No one had tried growing polio in human cells. Since polio attacked the nervous system to cause paralysis, Sabin and Olitsky surmised that it would grow in nerve cells. And so they minced the fetal brains and spinal cords and placed the resulting bits of tissue in wide-bottom flasks. Then they added poliovirus from the ground-up spinal cords of infected monkeys. The virus multiplied in the fetal nerve cells—as proven by the fact that when the scientists took fluid from the cultures bathing the fetal cells and injected it into the brains of monkeys, the animals became paralyzed.
Ironically, the paper that Olitsky and Sabin published actually slowed the hunt for a polio vaccine. Why? Because the Rockefeller duo also reported “complete lack of growth” of polio in cultures of other organs from the fetuses, including kidneys and lungs. The “special affinity of the virus for nervous tissue” disqualified the virus for vaccine-making purposes, because viral vaccines contain tiny bits of the cells in which they are made, and nerve cells, when injected into people, were known to occasionally cause a dangerous and sometimes fatal allergic reaction: an inflammation of the brain and spinal cord called encephalomyelitis.
And so very little progress against polio was made until twelve years later, at the Enders lab in Boston. Early in 1948 Enders, Weller, and Robbins were deep into studies trying to grow mumps, measles, influenza, and chicken pox viruses in culture. Enders had called on a physician colleague at the Boston Lying-In Hospital, to provide aborted embryos and fetuses.
He received several from abortions conducted at 2.5 to 4.5 months of pregnancy, as well as a stillborn infant delivered at seven months of pregnancy. Weller minced the skin, muscle, and connective tissue from the fetal arms and legs and distributed it in flasks. The plan was to inoculate the flasks with chicken pox virus from the throat of a sick child. But as they were preparing to do so, Enders casually suggested that Weller and Robbins also inoculate an equal number of flasks with poliovirus from infected mouse brains that were also on hand in the lab. The experiment was timely because virologists, Enders among them, were beginning to doubt the handed-down wisdom that polio would only grow in nervous tissue. For one thing, the virus was being found in quantity in the feces of polio-infected people. Enders was skeptical that a virus that resided strictly in nerve cells could turn up in such profusion in the intestinal tract.
The chicken pox cultures grew nothing. But the poliovirus grew spectacularly, and when the scientists injected fluid from the polio flasks into the brains of mice and monkeys, they became paralyzed. The Enders lab had made an enormous leap. It turned out that Sabin and Olitsky had failed in their experiments thirteen years earlier because they were using a particular strain of polio that would grow only in nerve tissue. Other strains were far less choosy.
The momentous discovery was described in a short article buried in the back of the journal Science in January 1949.11 When polio virologists saw the report, “it was like hearing a cannon go off,” Rivers, the dean of U.S. microbiologists, recalled later.12 Not only had they cornered polio, but Enders and his colleagues had delivered the methods that would allow scientists to grow, without limit, many kinds of viruses in many kinds of tissues.
The Enders lab’s breakthrough soon made possible the isolation of scores of new viruses—including viruses that infected only humans and grew only in human cells. And scientists could now readily study the effects of those viruses on cells in the lab, rather than in living animals. Of most immediate import for the public, the discovery also made possible within a few years the industrial-scale growth of poliovirus in nonnervous tissue in lab dishes, allowing the development of polio vaccines.
In 1954 the Nobel Committee in Sweden honored Enders, Weller, and Robbins with that year’s prize in physiology or medicine. Their discovery had thrown open the doors to virology. It also made tissue culture a vital part of coming advances. He didn’t know it yet, but Leonard Hayflick would land squarely in the middle of the new push forward.
• • •
Hayflick graduated from the University of Pennsylvania in the spring of 1951 with a BA in arts and sciences and a double major in microbiology and chemistry. He went to work as a research assistant at a drug company called Sharp & Dohme in Glenolden, a Philadelphia suburb. There he helped make a product to dissolve clotted blood and pus in infected surgical wounds. Soon Sharp & Dohme merged with the big drug company Merck, which had built a brand-new research facility twenty-seven miles northwest of Philadelphia in West Point.
