“I wanted no time sheets . . . no specified vacations. No departments, no walls behind which petty jealousies, self-interest and pockets of power could flourish,” Koprowski said. “I wanted to attract mature scientists who were talented, experienced—the kind of self-starting, disciplined people who could make it on Wall Street or anywhere else.”40 Koprowski was arguably the best-suited virologist in the world to lure top minds to his new Wistar Institute. He had a near-visionary sense of who was doing original and important work and an astute eye for talent. And he was a networker par excellence. (He once invited the poet T. S. Eliot to tea when he discovered that they were aboard the same transatlantic ship. The poet obliged.)41
Koprowski had carefully cultivated relationships with top scientists from Germany to Sweden to the United Kingdom. But he began by bringing with him to the Wistar several close colleagues from Lederle. When they arrived, they may have questioned their decisions. The building was decrepit. Its hallways were lit by bare hundred-watt bulbs powered by a generator; only small portions of the building connected to the city’s power grid. The new arrivals blew circuits when they plugged in their equipment. David Kritchevsky, a cholesterol expert and Koprowski confidant, later recalled that when he turned on the water in one lab, it ran rust-colored for twenty minutes before a pipe burst and water flooded the floor.42
Koprowski instituted an unprecedented housecleaning. He steam-cleaned the brownstone facade and consolidated the mausoleum-like museum in one wing of the first floor. He sent many anatomical specimens to other museums but relegated the bottle containing founder Isaac Wistar’s brain to a basement storeroom.43 He jettisoned the whale skeleton, sold the famous albino rat colony, and purged the nineteenth-century library, although he ended up keeping its librarian, Bill Purcell, a slight, long-haired freethinker with an extensive collection of erotica.
Koprowski then spent a lot of money—$567,000, or $4.8 million in 2016 dollars—on renovations. Nearly half of it came from the Wistar Institute’s cash coffers. Most of the rest came from the U.S. government. He rewired the building for AC current, repaired pipes, and put in central air-conditioning. He created conference rooms and administrative offices. He purchased autoclaves and centrifuges and an electron microscope. In the basement he installed a big room for washing lab glassware, complete with a fourteen-foot BetterBuilt washing machine. But above all, every possible bit of floor space was dedicated to a score of state-of-the-art labs for virology and biochemistry and pathology—and for tissue culture. For Koprowski’s cadre of outstanding scientists, nothing but the best facilities would do.44
Despite his domineering personality, Koprowski was not a micromanager. His goal was to set his scientists free, in an atmosphere where they were protected from financial worry and teaching obligations, to pursue the scientific questions that obsessed them. The resulting discoveries, he hoped, would vault his Wistar Institute into the pantheon of U.S. research giants, beside the likes of the Rockefeller Institute and Johns Hopkins University. He was making a big gamble by guaranteeing the salaries of his new, top-notch recruits on the assumption that he would find the government and private funding to support them. That project would become his bugbear. But at the outset his inspiration and his promise lured the brilliant minds he was looking for—people like Rupert Billingham, an eminent British transplantation expert, and Eberhard Wecker, a virologist who left his job at the famed Max Planck Institute in Tübingen, Germany, to join Koprowski’s new project.
Koprowski wasn’t thinking of Hayflick as a member of this elite group when he hired him. In his view virologists were the stars of the biological drama. Cell culturists like Hayflick were mere supporting actors, providing bottles of cells for the virologists to use in their groundbreaking experiments. What’s more, the composition of Koprowski’s inner circle—all of them born and, usually, educated abroad—reflected his generally low estimation of American scientists. The slight, serious Hayflick, with his Philadelphia accent and his lack of panache, didn’t fit in with those worldly Europeans. He never would.
Still, Hayflick was given prime real estate: a big, brand-new lab that a visitor could find by climbing the grand wrought-iron staircase in the spacious atrium, stopping at the second floor, turning left, and entering the second door on her right. Inside she would find glistening, glass-fronted cabinets stocked with flasks and pipettes, shiny black countertops, and big windows on the far wall looking west along Spruce Street in the heart of the university campus. Here, under the windows, Hayflick positioned an “inverted” chemist’s microscope that he adapted to cell-culture work soon after he landed at the Wistar. It allowed him, instead of peering downward through a large vessel, to peer upward through the glass bottoms of his culture bottles, focusing at close range on the cells growing there in single layers. (The innovation spread and is ubiquitous in cell-culture labs today. Hayflick’s original inverted microscope was acquired by the National Museum of American History in 2006.)
