The Longevity Seekers: Science, Business, and the Fountain of Youth

By Ted Anton

People have searched for the fountain of youth everywhere from Bimini to St. Augustine. But for a steadfast group of scientists, the secret to a long life lies elsewhere: in the lowly lab worm. By suppressing the function of just a few key genes, these scientists were able to lengthen worms’ lifespans up to tenfold, while also controlling the onset of many of the physical problems that beset old age. As the global population ages, the potential impact of this discovery on society is vast—as is the potential for profit.

With The Longevity Seekers, science writer Ted Anton takes readers inside this tale that began with worms and branched out to snare innovative minds from California to Crete, investments from big biotech, and endorsements from TV personalities like Oprah and Dr. Oz. Some of the research was remarkable, such as the discovery of an enzyme in humans that stops cells from aging. And some, like an oft-cited study touting the compound resveratrol, found in red wine—proved highly controversial, igniting a science war over truth, credit, and potential profit. As the pace of discovery accelerated, so too did powerful personal rivalries and public fascination, driven by the hope that a longer, healthier life was right around the corner. Anton has spent years interviewing and working with the scientists at the frontier of longevity science, and this book offers a behind-the-scenes look at the state-of-the-art research and the impact it might have on global public health, society, and even our friends and family.
With spectacular science and an unforgettable cast of characters, The Longevity Seekers has all the elements of a great story and sheds light on discoveriesthat could fundamentally reshape human life.  

• Language: English
• Publisher: University of Chicago Press
• Release date: May 1, 2013
• ISBN: 9780226020952

Book preview

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 pathways. They offer a direct evolutionary gift, from ancient common default signals governing growth, reproduction and stress response, of potentially longer and healthier lives. When the implications of that gift were understood, the science exploded in the media, medicine and industry, and companies and governments invested more than a billion dollars to wrest the secrets of youth from the laboratory.

For eleven years, I followed the scientists’ conferences, visited their labs, hung out in their homes, and traveled the world to understand the latest discoveries. I became obsessed by their arguments and the long, beautiful, twisting molecules that triggered them. In those years I watched as the science exploded. The backlash unleashed campaigns of mass persuasion, changing the relationships among academic, corporate, and government institutions, raising questions about what a scientist is and does, and the roles of science and science funding in our time.

This story offers a parable of science, from the contribution of idealistic undergraduate to seasoned researcher, from giant government funding agency to private billionaire, as it intersected with capital and human desire in the biggest dream of all.

Aging is universal. We live it every day. We see it in our friends and families. Extending healthful longevity made the ultimate science prize. No other science field is like it, not global warming or energy or the origins of the universe. None of those may give us a few more minutes on earth. Perhaps tweaking a worm, fly, or mouse gene could.

During these years, my father suffered a stroke and a number of people I loved have either died or shown the most debilitating effects of aging. As I entered my fifties, I felt for the first time the hint of my mortality, real as the roughness of a stone. To slow aging is to alter the program of our life. This is the story of the quest to understand and defy one of the universe’s most inexorable forces. To understand it is to see the world anew.

PART 1: FROM OBSCURITY

Gilgamesh thought he would be immortal. The vase painters of ancient Athens recorded their balding selves having outlandishly youthful sex. Beneath all our exploration of longevity lies a bargain. To live longer, or better, many of us would give almost anything. Chapter 1 describes the traditional evolutionary theories explaining aging as a trade-off and explores two small 1980s discoveries in an obscure worm that seemed to suggest otherwise.

Chapter 2 profiles the biggest discovery of its time, made by Cynthia Kenyon at the University of California, San Francisco, in 1993. This was followed by a second discovery in 1999 by outspoken MIT researcher Lenny Guarente, described in chapter 3.

Chapter 4 explains what happened when researchers learned they were looking at versions of human genes. Into the personal struggles of two researchers converged new business and science forces as their discoveries about ancient molecular genetic processes suddenly gained attention. With the attention came disputes, mistakes, and competition.

The idea met with objection but inspired disaffected thinkers and a few investors. Chapter 5 explores the first businesses of longevity in 2000–2003. Few discoveries moved so fast from such outlier status to the interest of finance while inspiring intense criticism.

Chapter 6 tells the story of the first compound to affect a human longevity enzyme, a trigger called resveratrol, discovered by David Sinclair, an outspoken young Australian graduate of Guarente’s lab in his first years at Harvard. Sinclair started his own company, Sirtris, and raced the company of his former lab director to apply their discoveries.

Two genes became celebrity genes, each gaining followers and critics who explored their many effects in hundreds of labs, described in chapter 7. Some significant proponents of the longevity idea were wrong, however, and provoked a powerful backlash in conferences, media, and university hallways. Part 1 concludes with the question: What happened when you took antisocial and brilliant scientists, threw a ton of money at them, and asked them to perform antiaging miracles?

1

Greater Than the Double Helix Itself: 1980–1990

In all our exploration of longevity, going to the beginning of language and latest of human follies, lies a bargain. To overcome aging and death, most of us would give almost anything. That slinking wish lies at the foundation of much of our storytelling and many of our founding mythologies. The fear of death is so unbearable we traveled the world seeking a fountain of youth.

Partly for that reason, scientists have insisted that the processes of aging were random and uncontrollable. In 1825, the British actuary Benjamin Gompertz went so far as to quantify the depressing inevitability of our decline. He calculated that after puberty, the human death rate doubles every eight years. The older you get, the more likely you are to die. Some theory. There was no fountain of youth nor the possibility of a fountain of youth.