Sharp & Dohme had been something of a scientific backwater. At the state-of-the-art Merck labs Hayflick was exposed to new and exciting things. He began to learn about viruses like bacteriophages, which attack and invade bacteria. He saw firsthand the excitement of the hunt for new antibiotics at a time when the drugs were transforming medical practice. He also saw for the first time highly educated commercial scientists in action. A revolutionary ambition began to take hold in Hayflick’s head and heart. He had never let himself consider getting a PhD.13, 14
Hayflick applied and was admitted to the doctoral program in medical microbiology at the University of Pennsylvania. He enrolled in the fall of 1952. He had saved enough money to pay the tuition and to get by if he continued to live at home. After his first year in the program, he would receive university scholarships and a fellowship that supported him through the rest of his PhD studies.
Just before Hayflick left Merck, Sharp & Dohme in June 1952, he met a talented young artist who worked preparing slides for scientists at the West Point facility. The pair discovered that they both planned to travel in Europe that summer and that their separate itineraries had them crossing paths in Paris.
Ruth Louise Heckler was a slim, self-assured twenty-six-year-old with a broad smile and a quiet demeanor that comported well with Hayflick’s own. She was from a churchgoing Pennsylvania Dutch family in Lansdale, a railroad town not far north of Philadelphia, where her father worked as an accountant for the Lehigh Coal & Navigation Company. She had studied life drawing and book illustration at the Philadelphia Museum School of Industrial Art before coming to Merck.
Heckler was drawn to Hayflick’s mind—his ability to analyze problems clearly and quickly.15 He was drawn to her quiet self-assurance, her intelligence, and her questioning of religious authority; she had rejected the Lutheranism of her childhood and begun attending Quaker meetings. He also found her beautiful: one day as they walked in Paris, he put his arm around her waist. On October 2, 1955, with Hayflick in the final year of his PhD, the couple were married in a simple, intimate service at the 150-year-old Arch Street Friends Meeting House in Philadelphia. There was a dry reception in the hall next door, and then the newlyweds walked to a nearby Reform synagogue on Broad Street, where a rabbi blessed their union.
• • •
For his PhD thesis Hayflick studied a mysterious group of microbes then called pleuropneumonia-like organisms, or PPLOs. (They have long since been renamed Mycoplasma.) These microbes had been known for two centuries to cause a highly contagious pneumonia in cows in Europe, but they were still poorly understood. Too large to be viruses and yet smaller than bacteria, they defied categorization and their links to other animal and human diseases were murky.
Hayflick was intrigued by PPLOs and grew to be equally taken with the newly exciting art of tissue culture. His graduate mentor—assistant professor Warren Stinebring, a soft-spoken, stocky former college football player—was full of energy about a course he had just taken in tissue culture, one of the first of its kind. He wanted to train Hayflick. Hayflick didn’t want to be distracted from his PPLOs but agreed to a compromise: for his thesis project he would grow PPLOs in tissue culture. Hayflick was working in primitive conditions by today’s standards. He grew his PPLOs in a chicken incubator bought for less than $40 from a Sears Roebuck catalog.
Early in his graduate studies Hayflick began to spend time at a nearby institute that would have a huge and lasting impact on his
professional life. He recalls being asked to investigate an outbreak of a middle-ear infection in a famous colony of pink-eyed, snow-white research rats. The albino rats were known to all as Wistar rats, because they were developed and resided at the Wistar Institute of Anatomy and Biology. They were an important laboratory tool, but the infections had upset their balance and left them spinning in purposeless circles. PPLOs were possibly the culprit.
