The Vaccine Race

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The Vaccine Race Page 7

by Meredith Wadman


  During the 1950s scientists had launched dozens of cell lines from apparently normal human tissue. But with time—sometimes with very little time—these cells began to behave strangely. They displayed bizarre, disorganized shapes and sizes and bloated nuclei. And they developed abnormal numbers of chromosomes. There were lab-grown knee-joint cells with 133 chromosomes, liver cells with anywhere between 65 and 90 chromosomes, and foreskin cells with 72 chromosomes—the last from a four-day-old baby.10 To Hayflick and his contemporaries, such changes signaled one thing: cancer.*

  Abnormal chromosomes had first been associated with cancer seventy years earlier, in 1890, when a young German pathologist named David Paul von Hansemann first recognized chromosomes in abnormal configurations in dividing cancer cells.11 Von Hansemann, peering through a microscope, saw in cancer cells split, frayed, broken chromosomes and chromosomes that hadn’t doubled in number, as they normally should before cell division, but rather tripled or quadrupled. Not long after this, another German scientist, Theodor Boveri, after studying aberrantly fertilized sea urchin eggs, proposed that abnormal numbers of chromosomes resulted when the stringy DNA packages didn’t segregate themselves properly during cell division. The resulting cells, he suggested, might ultimately tilt into uncontrolled growth.12 But with the tools on hand at the time, he had no way of proving his hunch.

  It would be 1960 before two researchers, working near Hayflick in Philadelphia, discovered the first link between a chromosomal aberration and a cancer. Peter Nowell, a tumor biologist at the University of Pennsylvania School of Medicine, and David Hungerford, a graduate student at the Fox Chase Cancer Center in Philadelphia, examined the bone marrow cells of adults with chronic myelogenous leukemia, a blood-cell cancer. In almost all of the patients, chromosome 22 was abnormally short. They christened this chromosome, with its lopped-off head, “the Philadelphia Chromosome.”13 Their discovery confirmed what many scientists had long suspected: cancer was, at least in part, a disorder of genes gone awry.

  For Hayflick in 1959, even before the discovery of the Philadelphia Chromosome, the aberrant chromosome numbers in these dozens of lab-launched cell lines presented evidence enough that the cells were not normal and would not do for his experiment. Yet as he confronted a paucity of normal cells that had been launched in lab dishes, he did have some indication that the feat was not impossible. Tjio, the codiscoverer of the normal number of human chromosomes, had since moved from Sweden to the University of Colorado, to the lab of another leading scientist there named Theodore Puck. Together the pair had grown apparently normal cells from patients, or their leftover surgical tissues. They had created cell lines from the uterus, the testis, and the prepuce, a fold of skin surrounding the clitoris. They reported that the cells from each line still had forty-six chromosomes and that those chromosomes looked normal under the microscope, even after five months of vigorous dividing in lab dishes.14

  Even so, Hayflick had reservations about using leftover surgical samples, or even skin samples from volunteers, to try to grow normal cells in lab bottles. As a microbiologist he was well aware that cells from any human being who has been on the planet for any length of time are potentially contaminated with disease-causing viruses. He had seen firsthand during his time in Galveston the adenoviruses that lurked in people’s tonsils and adenoids. Herpes simplex virus was known to lie latent in nerve cells. Hepatitis viruses were assumed to simmer quietly in livers, and scientists were discovering all manner of rhinoviruses—a major cause of the common cold—inhabiting human noses and throats. It would be pointless to expose cells obtained from adults to the fluid that had bathed his cancer cells in the lab. If the ostensibly normal cells became cancerous, he wouldn’t know if this was due to a virus from the fluid or to some hidden virus already residing in the cells. However, there was one obvious source of tissue that, while not absolutely guaranteed to be virus free, was far more likely to be clean.