One wall of the lab was lined with a pair of tiny “sterile” rooms containing not much but black counters with knee space underneath them. The larger of the two could just accommodate two people. Here, in what were the most microbe-free conditions available in the late 1950s, Hayflick and his technicians would work with cultures, flipping on an ultraviolet light in the ceiling when they left at night in the hope that any bacteria lounging on the counters would be dead by morning. (In the morning, avoiding any glance at the UV light, they would crack the door just enough to reach in and flip the switch off. If a worker forgot to do this, as happened occasionally, he or she would later emerge with singed eyelashes and a sunburn.)
Biologists in labs today, where special filters in highly sophisticated hoods suck microorganisms from the surrounding air, might be amazed at the crude additional measures that Hayflick was reduced to in his ongoing battle against contamination. Every few days, before he left for the day, Hayflick would plant petri dishes full of agar on the countertops and leave the UV light off for the night. In the morning he would collect the petri dishes and incubate them. If after a couple of days they had grown one or two bacterial colonies, that was okay. If there were more than that, he would dispatch a technician with a bucket of antibacterial solution to wash down the rooms.
Next door to Hayflick’s lab there was a walk-in room lined with wooden shelves and equipped with a heavy, pea-green metal door. It was an incubation room, where cell cultures could be grown at carefully regulated warm temperatures—often near 98.6 degrees Fahrenheit, which is body temperature. Soon Hayflick was hard at work providing a steady supply of cells to the Wistar’s growing cadre of scientists. Some requests from the staff scientists were easy to fill, like those for the hardy, hugely popular HeLa cells.*
Other requests were tougher to accommodate, such as those for freshly harvested cells from particular rodent organs. These required Hayflick to obtain the animals, sacrifice them, and then coax the cells of the organ in demand to grow in a dish. Hayflick was also kept busy tweaking methods for growing the monkey kidney cells that Koprowski’s group was using in its race to beat Sabin to a live polio vaccine.45
No matter the demands of his job, the hungry Hayflick was not going to be reduced to the role of cell supplier for supposedly greater minds. He began to launch his own experiments. One of the first that occurred to him might sound strange, but to Hayflick it was perfectly natural and obvious, especially because he knew that at least one other group had already succeeded with the same project. Cell biologist Jørgen Fogh and his colleagues Elsa Zitcer and Thelma Dunnebacke at the University of California at Berkeley had developed two continuously replicating cell cultures—known as “cell lines” because they would divide indefinitely in the lab—from a new source. They had used human amnion, the tough membrane that envelops the fluid in which the growing human fetus floats in the womb.46
Ruth Hayflick was expecting the couple’s third child in November 1958. On a foggy, rainy day, i
n the obstetrics department at the Hospital of the University of Pennsylvania—directly across the street from the Wistar Institute—she delivered a baby girl that her parents named Susan. Leonard Hayflick was standing ready near the delivery room, holding a big stainless-steel pan. (Like most fathers in that era, he was not at his wife’s side as she gave birth.) When Susan was safely delivered, Hayflick collected the heavy, bloody, purple placenta.
He walked with it for five minutes: out of the delivery suite, through the hospital, and across Spruce Street to the Wistar. It was the Wednesday evening before Thanksgiving and he had the lab to himself. He liked it that way. Working in one of the sterile rooms, he dissected away from the placenta the strong, semiopaque amniotic membrane. He placed it in a solution of trypsin, a digestive enzyme collected from the pancreas of slaughtered pigs. The trypsin readily broke the amnion into its component cells.
That December, as the Hayflicks navigated Hanukkah and Christmas with a two-year-old, a one-year-old, and a newborn baby, the cells from Susan’s amnion incubated in small flasks in the warm room beside Hayflick’s lab, bathed in a nutritious medium of salts, amino acids, vitamins, and calf serum—the fluid component of calf’s blood. Hayflick had already named the cells: WISH, for “Wistar Institute, Susan Hayflick.”