The Wistar, as people called it, was a gracious, V-shaped, three-story building of light brown brick located on prime real estate in the heart of the University of Pennsylvania campus. A stone’s throw from the iconic statue of Benjamin Franklin on Penn’s main quad, the institute was the oldest freestanding biological research organization in the country. It was completely independent of Penn, having been founded in 1892 by a wealthy, eminent Philadelphia family. The Wistars included Caspar Wistar, an eighteenth-and-nineteenth-century physician and anatomist who wrote the first U.S. textbook of anatomy and in the process amassed and preserved a huge number of anatomical specimens. Caspar Wistar’s great-nephew, Isaac Wistar, a Civil War brigadier general and a prominent Philadelphia attorney, established and endowed the institute to preserve and display his great-uncle’s impressive collection.16
The brain of Isaac Wistar—at his request—was preserved in a big glass jar in the basement of the institute, along with his right arm, shriveled from a Civil War wound. His ashes were, and still are, in an urn that overlooks the atrium. (If officials of the newly founded institute had had their way in the 1890s, they would also have displayed the gray matter of the psychopath Henry Holmes. The Wistar tried without success to obtain his brain for study after the hanging of the serial killer who haunted the 1893 Chicago World’s Fair.)17
In the mid-1950s the Wistar Institute was a strange mix of faded elegance and creepiness. It boasted terra-cotta detail on its facade, an airy atrium surrounding a broad wrought-iron staircase, and a public museum on the first floor that was the stuff of horror movies. There were reptiles from Borneo and the bladder stones of Chief Justice John Marshall (removed without benefit of anesthesia). There were human bones gathered on the field after the 1815 Battle of Waterloo and a wide selection of human skulls used to teach medical and dental students. There were seven wax-injected human hearts. There was an intact skeleton of what had been Siamese twins. And floating in formalin, in patented display cases, there was the largest collection of embryos and fetuses in the country, many of them with abnormalities like clubfoot and cleft palate.18
But despite the crowds of schoolchildren who regularly trooped through the locally famous museum, the Wistar Institute in the mid-1950s was slowly dying from decades of neglect. Its wiring and plumbing were failing. Its senior staff comprised exactly three scientists, two of them in their eighties. And since 1940 its inertia-ridden board of managers had left the institute to be run by a less-than-ideal acting director. Perceiving the lack of leadership, junior scientists came and went very quickly.19
This acting director—a short, quick, domineering man named Edmond Farris—was a middling PhD scientist and not a physician at all, but he had made himself indispensable to certain Philadelphia couples by launching an infertility clinic that he ran out of the Wistar, fueled by the sperm donations of University of Pennsylvania students.20 In addition to artificial insemination, Farris’s services included microscopic examination of the male partner’s sperm for deficiencies. He also ran pregnancy tests by injecting a woman’s urine into a prepubescent female rat from the Wistar colony. If the rat went into heat despite its immaturity, that indicated the presence in the woman’s urine of a female hormone made only during pregnancy. (Early in 1956, two decades before home pregnancy tests were available, Hayflick and his wife took advantage of the in-house services. The couple’s first child, Joel, arrived later that year.)
The lab that Hayflick chose for pursuing his rat assignment, on the otherwise-empty second floor, had antique Bunsen burners and wrought-iron filigree. Hanging outside the door, suspended from the high ceiling of the atrium, was the skeleton of a seventy-foot finback whale sold to the institute in 1897 by the renowned paleontologist Edward Drinker Cope.21 Far from putting him off, the eerie, empty environs fascinated Hayflick, who enjoyed working alone in the lab on the second floor or thumbing through the collection of ancient scientific books in the eighteen-thousand-volume library. Occasionally he encountered one of Edmond Farris’s happy customers climbing the wrought-iron staircase with a new baby in her arms.22
In the spring of 1956 Hayflick received his PhD. He had, indeed, shown that PPLOs could be grown in tissue culture.23 (He also confirmed that a PPLO had sickened the Wistar rats.) He was no longer an uncertain undergraduate. And he had new, outside affirmation of his abilities. He had won a postdoctoral fellowship endowed by A. C. McLauglin, a Colorado oil tycoon. It would take him to Galveston, Texas, to the lab of Charles Pomerat, the man who was arguably the best tissue culturist in the world. The fellowship paid a considerable sum in Hayflick’s world: $5,500, tax free. He and Ruth moved to Galveston in August 1956.
• • •
The charismatic Pomerat, a bald, portly man who wore a butcher’s apron and favored white duck trousers, ran a big lab in the basement of the psychiatry building at the University of Texas Medical Branch in Galveston. It was a place that hummed with activity, its tone set by its chatty leader, who was not only a pioneer cell culturist but also an outstanding chef and an accomplished artist. Pomerat had pioneered a new tool: time-lapse microscopic photography of cells in action, with exposures made every thirty or forty seconds and rendered on reel-to-reel films.
At any given time Pomerat would have several cameras peering down long tubes running down to the microscopes, where they focused on cells in a minuscule chamber. The lab was full of a constant clicking of shutters and attendant flashes of light emanating from the tops of the microscopes.