  A fetus is protected in the womb. Tucked away in its mother’s body, it isn’t exposed to the raft of illness-inducing microbes that babies and toddlers meet on diaper-changing tables, in preschool classrooms, and on kitchen floors. What’s more, when its pregnant mother is exposed to unwelcome bacteria and viruses, the fetus is protected from most of them by its mother’s germ-attacking antibodies and her invader-targeting immune cells. Those malevolent microbes that aren’t dispensed with in the mother’s throat, digestive tract, and blood can still be attacked in the fetus, because some maternal antibodies cross the placenta. There are exceptions: a handful of disease-causing viruses can escape immune defenses and infect the growing fetus. But compared with the viral exposures of adults, the odds of any one of these affecting a given fetus are remote. In particular, Hayflick in 1959 did not have to worry about one such virus that is notorious today: HIV. So as Hayflick cast about for the cleanest tissue he could find, he kept circling back to a conclusion that seemed inevitable: growing cells from aborted fetuses was his best bet for developing normal human cells.

  • • •

  As the work of Albert Sabin and John Enders and their colleagues in the 1930s and 1940s makes clear, Hayflick was not the first scientist to turn to aborted fetuses to probe a biological question. He himself, while working as a graduate student at the Wistar in the mid-1950s, had seen fetuses waiting to be taken to the incinerator in the Wistar courtyard after being dissected for experiments using cells from fetal pituitary glands. As he completed his graduate studies, scientists in Stockholm were using cells from aborted human fetuses in what became a failed effort to make the first human cell–based polio vaccine. And Levan and Tjio, also working in Sweden, had examined lung cells from four aborted fetuses to pin down the normal number of human chromosomes.

  As he looked for a source of aborted fetuses, Hayflick was operating in one of two parallel universes that existed in the United States in 1959. According to the law, abortion was a criminal offense in every U.S. state. The 1939 statute that was on the books in Pennsylvania, unlike those in the other forty-nine states, didn’t even make an exception if the woman’s life would be endangered by carrying a pregnancy to term.15 It read:

  Whoever, with intent to procure the miscarriage of any woman, unlawfully administers to her any poison, drug or substance, or unlawfully uses any instrument, or other means, with the like intent, is guilty of felony, and upon conviction thereof, shall be sentenced to pay a fine not exceeding three thousand dollars ($3,000), or undergo imprisonment by separate or solitary confinement at labor not exceeding five (5) years, or both.16

  If the fetus died—in other words, if the abortion was successful—the penalty for the person who performed the abortion was doubled to $6,000 and ten years in solitary confinement at labor. The harsher penalty also applied if the mother died during the procedure.17

  The law conspicuously failed to define an “unlawful” abortion; the very word suggested that if there were “unlawful” abortions there might also be “lawful” procedures. That ambiguity, however, did not stop Pennsylvania authorities from taking enforcement seriously. They prosecuted both unqualified, back-alley operators and physicians who operated as solo providers: people like Lamar T. Zimmerman in Montgomery County (which includes Philadelphia’s upscale northwestern suburbs), a physician who was convicted in 1967 of performing an illegal abortion; and Benjamin King, MD, of Allegheny County (which encompasses Pittsburgh), who was sentenced to two to five years in prison in 1968.18

  At the same time in a different setting—the Hospital of the University of Pennsylvania and other major hospitals that comprised the other, parallel universe—legal authorities tolerated abortion. They were carrying on a tradition that had evolved over decades, beginning as early as 1867. Then, an Illinois law declared that abortion was criminal “unless done for bona fide medical or surgical purposes.” It didn’t define those purposes but left it to the medical profession to do so.19

  The term “therapeutic abortion” came to be use
d to describe those abortions that were understood—at least by supportive physicians and legal authorities—not to be criminal. A therapeutic abortion was performed by a qualified doctor who judged it necessary, even if the reasons for that necessity floated in a legal gray zone that would not finally be dispelled until the 1973 Supreme Court decision in Roe v. Wade. In that landmark ruling, the high court struck down state criminal laws and said that, except to protect the mother’s health, states could not restrict abortions before fetuses became capable of meaningful life outside the womb.

  In the early decades of the twentieth century, so-called therapeutic abortions were performed in doctors’ private offices and in homes. During the 1930s they migrated increasingly to clinics and hospitals, and their numbers grew as women responded to the crushing economics of the Depression.20 In Philadelphia, however, access was clearly limited: a survey presented to the Obstetrical Society of Philadelphia reported that 329 women died in the city from self-induced or nonphysician-induced abortions between 1931 and 1940, or about 10 women for every 1,000 babies born.21

  The growing numbers of physician-assisted abortions led states to enact tighter abortion laws, like the 1939 statute in Pennsylvania.22 In turn, doctors and hospitals moved to try to protect themselves legally. In the 1940s and 1950s they set up what they called “therapeutic abortion committees” in hospitals. The committees were made up of small groups of doctors appointed to officially receive and evaluate abortion applications.