On New Year’s Eve Day that year, Hayflick peered into his microscope at the dividing WISH cells and discovered that they didn’t look at all normal. They showed typical signs of having become cancer cells. In the paper he published about the cells, Hayflick used the cells’ volume and multiplying time to calculate that they must have become cancerous not while Susan was in the womb but when one cell mutated on or about December 21, 1958. That mutation, he proposed, had made that single cell far better able to proliferate in lab conditions than the normal cells, which were soon overrun entirely by the furiously multiplying cancer cells.47 (Hayflick did not commence to worry about Susan’s health; by now it was clear that cells in lab bottles often developed abnormalities, presumably related to their lives in the lab.)
Several years later a geneticist named Stanley Gartler at the University of Washington revealed that WISH, along with many other cell lines used in the 1950s and 1960s, had been contaminated with cancerous HeLa cells, which were so vigorous and hardy that they easily infected other cultures where they didn’t belong.48 As Wistar’s resident cell culturist, Hayflick supplied HeLa cells to Wistar scientists, including Koprowski’s polio researchers, who used them to measure the levels of polio virus in vaccines.49 So it is easy to imagine how cross-contamination might have occurred.
Hayflick is adamant to this day that his WISH cells were not invaded by HeLa. Someone else, in some other lab, must have obtained them and contaminated them, he said in a 2014 interview, and then sent them into the cell banks that today advertise them to biologists marked with the prominent warning that they are actually HeLa cells. Gartler, in 2016, begged to differ. “It is clear from Hayflick’s paper [first describing the derivation of the WISH cells] that they were already contaminated,” he wrote in an e-mail.
True to her beginnings, Susan Hayflick grew up to become a medical doctor and an expert geneticist. Today she is a professor of molecular and medical genetics, pediatrics, and neurology at the Oregon Health & Science University in Portland.
CHAPTER FOUR
Abnormal Chromosomes and Abortions
Philadelphia, 1959
The practice of abortion in American hospitals is inequitable, inconsistent, and largely illegal. The basic reason for this is that this aspect of twentieth-century medicine is being governed by nineteenth-century laws.
—Robert E. Hall, an obstetrician and gynecologist at Columbia University in New York, 19671
On an exceptionally lovely weekend in April 1959, with the Wistar Institute’s impressive renovations recently completed, Koprowski threw his born-again institute a coming-out party. In typical Koprowski fashion, it was a big, bold, first-class affair, kicked off by a VIP dinner under the vaulted ceiling and among the hieroglyphic-inscribed pillars of the Egyptian Room of the university museum.
That weekend the institute’s new labs were formally opened, and five hundred biologists packed a two-day symposium entitled “The Structure of Science,” where they were treated to a star-studded list of speakers. These included dignitaries like the mayor of Philadelphia, the U.S. surgeon general, and the president of the National Academy of Sciences, as well as top scientists like Peter Medawar, the British transplantation expert who would win a Nobel Prize the following year—and whose younger partner, Rupert Billingham, Koprowski had already recruited to the Wistar as part of his A-team of scientists. But the most buzz may have been around the presence of Francis Crick, who, with James Watson, had described the structure of DNA only six years earlier. (Barbara Cohen, the young lab technician who was working for Koprowski at the time, asked to recall the event fifty-five years later, remembered only being dazzled by Crick’s presence.)
Hayflick also launched something new that April.2 He began pursuing a question that was swirling in the scientific air and that had begun to intrigue him too. Could viruses cause cancer in humans? The notion that viruses might be implicated in the dread disease was not a new one. As early as 1842, Domenico Rigoni-Stern, an observant surgeon in Padua, Italy, noted that nuns, shut away as they were from the world’s temptations, were afflicted with cervical cancer far more rarely than other women.3 There were no tools available to test the implication of his observation—that a sexually transmitted agent might cause the disease. The first hard evidence for a viral role in cancer didn’t come until 1908, when two scientists at the University of Copenhagen, Vilhelm Ellerman and Olaf Bang, showed that healthy chickens infected with fluid from chickens with leukemia—fluid filtered to remove cells and bacteria—contracted leukemia.4 Their finding might have garnered more notice if it had been more widely recognized at that time that leukemia was a cancer.
