VIKING
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Copyright © 2017 by Meredith Wadman
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PHOTOGRAPH SOURCES AND CREDITS
INSERT: here: Norman Cohen; here: The Wistar Institute, Wistar Archive Collections, Philadelphia, PA; here: University of Pennsylvania, University Archives and Records Center; here: University of Pennsylvania, University Archives and Records Center; here: Leonard Hayflick; here: Katherine Aird; here and here: Eva Herrström; here: Margareta Böttiger; here: Ernholm family; here: Smithsonian Institution, Division of Medicine & Science, National Museum of American History; here: U.S. National Library of Medicine, History of Medicine Division; here: American Media, Inc.; here: James A. Poupard; here: Frank P. Montone/ Special Collections Research Center, Temple University Libraries, Philadelphia, PA: here: University of Pennsylvania, University Archives and Records Center; here: Edward A. Hubbard/U.S. National Library of Medicine; here: Smithsonian Institution, Division of Medicine & Science, National Museum of American History; here: Royal Prince Alfred Hospital Museum and Archives; here: Frederick A. Murphy, University of Texas Medical Branch, Galveston, Texas; here: The Wistar Institute, Wistar Archive Collections, Philadelphia, PA; here: Mary and Steve Wenzler; here: Philadelphia Archdiocesan Historical Research Center, Robert and Theresa Halvey Photograph Collection; here: Merck Archives—Merck, Sharp & Dohme Corp., 2016; here and here: March of Dimes Foundation; here: Dorothy M. Horstmann papers (MS 1700). Manuscripts and Archives, Yale University Library; here: Children’s Hospital of Philadelphia; here: Merck Archives—Merck, Sharp & Dohme Corp., 2016; here: Leonard Hayflick; here: National Institutes of Health; here: Jerry Huffman; here: poster reprinted with the permission of the Helen Keller National Center for Deaf-Blind Youths and Adults; here: Frederick A. Murphy, University of Texas Medical Branch, Galveston, Texas; here: The Wistar Institute, Wistar Archive Collections, Philadelphia, PA; here and here: Meredith Wadman
LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA
Names: Wadman, Meredith, author.
Title: The vaccine race : science, politics, and the human costs of defeating disease / Meredith Wadman.
Description: New York, New York : Viking, [2016] | Includes bibliographical references and index.
Identifiers: LCCN 2016044189 (print) | LCCN 2016045456 (ebook) | ISBN 9780525427537 (hardback) | ISBN 9780698177789 (ebook)
Subjects: | MESH: Measles-Mumps-Rubella Vaccine–history | Human Experimentation–history | History, 20th Century | United States
Classification: LCC RA644.M5 (print) | LCC RA644.M5 (ebook)
NLM WC 11 AA1 | DDC 614.5/23–dc23
LC record available at https://lccn.loc.gov/2016044189
While the author has made every effort to provide accurate telephone numbers, Internet addresses, and other contact information at the time of publication, neither the publisher nor the author assumes any responsibility for errors or for changes that occur after publication. Further, the publisher does not have any control over and does not assume any responsibility for author or third-party Web sites or their content.
Version_1
For my mother, Barbara Constance Greenfield Wadman
And in loving memory of my father, Hamilton Gray Wadman
A sane society whose riches are happy children, men and women, beautiful with peace and creative activity, is not going to be ordained for us. We must make it ourselves.
—Helen Keller
CONTENTS
Title Page
Copyright
Dedication
Epigraph
Prologue
PART ONE: THE CELLS
Chapter One: Beginnings
Chapter Two: Discovery
Chapter Three: The Wistar Reborn
Chapter Four: Abnormal Chromosomes and Abortions
Chapter Five: Dying Cells and Dogma
Chapter Six: The Swedish Source
Chapter Seven: Polio Vaccine “Passengers”
Chapter Eight: Trials
PART TWO: RUBELLA
Chapter Nine: An Emerging Enemy
Chapter Ten: Plague of the Pregnant
Chapter Eleven: Rabies
Chapter Twelve: Orphans and Ordinary People
Chapter Thirteen: The Devils We Know
Chapter Fourteen: Politics and Persuasion
Chapter Fifteen: The Great Escape
Chapter Sixteen: In the Bear Pit
Chapter Seventeen: Cell Wars
Chapter Eighteen: DBS Defeated
Chapter Nineteen: Breakthrough
PART THREE: THE WI-38 WARS
Chapter Twenty: Slaughtered Babies and Skylab
Chapter Twenty-one: Cells, Inc.