  The Hospital of the University of Pennsylvania—HUP for short—was a huge, imposing institution whose sheer, ten-story brick facade towered over the south side of the Ivy League university’s campus in west Philadelphia and, at certain times of the day, literally cast its shadow on the Wistar Institute. The oldest university-owned teaching hospital in the country, HUP was established in 1874. By 1959 it had accrued all the power that came with being the most prestigious hospital in Philadelphia.

  Like many major hospitals, HUP had put a therapeutic abortion committee in place by 1955, and possibly earlier.23 One doctor who performed abortions as an obstetrician/gynecologist at HUP in the late 1950s through 1962 recalled the committee as a casual group in a 2014 interview. “Frankly, if a patient wanted an elective abortion, you simply called a colleague or two and said, ‘Would you approve this?’ The committee never even really met. . . . If it ever came to a legal issue . . . we could say we talked on the phone” and approved it.24

  But by 1963 that relaxed approach had changed, for reasons that aren’t clear. Written rules approved by the hospital’s medical board that year required that the committee receive written applications from physicians proposing to perform an abortion. Each of three anonymous obstetrician/gynecologists serving on the committee was required to issue a written opinion on each application. In cases where it was appropriate, a different kind of specialist, often a psychiatrist, could be enlisted to pass judgment on an application. If a member of the committee wished, he—and it was almost always a “he”—could interview and examine the patient.25

  Women who saw private doctors—that is, women who were, in general, wealthier, whiter, and better connected—were far more likely to obtain abortions through the committee than so-called clinic patients—poorer, often black patients who were seen at the subsidized, hospital-based outpatient clinic that HUP operated. Still, by the late 1950s it was increasingly difficult for women of any color to get therapeutic abortions, whose numbers dwindled in the conservative climate of the 1950s.26 That did not change in the 1960s. One educated estimate published in 1967 put the ratio of illegal abortions to hospital abortions at one hundred to one.27

  As Hayflick remembers it, he was able to begin obtaining fetuses in 1959 because of Hilary Koprowski’s connection to Isidor Schwaner Ravdin, HUP’s surgeon in chief and the vice president of medical affairs at the university.

  If the Hospital of the University of Pennsylvania was the preeminent hospital in the city, I. S. Ravdin—“Rav,” as he was known to close colleagues—was the preeminent power in the hospital. He had been chair of HUP’s Department of Surgical Research since 1935—though he may have been prouder of his stint building and running a jungle hospital in Burma during World War II. A short, mustachioed man with dark, receding hair and preternatural energy—his secretary at the time, Betsy Meredith, remembers him as “like a pea on a hot griddle”—Ravdin terrified medical students and residents alike and was used to his orders being obeyed immediately, if not sooner.28 His influence extended well beyond HUP to the halls of power in Washington. In 1956 he was photographed on a podium at the Republican National Convention, triumphantly raising the hand of President Dwight D. Eisenhower.29 Two months earlier, Ravdin had been summoned to Washington to operate on Eisenhower, who had developed a life-threatening bowel obstruction. By 1959 Ravdin was busy hatching a grand, new 374-bed building extending HUP, named after himself.

  Supplicants coming to see Ravdin would watch him pull out a Dictaphone and fire off a letter that would result in whatever string they wanted pulled in the vast machinery of the hospital getting pulled—or not. One of these requests, according to Hayflick, came from Koprowski, who asked for the ferrying of aborted fetuses to an obscure junior scientist at the Wistar Institute.

