority. In high school, she played jokes on the band master even though she dreamed of a concert career playing French horn. She hung a banner, “Know the truth and it shall make you free,” in her bedroom, where she allowed a parakeet to fly free and taught it to pick playing cards from her hand. She wrote stories, played guitar, kept a huge aquarium, and sewed her own clothes. She yearned to do something great. That morning the rain had finally stopped. The lab emptied as people headed out to enjoy the sunshine. An opera played on the radio. At her bench, Kenyon noticed one of the petri dishes of tiny worms. She pulled over a microscope to take a closer look. The tiny worms were called Caenorhabditis elegans, “elegans” for their elegant, sinuous, near-transparent bodies. C. elegans lives in the temperate soils and decaying fruits of the earth. It consists of almost every tissue that a human body contains, but is only the size of a comma in a printed sentence. The worms in Kenyon’s dish barely moved. Their skin bunched in weedy, menacing clumps. Their backs looked bloated and thick. They looked old and near death. They looked, she thought suddenly, like people. They aged just like humans. Then she realized she too was getting old, and someday she would die. The mystery the lab studied was the molecular plan of growth, repeated beautifully every time, that controlled the way nerve and other cells organized in patterns to build an animal. It took tens of millions of steps to make an animal from a one-celled embryo, each choreographed by a mysterious gene program. The revolutionary discovery was that single genes, shared among species, controlled many of key steps of the growth program. But the revolution was over, and Kenyon had mostly missed it. No one thought that a similar pattern might determine the rate of our decline. Aging was random decay, and no one wanted to study that. Yet aging was one of life’s most important processes, she thought, and all biological processes, they were learning, were controlled by genes. If everything was in some way controlled, then aging might be as well. Some moments you feel or see something that sticks in the unconscious like a dream. Outside her window the traffic light changed. She looked at the plate of worms. They barely moved. She never forgot that moment. It was a beautiful day and her heart was pounding. This is the story of the race to understand the genes of healthful human longevity. For years, researchers have extended the life of lab animals up to ten times their normal span. Working on tiny worms, flies, fungi, and mice, scientists discovered molecules that sense nutrient and energy levels and extend fitness into late life. The question was whether the same may be true for humans. Scientists’ new insight was that the rate of aging may not be random and chaotic, but rather a controlled and perhaps manipulable process. By changing the activity of only a few genes, we may be able to live much longer, healthier lives. No science ever received quite so much public fascination because few have offered such immediate promise of potential social impact. We face an aging crisis. If current trends continue, the numbers of people older than 60 years will more than double by 2050. By that year, one in three people in the developed world will be older than sixty. The intensity of this “silver tsunami” is even greater in the developing world, where countries will have less time to adjust. Across the globe, the number of centenarians will increase eighteen-fold in the next fifty years. Even though we are living longer, we still suffer the tragedy of late-onset illness. By a large margin, most health care costs are incurred at the end of life. A host of policy makers today are arguing about what the aging world means and how to address it. This book tells the story of a potential science revolution and of the new money changing the way scientific ideas emerge. It begins with geneticist Cynthia Kenyon, 59, who found one of the world’s first longevity genes and cofounded a company to find a drug to extend healthful human life, competing with several new companies, many funded by the barons of the information age. Rather than spending billions of dollars to battle the various diseases of aging, these researchers argued, we might better spend our efforts on a new way of thinking, at the level of molecular tipping points in the cell that make the beautiful circuits and feedback loops that can either maintain or damage our health. These tipping points come in small switches triggered by nutrients, energy levels, and other changes in the environment. These switches can almost miraculously calibrate the rate of aging in many species, from familiar lab models to humans. This is the biography of an idea. The idea is that the quality of aging could be altered by tweaking single genes. It originated among a handful of outsiders, working on tiny animals outside the mainstreams of traditional aging study. There was no textbook or blueprint for pursuing that idea, but there was a culture of small groups often at odds with each other. The early researchers fought for money, and, if they got it from the super-rich, they worked without many of the ties of conventional funding. In the scramble for scientific credit and financial gain, the battle to survive required skills of control, cooperation, and competition for resources, much like the genes themselves. Aging remains one of life’s great unsolved riddles. For all our biological knowledge, we still do not know exactly what aging is. Life can defy entropy, the tendency of systems to wear down over time. Healthful life span may last as long as it wants or needs to. Some organisms live centuries or longer. We now know something of the gene, cell, and hormone signals that help them do so. This book explores the mystery of those intricate cell signals and the battles of scientific personalities to expose them. The discoveries offer deep insights, but equally as illuminating was the confluence of dreams, personal crises, intense work, altruism, and greed that made one of the most contentious science stories of our time. Few recent scientific discoveries have moved from such an outlier status to the pinnacle of business, while riling up more critics. Some ideas won, and some of the biggest lost out. We are all intrigued by the questions of life and death, the more so the older we get. What are the proper stages of life? In ancient Rome, people lived twenty- nine years. In the Middle Ages, the afterlife and current life were intimately commingled because they had to be. In the last twenty-five years a technical revolution made it possible to answer such questions as: What causes aging? Can we alter its rate? Does life do so naturally? What would be the meaning of such discoveries, and which are the ones most likely to affect the ways we live? This book explores the attempts to answer these big questions. To do so could change our definition of who we are and how we imagine ourselves. The book’s main subjects are four genes and their molecular signaling