In the early years of the twentieth century, however, scientists applied the power of Darwin’s theory of natural selection to the question of aging. They saw that the influence of natural selection fades over a lifetime, affecting only the hormones and behaviors that contribute best to an organism’s chance to survive long enough to reproduce. Youth hormones like estrogen in women and testosterone in men are favored, because they grant reproductive fitness even though they may harm us later in life. By the middle of the twentieth century, this trade-off idea between youth and age had a name: antagonistic pleiotropy. Pleiotropy means that one gene has many effects. Antagonistic pleiotropy means that virility or fertility genes that trigger youth hormones to keep us vigorous and attractive can later cause us to age more rapidly.

The discovery of such hormones led to a wave of early charlatans who transplanted goat and monkey testicles into their patients, preying on the eternal insecurities of potency in all of us. In the 1920s, the Viennese-born doctor Eugene Steinach promised that vasectomies would increase male longevity. Austria’s leading scientist, Sigmund Freud, and America’s biggest cynic, H. L. Mencken, both got themselves Steinached. The Kansas-born John Brinkley, who twice ran for state governor, made a fortune by implanting goat testicles right beside the natural ones of his patients. Brinkley was so successful with his dangerous surgeries that he single-handedly gave life to the fledgling American Medical Association as it tried to stop him. When they did so, he took his radio personality to Mexico and founded the first of the great border-blasting broadcasters that gave the world rock and roll.

But what exactly causes aging? Several twentieth-century ideas sprang up to explain it. The genetic mutation accumulation theory suggested that it was unrepaired damage to DNA. Another idea, the error catastrophe theory, offered that cellular mistakes build until they reach a tipping point of disaster. Yet another theory, called hormesis, offered that a little stress improves longevity. The free radical theory of aging, which claimed that the reactive waste molecules of oxidation cause the body to break down when they bind to other compounds in the cell, became a widely accepted idea. But the main scientific point, driven home by serious research in order to counteract all the quackery, was that aging processes are always chaotic, disconnected, and uncontrollable.

Most researchers were influenced by evolutionary biologist George Williams, who in 1957 said that the processes of aging had to be random, never due largely to the changes in a single system. His idea made the scientific quest for longevity unsavory. "This conclusion banishes the ‘fountain of youth’ to the limbo, Williams concluded, of scientific impossibilities."

The discovery in 1965 by biologist Leonard Hayflick at Philadelphia’s Wistar Institute that normal human cells in a cell culture divide only fifty-two times, never more, confirmed the inevitable limit to human life span. The discovery was even called the Hayflick limit. Scientists like Williams and Hayflick pounded out a jeremiad against the pop science of longevity. Their thought generated overwhelming doubt, which made studying the biology of aging an uphill battle for serious researchers.

There was one discovery, however, that tantalized the later generation of aging researchers. In the Depression, a Cornell University veterinary professor concerned about diet observed that when he trimmed back the feed of his animals, they actually lived longer than normal. In the era of soup lines and hunger, Clive McCay found that rats and mice lived 40 percent longer if you cut their feed by 30 percent. McCay published his longevity findings in 1934 in a respected journal and went on a long publicity tour. But he was not in the mainstream of aging research at the time. Some of the mice were sterile and many of rats showed reduced litters, so it was thought they had sacrificed reproduction for lengthened life. The assumption, quite reasonably, was that the long-lived, half-starved animals had a lower metabolism or a loss of fat.

A charismatic character who described himself as a bit of a Bolshevik, McCay was a biochemist and professor of animal husbandry who planned the meal rations for America’s World War II soldiers. He got himself a lot of publicity, but his caloric restriction idea languished. Few serious scientists wanted to pursue it.

By the 1960s, a contrary, ascetic mathematician and immunologist named Roy Walford latched onto caloric restriction in a best-selling book called Maximum Life Span. At UCLA, Walford became a low-calorie diet champion and practitioner who influenced millions, attracting followers like Timothy Leary and inspiring significant new researchers to enter the field. His work led to a cascade of scientific papers on caloric restriction in mice, rats, monkeys, and even humans, sparking the founding of the Calorie Restriction Society International in, appropriately, Las Vegas in 1994. But his best-selling books were often reviled by experts in gerontology. Walford passed away at the age of seventy-four, a gaunt figure permanently damaged by poor atmospheric conditions in his biosphere experiment in the Arizona desert. Still, he found that the biospherans’ restricted diet had lowered their cholesterol, blood pressure, and blood glucose levels. He and his followers promoted the healthful effects of caloric restriction with science studies and popular books, and a following across the world came to include some important new biologists of aging.

Policy makers were thinking about aging, though, because they had to. By the end of the twentieth century, the percentage of Americans over the age of sixty-five was projected to grow from 20 percent to 41 percent of the total population. In 1974, Congress created the National Institute on Aging (NIA) as a new division of the National Institutes of Health in a nation suddenly aware that it was graying fast. How would the members of a developed country fare in a world that half a century earlier would have considered them lucky to make it to fifty-five? The American NIA pushed academic science to take on the big but unsavory biomedical quest to improve the quality of aging. The main concerns were the rising rates of cancer, heart disease, and dementia. The incidence of Alzheimer’s disease, which got its name just ten years before, was expected to increase fourfold, up to sixteen million sufferers, by 2030.

In the late 1970s, a few academic conferences on the genetics of aging had sprung up. "If we found one thing, a trick say, that led to the mechanism