Chapter Twenty-two: Rocky Passage
Chapter Twenty-three: The Vaccine Race
Chapter Twenty-four: Biology, Inc.
Chapter Twenty-five: Hayflick’s Limit Explained
Chapter Twenty-six: Boot-Camp Bugs and Vatican Entreaties
Chapter Twenty-seven: The Afterlife of a Cell
Epilogue: Where They Are Now
Photographs
Acknowledgments
Notes
Selected Bibliography
Index
Prologue
The role of the infinitely small in nature is infinitely great.
—Louis Pasteur, nineteenth-century French microbiologist1
On October 9, 1964, a baby girl was born at Philadelphia General Hospital. She arrived early, when her mother was about thirty-two weeks pregnant. The baby weighed 3.2 pounds and was noted to be blue, floppy, and not breathing. The only sign of life was her slow heartbeat. Nonetheless, she clung to life, and her seventeen-year-old mother named her.
One month later the baby was still in the hospital, and a doctor leaning close with a stethoscope heard a harsh heart murmur. A chest X-ray showed that she had a massively enlarged heart because a hole in the muscular organ was preventing it from pumping blood efficiently. Doctors also noticed that the baby was staring into space, not fixing her gaze on anything. An ophthalmologist was called in. It emerged that the baby had cataracts blinding both eyes. Later other signs indicated that she was profoundly deaf, although a formal hearing test was never conducted.
In January 1965, after surgery attempting to repair one of the cataracts, the mother took her three-month-old daughter home. Nine days later the baby was back in the hospital with diarrhea. She remained in the hospital, where she suffered from recurring respiratory infections. She had trouble gaining weight, which is a common problem in infants with heart problems like hers. A psychologist who assessed her in July 1965, after a second heart defect was found, judged the nine-month-old to be the size of a two- or three-month-old infant and at about that stage of development; she couldn’t sit up or grasp an object placed in her hand.
The baby needed heart surgery if she was going to survive. Just before her first birthday, surgeons cut a seven-inch incision in her chest wall and repaired her heart. After the operation she remained in the hospital. The chronic respiratory infections continued. The baby w
as sixteen months old and weighed eleven pounds when she died of pneumonia at 3:30 a.m. on February 18, 1966. She had lived all but nine days of her brief life at Philadelphia General Hospital.
The young mother had told the doctors something when she brought her daughter back to the hospital. When she was one month pregnant, she had had German measles, which is also known as rubella.2
• • •
The early 1960s marked a coming of age for the study of viruses like the one that causes rubella—tiny infectious agents that invade cells and hijack their machinery in order to reproduce themselves. Biologists, with new tools in hand, were racing to capture viruses in throat swabs or urine or even snippets of organs from infected people and to grow them in lab dishes. Isolating a virus in the lab made it possible to make a vaccine against it. And making antiviral vaccines promised huge inroads against common childhood diseases like measles, mumps, and rubella, along with less-common killers like hepatitis. The principle of vaccination is simple: if a person is injected with, or swallows, a tiny amount of a virus—either a killed virus or a weakened live virus—that person will develop antibodies against the virus. Then, if he or she is exposed in the future to the naturally occurring, disease-causing form of the virus, those antibodies will attack the invader and prevent it from causing disease.