  Ravdin was a consummate political player in matters of sexuality, contraception, and abortion. He had to be. In heavily Catholic Philadelphia the church was a hugely powerful presence, always hovering in the background of hospital and university politics. When the medical school set up a Division of Family Studies in 1952, the division’s affiliation with the liberal Marriage Council of Philadelphia caused the medical school dean to write to Ravdin, flagging concern “that this plan might be mis-interpreted by the Catholic Church as being concerned with birth control.”30

  Still, by 1960 the church and society at large were confronting a wave of change. At HUP it appeared one morning in the form of bright orange flyers blanketing the hospital’s huge Gates Pavilion. THE ROMAN CATHOLIC CHURCH AND THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA, ran the title on the eight-by-eleven-inch sheets, which complained vociferously that even Jewish and Protestant patients seen by hospital doctors couldn’t get fitted for diaphragms owing to pressure from the church.31

  The flyers provoked a flurry of letters between hospital higher-ups—not refuting their truth but trying to figure out who had used hospital paper and mimeograph machines to make them. (It appears that the culprits were never found out.) “It is, as you can see, an inflammatory statement and might very easily get the University into several embarrassing situations,” Ravdin wrote to Franklin Payne, the chairman of the Department of Obstetrics and Gynecology. “The paper which was used . . . has also been used in your Department, with a mimeograph machine similar to that which your Department has.”32

  Privately Ravdin very likely agreed with the flyers. But his job was to protect his institution, and in the effort he steered a careful path between women’s-rights advocates on one side and, on the other, the church. He was photographed beaming at Pope Pius XII in Rome in 1958, in a moment that he recalled as a “wonderful occasion.”33 Still, when he was invited to a Planned Parenthood luncheon a few years later, he wrote to the organizers that he would be “very happy” to attend.34

  Koprowski’s legendary charm had fallen flat with Ravdin, who in mid-1959 was rapidly coming to consider the ebullient Pole manipulative and untrustworthy; one year later Ravdin would lead the failed attempt by a faction of the Wistar Board of Managers to oust Koprowski.35 But Ravdin almost certainly agreed to Koprowski’s request that the hospital ferry fetuses to Hayflick for a simple reason: he believed in scientific progress and was not willing to let personal politics get in the way of it.

  Ravdin had been helping Wistar scientists from his earliest days as surgeon in chief. “We can assist you in providing any amount of tumor tissue for your work. Just let me know what you want and when you want it,” he wrote to the elderly
cancer scientist Margaret Lewis after she asked for samples from malignant tumors in 1947.36 A decade later William McLimans, a Wistar virologist, wrote to Ravdin that he had found interesting results in tissue that Ravdin had provided from the breast cancers of twelve HUP patients. He wondered if he could look at their medical records. “This letter will give you access to our Record Room in the Hospital,” Ravdin wrote back.37

  Hayflick himself had likely already benefited from I. S. Ravdin’s support: when Hayflick needed tumor samples to begin his investigation of whether viruses might cause human cancers, it was I. S. Ravdin’s son, Robert Ravdin, then a young general surgeon at HUP with an office four doors down from his father’s, who provided them.38

  In mid-1959 Hayflick began working with the first of a series of fetuses that would arrive, whole, in his lab after he received a phone call from HUP informing him that an abortion had been done and a fetus was available. The gynecological surgeons supplied fetuses from pregnancies of three to four months, so that their major organs were developed enough to be dissected and removed for Hayflick’s purposes.39

  Hayflick’s receipt of the fetuses was not subject to paperwork or permissions beyond the go-ahead from I. S. Ravdin that had set the process in motion. The transfers were informal, as virtually all such arrangements were in those days. And while the physical movement of the fetuses was not hidden as one would hide an illicit transaction, it was not paraded openly either, legal realities and moral sensibilities being what they were.

  At eighteen weeks of gestation—in medical parlance, this means eighteen weeks since the mother’s last menstrual period and therefore roughly sixteen weeks after sperm and egg meet at conception—a human fetus is roughly 5.5 inches long, from the top of its head to its rump. (Its legs are tucked up in the fetal position.) It has arms and legs, fully formed fingers and toes, a nose and mouth and lips and ears and fingernails. It can blink, grasp, sleep, move its mouth, and kick. Its skin is so new and translucent that the underlying vessels look like vivid red highways on a complicated road map. True, its eyes are still closed, and its head is huge compared with the rest of its body, giving it a slightly alien appearance. The nerve pathways in its brain that will lead to consciousness are just beginning to sprout.40 It cannot survive outside the womb. But there is no mistaking it for anything but an incipient human being.

 

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