But three years later a young American pathologist named Peyton Rous, working at the Rockefeller Institute, showed that a virus caused chicken sarcoma—a malignant tumor of connective tissue. Rous had taken fluid from a sarcoma in one chicken, filtered it—again, the ultrafine filter caught bacteria but not viruses—and injected it into other chickens, which then grew the same cancer. The young scientist was greeted mostly with indifference to his discovery that cancer could be transmitted between the chickens “by an agent separable from the tumor cells.”5 It wasn’t thought that a finding about chicken cancer could be relevant to human beings. Rous’s “agent” would later be named Rous sarcoma virus and would play a huge role in the study of cancer causation.
Conventional wisdom among biologists in the first half of the twentieth century held that cancer was caused by environmental factors, like smoking or chimney soot or, according to others, by gene mutations. As late as the mid-1950s, the influential Australian biologist Frank Macfarlane Burnet, who in 1960 would win a Nobel Prize for his work in immunology, pointedly dismissed the notion that viruses could cause cancer.6 However, by 1959, when Hayflick tackled the question, many biologists were pushing back, even against the likes of Burnet. They had ammunition in the fact that, over the decades since Rous’s discovery, more than a dozen viruses had been discovered to cause either benign or malignant tumors in a variety of animals, including rats, mice, and cats—if not in humans. Then, in 1958, an Irish surgeon named Denis Burkitt threw a tantalizing new piece of information into the mix. He discovered an aggressive childhood lymphoma in sub-Saharan Africa. Its distribution, in malaria-ridden areas, suggested an infectious cause. The same year, the National Institutes of Health (NIH) launched a well-funded effort to track down human “cancer viruses.”
Koprowski began organizing, with other leading scientists including Rous, an American Cancer Society conference on the subject of viruses and cancer causation. In July 1959 Time magazine ran a cover story featuring two researchers from the NIH, Bernice Eddy and Sarah Stewart, w
ho had discovered a mouse virus that caused tumors in hamsters, rabbits, and rats. “The hottest thing in cancer is research on viruses as possible causes,” John Heller, the chief of the NIH’s cancer institute told Time.7
Hayflick recognized that he had a skill set that equipped him well to tackle the topic: he knew a good deal about microbiology, and he knew more than most scientists about growing cells in the lab. He went at the question with the traits that defined his style: thoroughness, patience, determination, and an outsized tolerance for seemingly mundane, repetitive work. (Some former colleagues call his style unimaginative, dogged, and plodding.)
With the help of a surgeon named Robert Ravdin, across the street at the Hospital of the University of Pennsylvania, he got hold of 300 human tumor samples and coaxed 225 of them to grow in lab dishes bathed in nutritious medium.8
Hayflick’s next step was based on a reasoned assumption: if any of these tumors were caused by a virus, that virus was likely still lurking within them, replicating itself inside the cells and then bursting or budding out, flooding the surrounding fluid medium with millions of individual virus particles. Hayflick began collecting samples of that lab-dish fluid and freezing it.
When he was ready, his next step would be to thaw that fluid and pour it over noncancerous cells in culture. If cancer-causing viruses were in the fluid, then it stood to reason that they might infect some of the normal cells, causing them to become cancerous. But where to get certifiably noncancerous cells that could survive and multiply in the lab?
Fortunately for Hayflick, there was now a new benchmark for normalcy in cells. In a classic 1956 paper, “The Chromosome Number of Man,” Albert Levan and Joe Hin Tjio, two scientists working in Lund, Sweden, had used a new microscopic technique to pin down the normal number of human chromosomes.9 Biologists now knew beyond doubt that normal human cells had, residing in their nuclei, forty-six chromosomes: twenty-three inherited from each parent. A cell that carried this normal complement of chromosomes was called a “diploid” cell. (The only normal human cells that don’t carry forty-six chromosomes are sperm and eggs, which, because they carry half as many chromosomes, twenty-three, are called “haploid.”)
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