But if the concept is simple, making effective vaccines is anything but. In the early 1960s that reality was all too evident in recent tragedies. In 1942 as many as 330,000 U.S. servicemen were exposed to the hepatitis B virus in a yellow fever vaccine that was contaminated with blood plasma from donors—plasma that was used to stabilize the vaccine. It turned out that some of those donors carried hepatitis B. About 50,000 of the vaccinated servicemen came down with the dangerous liver disease and between 100 and 150 died.3 In 1955 a California-based company called Cutter Laboratories made polio vaccine with live, disease-causing virus in it, paralyzing 192 people, many of them children, and killing ten.4 Every senior U.S. government employee involved in overseeing the Cutter process lost his or her job—right up through the director of the National Institutes of Health and the secretary of health, education, and welfare.5
Then in the summer of 1961, Americans learned that the monkey kidney cells used to make the famous Salk polio vaccine often harbored a monkey virus called SV40. Tens of millions of American children had already received contaminated injections, and while the jury was still out on the tainted vaccine’s long-term health consequences, the unknown risks were weighing on regulators in the United States and elsewhere.
It was against this backdrop that, on a drizzly June morning in 1962, a young scientist went to work in his lab at the Wistar Institute of Anatomy and Biology, an elegant 1890s brownstone tucked in the heart of the University of Pennsylvania campus. Leonard Hayflick had just turned thirty-four years old. A serious, slight, reserved man with close-cropped dark hair, Hayflick was a product of working-class Philadelphia and was hungry to make his name. He was in love with biology and was plenty smart—he had come to believe—but that fact was far from appreciated. His boss, the famous polio-vaccine pioneer Hilary Koprowski, saw him as a mere technician, hired to serve up bottles of lab-grown cells to the institute’s impressive cadre of biologists.
This hadn’t deterred the ambitious Hayflick. The previous year the junior scientist had published a paper challenging a major piece of scientific dogma: the belief that cells grown in a lab bottle, if properly nurtured, would multiply indefinitely. His findings had been met with skepticism from some outstanding biologists. Let the critics carp, he thought. Time would prove that he was right—that normal cells cultivated in the lab eventually died, just like human beings.
On this drizzly day, however, Hayflick’s mind was not on cell death but on cell birth. Today, he hoped, he was going to launch a group of normal human cells that would revolutionize vaccine making. He had been waiting months for this opportunity—waiting for the arrival of the lungs that would be the source of these new cells. Cells were needed to make antiviral vaccines because outside of cells viruses can’t multiply. And huge quantities of viruses were needed to produce vaccines. Now, at last, the lungs were here in his bustling second-floor lab, two purplish things floating in clear pink fluid in a glass bottle. They had traveled all the way from Sweden packed on wet ice, courtesy of a Koprowski colleague who was a top virologist at the prestigious Karolinska Institute in Stockholm.
Several days earlier a woman living near Stockholm had had an abortion. Most Swedish physicians frowned upon the procedure, but it was legal, even for not-strictly-medical reasons. The woman was sixteen or seventeen weeks pregnant and had several children already. Her husband, she told her doctors, was an unsupportive alcoholic. The decision was clear. She sought out a sympathetic gynecologist, Eva Ernholm, one of the rare women in Swedish medical ranks, to perform the procedure.
After the abortion the eight-inch-long female fetus was wrapped in a sterile green cloth and delivered to a yellow brick outbuilding on the grounds of the National Bacteriological Laboratory in northwest Stockholm. Here, in what they nicknamed the “monkey house” because it was also home to monkeys used in making polio vaccine, young PhD and medical students were occasionally called on to dissect out the lungs of aborted fetuses for shipping to the Wistar Institute. It wasn’t a pleasant task, but when their boss, Sven Gard, the top virologist at the Karolinska Institute, asked them to do it, they obliged, slipping on head covers and changing from white wooden clogs to red or blue ones when they entered the sterile rooms. Other employees, working nearby in a grand building with a spiral staircase, were responsible for packing the lungs on ice and transporting them to Bromma Airport for the transatlantic flight that would eventually bring them to Philadelphia.