Hayflick used the cameras to study adenoviruses, a class of viruses that had recently been discovered in human tonsils and in the adenoid tissue after which they were named: glandular tissue in the back of the throat. He was able to observe the effects, hour by hour, as adenoviruses destroyed cells. Holes would appear in the cells’ cytoplasm; the cells would sprout abnormal, armlike extensions. Finally, they would break apart. Hayflick did not make any grand discoveries in Galveston, nor could he publish in journals the reel-to-reel films he produced. But he became increasingly expert in cell culture, and he rubbed shoulders with and learned from first-rate scientists like Morris Pollard, an eminent virologist. Hayflick also met a colleague of his own age who would play an important part in his career. Paul Moorhead was a blue-eyed Arkansan with adamantly liberal politics and a passion for chromosomes—the long, stringy bundles of DNA that are housed in a cell’s nucleus and contain its genetic material.
Ruth gave birth to Joel in November 1956. The Hayflicks’ second child, Deborah, was born thirteen months later, while Hayflick was still in the Pomerat lab. Once or twice a night he would wake, give a bottle to a baby or two, then drive to the lab to adjust the microscope, which would inevitably slide out of focus after a few hours.
Early in his second year in Galveston, Hayflick began looking toward his next step. He heard that the Wistar Institute, after nearly two decades under an acting director, had finally hired a permanent chief. He was a polio vaccine pioneer named Hilary Koprowski, and he was looking for a cell culturist. Hayflick applied and received an offer. It was “scut work,” providing cell cultures to Wistar scientists, and not the pure research position he would have preferred.24 Still, it could lead to bigger things, and he was sure he could squeeze in his own research on the side. It would also take him and Ruth back to their families and friends in Philadelphia. He began work at the Wistar, his old stomping ground, in April 1958, one month shy of his thirtieth birthday.
CHAPTER THREE
The Wistar Reborn
Philadelphia, April–December 1958
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I told this guy, I said, “You know, Hilary Koprowski is Wistar. . . . Hilary built the Wistar. No matter what you think about him, it’s great because of Hilary.”
—Maurice Hilleman, former Merck vaccine chief, in a 2004 interview1
Hilary Koprowski was a brilliant, erudite, Polish-born virologist who was equal parts disarming charm and ruthless ambition. He was a short, stocky man with prominent cheekbones and light, piercing eyes. He spoke with a marked accent. A polymath who quoted the poets Arthur Rimbaud and Ezra Pound as fluently as he discussed viruses and antibodies, Koprowski was a graduate of the Warsaw Conservatory of Music who had considered a career as a concert pianist at the same time as he pursued a degree at the Warsaw University Medical School. A magnetic combination of old-world romantic, ambitious, forward-thinking scientist, and gregarious bonhomme, Koprowski was equally at home playing cards on the floor of a young technician’s apartment or wining and dining Europe’s finest biologists. Wherever he was, he made a lasting impression—as he did on the lab technician Barbara Cohen, who was twenty-one years old when Koprowski hired her as the first member of his polio research group at the Wistar. “He would just fix you with these ice blue eyes, just, like, freeze you,” Cohen recalled in a 2014 interview. “He would just be intensely in your presence.”2
“When he wished to charm, he was gay and confidential, his eyes flashed warmly, he used your Christian name like a caress, he would take you by the arm as if you and he were the only two people who mattered, two superior beings in a rather ridiculous, muddleheaded world,” the author John Rowan Wilson observed.3A consummate networker, Koprowski was nonetheless not above sneaking out the back door of his lab into an adjoining lab’s sterile room when a boring visitor arrived at his receptionist’s desk. His eyes would sparkle and his voice dance with delight so that “you could not be cross with him” as he dished up choice remarks about the person he was avoiding, recalled Ursula Roth, a Koprowski technician in the mid-1960s.4 Nor did Koprowski shy from foisting an eminent but dull British scientist on his junior colleagues for the day, before taking that scientist home to an elegant dinner. He was hoping for a return invitation, because the colorless colleague owned a piano on which Beethoven had composed a sonata and on which Koprowski longed to lay his strong, stout fingers.5
The Vaccine Race Page 4