• • •
Hayflick was convinced that compared with monkey kidney cells, which were often laden with lurking viruses, normal human cells would serve as cleaner, safer vehicles for making antiviral vaccines. And he knew that he was uniquely positioned to produce a long-lasting supply of such cells. He had spent the previous three years perfecting the procedure that would do it.6
Hayflick took the bottle with the little lungs floating in it into a tiny room off his lab—what passed for a “sterile” room in 1962. He picked up a pair of tweezers, dipped them in alcohol, and passed them through the flame of a Bunsen burner. He waited for them to cool and then, gently, one at a time, lifted the lungs out of the bottle and laid them on a petri dish. The underdeveloped organs were each no larger than his thumb above the knuckle. He assembled two scalpels, held the blades at right angles to each other, and began carefully slicing the lungs. He didn’t stop until he had cut them into innumerable pieces, each about the size of a pinhead.
Hayflick nudged the minute pieces of lung into a wide-mouthed glass flask. The translucent pink fluid inside the flask looked innocent enough, but it was full of digestive enzymes from slaughtered pigs. These biological jackhammers broke up the “mortar” between the lung cells, freeing millions upon millions of them.
Later, he transferred the resulting cells into several flat-sided glass bottles and poured nutritious solution over them. He loaded the bottles onto a tray and walked them into an incubation room beside his lab. Here the temperature was a cozy 96.8 degrees Fahrenheit. He laid the bottles on their sides on a wooden shelf and closed the door carefully behind him.
The cells began to divide.
Hayflick already had a name for them: WI-38.
• • •
The WI-38 cells that Hayflick launched on that long-ago summer day were used to make vaccines that have been given to more than 300 million people—half of them U.S. preschoolers. A copycat group of cells, developed using the method that Hayflick pioneered, has been used to make an additional 6 billion vaccines. Together these vaccines have protected people the world over from a whole range of viral illnesses: rubella, rabies, chicken pox, measles, polio, hepatitis A, shingles, and
adenovirus—a respiratory infection that flourishes where people live in close quarters. (Every U.S. military recruit—more than 9 million of them since 1971—is vaccinated with an adenovirus vaccine made using WI-38 cells.)7
In the United States the rubella vaccine made in WI-38 cells and still given to young children has wiped out homegrown rubella. That vaccine was developed at the Wistar, by Hayflick’s colleague Stanley Plotkin, in the midst of a devastating rubella epidemic that swept the country in 1964 and 1965. That rubella outbreak damaged tens of thousands of American babies—including the baby described above who lived most of her short life at Philadelphia General Hospital. This book will tell the story of that epidemic and of the race that followed to develop a rubella vaccine.
How can it be that these WI-38 cells launched so long ago are still in use today? Partly because Hayflick made such a large initial stock of them: some eight hundred tiny, wine bottle–shaped ampules that he froze in the summer of 1962. Partly because the cells, when frozen, stop dividing, but then gamely begin replicating again when they are thawed—even after decades. And partly because of the power of exponential growth. Each petite glass vial that Hayflick froze contained between 1.5 million and 2 million cells. And the cells in those vials had, on average, the capacity to divide about forty more times. Early on, Hayflick did the math and determined that the newly derived cells covering the floor of just one of his small glass lab bottles, if allowed to replicate until they died, would produce 22 million tons of cells. He had created in those eight hundred vials a supply of cells that for practical purposes was almost infinite.
And so, in addition to their use in vaccine making, the WI-38 cells became the first normal, noncancerous cells available in virtually unlimited quantities to scientists probing the mysteries of cell biology. Because they were easily infected with many viruses, they became important to disease detectives tracking viruses in the 1960s, before more sophisticated technology came along. Biologists still reach for WI-38 cells when they need a normal cell to compare against a cancerous one or to bombard with a potential new drug to see if it’s toxic. The cells are also a workhorse of aging research, because they so reliably age in lab dishes. They are held in such high regard by scientific historians that original ampules of WI-38, and of polio vaccine made using it, are part of the collection of the National Museum of American History.
The Vaccine Race Page 1